Fundamentalsof

Fundamentals of

Pharmacology
for Paramedics
EDITED BY
IAN PEATE
SUZANNE EVANS
LISA CLEGG
https://t.me/ems_book
Fundamentals of

Pharmacology
for Paramedics
To all those health professionals who have put themselves in harm’s way to care for patients in the
front lines of the COVID-19 pandemic.
Fundamentals of

Pharmacology
for Paramedics
Edited by

IAN PEATE, OBE, FRCN

Senior Lecturer
University of Roehampton
London, UK

SUZANNE EVANS, PhD

Associate Professor
University of Newcastle Australia
Callaghan, Australia

LISA CLEGG, PhD, MHLTHSC, BHLTHSC

Senior Lecturer
Charles Sturt University
Australia
This edition first published 2022
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Library of Congress Cataloging-in-Publication Data

Names: Peate, Ian, editor. | Evans, Suzanne, editor. | Clegg, Lisa, editor.
Title: Fundamentals of pharmacology for paramedics / edited by Ian Peate,
Suzanne Evans, Lisa Clegg.
Description: Hoboken, NJ : Wiley-Blackwell, 2022. | Includes
bibliographical references and index.
Identifiers: LCCN 2022000521 (print) | LCCN 2022000522 (ebook) | ISBN
9781119724285 (paperback) | ISBN 9781119724315 (Adobe PDF) | ISBN
9781119724322 (epub)
Subjects: MESH: Pharmacology–methods | Emergency Medical Technicians
Classification: LCC RM300 (print) | LCC RM300 (ebook) | NLM QV 704 | DDC
615.1–dc23/eng/20220119
LC record available at https://lccn.loc.gov/2022000521
LC ebook record available at https://lccn.loc.gov/2022000522

Cover Design: Wiley

Cover Image: © sturti/Getty Images

Set in 9/11pt Myriad by Straive, Pondicherry, India

10 9 8 7 6 5 4 3 2 1
Contents

Contributors xiii
Preface xxi
Acknowledgements xxiii
Prefixes, suffixes and abbreviations xxiv

Chapter 1 Introduction to pharmacology 1

Suzanne Evans and Tanya Somani
Aim 1
Naming and classifying drugs 5
How drugs bring about their actions 6
How are we able to manipulate physiological function using drugs? 6
Receptors as sites of drug action 7
Enzymes as sites of drug action 7
Ion channels 7
Transport molecules 9
Selectivity of binding and its effect 11
The drug–body interaction is a dynamic process 11
Conclusion 14
Glossary 14
References 15
Further reading 15
Multiple-choice questions 15

Chapter 2 How to use pharmaceutical and prescribing reference guides 18

Nigel Conway and Jennifer Dod
Aim 18
Introduction 19
HCPC Standards of conduct, performance and ethics 19
HCPC Standards of proficiency for paramedics 20
Joint Royal Colleges Ambulance Liaison Committee (JRCALC)
Clinical Practice Guidelines 21
JRCALC Update information 22
How to navigate the JRCALC Guidelines 23
JRCALC Pocket Book 30
JRCALC Guidelines digital application (app) 31
Useful additional resources 32
British National Formulary (BNF) 32
Monthly Index of Medical Specialities 33
Electronic Medicines Compendium (EMC) 34
Conclusion 34
Disclaimer 35
References 35
Further reading
Multiple-choice questions
Contents

Chapter 3 Legal and ethical issues 37

vi Claire Leader, Emma Senior, Deborah Flynn and Paul Younger
Aim 37
Introduction 38
The law 38
Ethical principles and theories 39
Regulatory bodies 43
Research 45
Conclusion 47
Glossary 47
References 48
Further reading 49
Multiple-choice questions 50

Chapter 4 Medicines management and the role of the paramedic 52

Annette Hand, Carol Wills and Paul Younger
Aim 52
Introduction 53
Medicines management 53
Manufacturing, marketing, procurement and sale 54
Selection 55
Supply 55
Patient-specific directions 56
Prescriptions 56
Patient Group Directions 56
Exemptions 57
Prescribing 59
Handling and administration 60
Special consideration: Controlled Drugs and critical medications 62
Groups requiring special considerations 63
Monitoring for side-effects 64
Medicines optimisation 64
Safety in medicines management 65
Storage and disposal 66
Conclusion 66
References 66
Further reading 68
Multiple-choice questions 68

Chapter 5 Pharmacodynamics and pharmacokinetics 70

Dan Davern
Aim 70
Introduction 70
Professional regulatory council 71
Programmes of education and training 71
Pharmacokinetics 71
The pharmacokinetic processes 71
Phase 1: absorption 72
Phase 2: distribution 76
Phase 3: metabolism (biotransformation) 77
Phase 4: elimination 79
Pharmacodynamics
Agonists and antagonists
Contents

Drug potency and efficacy 84

Therapeutic index 84 vii
Adverse drug reactions 85
Conclusion 87
References 87
Further reading 87
Multiple-choice questions 88

Chapter 6 Drug formulations 90

Sarah Dineen-Griffin and Barbara C. Wimmer
Aim 90
Introduction 91
Routes of drug administration 91
Parenteral administration 92
Intravenous administration 92
Subcutaneous administration 93
Intramuscular administration 93
Intraosseous administration 95
Intrathecal administration 95
Intradermal administration 95
Formulations 97
Localised versus long-acting injectable formulations 97
Topical formulations 97
Inhaled formulations 99
Enteral formulations 101
Rectal formulations 105
Conclusion 105
Glossary 106
References 106
Further reading 108
Multiple-choice questions 108

Chapter 7 Adverse drug reactions 110

Matt Dixon
Aim 110
What is an adverse drug reaction? 110
Classification of adverse drug reactions 111
How prevalent are adverse drug reactions? 111
Who is more likely to experience adverse drug reactions? 112
Recognising signs and symptoms of adverse drug reactions 114
Anaphylaxis 114
Rashes and skin eruptions 115
Serum sickness 115
Renal disorders 115
Geriatric syndrome 116
Idiosyncratic reactions 117
Preventing adverse drug reactions 117
Managing adverse drug reactions 117
Reporting adverse drug reactions 119
Conclusion 122
References 122
Further reading
Multiple-choice questions
Contents

Chapter 8 Analgesics 125

viii Tom Mallinson
Aim 125
Pain and analgesia 125
Understanding and assessing pain 125
Why do we treat pain? 126
Psychology of pain 126
Physiology of pain 127
Pain transmission 127
Pain modulation 128
Types of pain 129
Assessment of pain 131
Approach to analgesia 132
Paracetamol 133
Non-steroidal anti-inflammatory drugs 133
Inhalational analgesia 136
Opioids 137
Antagonists 141
Atypical analgesics 142
Antidepressants and antiepileptics 143
Adjuncts to analgesia 143
Magnesium sulfate 143
Local anaesthetics 143
Conclusion 144
Glossary 145
References 146
Further reading 147
Multiple-choice questions 147

Chapter 9 Antibacterials 149

Dean Whiting, Deborah Flynn and Dawn Ball
Aim 149
Introduction 149
Language and terminology 150
Antibacterial mechanisms of action 150
Disruption of bacterial cell wall synthesis: beta-lactams 151
Interference in folate metabolism: sulfonamides, trimethoprim 151
Inhibition of bacterial DNA synthesis: quinolones 151
Inhibition of bacterial protein synthesis: tetracyclines, aminoglycosides,
macrolides, chloramphenicol, lincosamides 151
Choosing the right treatment 151
Antimicrobial resistance 151
Preventing antimicrobial resistance 152
Antimicrobial stewardship (AMS) 153
Antibacterials by clinical use 153
Beta-lactams 153
Tetracyclines 157
Chloramphenicol 158
When administered in combination with phenytoin, monitor
seizure pattern. Aminoglycosides 159
Macrolides 161
Lincosamides
Contents

Conclusion 163
References 163 ix
Further reading 164
Multiple-choice questions 164

Chapter 10 Medications used in the cardiovascular system 167

Lisa Clegg and Fraser Russell
Aim 167
Cardiovascular diseases 167
Hypertension and heart failure 168
Management of hypertension and heart failure 168
Acute coronary Syndrome (ACS) 173
Management of acute coronary syndrome 173
Conclusion 177
Glossary 177
References 178
Further reading 179
Multiple-choice questions 180

Chapter 11 Medications used in the renal system 182

Anthony Kitchener
Aim 182
Introduction 183
Acute kidney injury 183
Chronic kidney disease 185
Management of CKD 185
Electrolyte abnormalities resulting from poor renal function 187
Hyponatraemia (low serum sodium) 187
Hypokalaemia (low serum potassium) and hyperkalaemia
(high serum potassium) 187
Urinary retention and incontinence 187
Drug-induced renal damage 188
Drugs that act on the renal system 188
Diuretics 188
Drugs used to treat urinary retention and urinary incontinence 193
Conclusion 195
Glossary 198
References 200
Further reading 201
Multiple-choice questions 201

Chapter 12 Medications and diabetes mellitus 203

Hayley Croft and Olivia Thornton
Aim 203
Introduction 204
Hormonal control of blood glucose 204
Monitoring diabetes 205
Measuring blood glucose 206
Measuring ketones 207
Drug use in diabetes 207
Insulin replacement therapy
Contents

Metformin 209
x Sulfonylureas 209
Incretin mimetics 210
SGLT-2 inhibitors 210
Thiazolidinediones 211
Alpha-glucosidase inhibitors 211
Drug use in diabetic emergencies 211
Hypoglycaemic emergency 211
Hyperglycaemic emergency 216
Management of hyperglycaemia 218
Conclusion 219
Glossary 219
References 220
Multiple-choice questions 221

Chapter 13 Medications used in the respiratory system 224

Jason McKenna
Aim 224
Introduction 225
Anatomy and physiology 225
Nervous system control 226
Common respiratory emergencies 227
Asthma 227
Chronic obstructive pulmonary disease 230
Croup 231
Pneumonia 232
Pneumothorax 232
Pulmonary oedema 233
Classes of medications 234
Bronchodilators 234
Diuretics 236
Nitrates 236
Steroids 237
Medical gases 238
Oxygen devices 238
Conclusion 239
Find out more 239
References 239
Further reading 241
Multiple-choice questions 241

Chapter 14 Medications used in the gastrointestinal system 243

George Bell-Starr and Ashley Ingram
Aim 243
Introduction 244
Anatomy and physiology of the gastrointestinal system 244
Nausea and vomiting 244
H1 receptor antagonists (antihistamines) 246
Dopamine (D2) receptor antagonists 246
Serotonin (5-HT3) receptor antagonists 246
Peptic ulcers 247
Helicobacter pylori infections
Contents

Non-steroidal anti-inflammatory drugs 248

Symptoms of peptic ulcer 248 xi
Constipation 249
Laxatives 249
Gastro-oesophageal reflux disease 251
Drug interventions (patients with confirmed endoscope diagnosis) 252
Paramedic practice 252
Antidiarrhoeals 254
Inflammatory bowel disease (IBD) 255
Crohn’s disease 255
Ulcerative colitis 255
Drug treatment for inflammatory bowel disease 255
Conclusion 257
References 257
Multiple-choice questions 258

Chapter 15 Medication and the nervous system 261

Geoffrey Bench, Alastair Dolan, Lena Solanki, Paul Doherty, Charlotte White,
Ricky Lawrence and Emma Beadle
Aim 261
Introduction 261
The nervous system 262
Parkinson disease and parkinsonism 262
Infections 264
Dementia 264
Drugs used in dementia 265
Cautions 266
Epilepsy 267
Antiepileptic medication 268
Psychogenic non-epileptic seizures (PNES) versus bilateral tonic
clonic seizures (BTCS) 268
Emergency medication in the prehospital setting 268
Strokes (including transient ischaemic attacks) 270
Definition of a stroke and a transient ischaemic attack 271
Assessment of a stroke 271
Treatment 272
Conclusion 274
References 274
Further reading/resources 275
Multiple-choice questions 276

Chapter 16 Medications used in mental health 278

Liam Rooney
Aim 278
Introduction 278
Neurotransmitters 279
Antidepressants 280
Selective serotonin reuptake inhibitors 281
Monoamine oxidase inhibitors 282
Serotonin and noradrenaline reuptake inhibitors 283
Serotonin syndrome 283
Other atypical antidepressants
Contents

Anxiolytics 285
xii Pregabalin 285
Benzodiazepines 285
Buspirone 286
Beta-blockers 286
Hypnotics 286
Benzodiazepines 286
Z-drugs 287
Mood-stabilising medications 287
Lithium 287
Valproate 287
Antipsychotics 288
Antipsychotic-related side-effects 288
Other side-effects 289
Dementia 291
Acetylcholinesterase inhibitors 291
Memantine 292
Attention deficit-hyperactivity disorder 292
Stimulants 292
Non-stimulants 292
Conclusion 293
Find out more about these conditions 293
Glossary 293
References 294
Further reading 296
Resources 296
Multiple-choice questions 296

Chapter 17 Immunisations 299

Michael Fanner
Aim 299
Introduction 299
Understanding the fundamental epidemiological concepts
and theories in preventing infectious diseases 300
Essential ways of examining infectious diseases 301
Becoming familiar with vaccine design to underpin clinical
practice knowledge 302
Vaccine design 302
Appreciating public concerns in the acceptability and uptake
of immunisations 303
Vaccine acceptability 307
Recognising the role of the paramedic in health promotion
and immunisation administration 308
Immunisations as prescription-only medicines 308
Embedding immunisation history taking in clinical assessment 309
Conclusion 315
References 316
Further reading 317
Multiple-choice questions 317
Normal Values 319
Answers 323
Index
Contributors

Dawn Ball
PGCert ROM, Dip IMC (RCSEd), MCPara. Senior Lecturer University of Cumbria, Enhanced Care
Paramedic (Bank) North East Ambulance Service.
Dawn started her medical career in the Royal Army Medical Corps in 1997 where she trained as a
combat medical technician. Deploying across the globe in both operational and humanitarian roles,
she gained invaluable experience in both trauma and primary care. In 2014 Dawn qualified as a
paramedic at the University of Cumbria and has since used her knowledge and experience to help
train others in combat casualty care and prehospital emergency care. Dawn has a keen interest in
trauma and paediatrics and regularly instructs on several Resuscitation Council UK courses.

Emma Beadle
BSc(Hons), PGCert, MCPara. Advanced Paramedic Practitioner (Urgent Care).
Emma has 20 years’ experience with the London Ambulance Service. She started as a qualified
ambulance technician and became a paramedic in 2007. In 2011 she joined the Clinical Education
department as a training officer with an IHDC instructor qualification. Emma graduated with a
degree in paramedic science with emergency care practice in 2012 from the University of
Hertfordshire. In 2016 she gained a postgraduate certificate in healthcare education from Anglia
Ruskin University. Currently Emma is an advanced paramedic practitioner in urgent care and is
studying for a master’s in advanced clinical practice at St George’s University London.

George Bell-Starr
FdSc, MCPara. Trainee Advanced Clinical Practitioner.
George began his career in paramedicine studying at the University of Worcester before starting
with South Western Ambulance Foundation Trust as a newly qualified paramedic in 2017. He has
continued to study, focusing particularly on clinical reasoning. His key areas of interest include men-
toring, developing paramedic practice and frailty. In late 2020 he began training as an advanced
practitioner in primary care within the Mid-Dorset Primary Care Network.

Geoffrey Bench
PGCert Medical Healthcare Education, Dip HE (Emergency Care), CAVA. Clinical Tutor/Driving
Instructor, L4CERADI Motorcycle Response Unit/Cycle Response Unit, Paramedic.
Geoff began his ambulance career as an emergency medical technician (EMT) with the London
Ambulance Service (LAS) 27 years ago, progressing to paramedic and then emergency care practi-
tioner. Geoff has a passion for motorcycles which culminated in him joining the Motorcycle Response
Unit with the LAS. Geoff moved into the education department 7 years ago and still works clinical
shifts to maintain the high standards he sets himself.

Lisa Clegg
PhD, MHlthSc, BHlthSc. Senior Lecturer.
Dr Lisa Clegg has worked in healthcare delivery since 1980. After qualifying as a registered nurse,
Lisa worked in several different areas within the hospital and aged care settings. From 1998 to 2009
she was employed with Ambulance Tasmania in the roles of paramedic, intensive care paramedic
and paramedic educator. Whilst employed as a paramedic educator, Lisa worked with University of
Tasmania academics to develop and deliver the Associate Degree in Paramedicine. In 2009 Lisa was
appointed senior lecturer in paramedicine at the University of Tasmania where she was part of a
team that developed and delivered the Bachelor of Paramedic Practice (BPP). Lisa was course co-
ordinator for the BPP for 2 years. In 2016, Lisa was appointed as a senior lecturer in paramedicine at
Contributors

the University of the Sunshine Coast (USC). Lisa has completed a PhD researching mental healthcare
xiv in out-of-hospital practice. In 2021, Lisa commenced employment as a senior lecturer in paramedi-
cine at Charles Sturt University (CSU).

Nigel Conway
MSc, BA (Hons). Cert Ed, RODP, Principal Lecturer, Programme Leader.
Nigel qualified in 1988 as an operating department practitioner initially working in a number
of anaesthetic and surgical specialties in Oxford. He went on to develop his clinical career in
the Midlands, London and the south coast of the UK. Alongside this Nigel continued to study,
leading to roles in clinical practice education, lecturer practitioner and full-time academic
employment in higher education, working his way up to principal lecturer. He has a wealth of
experience, having lead and taught on a number of undergraduate and postgraduate healthcare
programmes including paramedic science, non-medical prescribing, leadership and management
and community nurse upskilling projects in the UK and internationally. He has also been involved
with professional and regulatory projects and published a number of professional healthcare-
focused articles and textbooks as well as undertaking a number of external examiner and clinical
advisory roles.

Hayley Croft
BPharm, GCert Diabetes, PhD (Pharmacy), AACP, MPS. Pharmacist – Accredited Consultant.
Hayley began her pharmacy career in Newcastle, New South Wales, Australia, becoming a pharma-
cist and then accredited consultant pharmacist practising in the primary health sector. She later
undertook a postgraduate certificate in diabetes education and management and a PhD in phar-
macy which has led to her developing role as a clinician scientist in multimorbidity care with a focus
on effective and safe utilisation of pharmacotherapies for complex, chronic patients. She has been
delivering clinical pharmacy services to patients living in the community since 2000 and has worked
in pharmacy education and research since 2007. Her key areas of interest are cardiometabolic health,
disability care and pharmacy practice and education. Hayley has published in international peer-
reviewed journals.

Dan Davern
MSc, GDip, BSc, Dip NQEMT-AP, MCPara.
Dan began his career completing a diploma in emergency medical technology – paramedic at the
Royal College of Surgeons in Ireland and working as a firefighter/paramedic with a statutory fire,
rescue and ambulance service. He later undertook a graduate diploma and master of science in
emergency medical science. He is currently a PhD candidate in the field of emergency medicine.
Dan currently practises as an advanced paramedic and is registered in both the UK and Ireland. He
has worked in education since 2010 and is currently Head of Institution at DX2 in Dublin. His key
areas of interest are prehospital airway management and clinical practice guideline development.
Dan sits on the NAEMT European Education Committee and Pre-Hospital Emergency Care Council’s
education and standards committee.

Sarah Dineen-Griffin
PhD, MPharm, GradCertPharmPrac, BBSci, AACPA, AdvPP(II), MPS. Lecturer.
Sarah is a lecturer in health management and leadership at Charles Sturt University, Australia.
She has been a research investigator on national and international pharmacy projects and has
published in international journals. At an international level, she is an editorial board member for
Pharmacy Practice and Research in Social and Administrative Pharmacy. Sarah is an executive com-
mittee member of the Community Pharmacy Section of the International Pharmaceutical
Federation. At a national level, she is Vice President of the Pharmaceutical Society of Australia’s
New South Wales Branch, and appointed to the Expert Advisory Committee leading the Review
of the Australian National Medicines Policy. Sarah was named Early Career Pharmacist of the Year
in 2021.
Contributors

Matt Dixon
MSc, PGCert, BSc (Hons), FdSc, MCPara. Advanced Clinical Practitioner/Bank Specialist xv
Paramedic (Urgent and Emergency Care).
Matt began his career in 2007 as a community first responder, graduating as a paramedic in 2011. He
initially worked on ambulances in Wiltshire, UK, providing the normal range of paramedic care, before
taking on additional responsibility as a mentor and educator working with new students and develop-
ing colleagues. He moved into urgent care in 2016, completing an MSc and working in a senior admis-
sion avoidance role within the ambulance service. In 2018 he left to work in general practice in a surgery
in Bristol, going on to be one of the first paramedic prescribers in the UK. He has a small portfolio of
publications and recently has written on the topic of prescribing for paramedics and pharmacology.

Jennifer Dod
BSc (Hons), FdSc, Paramedic. Lecturer – Paramedic Practice.
Jenny graduated from the University of Sussex in 2006 with a first class honours degree in chemistry.
She then worked for 5 years as a research scientist for an Oxfordshire pharmaceutical company. She
worked in early-stage drug design and discovery on a variety of clinical projects, including those
targeting Alzheimer disease and neuropathic pain via sodium ion channels. In 2011 she joined
South Central Ambulance Service as an emergency care assistant. She qualified as an ambulance
technician in 2014 and gained a foundation degree in paramedic sciences from Oxford Brookes in
2015. After gaining her paramedic registration, she worked at Kidlington Ambulance Station as a
paramedic and clinical mentor. In 2018 she returned to Oxford Brookes to join the paramedic sci-
ences teaching team as a lecturer specialising in pharmacology. She is also a qualified prehospital
trauma life support instructor and is currently studying part time for a master’s in pharmacology.

Paul Doherty
Paramedic Science (FdSc), Paramedic Science (PGCert), Medical and Healthcare Education
(PGCert). Clinical Education Tutor.
Paul has worked for the NHS since 2012 and began his ambulance career with the London Ambulance
Service in 2013. After graduating from Teesside University, Paul undertook a PGCert in paramedic
science at Hertfordshire University. He has always been passionate about education and enjoyed
mentoring paramedic students before deciding to join the clinical education department at the LAS
in 2019 in a formal teaching role.

Alastair Dolan
Biomedical Science (BSc), Medical and Heathcare Education (PGCert), Clinical Education Tutor.
Alastair graduated from the University of Sheffield in 2007. He has worked for the London Ambulance
Service since 2009, starting as student paramedic and qualifying as a paramedic in 2012. Alastair
undertook a PGCert at Anglia Ruskin University in 2019, when he joined the London Ambulance
Services Clinical Education Team.

Suzanne Evans
Physiology (BSc), Neuropharmacology (PhD), Associate Professor, Biomedical Sciences.
Suzanne gained her PhD in neuroscience at the University of Wales in 1989 and has been researching
and teaching in universities in the UK, USA, the Caribbean, New Zealand and Australia ever since,
receiving numerous teaching awards along the way. She has taught human physiology, pathophysi-
ology and pharmacology at undergraduate and postgraduate level for many years and her special
interest is teaching and assessing these subjects in health professional degrees.

Michael Fanner
RN(Adult), SCPHN(HV), FHEA, PhD, PGDip, PGCert, BSc (Hons). Senior Lecturer.
Michael graduated in adult nursing (2012) and specialist community public health nursing/health
visiting (2013) at King’s College London and was awarded a PhD in social policy at the University of
Greenwich in 2020. Michael was a main architect of the UK’s first MSc in paramedic science (pre-
registration) and subsequent module leader for a range of paramedic theory modules. Michael is
Contributors

currently a senior lecturer in specialist community public health nursing at the University of
xvi Hertfordshire and is an external examiner for the BSc (Hons) paramedic science programmes at the
University of Huddersfield. Michael has research interests in ethically complex social issues in clinical
practice and is an associate editor for Child Abuse Review.

Deborah Flynn
Doctor of Nursing, MA Medical Education, PGC Academic Practice, BSc (Hons) Health and
Social Care, DipHE General Nursing, Registered Nurse (RN), Registered Teacher (NMC), Fellow
(FHEA), Senior Lecturer Adult Nursing, Northumbria University.
Deborah became a student nurse in 1986 at BG Alexander Nursing College and Johannesburg
General Hospital (now Charlotte Maxeke Johannesburg Academic Hospital) in Johannesburg,
South Africa, completing her studies as a registered nurse (general, community health and psy-
chiatry) and midwife in 1990. Deborah worked across the South African public and private sector
in general surgical and neuro medical wards. From 1993 to 2002, she worked as a staff nurse. rising
to a charge nurse, in Germany and Switzerland in a variety of disciplines. In 2002, she returned to
Britain to work as a staff nurse on an acute stroke unit. Entering the educational sector in 2005,
Deborah progressed from practice educator to senior lecturer and has taught on both under-
graduate and postgraduate programmes. In 2018, she completed her doctorate exploring student
nurses’ experience of humour use in the clinical setting. Her key interests are clinical skills, humour
in clinical care, stroke care, pharmacology and practice supervisor/assessor preparation.

Annette Hand
Prof. Doc (Health), MA, PGDip (CR), Dip HE, RGN. Nurse Consultant/Associate Professor/
Clinical Lead – Nursing.
Annette has a clinical academic position and divides her time between three roles. She has worked
within the Parkinson’s Northumbria Team in the UK for over 23 years, starting as the research associate
before obtaining a nurse specialist post. For the past 16 years she has worked as a nurse consultant in
Parkinson’s. Her main role is to co-ordinate the Parkinson’s service, support patients and their families
and manage a team of Parkinson’s specialist nurses. As an autonomous practitioner she is responsible
for diagnosis and management of all stages of Parkinson’s. She has worked on and been involved with
multiple research studies at a local, national and international level, including non-motor symptoms,
sexual dysfunction, information prescriptions and care needs in Parkinson’s. Her doctorate focused on
understanding carer strain and its relationship to care home placement for people with Parkinson’s.
Annette was appointed to an associate professor post with Northumbria University in recognition of
her research work within the field of Parkinson’s. She also has the UK national role of clinical lead for
nursing within the Parkinson’s UK Excellence Network, as part of the clinical leadership team. This role
was developed to support service improvements through education, knowledge exchange and
evidence-based practice and support the role of the Parkinson’s nurse across the UK.

Ashley Ingram
BSc (Hons), MCPara. Frailty Practitioner.
Ashley began his career with South Western Ambulance Foundation Trust as an ambulance care assis-
tant. Over the space of 7 years he worked his way up to a registered paramedic, training whilst working
full time. He worked as an ambulance paramedic for 3 years, during which time he took a keen interest
in palliative and end-of-life care. He has recently embarked on a primary care role as a frailty practi-
tioner. Working within a multidisciplinary team, they focus on admission avoidance, with patients who
reside in care homes in Dorset, UK. He looks forward to developing this role in the future.

Anthony Kitchener
MSc, PGCert. Paramedic Educationalist.
As a leader within the health and social care network, Ant has held senior management and
educationalist positions within the public, voluntary and academic sector. He holds a number of
publications, consultancies and award nominations. He is a Master of Science (Education) and a
Master of Arts (Educational Leadership) with various other clinical and professional qualifications.
Contributors

Ricky Lawrence
Clinical Education Tutor. xvii
Ricky has been working in the Clinical Education Standards for the past 2 years. He joined the London
Ambulance Service in 1982 after leaving the army, as a qualified ambulance technician working in
London, qualifying as a NHSTD registered paramedic in 1990. Since then he has had various roles
within the London Ambulance Service and a secondment to the Department of Health Equality and
Human Rights Group, as lead adviser on EQIA. He returned in 2007 as Equality and Inclusion Officer
until 2016 when due to organisational restructuring, he had a number of short roles in safeguarding
and infection prevention control before joining the CES department full time.

Claire Leader
RN, RM, PGCAP, MA, BSc (Hons), FHEA. Senior Lecturer.
Claire qualified as a registered nurse from York University in 1998 after which she moved to Leeds, work-
ing in cardiothoracic surgery and emergency nursing. In 2003 she commenced her midwifery educa-
tion at Huddersfield University where she was awarded a first class BSc (Hons). Working initially at
Sheffield Teaching Hospitals, she later moved to the North East where she commenced her role as a staff
midwife before moving into the area of research as a research nurse and midwife. She was awarded a
distinction for her MA in sociology and social research at Newcastle University in 2012. Claire moved to
Northumbria University in 2018 and is now a senior lecturer and programme lead for pre-registration
nursing programmes, while also studying for her PhD in the area of nurse and midwife wellbeing.

Tom Mallinson
BSc (Hons), MBChB, PGCHE, MRCGP(2020), MCPara, MCoROM, FAWM, FHEA, FRGS. Prehospital
Doctor, Rural Generalist, Responder Support Clinician.
Tom began his career in London, undertaking the IHCD ambulance aid and paramedic qualifications
alongside a Bachelor’s degree in paramedic science at the University of Hertfordshire. After working as
a paramedic for the London Ambulance Service NHS Trust, he attended Warwick Medical School to
qualify as a medical practitioner. He continued his studies with postgraduate qualifications in health-
care education, wilderness medicine and primary care. Tom has published a variety of primary research
and educational resources and is a member of the editorial board for the Journal of Paramedic Practice.

Jason McKenna
BSc, GDip, DipNQEMT AP. Advanced Paramedic Supervisor.
Jason began his prehospital career as an emergency medical technician within the private ambu-
lance services in Ireland. In 2011 he joined the National Ambulance Service as a student paramedic,
graduating from University College Dublin (UCD) with a diploma in emergency medical technology.
In 2015 he continued his education as part of the Bachelor degree programme in paramedic studies
at the University of Limerick. He subsequently joined the advanced paramedic programme, graduat-
ing from UCD in 2018 with a graduate diploma in emergency medical science. He is also a graduate
of the University of South Wales where he studied Acute Medicine. He is a registered assistant tutor
with PHECC and is involved with training and education of all levels of prehospital care from
community first responder to paramedic. His interests lie in prehospital education and research.

Ian Peate
OBE, FRCN. Visiting Professor of Nursing, St George’s University of London and Kingston
University London; Visiting Professor, Northumbria University; Visiting Senior Clinical Fellow,
University of Hertfordshire, and Editor-in-Chief of the British Journal of Nursing. Senior
Lecturer University of Roehampton.
Ian began his nursing career at Central Middlesex Hospital, becoming an enrolled nurse practising
in an intensive care unit. He later undertook 3 years’ student nurse training at Central Middlesex and
Northwick Park Hospitals, becoming a staff nurse and then a charge nurse. He has worked in nurse
education since 1989. His key areas of interest are nursing practice and theory. Ian has published
widely. He is editor in chief of the British Journal of Nursing, founding consultant editor of the Journal
Contributors

of Paramedic Practice and editorial board member of the British Journal of Healthcare Assistants. Ian
xviii was awarded an OBE in the Queen’s 90th Birthday Honours List for his services to nursing and nurse
education and was granted a fellowship from the Royal College of Nursing in 2017.

Liam Rooney
BSc (Hons), GDip, DipNQEMT-AP. Assistant Tutor.
Liam has worked as a firefighter/paramedic with Dublin Fire Brigade since 2007, where he com-
pleted his diploma in emergency medical technology – paramedic with the Royal College of
Surgeons, Ireland. In 2016 he completed a BSc (Hons) in paramedic studies at the University of
Limerick, winning the Graduate Entry Medical School Award for overall performance. In 2017, he
undertook a graduate diploma in emergency medical science through University College Dublin.
Liam currently practises as an advanced paramedic in Ireland. In 2017, he joined the faculty of DX2,
where he delivers multiple courses in prehospital education. He has a keen interest in geriatric medi-
cine and pain management in dementia patients.

Fraser D. Russell
BSc (Deakin), PhD (Univ. Melb.). Associate Professor, University of the Sunshine Coast,
Queensland, Australia.
Fraser’s PhD investigating the regulation of cardiac beta-adrenoceptors was awarded by the University
of Melbourne in 1994. A series of successful postdoctoral appointments followed at the University of
Cambridge, UK (1995–1998), University of Otago, NZ (1998–2000) and University of Queensland,
Australia (2000–2004). Fraser’s research interests have focused on providing a better understanding of
the intracellular trafficking and cardiovascular function of endothelin-1, urotensin II and glial cell line-
derived neurotrophic factor. Since taking a faculty position at the University of the Sunshine Coast
(2005–), Fraser has developed a research programme in natural product therapies, with a focus on
providing new ideas for the management of patients with abdominal aortic aneurysm and aberrant
wound healing responses, where there are limited pharmacological treatment options.

Emma Senior
MSc Academic and Professional Learning, BSc (Hons) Promoting Practice Effectiveness (Public
Health/Health Visiting), DipHE Nursing Studies (Adult), Registered Nurse (RN), Registered
Specialist Community Public Health Nurse (SCPHN), Registered Teacher (NMC), Fellow (FHEA).
Senior Lecturer, Northumbria University.
Emma is an NMC registered teacher, nurse and health visitor with over 10 years of experience in the
NHS and 10 years teaching experience with Northumbria University. She began her nurse career in
theatres specialising in women’s and children’s health before qualifying as a health visitor in 2006.
She then went on to work as a sexual health advisor across North Yorkshire where she was able to
work collaboratively with a range of services and organisations which included the military, primary
care and secondary education. Emma joined higher education in 2009, taking her first post as a
senior lecturer/practitioner implementing a workforce development initiative called Northumbria
Integrated Sexual Health Education (NISHE) for postqualified nurses across County Durham and
Darlington and then project managed delivery across the south west of England with the University
of West England. This involved the development and delivery of e-learning educational materials
along with supporting academic staff and students in their practice setting. In 2012, Emma joined
the pre-registration nurse team where she has been able to introduce, develop and co-ordinate
e-learning packages on the programme. Along with teaching pre-registration healthcare, Emma has
maintained her postregistration nurse teaching within sexual health, safeguarding and public
health within the Specialist Community Public Health Nurse programme. During her time at
Northumbria University, Emma was part of the workforce development team working in collabora-
tion with external partners to create education packages to develop the workforce. In 2015, Emma
became involved with and is programme lead for Northumbria University’s innovative programme
for professional non-surgical aesthetic practice which has been a trailblazer nationally. Emma’s key
areas of interest are public health, sexual health, military families and technology-enhanced learn-
ing. She has published widely in journals and is a fellow of the Higher Education Academy.
Contributors

Lena Solanki
DipHe Paramedic Practice. Paramedic Clinical Tutor. xix
Lena’s career began in 1998 with the Lancashire Ambulance Service as a call taker. After a brief
spell adjusting to life as a new mum, she started training with the London Ambulance Service in
2010 as a student paramedic. She joined the clinical education and standards department in
2018 and trained as a clinical tutor, achieving her teaching qualification in 2020. Lena has enjoyed
her career with the London Ambulance Service and finds it immensely rewarding. Lena likes to
help others especially during their times of need and supports them in achieving their goals.

Tanya Somani
MSc. Registered Paramedic.
Tanya began her career in paramedicine in 2008 practising in metropolitan and regional NSW
Australia. Tanya completed a Bachelor Paramedicine (University of Tasmania) and undertook volun-
teer work in Papua New Guinea. She developed an interest in infection control, attaining a graduate
certificate in clinical redesign (University of Tasmania), with a focus on environmental cleaning of
ambulances, and an infection prevention and control qualification from the Australian College of
Infection Prevention and Control. Tanya worked as part of the Sydney Metropolitan Ambulance
Infrastructure program as program manager for the Make Ready Model and as station officer. Tanya
has been the recipient of the Safety Thinker Award 2021 for NSW Ambulance, International Woman
of the Year award 2021 from Council Ambulance Authorities and received a Commissioner Citation
in 2021. Currently she is health relationship manager for NSW Ambulance. Tanya is passionate about
patient and paramedic safety with a focus on systems improvement and project management.

Olivia Thornton
BEnvSc, Dip Pre-hospital Care, MPharm (Dist), AACPa, MSHPA. Pharmacist – Accredited Consultant.
Olivia began her career as a paramedic with the New South Wales Ambulance Service. During her 10
years of service as a paramedic, she worked at multiple sites in NSW, including metropolitan and
regional areas. Olivia undertook a master’s in pharmacy through the University of Newcastle, gradu-
ating with distinction. Her pharmacy career has included working in community pharmacy, hospital
pharmacy, consultancy work and as a clinical associate lecturer for an undergraduate pharmacy
program. She has an interest in improving medication safety for people with complex chronic health
conditions throughout their medical journey, including during hospital admissions, aged care/
disability care or at home. Her clinical interest areas are pre- and postsurgical admission, diabetes,
Parkinson disease and mental health pharmacology.

Charlotte White
BSc (Hons) Paramedic Science and PGCert Medical Healthcare Education. Education Centre Manager.
Charlotte has worked in paramedicine since 2012. Previously, she worked within a learning disability and
dementia setting, then moved into clinical settings in numerous hospitals. Charlotte has enjoyed mentor-
ing students during her operational duties, which sparked her passion to move into a formal education
working environment, where she is currently undertaking a secondment. Charlotte enjoys the dynamic
and challenging work education can bring, always striving for continuous developmental practice.

Dean Whiting
RN, BN (Hons), BSc (Hons), PgCAP, PgDip(ACP), MSc, FHEA. Principal Lecturer in Advanced
Clinical Practice, University of Hertfordshire. Advanced Clinical Practitioner, Berryfields
Medical Centre, Buckinghamshire. Advanced Clinical Practitioner, London Scottish RFC.
Dean began his career in the British Army as a combat medical technician and then studied at the
Royal Centre for Defence Medicine and the University of Portsmouth to become a registered nurse.
During his time in the military, he mainly specialised in trauma and critical care nursing and was
fortunate enough to work all over the UK and around the world. Since 2012, Dean has worked in
higher education and pursued a clinical career in general practice and sports nursing. He now leads
the MSc in Advanced Clinical Practice at the University of Hertfordshire.
Contributors

Carol Wills
xx MSc Multidisciplinary Professional Development and Education, PGDip Advanced Practice,
Bsc (Hons) Specialist Community Public Health Nursing (SCPHN) (Health Visiting), DipHE
Adult Nursing, Registered Nurse (RN), Enrolled Nurse (EN), Registered Health Visitor (HV),
Community Practitioner Prescriber (NP), Registered Lecturer/Practice Educator (RLP), Senior
Fellow (SFHEA), Subject and Programme Leader Non-Medical Prescribing at Northumbria
University.
Carol began her career undertaking enrolled nurse training in 1983 at Hexham Hospital in
Northumberland. She then worked within neurotrauma at Newcastle General Hospital and then for
several years in coronary care and intensive care at Hexham Hospital. This experience and additional
training to complete registered nurse qualification then stimulated her to focus on primary care and
prevention of ill health. Carol worked as a practice nurse and nurse practitioner in Newcastle city
centre and as a staff nurse within Northumberland community nursing teams before going on to
complete a health visiting degree and working in Newcastle as a health visitor for several years.
During this time, she undertook several leadership and teaching roles including immunisation train-
ing co-ordinator, community practice teacher and trust lead mentor. Carol has been a senior lecturer
at Northumbria University since 2002 and has led several postgraduate professional programmes
including MSc Education in Professional Practice (NMC Teacher programme), PGDip SCPHN and the
Non-Medical Prescribing programme. She has also undertaken national roles including Policy
Advice Committee member and Treasurer for the UK Standing Conference SCPHN Education and
subject expert for several quality approval panels and external examiner roles. Her key areas of inter-
est and research are around developing learning and teaching and advanced level practice.

Barbara C. Wimmer
BPharm (Hons), MSc (Clin Pharm), PhD. Lecturer.
Barbara brings together experience in community and hospital pharmacy and clinical research in
Europe and in Australia. She worked in community pharmacies as pharmacist in charge and is an
approved hospital pharmacist. Barbara has experience teaching pharmacology to nursing students
and oversaw quality assurance in a hospital setting in Austria. Following on from her master of
clinical pharmacy at the University of Strathclyde, Scotland, she returned to Steyr Hospital in Austria
to lead the service for drugs information and clinical pharmacy. Barbara’s PhD studies at Monash
University in Melbourne focused on factors associated with medication regimen complexity. She
joined the University of Tasmania in 2016 and teaches clinical pharmacokinetics to undergraduate
students.

Paul Younger
MClinRes, PGCert (Medical Ultrasound), PGCE, BSc(Hons), BA(Hons), DipPUC, FCPara.
Advanced Paramedic Practitioner. North East Ambulance Service.
Paul joined the North East Ambulance Service in 2002, completing his paramedic training in 2005.
He has a master’s in clinical research from Newcastle University, a PGCE, and a postgraduate qualifi-
cation in medical ultrasound. He studied non-medical prescribing at Northumbria University,
becoming one of the first paramedics in the UK to complete their training. He works clinically as an
advanced practitioner for the North East Ambulance Service. A member of the College of Paramedics
council and board since 2010, he has held various posts including regional and alternative regional
representative for the North East, vice and deputy chair before being appointed as vice president in
2021. For his work with the profession and the college, Paul was made a fellow of the College of
Paramedics in 2016. He has presented on paramedic practice at conferences around the world,
including the UK, USA, Canada, Australia, Finland and The Netherlands.
Preface

The key aim of Fundamentals of Pharmacology for Paramedics is to provide the reader with an under-
standing of the essentials associated with pharmacology and paramedic practice so as to enhance
patient safety and patient outcomes. This book can help readers improve and expand their expertise
and self-confidence within the field of paramedicine and enable them to recognise and respond
appropriately to the needs of those they offer care and support to, wherever this may be. The con-
tributors to the text are all experienced clinicians and academics who have expertise in their sphere
of practice.
Pharmacology is the study of how drugs, medicines and substances work together with the body
when they are being used for the management of illness, disease, pain relief and other conditions.
This can be everything from drugs that are used in respiratory care to the action of medications used
as a vaccine.
The paramedic scope of practice at the point of registration continues to be developed within pre-
registration programmes of study around the world, ensuring that the newly qualified paramedic has
the required knowledge and skills to provide best practice healthcare to patients. In many countries,
this also includes ensuring that pre-registration paramedic students are ‘prescriber ready’ once they
have successfully completed their undergraduate programme of study.
If undergraduate paramedic students are to offer care that is safe and effective, then they must be
prepared in such a way that they become accountable practitioners who are able to carry out their
role in a meaningful manner that adheres to professional standards and aligns with the law.
Fundamentals of Pharmacology for Paramedics will help paramedics add to their repertoire of skills as
they gain appropriate pharmacological knowledge. Whilst there is a need to ensure that emphasis is
placed on the principles of safe drug administration in undergraduate curricula, there is also a need
to ensure that students are provided with the pharmacological foundations associated with the big-
ger issues related to medicines management. Knowing how to study this subject effectively is about
developing an effective workable learning strategy. Fundamentals of Pharmacology for Paramedics
provides the reader with an overview of the key issues that can support them as they begin to under-
stand and apply the complexities associated with pharmacology as well as the exciting challenges
that are ahead of them.
The text integrates comprehensive knowledge of pharmacology enabling the reader to formulate
a plan of care that can improve the overall health and wellbeing of the patient. When advising on and
dispensing or administering medicines, this must be done within the limits of the individual’s educa-
tion, training and competence, professional body guidance and other relevant policies and regula-
tions. It is essential to ensure that you keep to the laws of the country in which you are practising.
The paramedic must know the names, mechanism of action, indications, contraindications, com-
plications, routes of administration, side-effects, interactions, dose and any specific administration
considerations for a range of medications. They have to understand relevant pharmacology as well as
the administration of therapeutic medications.
The chapters in this book offer a range of teaching and learning resources that can help you come
to terms with the often complex area of pharmacology and paramedicine. The book can be used in a
number of ways; for example, you may choose to read Chapters 1–7 first and then dip in and out of
the remaining chapters as you need them. Trying to learn everything at once has the potential to
cause confusion which can eventually result in a loss of confidence, affecting your ability to learn and
assimilate. Avoid trying to learn large volumes of information and copious amounts of detail all at
once; focus instead on only those details that can help you achieve your aims.
Often pharmacology modules, as part of the wider curriculum, will require the student to safely
administer the appropriate medication, correctly monitor medicated patients in accordance with
established protocols/policy, understand the drug’s mechanism of action, indication for use, routes
Preface

of administration, how the drug is absorbed, distributed, metabolised and eliminated, contraindica-
xxii tions, drug interactions and a lot more. Recognising each drug you use and learning the differences
and similarities between drugs is key to understanding the fundamentals of pharmacology.
Pharmacology is an important subject and it is vital that you effectively learn the various drugs, their
categories, mechanisms of action, pharmacodynamics and pharmacokinetics. The 17 chapters in this
book will help you come to terms with what is often seen as a complex and sometimes terrifying
subject.
The paramedic scope of practice at the point of registration continues to be developed within
pre-registration programmes of study, ensuring that the newly qualified paramedic is fit for practice.
The scope of practice for specialist, advanced and consultant paramedics is being defined and
refined around the world. A sound understanding of the fundamentals of pharmacology related to
paramedicine will help you attain the goals that you set today.
We hope you enjoy using this book as you develop personally and professionally. Having a detailed
understanding of how drugs work and why they are given has the potential to help you become a
great paramedic.

Ian Peate, London, UK

Suzanne Evans, Newcastle, New South Wales, Australia
Lisa Clegg, New South Wales, Australia
Acknowledgements

Ian wishes to thank his partner Jussi Lahtinen for his unfailing encouragement and Mrs Frances
Cohen for her ongoing support.
Suzanne would like to thank everyone who has contributed to the writing of this text at such a
difficult time for health professionals.
Lisa wishes to thank her wife Jennie for her ongoing love and support.
Prefixes, suffixes and
abbreviations

Prefix: A prefix is positioned at the beginning of a word to modify or change its meaning. Pre means
‘before’. Prefixes may also indicate a location, number, or time.
Suffix: The ending part of a word that changes the meaning of the word.
Prefix or suffix Meaning Example(s)
a‐, an‐ not, without analgesic, apathy
ab‐ from; away from abduction
abdomin(o)‐ of or relating to the abdomen abdomen
acous(io)‐ of or relating to hearing acoumeter, acoustician
acr(o)‐ extremity, topmost acrocrany, acromegaly,
acroosteolysis, acroposthia
ad‐ at, increase, on, toward adduction
aden(o)‐, aden(i)‐ of or relating to a gland adenocarcinoma, adenology,
adenotome, adenotyphus
adip(o)‐ of or relating to fat or fatty tissue adipocyte
adren(o)‐ of or relating to adrenal glands adrenal artery
‐aemia blood condition anaemia
aer(o)‐ air, gas aerosinusitis
‐aesthesi(o)‐ sensation anaesthesia
alb‐ denoting a white or pale colour albino
‐alge(si)‐ pain analgesic
‐algia, ‐alg(i)o‐ pain myalgia
all(o‐) denoting something as different, or as an alloantigen, allopathy
addition
ambi‐ denoting something as positioned on ambidextrous
both sides
amni‐ pertaining to the membranous fetal sac amniocentesis
(amnion)
ana‐ back, again, up anaplasia
andr(o)‐ pertaining to a man android, andrology
angi(o)‐ blood vessel angiogram
ankyl(o)‐, ancyl(o)‐ denoting something as crooked or bent ankylosis
ante‐ describing something as positioned in antepartum
front of another thing
anti‐ describing something as ‘against’ or antibody, antipsychotic
‘opposed to’ another
arteri(o)‐ of or pertaining to an artery arteriole, arterial
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

arthr(o)‐ of or pertaining to the joints, limbs arthritis xxv
articul(o)‐ joint articulation
‐ase enzyme lactase
‐asthenia weakness myasthenia gravis
ather(o)‐ fatty deposit, soft gruel‐like deposit atherosclerosis
atri(o)‐ an atrium (especially heart atrium) atrioventricular
aur(i)‐ of or pertaining to the ear aural
aut(o)‐ self autoimmune
axill‐ of or pertaining to the armpit axilla
(uncommon as a prefix)
bi‐ twice, double binary
bio‐ life biology
blephar(o)‐ of or pertaining to the eyelid blepharoplast
brachi(o)‐ of or relating to the arm brachium of inferior colliculus
brady‐ ‘slow’ bradycardia
bronch(i)‐ bronchus bronchiolitis obliterans
bucc(o)‐ of or pertaining to the cheek buccolabial
burs(o)‐ bursa (fluid sac between the bones) bursitis
carcin(o)‐ cancer carcinoma
cardi(o)‐ of or pertaining to the heart cardiology
carp(o)‐ of or pertaining to the wrist carpal tunnel
‐cele pouching, hernia hydrocele, varicocele
‐centesis surgical puncture for aspiration amniocentesis
cephal(o)‐ of or pertaining to the head (as a whole) cephalalgy
cerebell(o)‐ of or pertaining to the cerebellum cerebellum
cerebr(o)‐ of or pertaining to the brain cerebrology
chem(o)‐ chemistry, drug chemotherapy
cholecyst(o)‐ of or pertaining to the gallbladder cholecystectomy
chondr(i)o‐ cartilage, gristle, granule, granular chondrocalcinosis
chrom(ato)‐ colour haemochromatosis
‐cidal, ‐cide killing, destroying bacteriocidal
cili‐ of or pertaining to the cilia, the eyelashes ciliary
circum‐ denoting something as ‘around’ another circumcision
col(o)‐, colono‐ colon colonoscopy
colp(o)‐ of or pertaining to the vagina colposcopy
contra‐ against contraindicate
coron(o)‐ crown coronary
cost(o)‐ of or pertaining to the ribs costochondral
crani(o)‐ belonging or relating to the cranium craniology
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

xxvi ‐crine, ‐crin(o)‐ to secrete endocrine
cry(o)‐ cold cryoablation
cutane‐ skin subcutaneous
cyan(o)‐ denotes a blue colour cyanosis
cyst(o)‐, cyst(i)‐ of or pertaining to the urinary bladder cystotomy
cyt(o)‐ cell cytokine
‐cyte cell leukocyte
‐dactyl(o)‐ of or pertaining to a finger, toe dactylology, polydactyly
dent‐ of or pertaining to teeth dentist
dermat(o)‐, derm(o)‐ of or pertaining to the skin dermatology
‐desis binding arthrodesis
dextr(o)‐ right, on the right side dextrocardia
di‐ two diplopia
dia‐ through, during, across dialysis
dif‐ apart, separation different
digit‐ of or pertaining to the finger (rare as a root) digit
‐dipsia suffix meaning ‘(condition of ) thirst’ polydipsia, hydroadipsia, oligodipsia
dors(o)‐, dors(i)‐ of or pertaining to the back dorsal, dorsocephalad
duodeno‐ duodenum duodenal atresia
dynam(o)‐ force, energy, power hand strength dynamometer
‐dynia pain vulvodynia
dys‐ bad, difficult, defective, abnormal dysphagia, dysphasia
ec‐ out, away ectopia, ectopic pregnancy
‐ectasia, ‐ectasis expansion, dilation bronchiectasis, telangiectasia
ect(o)‐ outer, outside ectoblast, ectoderm
‐ectomy denotes a surgical operation or removal mastectomy
of a body part; resection, excision
‐emesis vomiting condition haematemesis
encephal(o)‐ of or pertaining to the brain; also see encephalogram
cerebr(o)‐
endo‐ denotes something as ‘inside’ or ‘within’ endocrinology, endospore
enter(o)‐ of or pertaining to the intestine gastroenterology
epi‐ on, upon epicardium, epidermis, epidural,
episclera, epistaxis
erythr(o)‐ denotes a red colour erythrocyte
ex‐ out of, away from excision, exophthalmos
exo‐ denotes something as ‘outside’ another exoskeleton
extra‐ outside extradural haematoma
faci(o)‐ of or pertaining to the face facioplegic
fibr(o) fibre fibroblast
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

fore‐ before or ahead forehead xxvii
fossa a hollow or depressed area; trench or fossa ovalis
channel
front‐ of or pertaining to the forehead frontonasal
galact(o)‐ milk galactorrhoea
gastr(o)‐ of or pertaining to the stomach gastric bypass
‐genic formative, pertaining to producing cardiogenic shock
gingiv‐ of or pertaining to the gums gingivitis
glauc(o)‐ denoting a grey or bluish‐grey colour glaucoma
gloss(o)‐, glott(o)‐ of or pertaining to the tongue glossology
gluco‐ sweet glucocorticoid
glyc(o)‐ sugar glycolysis
‐gnosis knowledge diagnosis, prognosis
gon(o)‐ seed, semen; also, reproductive gonorrhoea
‐gram, ‐gramme record or picture angiogram
‐graph instrument used to record data or picture electrocardiograph
‐graphy process of recording angiography
gyn(aec)o‐ woman gynaecomastia
haemangi(o)‐ blood vessels haemangioma
haemat(o)‐, haem‐ of or pertaining to blood haematology
halluc‐ to wander in mind hallucinosis
hemi‐ one‐half cerebral hemisphere
hepat‐ (hepatic‐) of or pertaining to the liver hepatology
heter(o)‐ denotes something as ‘the other’ (of two), heterogeneous
as an addition, or different
hist(o)‐, histio‐ tissue histology
home(o)‐ similar homeopathy
hom(o)‐ denotes something as ‘the same’ as homosexuality
another or common
hydr(o)‐ water hydrophobe
hyper‐ denotes something as ‘extreme’ or hypertension
‘beyond normal’
hyp(o)‐ denotes something as ‘below normal’ hypovolaemia
hyster(o)‐ of or pertaining to the womb, the uterus hysterectomy
iatr(o)‐ of or pertaining to medicine, or a physician iatrogenic
‐iatry denotes a field in medicine of a certain podiatry, psychiatry
body component
‐ics organised knowledge, treatment obstetrics
ileo‐ ileum ileocaecal valve
infra‐ below infrahyoid muscles
inter‐ between, among interarticular ligament
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

xxviii intra‐ within intramural
ipsi‐ same ipsilateral hemiparesis
ischio‐ of or pertaining to the ischium, the hip ischioanal fossa
joint
‐ismus spasm, contraction hemiballismus
iso‐ denoting something as being ‘equal’ isotonic
‐ist one who specialises in pathologist
‐itis inflammation tonsillitis
‐ium structure, tissue pericardium
juxta‐ (iuxta‐) near to, alongside or next to juxtaglomerular apparatus
karyo‐ nucleus eukaryote
kerat(o)‐ cornea (eye or skin) keratoscope
kin(e)‐, kin(o)‐, movement kinaesthesia
kinesi(o)‐
kyph(o)‐ humped kyphoscoliosis
labi(o)‐ of or pertaining to the lip labiodental
lacrim(o)‐ tear lacrimal canaliculi
lact(i)‐, lact(o) milk lactation
lapar(o)‐ of or pertaining to the abdomen wall, laparotomy
flank
laryng(o)‐ of or pertaining to the larynx, the lower larynx
throat cavity where the voice box is
latero‐ lateral lateral pectoral nerve
‐lepsis, ‐lepsy attack, seizure epilepsy, narcolepsy
lept(o)‐ light, slender leptomeningeal
leuc(o)‐, leuk(o)‐ denoting a white colour leukocyte
lingu(a)‐, lingu(o)‐ of or pertaining to the tongue linguistics
lip(o)‐ fat liposuction
lith(o)‐ stone, calculus lithotripsy
‐logist denotes someone who studies a certain oncologist, pathologist
field
log(o)‐ speech logopaedics
‐logy denotes the academic study or practice haematology, urology
of a certain field
lymph(o)‐ lymph lymphoedema
lys(o)‐, ‐lytic dissolution lysosome
‐lysis destruction, separation paralysis
macr(o)‐ large, long macrophage
‐malacia softening osteomalacia
mammill(o)‐ of or pertaining to the nipple mammillitis
mamm(o)‐ of or pertaining to the breast mammogram
manu‐ of or pertaining to the hand manufacture
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

mast(o)‐ of or pertaining to the breast mastectomy xxix
meg(a)‐, megal(o)‐, enlargement, million splenomegaly, megameter
‐megaly
melan(o)‐ black colour melanin
mening(o)‐ membrane meningitis
meta‐ after, behind metacarpus
‐meter instrument used to measure or count sphygmomanometer
metr(o)‐ pertaining to conditions of the uterus metrorrhagia
‐metry process of measuring optometry
micro‐ denoting something as small, or relating microscope
to smallness
milli‐ thousandth millilitre
mon(o)‐ single infectious mononucleosis
morph(o)‐ form, shape morphology
muscul(o)‐ muscle musculoskeletal system
my(o)‐ of or relating to muscle myoblast
myc(o)‐ fungus onychomycosis
myel(o)‐ of or relating to bone marrow or spinal myeloblast
cord
myri‐ ten thousand myriad
myring(o)‐ eardrum myringotomy
narc(o)‐ numb, sleep narcolepsy
nas(o)‐ of or pertaining to the nose nasal
necr(o)‐ death necrosis, necrotising fasciitis
neo‐ new neoplasm
nephr(o)‐ of or pertaining to the kidney nephrology
neur(i)‐, neur(o)‐ of or pertaining to nerves and the neurofibromatosis
nervous system
normo‐ normal normocapnia
ocul(o)‐ of or pertaining to the eye oculist
odont(o)‐ of or pertaining to teeth orthodontist
odyn(o)‐ pain stomatodynia
‐oesophageal, gullet gastro‐oesophageal reflux
oesophag(o)‐
‐oid resemblance to sarcoidosis
‐ole small or little arteriole
olig(o)‐ denoting something as ‘having little, oliguria
having few’
‐oma (sing.), tumour, mass, collection sarcoma, teratoma
‐omata (pl.)
onco‐ tumour, bulk, volume oncology
onych(o)‐ of or pertaining to the nail (of a finger or onychophagy
toe)
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

xxx oo‐ of or pertaining to an egg, a woman’s oogenesis
egg, the ovum
oophor(o)‐ of or pertaining to the woman’s ovary oophorectomy
ophthalm(o)‐ of or pertaining to the eye ophthalmology
optic(o)‐ of or relating to chemical properties of opticochemical
the eye
orchi(o)‐, orchid(o)‐, testes orchiectomy, orchidectomy
orch(o)‐
‐osis a condition, disease or increase ichthyosis, psychosis, osteoporosis
osseo‐ bony osseous
ossi‐ bone peripheral ossifying fibroma
ost(e)‐, oste(o)‐ bone osteoporosis
ot(o)‐ of or pertaining to the ear otology
ovo‐, ovi‐, ov‐ of or pertaining to the eggs, the ovum ovogenesis
pachy‐ thick pachyderma
paed‐, paedo‐ of or pertaining to the child paediatrics
palpebr‐ of or pertaining to the eyelid (uncommon palpebra
as a root)
pan‐, pant(o)‐ denoting something as ‘complete’ or panophobia, panopticon
containing ‘everything’
papill‐ of or pertaining to the nipple (of the papillitis
chest/breast)
papul(o)‐ indicates papulosity, a small elevation or papulation
swelling in the skin, a pimple, swelling
para‐ alongside of, abnormal paracyesis
‐paresis slight paralysis hemiparesis
parvo‐ small parvovirus
path(o)‐ disease pathology
‐pathy denotes (with a negative sense) a sociopathy, neuropathy
disease, or disorder
pector‐ breast pectoralgia, pectoriloquy,
pectorophony
ped‐, ‐ped‐, ‐pes of or pertaining to the foot; ‐footed pedoscope
pelv(i)‐, pelv(o)‐ hip bone pelvis
‐penia deficiency osteopenia
‐pepsia denotes something relating to digestion, dyspepsia
or the digestive tract
peri‐ denoting something with a position periodontal
‘surrounding’ or ‘around’ another
‐pexy fixation nephropexy
phaco‐ lens‐shaped phacolysis, phacometer,
phacoscotoma
‐phage, ‐phagia forms terms denoting conditions relating sarcophagia
to eating or ingestion
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

‐phago‐ eating, devouring phagocyte xxxi
‐phagy forms nouns that denotes ‘feeding on’ the haematophagy
first element or part of the word
pharmaco‐ drug, medication pharmacology
pharyng(o)‐ of or pertaining to the pharynx, the pharyngitis, pharyngoscopy
upper throat cavity
phleb(o)‐ of or pertaining to the (blood) veins, a phlebography, phlebotomy
vein
‐phobia exaggerated fear, sensitivity arachnophobia
phon(o)‐ sound phonograph, symphony
phot(o)‐ of or pertaining to light photopathy
phren(i)‐, phren(o)‐, the mind phrenic nerve, schizophrenia
phrenico
‐plasia formation, development achondroplasia
‐plasty surgical repair, reconstruction rhinoplasty
‐plegia paralysis paraplegia
pleio‐ more, excessive, multiple pleiomorphism
pleur(o)‐, pleur(a) of or pertaining to the ribs pleurogenous
‐plexy stroke or seizure cataplexy
pneumat(o)‐ air, lung pneumatocele
pneum(o)‐ of or pertaining to the lungs pneumonocyte, pneumonia
‐poiesis production haematopoiesis
poly‐ denotes a ‘plurality’ of something polymyositis
post‐ denotes something as ‘after’ or ‘behind’ post‐operation, post‐mortem
another
pre‐ denotes something as ‘before’ another (in premature birth
[physical] position or time)
presby(o)‐ old age presbyopia
prim‐ denotes something as ‘first’ or ‘most primary
important’
proct(o)‐ anus, rectum proctology
prot(o)‐ denotes something as ‘first’ or ‘most protoneuron
important’
pseud(o)‐ denotes something false or fake pseudoephedrine
psor‐ itching psoriasis
psych(e)‐, psych(o) of or pertaining to the mind psychology, psychiatry
‐ptosis falling, drooping, downward placement, apoptosis, nephroptosis
prolapse
‐ptysis (a spitting), spitting, haemoptysis, the haemoptysis
spitting of blood derived from the lungs
or bronchial tubes
pulmon‐, pulmo‐ of or relating to the lungs pulmonary
pyel(o)‐ pelvis pyelonephritis
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

xxxii py(o)‐ pus pyometra
pyr(o)‐ fever antipyretic
quadr(i)‐ four quadriceps
radio‐ radiation radiowave
ren(o)‐ of or pertaining to the kidney renal
retro‐ backward, behind retroversion, retroverted
rhin(o)‐ of or pertaining to the nose rhinoplasty
rhod(o)‐ denoting a rose‐red colour rhodophyte
‐rrhage burst forth haemorrhage
‐rrhagia rapid flow of blood menorrhagia
‐rrhaphy surgical suturing nephrorrhaphy
‐rrhexis rupture karyorrhexis
‐rrhoea flowing, discharge diarrhoea
‐rupt break or burst erupt, interrupt
salping(o)‐ of or pertaining to tubes, e.g. Fallopian salpingectomy, salpingopharyngeus
tubes muscle
sangui‐, sanguine‐ of or pertaining to blood exsanguination
sarco‐ muscular, flesh‐like sarcoma
scler(o)‐ hard scleroderma
‐sclerosis hardening atherosclerosis, multiple sclerosis
scoli(o)‐ twisted scoliosis
‐scope instrument for viewing otoscope
‐scopy use of instrument for viewing endoscopy
semi‐ one‐half, partly semiconscious
sial(o)‐ saliva, salivary gland sialagogue
sigmoid(o)‐ sigmoid, S‐shaped curvature sigmoid colon
sinistr(o)‐ left, left side sinistrocardia
sinus‐ of or pertaining to the sinus sinusitis
somat(o)‐, body, bodily somatic
somatico‐
‐spadias slit, fissure hypospadias, epispadias
spasmo‐ spasm spasmodic dysphonia
sperma(to)‐, semen, spermatozoa spermatogenesis
spermo‐
splen(o)‐ spleen splenectomy
spondyl(o)‐ of or pertaining to the spine, the spondylitis
vertebra
squamos(o)‐ denoting something as ‘full of scales’ or squamous cell
‘scaly’
‐stalsis contraction peristalsis
‐stasis stopping, standing cytostasis, homeostasis
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

‐staxis dripping, trickling epistaxis xxxiii
‐stenosis abnormal narrowing in a blood vessel or restenosis, stenosis
other tubular organ or structure
stomat(o)‐ of or pertaining to the mouth stomatogastric, stomatognathic
system
‐stomy creation of an opening colostomy
sub‐ beneath subcutaneous tissue
super‐ in excess, above, superior superior vena cava
supra‐ above, excessive supraorbital vein
tachy‐ denoting something as fast, irregularly tachycardia
fast
‐tension, ‐tensive pressure hypertension
tetan‐ rigid, tense tetanus
thec‐ case, sheath intrathecal
therap‐ treatment hydrotherapy, therapeutic
therm(o)‐ heat thermometer

thorac(i)‐, thorac(o)‐, of or pertaining to the upper chest, chest; thorax

thoracico‐ the area above the breast and under the
neck
thromb(o)‐ of or relating to a blood clot, clotting of thrombus, thrombocytopenia
blood
thyr(o)‐ thyroid thyrocele
thym‐ emotions dysthymia
‐tome cutting instrument osteotome
‐tomy act of cutting; incising, incision gastrotomy
tono‐ tone, tension, pressure tonometer
top(o)‐ place, topical topical anaesthetic
tort(i)‐ twisted torticollis
tox(i)‐, tox(o)‐, toxin, poison toxoplasmosis
toxic(o)‐
trache(a)‐ trachea tracheotomy
trachel(o)‐ of or pertaining to the neck tracheloplasty
trans‐ denoting something as moving or transfusion
situated ‘across’ or ‘through’
tri‐ three triangle
trich(i)‐, trichia, of or pertaining to hair, hair‐like structure trichocyst
trich(o)‐
‐tripsy crushing lithotripsy
‐trophy nourishment, development pseudohypertrophy
tympan(o)‐ eardrum tympanocentesis
‐ula, ‐ule small nodule
ultra‐ beyond, excessive ultrasound
Prefixes, suffixes and abbreviations

Prefix or suffix Meaning Example(s)

xxxiv un(i)‐ one unilateral hearing loss
ur(o)‐ of or pertaining to urine, the urinary urology
system; (specifically) pertaining to the
physiological chemistry of urine
uter(o)‐ of or pertaining to the uterus or womb uterus
vagin‐ of or pertaining to the vagina vagina
varic(o)‐ swollen or twisted vein varicose
vasculo‐ blood vessel vasculotoxicity
vas(o)‐ duct, blood vessel vasoconstriction
ven‐ of or pertaining to the (blood) veins, a vein, venospasm
vein (used in terms pertaining to the
vascular system)
ventricul(o)‐ of or pertaining to the ventricles; any cardiac ventriculography
hollow region inside an organ
ventr(o)‐ of or pertaining to the belly; the stomach ventrodorsal
cavities
‐version turning anteversion, retroversion
vesic(o)‐ of or pertaining to the bladder vesical arteries
viscer(o)‐ of or pertaining to the internal organs, viscera
the viscera
xanth(o)‐ denoting a yellow colour, an abnormally xanthopathy
yellow colour
xen(o)‐ foreign, different xenograft
xer(o)‐ dry, desert‐like xerostomia
zo(o)‐ animal, animal life zoology
zym(o)‐ fermentation enzyme, lysozyme

Abbreviations used in prescriptions

Abbreviation Latin English

a.c. ante cibum Before food
ad lib. ad libitum To the desired amount
b.d. or b.i.d. bis in die Twice a day
c. cum With
o.m. omni mane Every morning
o.n. omni nocte Every night
p.c. post cibum After food
p.r.n. pro re nata Whenever necessary
q.d. quaque die Every day
q.d.s. quaque die sumendum Four times daily
q.i.d. quater in die Four times daily
Prefixes, suffixes and abbreviations

Abbreviation Latin English

q.q.h. quater quaque hora Every four hours xxxv
R. recipe Take
s.o.s. si opus sit If necessary
stat. statim At once
t.d.s. ter die sumendum Three times daily
t.i.d. ter in die Three times daily
Chapter 1
Introduction
to pharmacology
Suzanne Evans and Tanya Somani

Aim
The aim of this chapter is to provide an introductory overview of the aspects of pharmacology that
are important for paramedic practice.

Learning outcomes
After reading this chapter, the reader will:
1. Be aware of the potential for error in every stage of drug administration, and strategies to avoid
medication error.
2. Be able to distinguish the generic and trade names of drugs, and know the conventions for generic
names of drugs in the same class.
3. Know the range of sites at which the majority of drugs act to produce their effects.
4. Understand the importance of correct choice, dosing and administration of a drug.

Test your knowledge

1. Which medicines are considered to be completely safe?
2. How can the risk of accidental harm from medicines be reduced?
3. When taking a medication history, what should you prompt a patient to include?
4. What is the generic name and what is the trade name of a medication and where is each name
located on the packaging?

Pharmacology is the study of medications. It includes the study of how and when to use them
safely and effectively, as well as the search for and the development of new and more effective
medications. Although in paramedicine, the term ‘medication’ is often used in reference to thera-
peutic agents and the term ‘drug’ in reference to illicit agents, in this chapter we will use the term

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 1 Introduction to pharmacology

‘drug’ with the broader meaning of ‘any substance that produces a change in physiological func-
2 tion’ when discussing the pharmacology of the active substances rather than formulated
preparations.
Health practitioners have at their disposal a formidable armoury of powerful pharmacological
agents which have the ability to save lives and relieve suffering. These same agents, used incorrectly,
are equally capable of causing death, suffering and irreparable damage. The use of these powerful
tools comes with a responsibility to know how to use them safely, and to have a deep understanding
of what they can do. Paramedics, often called on to select and correctly use medications in uncon-
trolled environments with the additional pressures of time and stress, have an even greater need to
be experts in the medicines they will administer, performing, as they do, the roles of physician, phar-
macist and nurse in the field. Add to this a constantly evolving scope of practice in paramedicine, and
it can be seen that the expectations placed on paramedics in the practice of pharmacotherapeutics
are very high.
Medication errors in healthcare generally are a significant problem, accounting for a large number
of hospitalisations and deaths per year. In prehospital care in particular, medication errors are
thought to be significantly under-reported (Batt, 2016; Hobgood et al. 2006; Lammers et al. 2014;
Nguyen, 2008). Data from a number of studies on medication errors in Australian hospitals suggested
that between 5% and 10% of administrations may be made in error (Roughead et al., 2013), and in
England alone, more than 237 million medication errors are made every year (Elliott et al., 2018).
Medication errors made in all areas of healthcare are a similar concern in the United States, the
European Union, and in most countries of the world. In recognition of the problem, in 2017 the World
Health Organization launched a global initiative to reduce severe, avoidable medication-associated
harm worldwide by 50% over 5 years.
Medication errors in paramedicine can include the general misuse of a medicine, such as adminis-
tering the wrong dose, using the wrong administration route, or failing to identify contraindications.
But, because the paramedic is responsible for all phases of the administration of the medication,
including the selection of the appropriate medication and the decision about whether and when to
use it, two other types of error can also occur: under- or overuse of medicines. The failure to use a
medication that could be of benefit to a patient, such as failing to give aspirin for acute coronary
syndrome, would be considered an error of underuse, while using an unnecessary medication, or
using a second medication to treat a side-effect produced by the first medication, could be consid-
ered errors of overuse (Batt, 2016).
The Institute of Safe Medication Practices (ISMP) Canada, in its 2020 safety bulletin, reported on a
multi-incident analysis of medication incidents involving paramedicine. This analysis identified the
following five main themes in medication errors in paramedicine:

1. The clinical assessment and management of patients, including taking a complete medical and
medication history.
2. Therapeutic product use, including misreading of labelling or mistaking products with similar
packaging.
3. Intravenous dosing and administration, including calculating dose and setting up pumps.
4. Handover communications, including communication to hospital personnel.
5. Inventory management, including correct restocking of the ambulance with medication and
correct positioning of drugs.

These themes serve to reinforce the multiple responsibilities of paramedics when it comes to admin-
istering medicines – paramedics are responsible for taking a complete patient history, calculating a
correct dose and administering the medication correctly, right through to ensuring the medication is
in the ambulance in the correct place before going out on the road. The scope for medication error
increases with each layer of responsibility.
A number of authors have suggested standard methodologies to ensure that the correct approach
to medicines use is followed every time, especially under high-stress conditions. The following mne-
monic for the assessment of patients was developed by ISMP Canada:
Introduction to pharmacology Chapter 1

SAMPLE
Signs 3
Allergies
Medication
Past pertinent history
Last oral intake
Events leading to injury

Students of paramedicine are usually familiar with the golden rules of safe administration of medi-
cines, published as 10 golden rules (McGovern, 1992) but also appearing in shortened forms. These
rules stipulate that when giving any medication:

1. Give the right drug

2. To the right patient
3. In the right dose
4. Via the right route
5. At the right time
6. Explain about the medication to your patient
7. Take a complete medication history
8. Find out about any allergies
9. Know about potential drug interactions
10. Document each medication administration.

These rules serve as a guide for safe administration of medicines in the field, but they can also be a useful
guide to learning pharmacology. Learning what drugs do and how they do it; who they can be given to
and when caution should be exercised; what dose ranges they should be used in; by what routes they
can be administered and the correct timing of their administration via these routes; what drugs they
cannot be combined with and why, are all part of the pharmacology every student of paramedicine must
learn and continue to add to as they gain professional experience and as new medicines become avail-
able. The need to be a lifelong learner is never more pressing than in the field of clinical pharmacology.
Companies selling medicines are required by law to provide basic information about the medicine
for patients before it is made available to them. In the UK, this information is known as the Patient
Information Leaflet (PIL), and in Australia it is the Consumer Medicines Information (CMI). The aim of
this information is to educate patients about their medicines so that they can ensure they are taking
them safely and effectively.
This information includes:

• What the medicine is used to treat (the indications of the medicine)

• Warnings about when the medicine should not be taken (the contraindications of the medicine)
• Warnings about when the medicine should be taken with caution
• Other medicines that should not be combined with the medicine (known as interactions)
• Possible side-effects (known as adverse effects)
• The dose to take and any special instructions regarding how to take the medicine
• What to do in the case of an overdose of the medicine
• How to store the medicine.
The language used in these documents has been chosen to make the information accessible to any
patient, hence the avoidance of too much technical language, but it is nonetheless the same infor-
mation that health professionals need in order to ensure the safe and effective administration of
medicines to their patients.

Skills in practice
The decision about whether to administer or withhold a medication requires a process of clinical
reasoning, based on your assessment of the patient, their medical and medication history and
the indications and contraindications of the medication.
Chapter 1 Introduction to pharmacology

An indication for a medication is a particular symptom or sign reported or displayed by a patient. An

4 indication should not be confused with a definitive diagnosis. In paramedicine, a primary assessment
and history taking should be carried out if possible, prior to establishing an indication. Administering
an indicated medication should only occur if the potential benefit of the medication is judged to out-
weigh the risk to the patient, such as in the following examples:

• An unconscious child who is hypoglycaemic is indicated for glucose 10% administration. The signs
used here as indications for the medication are both the finding of hypoglycaemia and the child’s
level of consciousness.
• A 50-year-old male patient who is experiencing crushing left-sided chest pain has an indication for
aspirin administration, provided you have established that he has no abnormal bleeding
tendencies.

Sometimes, despite there being an indication for a medication, you will not be able to administer it
because of a contraindication. A contraindication is a reason to withhold medication because it might
cause harm to the patient, as in the following examples:

• Aspirin is contraindicated for analgesia and fever in paediatric patients who are under 16 years of
age because of the risk of Reye’s syndrome. The syndrome is quite rare and only occurs in children,
but is very serious.
• Ipratropium, a bronchodilator commonly used with salbutamol for the treatment of bronchos-
pasm, is usually contraindicated in patients who have glaucoma, as a known side-effect is an
increase in intraocular pressure.
• Amiodarone is an antiarrhythmic indicated for tachyarrhythmias (cardiac arrhythmias which
involve an increased heart rate), but contraindicated in torsades de pointes, a potentially fatal
tachyarrhythmia which can result from long QT syndrome, because amiodarone will result in fur-
ther protraction of the QT interval.

As data about medications are gathered, indications and contraindications may change, so it is
important to remain abreast of these changes in your practice as a paramedic.

Episode of care
You attend a 49-year-old male patient complaining of left-sided central chest pain. He is diaphoretic,
pale and short of breath.
You ask him about his medical history. He reports he has a ‘high blood pressure problem’. You glance
at his medication list and do not recognise any common antihypertensive medications.
Your check his observations and gain a detailed history, while preparing him for a 12-lead ECG. The
ECG suggests a lateral myocardial infarct. Your provisional diagnosis is acute coronary syndrome and
you proceed with administering aspirin and a vasodilator.
En route he rapidly becomes hypotensive with a decreased level of consciousness. At hospital, you
discover he has recently commenced on a vasodilator for aggressive management of his pulmonary
hypertension. This medication was not on his medication list.

You may see medications that patients are taking for indications other than the listed indications.
Vasodilators such as sildenafil (Viagra®) and vardenafil (Levitra®) are often prescribed to males for
erectile dysfunction, but can also be used to treat pulmonary hypertension.
Patients may be unsure what they are taking medications for and it is imperative to gain a detailed
history prior to administration of any medication to ensure contraindications are not encountered.
Medications can be used for purposes other than their primary indication.
Introduction to pharmacology Chapter 1

Naming and classifying drugs 5

Every drug will have a number of names. Knowing the correct name of a drug is vital in the prevention
of medication errors, and becomes even more important when drugs can be identified by several
different names. All drugs will have an individual chemical name which conveys very accurately (at
least to a chemist!) the drug’s molecular structure. These names are usually long, difficult to say and
impossible to remember, and they are usually left to research chemists. Many drugs can also be
known by the name of the chemical class they belong to, such as opioids or benzodiazepines. But it
is the generic, or official, name of the drug that health practitioners should always recognise a drug
by. This name should be sufficiently different from any other drug name to minimise the risk of any
drug being mistaken for another. With a few exceptions, generic names are usually the same regard-
less of where in the world you are, and they often derive in some way from the name of the chemical
class of the drug, which is often convenient as it makes it easy to identify the class a drug belongs to
by its generic name. The generic names of drugs belonging to the statin class of drugs, for example,
end in -statin, with agents such as atorvastatin, rosuvastatin, fluvastatin and simvastatin. Generic
names of drugs belonging to the beta-blocker class end in -olol and include propranolol, atenolol,
pindolol and nebivolol.
Many drug formulations will also have a trade name given to the particular drug formulation by
the company that produced it. These names may relate to the generic name or they may relate more
closely to their therapeutic use, but because of the multiple formulations available and multiple
companies producing them, the trade names of drugs will vary widely depending on where the drug
is sold and what it is sold for. Needless to say, these names are not a reliable way to identify the drugs
but unfortunately, they are often the most prominent and eye-catching name on the packaging,
which will mean that patients will usually refer to drugs by the trade name, unless they are receiving
a generic version of the drug. To try and reduce confusion, the Australian government, for example,
passed a law, effective February 1, 2021, that requires prescribers to write the generic name of the
medication first on any prescription, either without a trade name or with the trade name in brackets
after it. Combined with requirements for drug manufacturers to make the generic name of the active
drug in the medication more prominent on the packaging than the trade name, the aim is to increase
awareness of the active ingredients in medications and to reduce confusion.
With the huge range of drugs currently licensed for use, there are often multiple individual drugs
available for any particular indication, so it is important that we also classify our drugs to make talk-
ing about them easier. We can classify drugs based on their chemical structures, mechanism of action
or broader area of therapeutic use. The functional classifications (those relating to what the drugs do
or what they are used for) are the most widely used, as they reflect the clinical uses of the drugs, but
we often refer to certain groups of drugs by their chemical classification, as usually all agents belong-
ing to a certain chemical class also have a predictable effect on function. Table 1.1 gives some exam-
ples of the ways in which drugs are named and categorised.

Look-alikes and sound-alikes

Mistaking one medication for another because the two names (either generic or trade names) sound
alike or the packages look alike is a common cause of medication error. Errors due to look-alike sound-
alike (LASA) medications have become so widespread that the World Health Organization launched a
worldwide effort to reduce medication errors that come about in this way (WHO, 2007), and many
governments have made changes to their medication labelling and naming The addition of ‘tall man’
writing in the name of a drug has been introduced in the UK, Canada, Australia and the US to make the
differences between drug names clearer. This technique involves capitalising the parts of the name that
are most likely to be misread, for example:

AmiloRIDE, AmlodiPINE, BuPROPion, BupreNORphine.

The mix of capitalised lettering in the name disrupts rapid reading and forces a more careful
observation of the name.
Chapter 1 Introduction to pharmacology

The main element in reducing medication errors, however, continues to be careful cross-checking of
6 LASA medications prior to administration, and ensuring that look-alike medications are not stored in
close proximity to each other. Because the packaging and appearance of medications can change, the
generic name of the medication should always be checked, and the identity of a medication should
never be assumed from its appearance without checking the label. For example, a 500 mL or 1000 mL
bag of clear fluid could be Hartmann solution, sodium chloride or glucose 10%.

Table 1.1 Categorisation of drugs based on clinical usage, general action or specific mechanism
of action.
Specific
mechanism
Generic name Trade names Chemical class Therapeutic use General action of action
Diazepam Valium® Benzodiazepines Anxiolytics Central nervous GABA
Valpam® system agonists
Antenex® depressants
Atorvastatin Lipitor® Statins Cholesterol Lipid-lowering HMG Co-A
Torvastat® synthesis inhibition agents reductase
inhibitors
Candesartan Candesan® - Antihypertensives Blood pressure- Angiotensin
Adesan® lowering agents receptor
Atacand® antagonists
Salmeterol Serevent® - Acute asthma Bronchodilators Long-acting
control beta-2
agonists
Diclofenac Voltaren® Analgesic, Non-steroidal Cyclo-
Voltarol® anti-inflammatory anti- oxygenase
Difenac® inflammatories inhibitors
Clonac®
GABA, gamma-aminobutyric acid; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A.

How drugs bring about their actions

With only one or two exceptions (such as drugs which absorb other substances, e.g. charcoal or resins),
drugs act by binding chemically to specific binding sites. It is this fact which explains the various observed
characteristics of a drug, for example, the relationship between the shape of a drug molecule and its
actions; the relationship between how readily it binds to its site of action and the concentration of drug
needed at the site of action to bring about a therapeutic effect; the relationship between the number of
different binding sites the drug can bind to and the number of different effects it produces; the strength
with which it binds to the site and length of time for which it exerts its effects, and so on.
The site at which a drug binds to have its effects is known as the receptor for that drug, and it may
be a receptor normally used by endogenous signalling molecules, such as hormones or neurotrans-
mitters, or a binding site on an enzyme, ion channel or transport molecule. A substance binding at
any of these sites would be able to alter physiological function when the structure to which the drug
is binding is itself responsible for producing various physiological changes.

How are we able to manipulate physiological

function using drugs?
Physiological systems make use of hundreds of specific signalling chemicals to carry out their own
signalling function and this provides an opportunity to use drugs to mimic or block the effects that
those endogenous signalling chemicals would produce. By employing drugs with chemical structures
Introduction to pharmacology Chapter 1

similar to those of endogenous chemicals, we gain an opportunity to ‘operate the levers’ of the
human machine. Not surprisingly, therefore, the vast majority of the drugs used act by altering the 7
function of one of these key pieces of signalling and transport machinery:

• Receptors
• Enzymes
• Ion channels
• Transport molecules
Drugs used as therapeutic agents act by manipulating physiological mechanisms, which reinforces
the importance of having an understanding of human physiological responses as the basis for under-
standing pharmacology. Without a sound knowledge and understanding of how physiological sys-
tems respond, it is impossible to make sense of how drugs will interact with those systems.

Receptors as sites of drug action

An opioid drug such as morphine acts by binding to the receptors for endogenous opioids and, by
activation of those receptors, produces similar actions to those generated by the endogenous opi-
oids, including analgesia and a range of other effects. Similarly, bronchodilator drugs such as terb-
utaline and salbutamol, used during an episode of acute asthma, produce their bronchodilator effect
by activating adrenergic beta receptors on the airways. These receptors would be activated physio-
logically by adrenaline and noradrenaline secreted during the fight or flight response, and the bind-
ing of adrenaline or noradrenaline to the beta receptors in the airways would produce a dilation of
the airways, allowing a more rapid ventilation of the lungs. A drug which is able to produce this effect
without producing the rest of the fight or flight response is a very useful therapeutic agent during an
episode of acute asthma (Figure 1.1).

Enzymes as sites of drug action

Enzymes are the large proteins that catalyse the thousands of biochemical reactions that maintain
physiological function. An enzyme carries out the catalysis (speeding up) of a particular reaction by
binding the reacting molecules and making it ‘easier’ for the reaction to occur (Figure 1.2). Drugs
which have enzymes as their targets tend to be inhibitors of those enzymes, preventing the normal
reacting substances from binding with the enzyme for catalysis.
Drugs such as non-steroidal anti-inflammatory drugs (NSAIDs), the prototype of which is aspirin,
act by inhibiting the enzyme cyclo-oxygenase, which is responsible for speeding up the reaction
producing a range of important signalling molecules known as prostaglandins. It is the reduced level
of prostaglandins as a result of blockade of cyclo-oxygenase that produces the range of effects asso-
ciated with NSAIDs. Another example of a widely used class of drugs which act by blocking an
enzyme is the statin class, including atorvastatin and fluvastatin. These drugs lower cholesterol levels
by inhibiting the enzyme HMG-CoA reductase, responsible for the production of cholesterol in living
cells.

Ion channels
Ion channels represent the only means for ions to cross cell membranes, and all cells contain multiple
species of ion channel in their membranes. These channels can be gated in a number of ways, and
drugs which can bind to specific channels can alter cellular activity profoundly by altering the pas-
sage of ions across the membrane, thereby altering the cell’s membrane potential. Most drugs that
act in this way block ion channels rather than open them.
The local anaesthetic lidocaine, for example, acts by binding to and inhibiting voltage-gated
sodium channels in neuronal cell membranes, preventing the generation of action potentials by the
affected neurons. Sensory neurons detecting touch, pressure and pain stimuli therefore become less
responsive to those stimuli, resulting in anaesthesia.
The benzodiazepine class of drugs, including agents such as midazolam and diazepam, act by
binding to a chloride ion channel in neuronal membranes.
Chapter 1 Introduction to pharmacology

(a) (b)
8

(c) (d)

(e)

Figure 1.1 Drugs which act at receptors. (a) A cell has receptors for a specific signalling compound
(e.g. a neurotransmitter or hormone) located on the cell membrane. (b) The endogenous signalling
molecule binds to its receptors, fitting the receptor perfectly. (c) The binding triggers a series of
actions inside the cell. These actions would be the normal response to that signalling compound. (d)
If the molecular structure of a drug is sufficiently similar to that of the endogenous signalling com-
pound, the drug will also be able to bind to the receptor and produce the same actions in the cell.
This drug would be known as an agonist at this receptor. (e) If a drug has a molecular structure
vaguely similar to that of the endogenous signalling compound, it may still be able to bind to the
receptor, but not fit it perfectly enough to produce the same actions in the cell. This drug could pre-
vent the endogenous signalling compound (and the agonist) getting to the receptor, thereby block-
ing their actions. This drug would be known as an antagonist at the receptor.
Introduction to pharmacology Chapter 1

(a) Reacting substances (b)

9

Enzyme
Enzyme

(c) (d)

Drug

Enzyme
Enzyme

Figure 1.2 Enzymes operate by binding reacting substances (a) and accelerating their reaction – in
this case the reaction is a combination of two molecules (b), then releasing the product from the
enzyme’s binding site (c). A drug which can also bind to this site can prevent the catalytic function of
the enzyme, thereby reducing the level of product (d).

This channel is opened normally by the inhibitory neurotransmitter GABA (gamma-aminobutyric

acid). Opening a chloride channel in the membrane allows the influx of negatively charged chloride
ions to the cell, which hyperpolarises the cell, making it less likely to produce action potentials. The
benzodiazepine class of drugs also act at this ion channel, albeit at a different site to GABA, but when
they bind, they enhance the inhibitory actions of GABA, and add to the hyperpolarisation of neurons
and the resulting nervous system depressant effect (Figure 1.3).

Transport molecules
The large, complex proteins responsible for active transport of substances across cell membranes
represent another valuable drug target for manipulation of physiological function.
There are active transporters or pumps in all cell membranes for sodium, potassium and calcium
ions, and these are activated when those ions have to be transported across the cell membrane
against their concentration gradient, i.e. from a lower to a higher concentration of ions. Ions can
Chapter 1 Introduction to pharmacology

(a) (b)
10

GABA binding site

Benzodiazepine
binding site

(c)

Figure 1.3 Benzodiazepines act by binding to a chloride channel. (a) The inhibitory neurotransmit-
ter GABA has its receptor on the ligand-gated chloride ion channel in neurons. The channel also has
a binding site for drugs of the benzodiazepine class. (b) Binding of GABA to its receptor opens the
channel, allowing chloride ions to flow into the neuron and hyperpolarise the membrane, inhibiting
further neuronal activity. (c) Binding of a benzodiazepine to its site will, in the presence of GABA,
further increase the flow of chloride ions into the cell by keeping the channel open for longer, thereby
further inhibiting neuronal activity.

move through open ion channels if they are travelling down their concentration gradient, but will
need active ‘pumping’ if they are to move the other way.
As with enzymes and ion channels, the drugs that bind transport molecules tend to inhibit the
transport when they bind. This alters cell function by interfering with the distribution of ions across
the cell membrane, thereby altering membrane potential. The cardiac glycoside drug digoxin, used
to treat cardiac failure, acts by binding to a transport molecule – the sodium/potassium ATP-ase or
sodium/potassium pumps on the cell membranes of cardiac muscle cells. Digoxin inhibits the function
of the sodium/potassium pumps, leading to an accumulation of sodium ions inside cardiac muscle
Introduction to pharmacology Chapter 1

cells, which in turn results in an accumulation of calcium ions in the cells (the additional intracellular
sodium ions stimulate another transporter, which pumps sodium ions out of the cell in exchange for 11
calcium ions). The increased level of calcium ions inside the cardiac muscle cells results in stronger
contractions, which translates to a stronger, more forceful heartbeat.

Selectivity of binding and its effect

Some drugs are very selective in their binding sites, and can bind to a very limited number of sites, or
only one site, but most drugs will be able to bind to more than one site. For example, a bronchodila-
tor medication that acts as an agonist at adrenergic beta receptors may bind at only beta-2 receptor
subtypes, in which case it would be a selective beta-2 agonist, but is more likely to bind to both
beta-1 and beta-2 receptors, because of the degree of chemical similarity between the two receptor
subtypes. The more selective a drug is for a single receptor, the fewer effects it is likely to bring about,
so a more selective drug is likely to be one with fewer side-effects. On the other hand, a less selective
drug which activates two or three related receptors may have more therapeutic uses, but it will also
have more side-effects. The selectivity of a drug will tend to decrease as the dose increases, because
binding to other receptor types will become more likely as the concentration of the drug increases.
This helps to explain the dose dependency of many side-effects of medications.

Clinical considerations
Salbutamol, also known as albuterol, is a beta-2 receptor agonist and is frequently administered in the
out-of-hospital setting for management of bronchospasm. It can also be used in the management of
hyperkalaemia because it stimulates the transport of potassium ions from the blood into skeletal mus-
cle cells. This effect is also mediated by the action of salbutamol on beta-2 receptors.
Many patients who have been prescribed salbutamol may have already self-administered their own
‘puffer’ prior to your arrival and may be tachycardic as a result. This is due to binding to beta-2 receptors
in cardiac muscle after absorption of salbutamol into the bloodstream. Tachycardia may predispose the
patient to arrhythmias, so regarding these patients as high risk for a cardiac event is warranted.
Muscle tremors may also occur in these patients, due to binding of the drug to beta-2 receptors in
skeletal muscle. Although the drug is quite selective for beta-2 receptors, it will also bind to beta-1 recep-
tors at high doses, so if the patient has used their puffer very extensively prior to your treatment, there
may be additional tachycardia due to an action on beta-1 receptors in the heart, increasing cardiac risk.

The drug–body interaction is a dynamic

process
The interaction between any administered drug and the person it is administered to is dynamic.
From the moment it is administered, the drug will be moving from its administration point to other
compartments of the body, being absorbed into the bloodstream, and leaving the blood to enter
other tissues or other body compartments, so the concentration of the drug in the blood and in vari-
ous tissues and body compartments will be changing. As the drug passes through the liver, it will be
acted on by metabolic enzymes which will convert it to a different form, which may be more or less
pharmacologically active, but certainly more water soluble. The drug travelling in the blood will also
be filtered by the kidneys, and the water-soluble form of the drug will be trapped there and excreted
in the urine.
As the drug is being carried around the body, some of it will arrive at and bind to its sites of action,
producing its effects. Even the binding of the drug to its receptors is a dynamic process, akin to mol-
ecules playing musical chairs with the receptors – molecules of the drug will bind and detach and
bind again rather than simply binding and remaining in place. Each time the molecule detaches from
its binding site, it may be whipped away and metabolised, and its place on the receptors may be
taken by another, competing molecule. This constantly changing relationship between the drug and
Chapter 1 Introduction to pharmacology

the living system it has been introduced into explains a great deal about how drugs have their effects.
12 The delay between administration and action of a drug, the duration of action of the drug, and the
ability to reverse or overcome the actions of one drug by giving another drug are all the result of this
dynamic interaction between drug and living system.
For the paramedic administering drugs into a system which may be free of other drugs but more
likely already contains some pharmacological agents, this constantly changing effect of the drug on
the patient will require you to have a good enough grasp on what these agents can do, either alone
or in combination, to be able to predict and maintain some control over their actions.
One challenge we are always faced with is getting enough of a drug from its site of administration
to its site of action for it to have a therapeutic effect. The drug is effectively in a race to reach its site
of action and have its effect before it is chemically degraded and removed from the body. A drug
which has a highly desirable therapeutic action may turn out to be useless from a clinical point of
view if it cannot be delivered to its site of action. So, a drug that is going to stand a chance of being
useful would usually possess characteristics which allow it to be easily absorbed into the blood-
stream, preferably after oral administration, which in turn would mean that the drug would not be
destroyed by the acid of the stomach or digestive enzymes. And although it would probably be
subject to metabolism by the liver, the metabolism should not be so rapid that it is almost completely
gone after a single pass through the liver (a phenomenon known as first-pass metabolism), as this
would mean that very little of the active drug remained in the bloodstream to circulate after absorp-
tion. Other routes of administration might avoid the problem of first-pass metabolism, but each
administration route will have its own advantages and disadvantages.

Clinical considerations
Administration of medications in the out-of-hospital setting can be challenging due to poor lighting,
uncontrolled environment or a chaotic scene. Practising all steps of safe medication administration is
key to reducing the risk of error (Chapter 4 discusses medicines management and the role of the para-
medic). Ensuring the same routine is exercised every single time you administer any medications will
embed safe practice so you do not overlook a crucial step during a high-acuity incident.
Hand hygiene is important to prevent introduction of harmful pathogens in the out-of-hospital envi-
ronment. Access to running water may not be practical in the out-of-hospital setting, so utilisation of
alcohol-based hand rub is the gold standard in this setting. Healthcare-associated infections generate
significant comorbidity and burden for the patient, the community and the healthcare system.
Healthcare-associated infections are avoidable and simple hygienic practice and aseptic technique are
crucial in breaking the chain of transmission from community, to patient and into care settings such as
hospitals.
Intravenous cannulation is a key source for bloodstream infections and risk mitigation efforts, such
as use of alcohol-based hand rub and not touching the area between cleaning the skin and immedi-
ately prior to cannulation, should be exercised.

Other routes of administration which are common in the out-of-hospital setting include intravenous,
intramuscular, topical, intranasal, endotracheal and intraosseous. See Chapter 6 for further discussion.
Once absorbed into the bloodstream, a drug needs to be able to penetrate to its sites of action
relatively quickly. If the drug was an antimicrobial being used to treat an infection of the blood, then
getting enough drug into the bloodstream for long enough would be all that was required. However,
if the drug were required to penetrate the central nervous system, for example, or get into joint
spaces or some other protected body compartment, then it would also have to be able to move out
of the bloodstream and travel through the cellular walls that form those body compartments. This
presents another challenge to a molecule; in order to get through cell membranes, a drug molecule
either needs to be soluble in lipids (lipophilic) or, if it is more water soluble (hydrophilic), then it
would have to be a very small molecule. Drugs that are highly lipid soluble are generally able to move
readily through cellular compartments without difficulty, and will therefore leave the bloodstream
Introduction to pharmacology Chapter 1

and enter the tissues, often concentrating there. Drugs that readily cross the blood–brain barrier,
such as those used in general anaesthesia, are highly lipid soluble, allowing them to pass very rapidly 13
into the protected environment of the brain, which explains their ability to produce general anaes-
thesia in a matter of seconds after being introduced into a vein.
The dose, route and timing of administration will all play key roles in the effectiveness of the drug.
This is discussed in greater detail in Chapter 5.

Episode of care
You are treating 94-year-old Nelida, who has fallen in her residential aged care facility while going to
the bathroom. She has a large bruise on the side of her head (temporal region) and a shortened and
rotated left leg, as well as a deep laceration to her left upper thigh caused by the shard of a mirror that
broke during the fall. Staff report that the patient has dementia but can still converse appropriately
most days. The patient is in extreme pain but her heart rate is not elevated. You realise this is probably
due to her being on a beta-blocker for hypertension. You administer intranasal fentanyl repeatedly en
route to hospital to treat her pain. On arrival, her level of consciousness has decreased. Reflecting on
what might have caused this, you consider that the combination of blood loss and a blunted compen-
satory response due to the beta-blockers, along with a reduced renal capacity due to her age, and the
fact that the repeated fentanyl doses have not been cleared as rapidly as expected has resulted in an
accumulation of medication, leading to adverse effects.
While this is not a contraindication of fentanyl, it is important to remember that older patients often
clear medications much more slowly than younger patients, and dosing may need to be adjusted to
account for this, to avoid adverse effects.

Skills in practice
Medications can come in varying concentrations and formulations for different modes of delivery.
Adrenaline is a naturally occurring catecholamine hormone produced by the adrenal glands and is
often also administered in the management of life-threatening presentations such as cardiac arrest,
anaphylaxis and croup.
The concentration of adrenaline can be expressed as 1:1000 or 1:10 000. This is expressed verbally as
‘one in one thousand’ and ‘one in ten thousand’ respectively. This ratio refers to the medication mass per
volume of solution:

1: 1000 1 gram of adrenaline per 1000 mL

1: 10 000 1 gram of adrenaline per 10000 mL

Adrenaline concentrations can and do vary, but the following is a guide to concentrations and routes
of administration for various indications:

Concentration Route of administration Indication

Adrenaline 1:1000 Intramuscular Anaphylaxis
Nebulised Croup
Asthma
Adrenaline 1:10 000 Intravenous Cardiac arrest
Cardiogenic shock
Chapter 1 Introduction to pharmacology

Administering medication to children

14 Historically, children were considered small adults, with the same physiology and metabolic require-
ments as an adult, but on a smaller scale. This is now known not to be the case, but many medications
are still not tested on children, so safe doses in this patient group are not established empirically. A
basic understanding of the differences between adult and child anatomy and physiology will ensure
safer administration of medication to children. For example, the child’s heart does not have the same
capacity to raise cardiac output by increasing its force of contraction and relies on increasing the heart
rate to compensate for increased demand. As a result, peripheral vasoconstriction usually occurs more
readily, in order to maintain blood pressure.
Medications which cause peripheral vasoconstriction need to be used with extra caution in children
because of this. Adrenaline will cause peripheral vasoconstriction when used to treat anaphylaxis or
asthma, and the beta-2 agonist salbutamol (albuterol) is also often contraindicated in children because
of the possibility of tachycardia. Using medications that cause tachycardia will place further demands
on a child’s heart, possibly at a time when it is already working hard to compensate. These medications
have to be dosed and administered with extreme care in children, and some may be contraindicated.

Reflection
How is dosing calculated for children? If you don’t know the weight of the patient and there is no one
to give you the weight, how would you estimate it, to ensure you give a safe and effective dose?
What special considerations need to be borne in mind when giving medications intranasally to
children?
When administering medications to a child, ensure consent is gained from the parent, caregiver or a
response given by the child is appropriate for their age and presentation. Ensure your approach to
treating a child extends to providing oversight to the parent/caregiver as well.

Conclusion
The out-of-hospital setting is not the same as the controlled environment of the hospital and the
unpredictable and uncontrolled nature of paramedicine requires that the practising paramedic per-
forms the work that would be done by three different health professionals in a hospital. This places a
great responsibility on the paramedic when it comes to the safe and effective use of medicines. The
paramedic must be an expert in both the correct choice and administration of medications. In addi-
tion, because the environment in which the paramedic is operating is particularly conducive to mak-
ing errors, the paramedic must also be constantly vigilant and ensure the stringent and consistent
checking of medication route, dose, time, expiration date and patient. As the scope of paramedic
practice increases and more medications are administered in the prehospital setting, the need for
paramedics to have a mastery of medicines becomes even greater.

Glossary
Agonist A drug that binds to a receptor and produces the same response as the
endogenous substance. For example, morphine is an agonist at opioid recep-
tors because it produces the same response as the endorphins produce.
Antagonist A drug that binds to a receptor and prevents the endogenous substance or
an agonist from binding and having its effect. Also known as a blocker,
because it blocks the activation of the receptor.
Contraindication A characteristic or condition which would prevent a patient from being
able to receive a certain medication.
First-pass metabolism The metabolism of a large proportion of an administered dose of a drug by
the liver almost immediately after absorption.
Indication A condition or symptom which a medication is approved to treat.
Introduction to pharmacology Chapter 1

Pharmacodynamics The actions of a drug on the body.

Pharmacokinetics The actions of the body on the drug. 15
Receptor The site at which a drug molecule binds to have its action.

References
Batt, A. Enhancing patient safety education for paramedics with the IHI Open School. http://prehospitalresearch.
eu/?p=6171
Elliott, R.A., Camacho, E., Campbell, F. et al. (2018). Prevalence and Economic Burden of Medication Errors in the NHS
in England. Sheffield: Policy Research Unit in Economic Evaluation of Health and Care Interventions (EEPRU).
Hobgood, C., Bowen, J.B., Brice, J.H., Overby, B. and Tamayo-Sarver, J.H. (2006). Do EMS personnel identify, report
and disclose medical errors? Prehospital Emergency Care 10(1): 21–27.
Institute for Safe Medication Practices Canada. (2020). Multi-incident analysis of incidents involving paramedi-
cine. ISMP Canada Safety Bulletin 20(1): 1–4.
Lammers, R., Willoughby-Byrwa, M. and Fales, W. (2014). Medication errors in prehospital management of simu-
lated pediatric anaphylaxis. Prehospital Emergency Care 18(2): 295–304.
McGovern, K. (1992). 10 Golden rules for administering drugs safely. Nursing 22(3): 49–56.
Nguyen, A. (2008). Bad medicine: preventing drug errors in the prehospital setting. Journal of Emergency Medical
Services 33(10): 94–100.
Roughead, L., Semple, S. and Rosenfeld, E. (2013). Literature Review: Medication Safety in Australia. Canberra:
Australian Commission on Safety and Quality in Health Care.
WHO Collaborating Centre for Patient Safety Solutions. (2007). Look-Alike Sound-Alike Medication Names. Patient Safety
Solutions: Solution 1. https://cdn.who.int/media/docs/default-source/integrated-health-services-(ihs)/psf/
patient-safety-solutions/ps-solution1-look-alike-sound-alike-medication-names.pdf?sfvrsn=d4fb860b_6&ua=1

Further reading
Australian Medicines Handbook (AMH). 2020 print edition or online: https://amhonline.amh.net.au
British National Formulary (BNF). 2020 print edition or online: www.bnf.org

Multiple-choice questions
1. A medication error occurs when:
(a) The wrong dose is administered
(b) A drug that would benefit a patient is not given
(c) A drug that it not necessary is given
(d) All of the above.
2. The purposes for which a medication can be used are the:
(a) Mechanism of action
(b) Contraindications
(c) Indications
(d) None of these.
3. The conditions in which a drug cannot be used are the:
(a) Mechanism of action
(b) Indications
(c) None of these.
4. When drugs such as alprazolam are referred to as benzodiazepines, they are being
classified according to their:
(a) Mechanism of action
(b) Indications
(c) Chemical class
(d) Original trade name.
Chapter 1 Introduction to pharmacology

5. When drugs such as reboxetine are referred to as antidepressants, they are being
16 classified according to their:
(a) Mechanism of action
(b) Indications
(c) Chemical class
(d) Original trade name.
6. A medication which is prescribed for an indication other than its listed indications is
being used:
(a) Illegally
(b) Off-label
(c) Even though it is contraindicated
(d) None of the above.
7. The drugs known as specific serotonin reuptake inhibitors, which include fluoxetine
(Prozac®), would act by binding to:
(a) A receptor for a neurotransmitter
(b) An ion channel
(c) An enzyme
(d) A transport molecule.
8. In general, the more selective a drug is in its binding sites:
(a) The fewer side effects it will have
(b) The more easily it will reach its site of action
(c) The more potent it will be
(d) The more it will interact with other drugs.
9. When administering adrenaline intravenously, which dilution is most appropriate?
(a) 1:100
(b) 1:1000
(c) 1:10 000
(d) 1:100 000
10. A drug that is an antagonist or blocker of a receptor is likely to ‘fit’ the receptor
chemically better than a drug that is an agonist.
(a) True
(b) False
11. A drug, such as a general anaesthetic, that can penetrate the blood–brain barrier very
rapidly after intravenous administration is likely to be:
(a) Highly water soluble
(b) A protein
(c) Highly lipid soluble
(d) No drugs can penetrate an intact blood–brain barrier.
12. A medication dose may need to be adjusted down in which of these situations?
(a) Renal failure
(b) High first-pass metabolism
(c) Diarrhoea
(d) Vomiting
13. The NSAID aspirin has its effects due to action at:
(a) An ion channel
(b) A neurotransmitter receptor
(c) A transport molecule
(d) An enzyme.
Introduction to pharmacology Chapter 1

14. You are attending a patient who has suffered trauma and lost a lot of blood. The
patient’s heart rate is normal, even though their blood pressure is low. Which of the 17
following medications being taken is most likely to be responsible for this?
(a) Ibuprofen
(b) Metformin
(c) Atenolol
(d) Tetracycline
15. If a drug undergoes extensive first-pass metabolism, which of these routes should be
avoided as administration routes for this drug?
(a) Intramuscular
(b) Intravenous
(c) Oral
(d) Intranasal
Chapter 2
How to use pharmaceutical
and prescribing reference
guides
Nigel Conway and Jennifer Dod

Aim
This chapter aims to introduce you to commonly used pharmaceutical and prescribing reference
guides and their use in paramedic practice. Specific focus is placed on the Joint Royal Colleges
Ambulance Liaison Committee (JRCALC) Clinical Practice Guidelines (2019).
For clarification:

• The JRCALC Clinical Guidelines (2019) full reference book will be referred to throughout this
chapter as JRCALC Guidelines
• The JRCALC Clinical Guidelines (2019) Pocket Book will be referred to in this chapter as JRCALC
Pocket Book
• The JRCALC Clinical Guidelines digital application (app) will be referred to in this chapter as
JRCALC app.

Learning outcomes
After reading this chapter, the reader will:

1. Be aware of the different pharmaceutical and reference guides that may be used in paramedic
practice
2. Understand how to navigate the:
•JRCALC Guidelines (full reference book)
•JRCALC Pocket Book
•JRCALC app
3. Be aware of other common pharmaceutical resources available to the paramedic.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
How to use pharmaceutical and prescribing reference guides Chapter 2

Test your knowledge

• How frequently are the hard-copy JRCALC Guidelines reviewed and republished? 19
• How many HCPC standards of proficiency are there?
• How many different forms of the JRCALC Guidelines are available?
• What is the unique feature of the ‘JRCALC plus’ feature?
• What are the core paramedic care approaches to the fundamentals of medicine management?

Introduction
The world of medications is vast and learning about them can be daunting for all allied healthcare
and nursing profession students, as well as registered professionals. The people you care for may
have extensive past medical history and lists of medications specific to treatment interventions. You
need to be able to assess, review, administer, consider interactions, monitor and evaluate the effects
of these medications.
Regulatory and professional bodies have specific standards of practice which are designed to be
applicable to all areas of a healthcare professional’s work. In the United Kingdom, paramedics are
accountable to the public and their profession through the Health and Care Professions Council
(HCPC). There are two sets of HCPC standards that govern paramedic practice:

• HCPC (2016) Standards of conduct, performance and ethics

• HCPC (2014) The standards of proficiency for paramedics (latest review point 2020 to be
published).

These two sets of standards apply to all areas of paramedic practice including medicines and phar-
macological management (i.e. knowledge, understanding and clinical application) as related specifi-
cally to the paramedic role.
The HCPC (2016) and HCPC (2014) standards are essentially frameworks within which all registered
UK paramedics must work. Ambulance services and paramedics outside the UK will be guided by
equivalent organisations. Examples of these are:

• Australian Council of Ambulance Authorities (CAA), covering Australia, New Zealand and Papua
New Guinea: www.caa.net.au/
• Paramedicine Board, Australia: www.paramedicineboard.gov.au/Professional-standards.aspx
• Australian Clinical Practice Guidelines: Ambulance and MICA Paramedics (2018): www.ambulance.
vic.gov.au/wp-content/uploads/2018/07/Clinical-Practice-Guidelines-2018-Edition-1.4.pdf.

HCPC Standards of conduct, performance

and ethics
This framework (HCPC, 2016) establishes what the expectations are for all UK-registered paramedics
specific to behaviour, public expectation and fitness to practise. The framework covers 10 specific
areas of paramedic practice in relation to conduct, performance and ethics which in the context of
this book can be applied to the specific area of medicines management as well as all other areas of a
paramedic’s practice. These are:

• Promote and protect the interests of service users and carers

• Communicate appropriately and effectively
• Work within the limits of your knowledge and skills
• Delegate appropriately
• Respect confidentiality
Chapter 2 How to use pharmaceutical and prescribing reference guides

• Manage risk
• Report concerns about safety
20
• Be open when things go wrong
• Be honest and trustworthy
• Keep records of your work.
Specific drugs and examples of application to paramedic practice, as well as legal and professional
issues, can be read and explored in the chapters that follow.

HCPC Standards of proficiency

for paramedics
This framework (HCPC, 2014) establishes what UK-registered paramedics must do specific to their
regulated profession, which in the context of this book can be applied to the specific area of medi-
cines management as well as all other areas of a paramedic’s practice. There are 15 areas of profi-
ciency covered by these standards with more detailed subsections under each proficiency. All
paramedics must comply with the standards of proficiency.

• Practise safely and effectively within their scope of practice.

• Practise within the legal and ethical boundaries of the profession.
• Maintain fitness to practise.
• Practise as an autonomous professional, exercising their own professional judgement.
• Be aware of the impact of culture, equality and diversity on clinical practice.
• Practise in a non-discriminatory manner.
• Understand the importance of and be able to maintain confidentiality.
• Communicate effectively.
• Work appropriately with others.
• Maintain records appropriately.
• Reflect on and review practice.
• Assure the quality of their practice.
• Understand the key concepts of the knowledge base relevant to their profession.
• Draw on the appropriate knowledge and skills to inform practice.
• Understand the need to establish and maintain a safe practice environment
In order to fulfil these requirements, paramedics must have a level of pharmaceutical knowledge and
an awareness of how and where to find appropriate information to support clinical practice.
Contemporary healthcare regimes have resulted in a breadth of emergent new products and com-
plex treatment regimens. As a paramedic student or clinician, you will need up-to-date, clear and
concise information to guide your practice. Examples of this can be found in later chapters in this
book as well as external sources such as the JRCALC and numerous other guides, websites, texts and
resources that are readily available. However, ensuring a robust and evidence-based or evidence-
informed selection of these is paramount. Some resources are web based, some print based and
some digital app based.
This chapter aims to introduce you to using pharmaceutical and prescribing reference guides with
a specific focus on:

• JRCALC Clinical Guidelines (JRCALC, 2019a)

• JRCALC Pocket Book (JRCALC, 2019b)
• JRCALC app.
Pharmaceutical and prescribing guides are vital and valuable resources to draw upon to ensure safe,
accountable and evidence-based paramedic practice and patient care.
How to use pharmaceutical and prescribing reference guides Chapter 2

Clinical consideration
As an undergraduate paramedic student or practising paramedic, there are core approaches to the
fundamentals of medicines administration you should apply. 21
For example, when administering any drug, the paramedic should make sure they have a full under-
standing of its mechanism of action and the expected physiological effect it will have on the patient.
When out in practice, make sure you know where to easily access this information in your JRCALC so
you can check it quickly in an emergency situation.

Joint Royal Colleges Ambulance Liaison

Committee (JRCALC) Clinical Practice
Guidelines
The JRCALC Clinical Practice Guidelines are an essential resource for paramedics and other health-
care professionals, in emergency care, on the road and in the community. The JRCALC books and
app combine expert advice with practical guidance to ensure uniformity in the delivery of high-
quality patient care. The books, available as either the comprehensive reference edition or the
pocket guide, cover a wide range of topics, from resuscitation, medical emergencies, trauma,
obstetrics and medicines to major incidents and staff wellbeing. They include an extensive UK
drugs formulary and Page for Age drugs tables to assist in making medicines administration sim-
ple. To date, the hard- copy publication has been revised every 2–3 years. The digital version, via
an app, is also available for prehospital clinicians to download. The electronic app version is
updated more regularly.
The JRCALC Guidelines make reference to the National Institute for Health and Care Excellence
(NICE) where appropriate. NICE guidelines inform the breadth of the National Health Service (NHS) in
England and are also subject to regular review, update or withdrawal. Independent providers and
ambulance services outside the UK should refer to their equivalent guidelines and institutions
informing these.

Paramedics must be aware that any subsequent changes in evidence-based guidance

after the date of any publication will not be incorporated within the published document. This empha-
sises the need for vigilance and awareness of possible emergent variations or changes in clinical prac-
tice and continuous professional development, as reflected within the HCPC paramedic standards of
proficiency. This also supports the increasing use by paramedics of the more regularly updated digital
format of the JRCALC Guidelines.

It is worth noting that the physical, hard-copy JRCALC Guidelines text books are available through
bookshops and are on sale separately from the digital app. The app is available to the public via the
internet on a subscription basis. Ambulance trusts in the UK can also develop a ‘service-specific’ ver-
sion of the JRCALC app. This is referred to as the ‘JRCALC plus’, with most ambulance trust in the UK
opting to use this resource for their employees rather than issuing hard-copy books. Independent
providers and ambulance services outside the UK who are interested in the ‘JRCALC plus’ option
should contact the publisher direct. This JRCALC (app) resource offers the most current guidance as
the digital format can be more easily updated.
Chapter 2 How to use pharmaceutical and prescribing reference guides

Most of the content of the JRCALC Guidelines is universally applicable to NHS ambulance services.
However, some modification of these may be evident in regional/individual ambulance services and
independent and non-UK ambulance service providers as approved by relevant clinical committees
22 or equivalents to best meet the needs of local service users. Another area of modification to the
JRCALC Guidelines for paramedics to be aware of may arise through research sanctioned by relevant
research ethics committees.

JRCALC Update information

It is worth noting that the JRCALC Guidelines contain a section at the beginning of the text called
‘Update Analysis – “what’s changed?”’. This consists of a table containing update information about
changes to specific guidelines since the last edition. It is split into sections which reflect those of the
book, making it easy to find if there has been an update within the new JRCALC publication to a
specific area of guideline since the previous edition (Figure 2.1).

Clinical considerations
• Always make sure you have a copy of your JRCALC Pocket Book or app with you.
• If you use your Pocket Book, make sure you check regularly for any updates which have happened
since your book was printed.
• You may inadvertently administer a medication incorrectly if you have not kept up to date with
the latest guideline changes.

The knowledge that informs the paramedic profession and the subsequent complex application of
this to clinical skills and treatment interventions are constantly changing and updating in response
to new research. It is essential for paramedics to keep up to date with the latest changes in policy and
procedure. A paramedic who is already familiar with using the guidelines should read through the
updated sections when a new edition is published to check any guideline changes which may affect
their practice.

Update Analysis – ‘What’s changed?’

SECTION 4
Trauma Revisions made in Supplementary Guidelines 2017.
Trauma Emergencies Updated to cover haemorrhage from renal dialysis arteriovenous graft and
in Adults – Overview fistulas included.
Head Injury Revised guideline.
Includes guidance for mild to moderate head injury, new conveyance
decision tool.
Removal of midazolam for traumatic brain injury – for enhanced care team
use only.
Limb Trauma Additional information on open fractures and re-alignment is included.
Burns and Scalds The adult and child guidelines have been merged.
NICE Red Flags are added, as is information on NARU Chemical Burns.

Figure 2.1 JRCALC Guidelines – Update Analysis. Source: Reproduced with permission from JRCALC
Guidelines (2019a).
How to use pharmaceutical and prescribing reference guides Chapter 2

How to navigate the JRCALC Guidelines

This is a comprehensive resource book containing a wide variety of clinical guidelines and information
for paramedics on a broad range of topics. Such a large reference guide can seem daunting at first; 23
however, the text is laid out in a logical order, making information easy to find and access. The
resource book is split into seven main sections.

1. General Guidance
2. Resuscitation
3. Medical Emergencies
4. Trauma
5. Maternity Care
6. Special Situations
7. Medicines

The approach taken by the Guidelines presents information specific to commonly used drugs and
the practical administration of these. In addition, the Guidelines build on this by identifying where a
particular drug should fit into the patient’s management plan in a variety of treatment settings (e.g.
emergency situations). As such, pertinent information on a particular drug will appear in the
Medicines section (section 7) but also in numerous other sections of the book, and successful naviga-
tion of this text by paramedics or other clinicians is essential to get the most out of the resource
specific to medicines management and clinical application.
It is worth noting that the drugs are presented in alphabetical order in the Medicines section of the
Guidelines.

Skills in practice: example of navigating

the JRCALC Guidelines
A paramedic looking for information about morphine sulfate will find relevant information about the drug
not only in the Medicines section (section 7) but also in other sections specific to other aspects of clinical
application such as General Guidance (section 1), Medical Emergencies (section 3) and Trauma (section 4).

General Guidance section (JRCALC Guidelines, section 1)

This section contains a large amount of general information for paramedics covering a broad range of
topics including staff health and wellbeing, pain management in adults and children, sexual assault and
safeguarding. Each topic has its own chapter within the section. Paramedics can find specific information
relating to medicines and their use in clinical practice in the Pain Management for Adults and Children
and End of Life Care chapters. It is essential for the paramedic to use the information in these chapters in
conjunction with the specific information found in the Medicines section (section 7). Referring only to
information on the Medicines pages may result in missing vital information about special applications or
clinical situations relating to a specific drug and lead to its incorrect administration in practice.

Clinical considerations
If administering an analgesic (e.g. morphine) or an opioid antagonist (e.g. naloxone) to a patient at the
end of their life, make sure you check the Guidelines in the End of Life Care chapter in the General
Guidance section (section 1) as well as the specific drug information contained in the Medicines section
(section 7).
The End of Life Care chapter contains more specific medication guidance relating to end-of-life care
situations and medications may be administered incorrectly if this special guidance is not adhered to.
Chapter 2 How to use pharmaceutical and prescribing reference guides

Resuscitation section (JRCALC Guidelines, section 2)

The Resuscitation section contains information and guidance on a number of topics relating to various
aspects of resuscitation. Chapters in this section include out-of-hospital cardiac arrest, basic and advanced
24
life support, foreign body airway obstruction, return of spontaneous circulation, death verification, death
of a child and tracheostomy and laryngectomy management. In addition to the general guidance for each
drug found in section 7, specific information about the drugs used in prehospital cardiac arrest situations
can be found in the overview section at the beginning of each chapter within this Resuscitation section.
For example, the advanced life support and return of spontaneous circulation chapters contain further
information about the use of drugs covered in section 7 but applied to a cardiac arrest situation.

Medical Emergencies section (JRCALC Guidelines, section 3)

This section contains a large amount of specific information relating to a breadth of medical emergencies
commonly encountered by paramedics in practice. Section 3 starts with two chapters giving an overview
of medical emergencies in adults and children which contain general information relating to medical
emergencies and patient assessment (see Table 2.1). The text then focuses on a number of specific aspects
of medical emergencies in more detail within which drugs identified in section 7 could be applied.
Each of these chapters is then further split into subsections: an introduction, incidence, severity
and outcome, pathophysiology and assessment and management. This provides a comprehensive
overview of each medical emergency and how it should be managed by paramedics in practice.
Paramedics should refer to this section to see whether a particular drug is used to treat a certain
condition and where that drug fits into patient management.

Clinical consideration
Both hydrocortisone and adrenaline 1:100 have anaphylaxis listed as an indication in their chapters in
the Medicines section (section 7). However, the Allergic Reactions Including Anaphylaxis chapter, in the
Medical Emergencies section (section 3), should be referred to for more information about where these
drugs fit into the management plan for such patients.

Table 2.1 Examples of emergency conditions covered in section 3.

Acute coronary syndrome Hyperventilation syndrome
Abdominal pain Hypothermia
Allergic reactions (including anaphylaxis) Implantable cardiovascular defibrillator
Altered levels of consciousness Management of resuscitation of patients with left
ventricular assist devices
Asthma in adults and children Meningococcal meningitis and septicaemia
Cardiac rhythm disturbances Mental health presentations
Chronic pulmonary disease Mental Capacity Act
Convulsions in adults Respiratory illness in children
Convulsions in children Sickle cell crisis
Dyspnoea Sepsis
Febrile illness in children Stroke/transient ischaemic attack
Gastrointestinal bleeding Traumatic chest pain
Glycaemic emergencies in adults and Overdose and poisoning in adults and children
children
Headache Paediatric gastroenteritis
Heart failure Pulmonary embolism
Heat-related illness
How to use pharmaceutical and prescribing reference guides Chapter 2

Paramedics need to be aware that just referring to the indications in the Medicines section (sec-
tion 7) may not give full information about where a drug fits into an ambulance service protocol for
management of a certain patient condition, and so the JRCALC guidance in the Medical Emergencies
section (section 3) should always be referred to alongside the Medicines section in order to ensure 25
best approach and correct patient management.

Trauma section (JRCALC Guidelines, section 4)

The Trauma section is laid out in a similar structure to the Medical Emergencies section. The initial
two chapters give an overview of trauma emergencies in adults and children and the subsequent
chapters each contain information about a specific trauma emergency and its paramedic manage-
ment (see Table 2.2).
All the individual chapters follow a similar format, offering information about the incidence, sever-
ity and outcome, pathophysiology and assessment and management of each trauma emergency. In
relation to drugs and their use in emergency situations, the Trauma chapter should be used similarly
to the Medical Emergencies chapters. Each chapter can be used to find more information about
drugs used in the treatment of a given emergency and, more specifically, exactly where a particular
drug fits into the treatment and management plan for patients in practice. Paramedics should use
this information in conjunction with the Medicines section (section 7) and specific drugs within it, in
order to find not only information about when a drug should be used and how it fits into a particular
management plan, but also information to ensure the drug is administered correctly, thus reducing
the possibility of drug errors.

Maternity Care (JRCALC Guidelines, section 5)

The notion of two lives scenarios (i.e. mother and baby) presents the paramedic with numerous chal-
lenges specific to this area of care. This section begins with an overview of obstetric emergencies and
contains chapters that guide the paramedic through the management of a range of maternity-
related presentations. Similarly to the previous sections, paramedics should refer to and check the
protocols for each given maternity situation to confirm whether drug therapy is appropriate for a
given maternal presentation. After checking the Maternity Care section, further information about
dosage or specific drug actions should be sought in the Medicines section (section 7).

Special Situations (JRCALC Guidelines, section 6)

This section contains chapters about specific situations paramedics may encounter and includes
information about major, high-risk and complex incidents such as individuals requiring care inter-
ventions but who have been incapacitated by police or other security services. Within this section
there are two chapters relating specifically to medicines.

• Atropine for CBRNe (chemical, biological, radiological and nuclear explosives).

• DuoDote® auto-injector (atropine combined with pralidoxime).
These two chapters contain information about the presentation, indications, actions, contraindica-
tions, cautions and side-effects of these drugs in relation to organophosphate and nerve agent
poisoning.

Table 2.2 Examples of specific trauma emergency conditions

and management covered in section 4.
Abdominal trauma Thoracic trauma
Head injury Falls in older adults
Limb trauma Burns and scalds
Spinal injury and spinal cord injury Electrical injuries
Major pelvic trauma Immersion and drowning
Chapter 2 How to use pharmaceutical and prescribing reference guides

Medicines (JRCALC Guidelines, section 7)

The Medicines section begins with an overview of medicines and goes on to present more detailed
information and particular characteristics about medications which can be administered by regis-
26
tered paramedics, provided they have the correct legal authority (HCPC, 2014; JRCALC, 2019a).
Chapter 3 of this text discuses legal and ethical issues further.
Individual ambulance trusts across the UK may have variations to their local protocols and Patient
Group Directives (PGDs), meaning that not all medicines listed in the JRCALC Guidelines are neces-
sarily given by all registered paramedics across counties or countries within the UK. Paramedics
should be cognisant of such variations in local protocols and check with their employing ambulance
service to find out which medicines can be administered by paramedics in their local ambulance
trust region.
It is important for paramedics to note that PGDs are also available for drugs which are not in
the JRCALC Guidelines. This means in some situations a paramedic may find themselves admin-
istering a drug which is not listed in the reference book. In such cases, the PGD will provide
guidance on the administration of these medicines specific to the local ambulance service
protocols.
The Medicines section is split into a short introductory chapter called Medicines Overview, a sepa-
rate chapter for each medicine listed and finally a ‘Page for Age’ section. The introductory chapter
contains general information for paramedics about medicines, including safety aspects, prescribing
terms, drug routes and paediatric doses. All paramedics should make themselves familiar with the
information in this chapter before administering any drugs in practice.
Each specific medicine chapter contains detailed information about the presentation of the medi-
cine, its mechanism of action, indications, contraindications, cautions and a table detailing dosage
and administration across the age span. All chapters have a similar layout with the specific drug dos-
age and administration technique featured in a table. This pragmatic layout allows paramedics to
quickly access pertinent drug information in an emergency situation (see Figure 2.2). Before admin-
istering a drug in practice, paramedics should always refer to the JRCALC Guidelines page specific to
that drug to ensure correct administration.
The JRCALC Pocket Book and digital app, section 2.6, also contain this information. This enables
paramedics to quickly and easily check medicines administration information in practice/on the
road.

Skills in practice
Be alert and aware of the common factors associated with the selection and administration of drugs.
In this example you should locate the medication dexamethasone in the JRCALC Guidelines.

• What are the indications for this drug?

• Are there any contraindications for this drug?
• What are the cautions associated with this drug?
• Are there any side-effects associated with this medication?
• What is the presentation of this drug?
• What is the route of administration and are there any recommendations related to its
administration?

Refer to JRCALC Clinical Guidelines (2019), pp. 317, 540, 563-564.

How to use pharmaceutical and prescribing reference guides Chapter 2

Aspirin ASP 27

Presentation Kidney or liver failure

300 milligrams aspirin (acetylsalicylic acid) in tablet. Gastric or duodenal ulcer

form, Dispersible or chewable. Current treatment with anticoagulants.

Indications Side Effects

Adults with: Increased risk of gastric bleeding.
Clinical or ECG evidence suggestive of Wheezing in some asthmatics.
myocardial infarction or ischaemia.
Additional Information
Actions In suspected myocardial infarction a 300 milligram
Has an antiplatelet action which reduces clot aspirin tablet should be given regardless of any
formation. previous aspirin taken that day.

Contra-indications Clopidogrel may be indicated in acute ST

segment elevation myocardial infarction – refer to
Known aspirin allergy or sensitivity. Clopidogrel.
Children under 16 years (see additional) Aspirin is contra-indicated in children under
information). the age of 16 years as it may precipitate Reye’s
Active gastrointestinal bleeding. syndrome. This syndrome is very rare and occurs
in young children, damaging the liver and brain. It
Haemophilia or other known clotting disorders.
has a mortality rate of 50%.
Severe hepatic disease.

Cautions
As the likely benefits of a single 300 milligram
aspirin outweigh the potential, risks, aspirin may be
given to patients with:
Asthma
Pregnancy

Dosage and Administration

Route: Oral – chewed or dissolved in water.
REPEAT DOSE
AGE INITIAL DOSE DOSE INTERVAL CONCENTRATION VOLUME MAX DOSE
Adults 300 milligrams NONE N/A 300 milligrams per 1 tablet 300 milligrams
tablet

Bibliography
British National Formulary. Available from: https://bnf.nice
org.uk/drug/aspirin.html, 2018.

Figure 2.2 Example of how specific drug (aspirin) information is presented within the JRCALC Medications
section. Source: Reproduced with permission from JRCALC Guidelines (2019a).

Page for Age (JRCALC Guidelines, no section number allocated)

The ‘Page for Age’ is the last section of text within the Guidelines and has no specific section
indicator. This section follows on from the Medicines section (section 7). The pages provide a
quick and easy way for paramedics to access key information relating to paediatric patients aged
from birth to 11 years. All the information is tabulated and each page is laid out in a logical and
straightforward way, making it easy to use in an emergency situation. The tables contain infor-
mation specific to patients of a particular age group and include normal vital signs, airway
device sizing, intravascular fluid doses, drugs for cardiac arrest and the other JRCALC Guidelines.
The drug tables have information about the route, dose, concentration and volume specific to
an age group, and provide an easy reference guide for use in practice. Paramedics should note
that the Page for Age section does not contain information about indications, contraindications
and cautions for a given drug, and these should be double- checked for each patient in the appro-
priate page of the Medicines section (section 7) before administering any drug (see Figure 2.3).
Chapter 2 How to use pharmaceutical and prescribing reference guides

28

Figure 2.3 Page for Age section. Source: Reproduced with permission from JRCALC Guidelines (2019a).
How to use pharmaceutical and prescribing reference guides Chapter 2

29

Figure 2.3 (Continued)

Reflection
Take some time to reflect on your reading and think about the following questions.

• How many sections of the main JRCALC Guidelines are there?

• At the end of which section does the Page for Age information appear?
• How many chapters are there in the Maternity Care section? In which section of the JRCLAC
Guidelines would you find information about specific trauma emergencies?
Chapter 2 How to use pharmaceutical and prescribing reference guides

JRCALC Pocket Book

This is a condensed version of the JRCALC Guidelines meant to be used as a quick reference guide in
30 practice. It is laid out in a similar format to the main reference book but with nine sections rather than
seven. The sections are as follows.

• Resuscitation
• Paediatrics
• Trauma
• Special Situations
• Maternity
• General
• Medical
• Medicines
• Page for Age
The main deviations from the layout of the large reference guide are the addition of a Paediatrics
section and the use of a separate section for Page for Age. The Pocket Book is very condensed and
contains only a fraction of the information found in the large guide. The first seven sections contain
tables, algorithms and flow charts with essential information for paramedics pertaining to a selection
of emergency situations commonly encountered in practice. These sections should be referred to in
order to find basic essential information in an emergency situation and are in no way meant to be a
comprehensive set of Guidelines.
The Pocket Book is a handy reference guide for use in practice and most paramedics will refer to it or the
app on a daily basis. Either one should always be referred to when administering any medications to check
indications, contraindications, dosage and any other pertinent information relating to the drug in ques-
tion. This best practice approach reflects the requirements of the paramedic standards of proficiency.
The Page for Age section of the Pocket Book is the only section which is completely unchanged from
the large reference guide, with the Pocket Book containing full information for each age group. This
enables paramedics to find key information on drug dosing by age group easily in an emergency.
Each drug in the Medicines section contains the same information as in the large guide and the
only difference in this section is that the more comprehensive Medicines Overview chapter in the
large guide is abridged to the Medicines: Best Practice Checklist in the Pocket Book. The Best Practice
Checklist is situated at the beginning of the Medicines section of the Pocket Book (see Figure 2.4).

Figure 2.4 Medicines Best Practice Checklist. Source: JRCALC Pocket Book, 2019.
How to use pharmaceutical and prescribing reference guides Chapter 2

This checklist should be referred to before giving any medication in practice and gives a list of drug
administration checks as well as reminders about drug administration routes and documentation. All
the drugs listed in the large guide appear in the Pocket Book and the Pocket Book contains full infor-
mation on presentation, indications, actions, cautions, contraindications, side-effects and dosage 31
and administration for each drug. This means the Pocket Book alone can be referred to when admin-
istering a medication in practice with no need to use the large guide.

Reflection
Take some time to think about your reading so far and make responses to the following questions.

• The Glycaemic Emergencies algorithm in the Glycaemic Emergencies in Adults and Children chap-
ter in the Medical Emergencies section of the JRCALC Guidelines (section 3) contains information
about when to administer which two drugs?
• Use your JRCALC Guidelines to find the correct drug dosages for administering morphine sulfate
to a 6-year-old patient by the IV/IO route and orally.
• Use your JRCLAC Guidelines to find the initial dose, repeat dose and maximum dose when admin-
istering atropine sulfate to an adult patient.
• The Heart Failure chapter in the Medical Emergencies section of the JRCALC Guidelines contains
specific information about which three drugs used as therapy for heart failure?

JRCALC Guidelines digital application (app)

The JRCALC Guidelines are also available as an app for smartphones, tablets and laptops. The big dif-
ference between the Pocket Book and app is that the app is essentially an electronic copy of the large
reference guide and is not abridged like the Pocket Book. Many paramedics now choose to use the
app over the Pocket Book as it contains the full reference guide. Another big advantage of the app is
that it automatically updates when Guidelines change so it does not end up out of date between
editions as the printed versions frequently do.
The app is available in two forms: the basic JRCALC Guidelines app (www.classprofessional.co.uk/
digital-products/apps/icpg-the-jrcalc-app-subscriptions/) and the JRCALC Guidelines plus app
(www.classprofessional.co.uk/digital-products/apps/jrcalc-plus-app/). The basic app is available
for purchase in either android or iPhone format. In contrast, the plus app is only available to employ-
ees of ambulance service trusts which have subscriptions to it. The basic app contains all the informa-
tion held in the main reference guide, while the ‘ plus app may contain more or less information
depending on how it has been customised to reflect the specific requirements of a particular ambu-
lance service trust and its employees. Ambulance trusts which purchase a subscription to the plus
app are able to restrict and remove content and can also add their own local guidelines or informa-
tion as required to best reflect their regional service needs.
The app is easy to navigate and is split into five main tabs: Dashboard, Guidelines, Medicines,
Algorithms and Page for Age. The Dashboard is the home page and allows easy access to updates
and Page for Age as well as allowing Medicines and Guidelines to be bookmarked for quick reference
(see Figure 2.5).
The Algorithms tab is unique to the app and contains all the algorithms from each of the Guidelines
displayed together in alphabetical order. This makes finding an algorithm for a particular condition
or situation easier, plus there is the option to navigate directly to the related full guidance from each
algorithm. Another useful feature of the app is the search function. This is situated at the top of the
Dashboard home page and enables users to search more easily.
The Guidelines, Medicines and Page for Age tabs of the app contain all the information that
the large reference guide holds. The Guidelines tab is split into the same sections as the large
guide and the guidelines within each section are displayed alphabetically (see Figure 2.5).
The Meds tab contains full information for each medicine and again is displayed alphabetically.
The tabs mean information is easy to access in an emergency and the app is well laid out and
very user friendly.
Chapter 2 How to use pharmaceutical and prescribing reference guides

32

Figure 2.5 Dashboard. Source: South Central Ambulance Service, JRCALC plus.

Test your knowledge

Know where to find this information to help inform your practice.

• The Pain Management in Adults And Children chapters can be found in which section of the
JRCALC Guidelines?
• According to the JRCALC Guidelines, for what conditions can paramedics administer adrenaline
1 mg in 1 mL (1 in 1000)?
• Which chapter in the Medical Emergencies section of the JRCALC Guidelines contains information
about which drugs to administer for patients having a seizure?
• Which section and chapter of the JRCALC Guidelines contain information for paramedics about
the administration of atropine in a CBRNE situation?

Useful additional resources

The JRCAL Guidelines in its different forms offers paramedics a core ‘go to’ reference point for univer-
sal clinical guidance. The next section of this chapter gives an overview of other valuable medication
resources to further inform and develop knowledge, understanding and application. These addi-
tional resources in both hard-copy and digital formats are commonly used by allied healthcare pro-
fessional and medical practitioners as evidence-informed texts relevant to their areas of practice.
The range of drugs covered within these additional resources is far broader than the JRCALC
Guidelines and may therefore be used by paramedics to develop their knowledge and understand-
ing in relation to broader medications, a patient’s medical history, other uses of drugs, drug interac-
tions and contraindications as well as cost. Postqualified paramedics going on to undertake
non-medical prescribing courses and clinical roles will need to be more familiar with these additional
resources, which include the following.

• British National Formulary (BNF)

• Children’s British National Formulary (CBNF)
• Monthly Index of Medical Specialities (MIMS)
• Electronic Medicines Compendium
For an excellent guide to the British National Formulary and other resources, we recommend you refer
to Pryor and Hand (2021).

British National Formulary (BNF)

Assembled by the Joint Formulary Committee, this is a reliable resource of information on medica-
tion. It includes drug information covering individual medication, groups of medication, uses,
How to use pharmaceutical and prescribing reference guides Chapter 2

side-effects and interactions (Young and Pitcher, 2016). The information provided is evidence
informed from drug manufacturer/supplier datasheets, literature, consensus guidelines and peer
review. The BNF makes use of a grading system of A–E and levels of evidence to help understand the
strength of evidence underpinning the associated recommendations given (Joint Formulary 33
Committee, 2019). The BNF is available in hard copy for both the Adult (BNF 2020a) and Children’s
(BNF 2020b) versions. The resources can also be accessed as a mobile app or online (bnf.nice.org.uk/).

Medication listed within pharmaceutical and prescribing guidance documents can be

presented with a generic and brand or trade name. The generic name is used to define:
• The chemical name of a medication
• A term referring to the chemical make-up of a medication rather than to the advertised
brand name under which the medication is sold
• A term referring to any medication marketed under its chemical name without advertising
• The medication’s active ingredient.
The brand or trade name of a medication is the name given by the pharmaceutical company that man-
ufactures it. It is usually easy to write and say for sales and marketing purposes. An example of this is
paracetamol (generic name) which can have the following brand or trade names: Panadol, Calpol.
The brand or trade name is often written more clearly on a medicine’s packaging; the generic name
will also be written somewhere on the packaging but often in small print. It is also not uncommon to
find that some packaging only has the generic name on it.
The production of a given generic medication by individual manufacturers using a different brand or
trade name can also result in a medication being presented differently. Examples of this can include a
variation in the colour, size and shape of a given medication depending on which company makes it.
The paramedic needs to be vigilant and aware of this potentially dangerous issue. It may be that the
pharmacist supplying an ambulance service or the patient with a given drug is getting it from a differ-
ent company, or the prescription has been written in a generic way rather than using a brand name.
Paramedics must take great care to check and ensure that any medication to be administered is the
correct medication.

Monthly Index of Medical Specialities

As you progress through your clinical experience and paramedic career, especially within the primary
care setting, you may also come across the MIMS prescribing guide (www.mims.co.uk/). This is an
up-to-date prescribing reference for healthcare professionals. MIMS is updated constantly online, to
reflect the latest approved prescribing information, along with the addition of new drugs and formu-
lations, and also removes products that are no longer available. MIMS is primarily intended for use by
GPs and healthcare professionals undertaking advanced roles working within primary care. All pre-
scribing healthcare professionals wishing to access this resource, including paramedics, will need to
subscribe to MIMS to access either the online version or the quarterly print edition.
MIMS is a helpful prescribing resource and provides:

• News on changes that affect medicines and prescribing

• Drug information for branded and generic products, updated daily
• At-a-glance drug comparison tables including dosing and monitoring regimens, available
presentations, prices, potential sensitisers and compatible devices
• Quick-reference summaries of key clinical guidance from authoritative national bodies including
NICE and the Scottish Intercollegiate Guidelines Network (SIGN)
• Online drugs shortages tracker showing branded and generic medicines that are out of stock
• Online visual guides to help you identify, compare and recommend diabetes and respiratory
administration devices.
Chapter 2 How to use pharmaceutical and prescribing reference guides

Electronic Medicines Compendium (EMC)

The EMC contains up-to-date, easily accessible information about medicines licensed for use in the
34 UK. It can be found at: www.medicines.org.uk/emc. The EMC contains more than 14 000 documents,
which have been checked and approved by either the UK or European government agencies which
license medicines. These agencies are the UK Medicines and Healthcare Products Regulatory Agency
(MHRA) and the European Medicines Agency (EMA). The EMC is updated continually and you can
browse for medicines or active ingredients using the A–Z buttons. The EMC contains regulated and
approved information on medicines available in the UK including the following.

• Summaries of Product Characteristics (known as SPCs or SmPCs): an SmPC informs healthcare

professionals how to prescribe and use a medicine correctly. It is based on clinical trials that a
pharmaceutical company has carried out and gives information about dose, use and possible
side-effects. A SmPC is always written in a standard format.
• Patient Information Leaflets (PILs, Package Leaflets or PLs): a PIL is the leaflet included in the pack
with any medicine. The PIL is a summary of the SmPC and is written for patients.
• Risk Minimisation Materials (RMMs): RMMs are resources for healthcare professionals which aim to
optimise the safe and effective use of a medicine. RMMs can come in a number of forms, such as
educational programmes, prescribing or dispensing guides, patient brochures or alert cards.
• Safety Alerts: these are issued by the regulator and/or marketing authorisation holder and contain
important public health messages or safety-critical information about a medicine.
• Product Information: this is any additional information about a product. It may include important
information such as change of packaging or issues related to stock levels.

Within the EMC there are audio and video resources that provide additional information in a user-
friendly format, promoting the safe and effective use of a medicine. For example, a video clip may
demonstrate how to administer a certain medicine correctly.

Conclusion
This chapter has provided an overview of the main pharmaceutical and prescribing reference guides
used within paramedic practice. Guidance has been given to encourage you to start to navigate the

Associated medications
The following are medications commonly used by paramedics in practice.

• Take some time to look these up in the JRCALC Guidelines, section 7, and find the appropriate
dose for an adult patient.
• Make sure you can find the appropriate dose for a range of paediatric patients from 0 to 11
(if applicable).

Think about the medications, how they are used in practice, route of administration, cautions and
contraindications. Make some notes about your own experiences of administering these drugs in
practice, thinking about how you used a reference guide to find the correct drug information. If you
are making notes about people you have offered care and support to, you must ensure that you have
adhered to the rules of confidentiality.

Medication Your notes

Morphine sulfate
Diazepam
Furosemide
Salbutamol
Adrenaline
How to use pharmaceutical and prescribing reference guides Chapter 2

JRCALC Guidelines in hard-copy, digital and app format. This guidance will help to ensure you know
where to find all the information needed about a medicinal product or device to guide safe and
effective paramedic practice. The differences between paper-based and online versions have been
highlighted to ensure you are aware where to access the most up-to-date and accurate drug infor- 35
mation. An introduction to additional resources has also been given.

Disclaimer
JRCALC is referenced within this chapter. Joint Royal Colleges Ambulance Liaison Committee guid-
ance is subject to regular review and may be updated or withdrawn. JRCALC has not checked the use
of its content in this chapter to confirm that it accurately reflects JRCALC publications.

References
British National Formulary. (2020a). Adult BNF. London: Pharmaceutical Press.
British National Formulary. (2020b). Children’s BNF. London: Pharmaceutical Press.
Health and Care Professions Council (HCPC). (2016). Standards of conduct, performance and ethics. www.hcpc-uk.
org/standards/standards-of-conduct-performance-and-ethics/
Health and Care Professions Council (HCPC). (2014). The standards of proficiency for paramedics. www.hcpc-uk.
org/standards/standards-of-proficiency/paramedics/
Joint Formulary Committee. (2019). How BNF publications are constructed: assessing the evidence. https://bnf.nice.
org.uk/about/how-bnf-publications-are-constructed.html
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). (2019a). Clinical Guidelines. Bridgwater: Class
Professional Publishing.
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). (2019b). Clinical Guidelines Pocket Book. Bridgwater:
Class Professional Publishing.
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). Basic app. www.classprofessional.co.uk/digital-
products/apps/icpg-the-jrcalc-app-subscriptions/
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). Plus app. www.classprofessional.co.uk/digital-
products/apps/jrcalc-plus-app/
Pryor, C. and Hand, A. (2021). How to use pharmaceutical and prescribing reference guides BNF/cBNF/MIMS. In:
Fundamentals of Pharmacology for Nursing and Health Care Students (eds I. Peate and B. Hill). Oxford: Wiley.
Young, S. and Pitcher, B. (2016). Medicine Management for Nurses at a Glance. Oxford: Wiley.

Further reading
Australian Clinical Practice Guidelines: Ambulance and MICA Paramedics. www.ambulance.vic.gov.au/wp-
content/uploads/2018/07/Clinical-Practice-Guidelines-2018-Edition-1.4.pdf
Australian Council of Ambulance Authorities (CAA): www.caa.net.au/
Australia, Paramedicine Board: www.paramedicineboard.gov.au/Professional-standards.aspx
Electronic Medicines Compendium: www.medicines.org.uk/emc
Joint Royal Colleges Ambulance Liaison Committee (JRCALC): www.jrcalc.org.uk/
National Institute for Health and Care Excellence (NICE). Information on medicines and prescribing: www.nice.org.
uk/about/nice-communities/medicines-and-prescribing
Scottish Intercollegiate Guidelines Network (SIGN): www.sign.ac.uk
UK Drug Tariff: www.nhsbsa.nhs.uk/pharmacies-gp-practices-and-appliance-contractors/drug-tariff

Multiple-choice questions
1. What is the correct dose for the administration of benzylpenicillin sodium for a 9-year-
old child?
(a) 1.2 grams
(b) 600 milligrams
(c) 300 milligrams
(d) 1 gram
Chapter 2 How to use pharmaceutical and prescribing reference guides

2. According to the JRCALC Guidelines, paramedics can administer dexamethasone for

which respiratory condition?
(a) Croup
36
(b) Asthma
(c) COPD
(d) Bronchiolitis
3. What does PGD stand for?
(a) Parental guidance drug
(b) Prescription-guided drug
(c) Patient group directive
(d) Patient-guided directive
4. Paramedics administer diazepam for the treatment of seizures and which other
condition?
(a) Tachycardia
(b) Anxiety
(c) Symptomatic cocaine toxicity
(d) Nausea and vomiting
5. When should a medication labelled p.c. be taken?
(a) After food
(b) Before food
(c) Every night
(d) Every morning
6. Which of the following is not a potential side-effect of clopidogrel?
(a) Dyspepsia
(b) Nausea
(c) Abdominal pain
(d) Diarrhoea
7. When administering GTN, paramedics should check whether the patient has already
taken which other drug?
(a) Sildenafil
(b) Aspirin
(c) Bisoprolol
(d) Clopidogrel
8. What is the maximum adult dose of morphine sulfate which can be administered via
the IV/IO route?
(a) 10 mg
(b) 20 mg
(c) 30 mg
(d) 40 mg
9. Which section of the JRCALC Guidelines features information about specific medical
emergencies?
(a) Section 1
(b) Section 2
(c) Section 3
(d) Section 4
10. The average heart rate of a child aged 6 years old is:
(a) 60-100 BPM
(b) 80-100 BPM
(c) 90-110 BPM
(d) 80-120 BPM
Chapter 3
Legal and ethical issues
Claire Leader, Emma Senior, Deborah Flynn and
Paul Younger

Aim
The aim of this chapter is to examine the legal and ethical considerations that are related to pharmacology
and medicines management in contemporary paramedic practice.

Learning outcomes
By the end of this chapter the reader will be able to:

1. Define commonly used legal and ethical concepts

2. Identify situations where legal and ethical considerations are required to make defensible decisions
3. Explain how legal and ethical considerations influence the decision-making process
4. Apply legal and ethical considerations to a variety of scenarios likely to be encountered in modern
healthcare settings.

The legal issues discussed in this chapter are predominantly related to the law in the UK. It is essential that
you keep to the laws of the country in which you are practising. You are required to have knowledge of
and keep to the relevant laws, policies, regulations and guidance about the advice you give people in
relation to prescribing, supplying, dispensing or administering medicines within the limits of your train-
ing and competence.

Test your knowledge

1. According to law, what must be established in order to prove a case of negligence?
2. Can a wife consent to treatment on behalf of their wife who lacks capacity?
3. What is the meaning of beneficence in relation to ethics?
4. Can a paramedic or other healthcare professional provide treatment for children without the
consent of their responsible parent in an emergency situation?
5. What is a professional body’s primary function?

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 3 Legal and ethical issues

Introduction
This section will introduce readers to fundamental ethical principles relating to paramedic practice
and the provision of healthcare, as well as some of the key legal concepts with which those studying
38 paramedicine should become familiar in order to ensure that decisions around pharmacology have
a legal and ethical basis.
Any decisions made about pharmacology require consideration of various issues: what you are
legally obliged to do, what you are professionally guided to do and what is in the best interests of the
person within the situation. In practice, the three usually exist together, but before considering them
as a whole, let’s start with the fundamentals and look at them separately.
This chapter will consider the three components that underpin high-quality decision making in
pharmacology:

• The law
• Ethical principles and theories
• Regulatory bodies.
The law
Laws exist to protect patients and the public. Recent years have seen changes in the culture within
healthcare in the UK, with a notable rise in litigation; this is much the same in other countries. Unlike
some countries where there is a ‘no blame’ process for medico-legal cases, the UK system operates a
‘fault criterion’ whereby fault has to be established for the complainant to prove a case. In the UK
clinical negligence claims quadrupled between 2007 and 2017 (National Health Service Improvement
(NHSI), 2019) leading to an exponential growth in the number of cases involving healthcare profes-
sionals who are forced to defend their practice in a court setting. Failing to monitor a particular drug
therapy, failure to recognise the prescription of a contraindicated drug, failure to warn patients of
adverse effects and neglecting to protect a patient from harm are all examples of pharmacology
cases whereby blame could be laid. As our professional remit grows, so does the legal expectation.
Given the amount of resources and information paramedics have access to, the defence of lack of
knowledge is wholly insufficient.
UK laws originate from two sources: common law, sometimes referred to as ‘case’ law, and statute
law known as ‘Act of Parliament’.
Common law or case law refers to cases that are tried in courts of law whereby a judge will give rule
to a set of legal precedents. Common law is constantly changing due to the ways in which judges
interpret the law and use their knowledge of legal precedent and common sense as well as applying
the facts of the case. Common law safeguards that the law remains common throughout the land
and can be divided into either criminal or civil law.
Statute law or Act of Parliament is law which is written down and codified into law. Acts begin
as bills which then become Acts once the bills have been heard and possibly amended in the
House of Commons and House of Lords before receiving Royal Assent. The Acts can either be
private or public. Private Acts may apply to detailed locations within the UK or they may grant
specific powers to public bodies such as local authorities. Public Acts are the laws that affect the
whole of the UK or one or more of its constituent countries: England, Wales, Scotland and Northern
Ireland.
Healthcare and the law in the UK are strongly entwined. The laws created to protect the health
of an individual can be seen when under the care of the hospital and its medical team, through to
public health and the legal requirements of health and safety. Across the UK, the laws and char-
ters that exist have been created to ensure that the rights and health interests of the individual
are protected throughout the duration of their medical care. Paramedics therefore have a legal
duty to act with reasonable care when providing services. This ‘duty of care’ is defined as a ‘legal
obligation imposed on individuals or organisations that they take reasonable care in the conduct
of acts that could foreseeably result in actionable harm to another’ (Samanta and Samanta, 2011,
p.89). This includes prescribing drug therapy and drug administration as well as consent,
Legal and ethical issues Chapter 3

Clinical consideration: the Bolam test

The majority of litigation in relation to medical malpractice comes under the category of negligence.
When considering cases of clinical negligence, courts will assess whether the health professional or
organisation in question acted in line with the practice accepted as proper by a body of health profes- 39
sionals specialising in the specific field under scrutiny. This is known as the Bolam test. The case (Bolam
v Friern Hospital Management Committee 1957) involved a patient who had suffered a fractured hip
during electroconvulsive therapy (ECT). No relaxant or other restraint had been given to the patient in
preparation for the treatment. The case explored this, along with the information the patient had been
offered. The question was asked of a group of similar professionals and it was assessed that the practi-
tioner had not been negligent as he had acted in accordance with accepted practice at that time. This
set the standard and the Bolam test is now utilised in cases of negligence as a benchmark for whether
the professional concerned acted in a reasonable manner. However, a judge can still make the assess-
ment that the body of opinion is not reasonable.

The Copyright, Designs The Access to General Data

Medicines and Patents Act (1988) Medical Reports Human Rights Health & Social Protection Regulation
Act (1968) (amended 2003) Act (1988) Act (1998) Care Act (2008) (2018)

Misuse of Drugs Data Protection The Access to The Freedom of Human Medicines
Act (1971) Act (1998) Health Records Information Act Regulation (2012)
Act 1990 (2000)

Figure 3.1 Acts and laws relevant to medical practice.

negligence and confidentiality, to name but a few. Failure to act with reasonable care could result
in a paramedic being held responsible in both criminal and civil courts as well as being called to
account by their regulatory body.
There are several Acts or laws that affect the provision of medicines which are illustrated in
Figure 3.1.

Ethical principles and theories

Making ethical decisions is about deciding on the right way to act in a given situation, which is
underpinned by the moral values held by an individual or group. In 1979, Beauchamp and Childress
(2009) developed a four-point theoretical framework to be used as a method of analysing ethical
dilemmas in clinical medicine. The framework included beneficence, non-maleficence, autonomy
and justice. These principles remain in healthcare along with the addition of a further two principles.
Today the following ethical principles apply.

• Beneficence
• Non-maleficence
• Autonomy
• Justice
• Veracity
• Fidelity
Chapter 3 Legal and ethical issues

The principles outlined here are commonly felt to underpin judgements health professionals
believe to be right. Firstly, beneficence, whereby we should endeavour to do good. This extends to
protecting others and defending their rights, preventing harm and helping others. It is argued by
some such as Pellegrino (1988) that beneficence is the only fundamental principle within healthcare
40 ethics and that the sole purpose of medicine should be to heal. By this assumption, medicines such
as contraception and treatments for conditions such as infertility, erectile dysfunction or aesthetics
could fall beyond its purpose. However, the notion of ‘healing’ is complex and dynamic, referring to
more than just the rectifying of an immediate physical ailment or condition. Contraception, fertility
treatment and plastic surgery support health and wellbeing in many direct and indirect ways, physi-
cally as well as psychologically, which is why the endeavour of beneficence is not as straightforward
as it would first appear.
In practice, in order to do good, the medical interventions and treatments can often carry a risk of
harm and therefore require justification. Non-maleficence means that by our actions, we should do
others no harm. The principle of non-maleficence therefore cannot be absolute and must be bal-
anced against beneficence. For example, when treating patients with cytotoxic chemotherapy drugs
for cancer, we balance beneficence (the potential to do good and eradicate the cancer) against non-
maleficence and the risk of the chemotherapy itself to cause the patient’s condition to deteriorate,
possibly leading to death.
It is also generally believed that people should have the right to make decisions about what is right
for them, provided they have sufficient capacity or understanding to do so. This principle is a respect
for the autonomy of the individual and relates to enabling patients to make self-determined deci-
sions regarding their care. Consent to treatment is a fundamental component of ethical patient care
in addition to a legal requirement. It involves a genuine agreement (verbal or written) to receive
treatment under circumstances where the patient has been assessed as competent, has been fully
informed and where there is no undue pressure exerted (Herring, 2018). Beauchamp and Childress
(2009) have argued that no decision can be truly autonomous, as patients rarely have the relevant
knowledge to hold a full understanding of treatment options and as such are vulnerable to the coer-
cion of health professionals such as paramedics who feel that they are best placed to make decisions
in the interests of their patients (paternalism).
However, patient groups have sought to increase autonomy for patients through changes in poli-
cies and practices which decrease the potential for coercion and increase patients freedom to act
(Williamson, 2010). An example of this has been seen in recent years, as a greater emphasis has been
placed on models of shared decision making between health professionals and patients. The shared
decision-making approach seeks a balance between paternalistic care and the informed consent
approach. Paternalistic care is where decisions about care are made by paramedics and other health
professionals (doctors, for example) and patients passively receive the care prescribed. This model
does not factor in patients’ own values and beliefs and can lead to patients feeling greater distress
where there is a negative outcome (Stewart and Brown, 2001). The informed consent approach offers
patients greater responsibility and will often involve health professionals offering patients all the

Clinical consideration
A shared decision-making approach to care has been shown to benefit patients in terms of their active
engagement in the treatment plan or taking the prescribed medications (Edwards and Elwyn, 2009). As
such, it is an ethical approach to care which has also been shown to reduce the incidence of medico-
legal claims where there is a negative outcome (Studdert et al., 2005). The paramedic should always
aim to fully involve patients in decisions about drug treatments to maximise engagement and increase
the potential for success.

information required and then leaving them to make the decision unsupported. This can lead to
patients feeling abandoned and unsure, creating anxiety and distrust (Corrigan, 2003; Deber
et al., 2007). The shared decision-making approach involves health professionals and patients work-
ing together to devise a plan of care that is in line with the best available evidence as well as the
values and beliefs of the individual patient, aligning to the principle of true autonomy.
Legal and ethical issues Chapter 3

Health professionals also abide by the principle of justice which is the belief that people should be
treated fairly, equally and reasonably. At its heart, justice is about equality but how equality is deter-
mined can be ambiguous and problematic in healthcare. An example of the difficulties posed within
this principle is often seen in relation to the fair and equal distribution of resources, ‘distributive justice’.
A drug for a specific condition may be available within one healthcare organisation but not available 41
to patients with the same or similar condition in another organisation. Sometimes colloquially labelled
the ‘postcode lottery’, this occurs as a result of differing priorities among those who make difficult
commissioning decisions about resources on a local level.
The paramedic should also be honest and tell the truth to enable someone to have the full infor-
mation relevant to them in order to make full rational choices about their care. This is known as
veracity and involves conveying accurate and objective information to the patient. Giving patients
full information regarding treatment options is the most common application of the veracity prin-
ciple. Disclosures of medication errors are also an example of veracity and the introduction in the
UK of the ‘duty of candour’ guidance for health professionals (GMC, 2014) highlights the impor-
tance of the veracity principle. Informing patients when something has gone wrong, apologising
and offering a remedy were measures that were advised in a report on the failings of the Mid-
Staffordshire Health Trust. Francis (2013) stated that candour and transparency were key compo-
nents of a safe and effective culture for patient care. However, in reality true veracity is a complex
notion. Returning to the example of the drug that is available in one healthcare organisation and
not another, health professionals engage in such rationing ‘inconspicuously’ (Williamson, 2010,
p.201) without necessarily informing patients that they are being denied something that could
benefit them. Aside from the greater ethical issues concerned with who makes the decisions and
how they are implemented, there is the more immediate concern relating to veracity and the deci-
sion whether to inform patients.
Finally, the principle of fidelity requires loyalty and trustworthiness; it involves keeping our prom-

Clinical considerations: consent to treatment

(adults)
Adults with capacity: the authority to treat comes solely from the patient. In UK law, consent by proxy is not
permitted for the care or treatment of adults who have the capacity to make an informed decision.
Adults lacking capacity: where a patient does not have the mental capacity to make an informed deci-
sion regarding their care due to an impairment or disturbance to the functioning of the mind, e.g. acute
confusional state, dementia, brain injury, being unconscious, then under the Mental Capacity Act
(MCA, 2005), the health professional can decide upon the treatment that is deemed in the best inter-
ests of the patient without the consent of the next of kin.
Section 3(1) of the MCA (2005) sets out the following benchmarks by which to assess an adult’s
capacity.
• They are unable to understand the information given to them relating to the decision.
• They are unable to retain the information.
• They are unable to weigh the information as part of the decision-making process.
• They are unable to communicate their decision.

ises, performing our duties and doing what is expected of us within our relationships with patients.
This principle can be conflicted where the health professional’s loyalty or obligation may be torn
between their patients and colleagues or the organisation for which they work. Conflict may also
arise as a result of the patient lacking capacity to make an informed choice and the health profes-
sional being compelled to over-ride the wishes of their patient in their best interests.
You are required to keep to all relevant laws about mental capacity that apply in the country in
which you are practising, ensuring that the rights and best interests of those who lack capacity are
still at the centre of the decision-making process.
Chapter 3 Legal and ethical issues

When ethical dilemmas in practice are encountered, consideration needs to be given to which
principles are in conflict and then consider which is more important. In helping to resolve ethical
dilemmas, ethical theories are called upon. Several exist, including:

42 • Utilitarian/consequentialism
• Deontological ethics
• Virtue ethics.

Clinical consideration: consent to treatment

(children)
16–17 year olds with capacity: according to section 8(1) of the Family Law Reform Act (1969), consent
can be sought from the child for medical and dental treatment. However, those with parental respon-
sibility may still consent on the child’s behalf.
16–17 year olds lacking capacity: anyone with parental responsibility can consent on behalf of a child
who lacks capacity. In situations where those with parental responsibility do not consent to treatment,
but treatment is felt to be in the best interests of the child, a court order may be obtained. In an emer-
gency situation, treatment may still be provided without parental consent where it is deemed a neces-
sity (Glass v United Kingdom 2004).
Under 16 years of age: an assessment of the child relating to ‘Gillick’ competence (Gillick v West
Norfolk and Wisbech Area Health Authority 1986) would determine whether the child has sufficient
maturity and understanding of what is involved to enable them to make a decision to consent to
treatment or not.

Utilitarian or consequentialism theory considers the rightness of an act as that which, when considering
the costs and benefits, creates the greatest good for the greatest number. For example, the issue of
immunisation is currently a controversial one with a minority of parents deciding to opt out of immunisa-
tion programmes for their children. This puts children and other vulnerable members of society at risk of
developing some diseases that were previously eradicated, such as measles (Public Health England, 2019),
with the associated implications for individuals, wider society and the health service. The utilitarian per-
spective would be that all eligible children should be immunised irrespective of the views/wishes of their
parents. Utilitarianism would not be concerned with the autonomy of the individual (the right to refuse
consent for the vaccine) as this is arguably in conflict with the greater good.
Deontological ethics or deontology is an approach to ethics that determines goodness or right-
ness from examining acts rather than consequences of the act, as in utilitarianism. Deontologists
look at rules and duties. For example, the action may be considered the right thing to do, even if it
produces a bad consequence, if it follows the rule that ‘one should do unto others as they would
have done unto them’. According to deontology, we have a duty to act in a way that does those
things that are inherently good. In this approach, the duty of care to the individual takes priority
over any other considerations. Going back to our example of immunisations, children are, in reality,
not forced to have immunisations where parents have opted out. A paramedic has a duty to ensure
that any care given is consented to, within the parameters of the MCA (2005) as outlined above.
Without this consent, we cannot inject a live vaccine into a child no matter what the potential
implications might be for wider society. So the act itself is good (abiding by rules of consent) but
the consequence may be a negative one (the child contracting measles and passing this on to oth-
ers). For deontologists, the ends or consequences of our actions are not important nor are our
intentions. Duty is the key consideration. However, it is not always clear what one’s duty is. Whilst
we may agree that our duty is to ‘do no harm’, there will be instances where the paramedic will have
to over-ride this with their duty of care.
Virtue ethics focuses on how we ought to behave, and how we should think about relationships,
rather than providing rules or formulas for ethical decision making. It considers the virtues a ‘good’
Legal and ethical issues Chapter 3

person would have: honesty, compassion, generosity, courage, for example (Velasquez et al., 1988).
With the common good in mind, these virtues will be applied to actions and decisions. A group of
virtues can be accredited to particular roles or professions, and it could be argued that nurses are
attracted to the profession because they already function according to these virtues.
What is deemed to be right is not therefore bound by absolute rules or duty, or purely the greatest 43
good, but also considers the virtues that individuals and society value. The ethical views held by
society affect healthcare laws and how they are implemented. As society’s moral values alter, legisla-
tion follows. An example of this was in 1967 when UK society’s beliefs changed regarding abortions.
It became largely accepted that in some cases they were necessary for saving women’s lives as well
as reducing the potential for suffering (psychologically as well as physically) of the woman and her
pre-existing family, and so the Act was introduced (Abortion Act 1967).

Regulatory bodies
In order to practice, healthcare professionals are aligned to a regulatory body such as the Health and
Care Professions Council (HCPC), Nursing and Midwifery Council (NMC), Paramedicine Board
Australia, or General Medical Council (GMC). The purpose of a regulatory body is primarily to protect
the public and as such they are established and based upon a legal mandate. Their function is regula-
tory and to impose requirements, restrictions and conditions as well as offering a means of support
and guidance to professionals. They also set standards in relation to practice activities, securing com-
pliance and enforcement of their practitioners. Regulatory bodies have traditionally provided their
practitioners with ethical guidance in the form of a ‘code’ or an ‘oath’ such as the HCPC Standards of
Conduct, Performance and Ethics, NMC Code of Conduct (2018), Paramedicine Board Australia Code
of Conduct (2018) or the Hippocratic Oath for doctors.

Episode of care
Whilst working on a double crewed ambulance (DCA), you are called to a bedsit that is used by
young intravenous drug users (IVDU). You notice that ambulances are only called to IVDU when they
are in cardiac or respiratory arrest or have bradypnoea. So the patient’s friends only call for help
when the patient’s condition becomes life threatening. You notice that this patient group does not
seek medical help in the same way many other patient groups do. You begin to think about why this
is the case, using the principles of ethical professional practice, beneficence (do good) and non-
maleficence (do no harm).

Within healthcare, regulatory bodies have a duty to protect, promote and maintain the health and
safety of the public. They do this by ensuring proper standards are in place in order to practice. Such
standards define the overarching goals and expected role and duties of their practitioners through
listing the obligations associated with their individual responsibilities and skill set. The overarching
goals are aspirational and represent an optimal position ethically, thus encouraging the individual to
strive towards the optimal position. Paramedics, like the public and their patients, possess their own
values and beliefs which in turn influence their practice.
Within this scenario, there is a possibility the patients or service user’s care has been affected by
the HCP’s implicit bias towards certain social groups. Several authors have emphasised that a well-
meaning, egalitarian (fair-minded) individual can have implicit biases which demonstrate the imbal-
ance between their unconscious ways of thinking and how they explicitly perceive themselves
treating people (Fitzgerald and Hurst, 2018; Lang et al., 2016). The elements of implicit bias (IB) are
one’s perceived stereotypes (a mental picture of what one thinks, knows and expects) and prejudices
(feelings) associated with certain categories of people, learnt through a shared culture, which over
time slip into one’s unconsciousness, which means they remain hidden (Lang et al., 2016). As Stone
and Moskowitz (2011) explained, this means that HCPs are unaware of their biases which impacts on
the quality of care delivered, seen in how they may judge and behave towards particular groups
(Kelly and Roedderts, 2008). Merino et al. (2018) highlighted that over 60% of HCPs harbour variants
Chapter 3 Legal and ethical issues

of IB towards marginalised/vulnerable groups. Examples of vulnerable or marginalised groupings

can be based on gender, age, weight, homelessness, ethnicity, immigration status, socio-economic
status, educational achievement, mental ill health, sexual orientation, intravenous drug use, disabili-
ties and social circumstances or anyone rendered vulnerable in certain situations (Fitzgerald and
44 Hurst, 2018).
There is consensus that stereotyping saves cognitive resources in stressful environments, a situation
in which HCPs often find themselves (Hall, 2017). By drawing on these stereotypes, the HCP is able to
make timely decisions based on the minimal information available in times of fatigue, tiredness, heavy
workload, uncertainty and inadequate support (Stone and Moskowitz, 2011). Nonetheless, there is a
clear link between IB and the quality of care delivered and how it potentially influences the HCP’s abil-
ity to engage in person-centred care (Merino et al., 2018). Fitzgerald and Hurst (2018) stated that a
HCP’s IB behaviour towards marginalised groups can impact on the service user’s access to healthcare
service by producing false diagnoses, non-referral to appropriate services, treatment options or with-
holding of treatment. Goyal et al. (2015) detailed how IB may have contributed to the creation of
health disparities as African-American children were less likely to receive adequate pain management
post appendectomy than their white counterparts. IB influences within clinical interactions can leave
the service user feeling uncomfortable as they pay attention to the HCPs non-verbal mannerisms such
as eye contact, physical closeness and speech errors which can demonstrate the HCP’s unease when
dealing with particular clientele (Stone and Moskowitz, 2011). This in turn may not only impede
patient–HCP communication but may affect patient concordance and willingness to seek future care.
Puddifoot (2017) suggested that IB can cause an ethical dilemma, demonstrated earlier, as there
is potential to do harm within these client groups through the HCP’s judgement and behaviour
based on their IB. Positive beneficence requires the HCP to consider benefits for others alongside
balancing the risks (Baillie and Black, 2015) which is compromised through the harbouring of IB.
Such behaviours are in direct contradiction to the professional regulatory bodies’ codes of profes-
sional performance, so the HCP should reflect on how they interact with certain client groups to
develop awareness of any implicit biases they may have (Lang et al., 2016). Additionally, Stone and
Moskowitz (2011) recommend attending courses to expand cultural competence by learning
about IB.
There are a number of guidelines set out by various professional bodies in relation to pharma-
cology. The General Medical Council (GMC) has outlined expectations of doctors’ ethical pre-
scribing practices which aim to provide more detailed advice on how to apply ethical principles
when prescribing and managing medicines (GMC, 2013). Additionally, the Royal Pharmaceutical
Society and the Royal College of Nursing collaborated in developing the ‘Professional Guidance

Clinical consideration
All paramedics have a responsibility to ensure that they are familiar with legislation related to the pre-
scribing, storage and administration of medicines within their sphere of practice. A list of key docu-
ments that will support you in the development of knowledge in this area is offered in the further
reading section.

on the Administration of Medicines in Healthcare Settings’ (Royal Pharmaceutical Society and

the Royal College of Nursing, 2019). These standards seek to promote patient safety in relation to
the administration of medicines by acknowledging the importance of guidance for health pro-
fessionals that is enabling and supportive while being clear and concise. The document recog-
nises the importance of a commitment to ethics, values and principles which put patients first. It
is incumbent upon the individual HCP to ensure that they are familiar with the most current
guidance related to their own sphere of practice to ensure that ethical and legal considerations
are applied.
Legal and ethical issues Chapter 3

Research
The legal and ethical standards which govern research into pharmacological treatments are very
specific to the context of clinical drug trials. During the Second World War, Jewish prisoners in Nazi
concentration camps were used as subjects in medical experiments against their will, leading to per- 45
manent disfigurement, disability, trauma and in many cases death. In response to these atrocities,
the Nuremberg Code (1947) was developed as international guiding ethical principles for the con-
duct of research involving human participants. They include principles of informed consent, non-
coercion and the right to withdraw as well as the importance of robust protocols underpinned by
beneficence. These principles were later encapsulated within the Declaration of Helsinki (1964,
amended in 2008) and further legislation has evolved to ensure the safety of human participants in
clinical trials, including the Data Protection Act (2018), Human Tissue Act (2004), the Medicines for
Human Use (Clinical Trials) Regulations (2004) and the Human Rights Act (1998).
Research is an important mechanism to ensure that the drug treatments we offer patients are
thoroughly tested for safety and efficacy. Additionally, there is strong evidence emerging that
research-active hospitals have better patient outcomes, highlighting the responsibility healthcare
providers have to offer their service users the opportunity to be involved in clinical trials (Ozdemir
et al., 2015). It is essential that legislation enables clinical researchers to conduct clinical trials in the
endeavour of medical advancement, while ensuring that participants are fully informed of the poten-
tial risks and benefits, are not coerced into consenting to participate and are aware of their right to
withdraw from participating at any time. The guiding principle is that the wellbeing and safety of the
participants are paramount and take priority over any other consideration.
Research ethics committees (RECs) have the remit to review any proposed research that
involves human participants. Made up of a number of lay people and professionals experienced
in their own field, it is the responsibility of the REC to interrogate the research protocol and identify
any aspects of the research consent and treatment processes which may pose an unacceptable
risk to participants or the public. Approval from a REC is essential before a trial can go ahead. As
the trial progresses, researchers will also need to seek ethical approval to make any amend-
ments to the protocol, which may be something as minor as a change of wording within a
participant information sheet, to something more substantial such as a change in the dose of

Skills in practice: how to use medical ethics

Not all decisions are made easily and, in some cases, there are multiple factors that influence decision
making such as personal experience, religious views, regulatory codes, legal issues and so on. In prac-
tice, a practitioner will use a combination of all such factors to reach a decision; this is sometimes
described as a systematic study of moral choices. In the first instance, the code of behaviour or conduct
presented by a regulatory body is considered correct. Within healthcare there are many examples of
ethical decision-making processes which include varying numbers of steps to follow. Overall, there is
the general adoption of principle-based ethics to guide decision-making practice within healthcare
which is evident in this example.
Step 1 – Ability to recognise an ethical issue. Ask yourself, could this scenario or decision cause harm or
damage to someone or some group? Are there choices between different alternatives – for example,
good and bad alternatives or maybe two bads or two goods? Is this situation bigger than what is effi-
cient? or what is legal? What are your initial gut reactions? By considering the scenario on an emotive
level, you can recognise your own assumptions, values and biases so that you can set them aside before
analysing the situation critically.
Step 2 – Gathering the facts. What facts are already known? What other relevant facts need to be gath-
ered? Who are the relevant stakeholders within this scenario and its outcome? Has everyone involved
been consulted? Are some concerns more important than others?
Step 3 – Evaluation of alternative options or actions. Include questions from a range of approaches.
From a utilitarian approach, ask which actions/options do the least harm and produce the most good?
Considering the deontological approach, which actions/options best respect all stakeholders’ rights?
Chapter 3 Legal and ethical issues

From a paramedic perspective, which actions/options treat people proportionately or equally? Which
actions/options best serve the whole community and not just some if its members? From a virtue per-
spective, also consider which actions/options lead me based on the type of person I want to be?
Step 4 – Make the decision. When all approaches have been considered, which actions/options best
46 address the scenario? Which actions/options are best based on all the stakeholders’ core values?
Consider what others might say when you have shared your chosen actions/options – can you justify
your choice?
Step 5 – Carry out the actions/options chosen and reflect on the outcome. Plan how your decision can be
implemented with the utmost care, paying attention to any concerns raised by stakeholders. Implement
your plan and evaluate. Reflect on the results of your choice of decision and what you have learned
from this specific scenario. Consider how the ethical problem could be prevented in the future.

Episode of care
As a paramedic on a DCA, you are called to Paul, a 65-year-old man who has been experiencing car-
diac chest pain for the last 45 minutes. You are about to administer sublingual glycerine trinitrate
(GTN) when the patient discloses that he used sildenafil 2 hours ago. You confer with a colleague
about the benefits and risks of administering GTN when the patient has already taken sildenafil. The
British National Formulary (Joint Formulary Committee, 2019) and JRCALC guidance show that a
severe interaction can take place, leading to profound hypotension. While the treatment may be
doing ‘good’ (beneficence), it also has the potential to do ‘harm’ (maleficence). It is imperative that
the paramedic discuss medication plans prior to treatment to ensure that patients are aware of the
impact this will have on their daily activities. In Paul’s case, although the GTN could lead to vasodila-
tion, decrease in pain, and improved cardiac blood flow, it could also cause his blood pressure to
drop, leading to hypotension. You explain to the patient that on this occasion you will not be admin-
istering the GTN, as the interaction with the sildenafil could lead to a dangerous blood pressure drop.
Always ensure that every decision made fully involves the patient and aligns with their own values
and lifestyle.

Episode of care
Maya is an 85-year-old woman who lives alone. She is usually independent with all her activities of liv-
ing and, although she does not like to leave the house, she is usually in good physical and mental
health. Her daughter visits her three times a week and has noticed some increased confusion over the
past few days. Today she has visited and felt it necessary to call the GP as Maya is extremely confused,
unable to mobilise, pyrexial, and smells strongly of malodorous urine. The GP calls for an ambulance to
transport the patient to hospital with a suspected urinary tract infection (UTI). The paramedic assesses
Maya and finds that she is dehydrated with a blood pressure of 70/46, dry oral membranes, passing
small amounts of urine. They decide to cannulate the patient to administer IV fluids on route to hospi-
tal. However, Maya becomes very distressed when the paramedic attempts to cannulate and Maya’s
daughter states that she does not consent to her mother receiving IV therapy. Maya has been assessed
as an adult lacking capacity by health professionals. In accordance with the Mental Capacity Act (2005)
and in Maya’s best interests, she is cannulated and receives the IV therapy. Over the course of the next
24 hours, her condition improves and her acute confusional state dissipates. The health professionals
have acted in accordance with legal standards. They have also balanced their duty to respect Maya’s
autonomy with their duty of care in ensuring beneficence (doing good by giving the required treat-
ment in Maya’s best interests) and non-maleficence (doing no harm by omitting care that was in her
best interests).
Legal and ethical issues Chapter 3

medication to be administered. These changes will be implemented in line with Good Clinical
Practice (GCP) principles (MHRA, 2012).
Despite these safeguards, notable incidences have occurred in recent years related to the conduct
of some clinical trials. For example, in 2006, volunteers in an early-phase drug trial at Northwick Park
Hospital became seriously ill. The story became headline news after six participants reacted badly to 47
the medication, suffering a severe immune response leading to organ failure and one participant
requiring the amputation of his fingers. This led to a full investigation and the resulting report
changed a number of practices in the running of drugs trials which sought to prevent this from hap-
pening again (Expert Scientific Group on Phase One Clinical Trials, 2006).
Fortunately however, the ethical and legal frameworks which surround clinical research limit these
incidences and provide principles and guidance for the safe conduct of research and researchers.

Conclusion
This chapter has sought to outline the fundamental legal and ethical principles relating to pharma-
cology in healthcare. The three key components that underpin high-quality decision making
with and for patients in our care are related to the law, ethical principles and regulatory bodies.
A variety of legislation has been discussed to offer an understanding of and insight into how
healthcare professionals manage and administer medicines within the confines of the law. The
interplay of legislation, ethical principles and professional regulation is a fine balance that health
professionals seek to strike in order to optimise the safety and efficacy of treatment. Legislation is
country specific and the paramedic must have an understanding of the laws in the country in
which they are practising.
Working in healthcare requires an acknowledgement of the areas of ambiguity and conflict that
may be encountered and while we seek to always ‘do good’, there are countless situations where this
endeavour may be obstructed by other considerations such as patient capacity or the wider public
interest.
Acknowledgement of the issues outlined within this chapter and a deeper understanding of how
to apply the knowledge of ethical principles will ultimately improve practice and provide safer and
higher quality patient care. It is incumbent upon all paramedics (and students) to act with integrity
within these frameworks and to make individualised decisions which are in the patients’ best interest
and, wherever possible, fully informed.

The following is a list of considerations, guiding legislation and ethical frameworks for safe and effective
practice. Find out more about what each of these involves and how this impacts upon the care of patients,
and make notes in the space provided.
The consideration Your notes
Mental capacity
Burden of proof for negligence
Human medicines regulation
Research ethics committee
Northwick Park drug trials controversy

Glossary
Accountability Taking responsibility for actions taken and being able to provide a
rationale for courses of action.
Autonomy Enabling patients to make self-determined decisions regarding their
care.
Beneficence Endeavouring to do good.
Bolam test Assessment of whether a health professional acted within the scope of
accepted practice.
Deontology The study of the nature of duty and obligation.
Chapter 3 Legal and ethical issues

Duty of care Legal obligation for individuals and organisations to take reasonable
care in the conduct of actions that could foreseeably result in actiona-
ble harm.
Egalitarianism Principle that all people are equal and deserve equal rights and
48 opportunities.
Fidelity Provision of care that is honest, responsible and fair.
Implicit bias Perceived stereotypes associated with certain categories of people which
over time slip into one’s unconsciousness. (See also unconscious bias.)
Justice Treating patients fairly, equally and reasonably.
Mental capacity Being able to make and communicate your own decisions.
Negligence Failure to provide adequate care.
Non-maleficence Endeavouring to do no harm.
Paternalism Health professionals asserting a dominant attitude over patients, mak-
ing decisions without the full involvement of patients.
Regulatory body A public organisation or government body which imposes require-
ments, restrictions and standards for practice.
Utilitarianism (or consequential) determing the rightness of an act by considering costs
and benefits and the greatest good for the greatest number of people.
Veracity Conveying honest, accurate and objective information to the patient
to support them in making a decision around medical care.
Virtue ethics Focuses on desirable ways of relating to others, including habits, atti-
tudes and emotion as well as conduct.

References
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Baillie, L. and Black, S. (2015). Professional Values in Nursing. Boca Raton: Taylor & Francis Group.
Beauchamp, T.L. and Childress, J.F. (2009). Principles of Biomedical Ethics, 6th edn. Oxford: Oxford University Press.
Corrigan, O. (2003). Empty ethics: the problem with informed consent. Sociology of Health and Illness 25(7):
768–792.
Data Protection Act (2018). www.legislation.gov.uk/ukpga/2018/12/contents/enacted
Deber, R., Kraetschmer, N., Urowitz, S. and Sharpe, N. (2007). Do people want to be autonomous patients? Preferred
roles in treatment decision-making in several patient populations. Health Expectations 10: 248–258.
Declaration of Helsinki. (2008). Ethical principles for medical research involving human subjects. www.who.int/
bulletin/archives/79%284%29373.pdf
Edwards, A. and Elwyn, G. (eds). (2009). Shared Decision-Making in Health Care. Achieving Evidence-Based Patient
Choice. Oxford: Oxford University Press.
Expert Scientific Group on Phase One Clinical Trials. (2006). Final Report. https://webarchive.nationalarchives.gov.
uk/20130105143109/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/
documents/digitalasset/dh_073165.pdf
Fitzgerald, C. and Hurst, S. (2018). Implicit bias in healthcare professionals: a systematic review. BMC Medical Ethics
18(19): 1–18.
Francis, R. (2013). Report of the Mid-Staffordshire NHS Foundation Trust Public Enquiry. London: Stationery Office.
General Medical Council. (2013). Good practice in prescribing and managing medicines and devices. www.gmc-uk.
org/-/media/documents/prescribing-guidance_pdf-59055247.pdf?la=en
General Medical Council. (2014). The professional duty of candour. www.gmc-uk.org/ethical-guidance/ethical-guidance-
for-doctors/candour---openness-and-honesty-when-things-go-wrong/the-professional-duty-of-candour
Gillick v West Norfolk and Wisbech area Health Authority and Department of Health and Social Security (1984) Q.B
as cited in Children’s Legal Centre (1985) Landmark decision for children’s rights. Childright, 22:11–18.
Glass v United Kingdom. App. No 61827/00, 39 Eur. H.R.Rep. 15 (2004).
Goyal, M.K. Kuppermann, N., Cleary, S.D. et al. (2015). Racial disparities in pain management of children with
appendicitis in emergency departments. JAMA Pediatrics 169(11): 996–1002.
Hall, A. (2017). Using legal ethics to improve implicit bias in prosecutorial discretion. Journal of the Legal Profession
42(1): 111–126.
Herring, J. (2018). Medical Law and Ethics. Oxford: Oxford University Press.
Human Rights Act (1998). www.legislation.gov.uk/ukpga/1998/42/contents
Legal and ethical issues Chapter 3

Human Tissue Act (2004). www.legislation.gov.uk/ukpga/2004/30/contents

Joint Formulary Committee. (2019). British National Formulary. https://bnf.nice.org.uk
Kelly, D. and Roedderts, E. (2008). Racial cognition and the ethics of implicit bias. Philosophy Compass 3(3):
522–540.
Lang, K.R. Dupree, C.Y., Kon, A.A. and Dudzinski, D.M. (2016). Calling out implicit bias as a harm in pediatric care.
Cambridge Quarterly of Healthcare Ethics 25: 540–552.
49
Medicines for Human Use (Clinical Trials) Regulations (2004). www.legislation.gov.uk/uksi/2004/1031/contents/
made
Medicines and Healthcare products Regulatory Agency (MHRA). (2012). Good Clinical Practice Guide. London:
Stationery Office.
Mental Capacity Act (MCA). (2005). www.legislation.gov.uk/ukpga/2005/9/contents
Merino, Y., Adams, L. and Hall, W.J. (2018). Implicit bias and mental health professionals: priorities and direction for
research. Psychiatric Services 69(6): 723–725.
National Health Service Improvement (NHSI). (2019). Clinical negligence and litigation. https://improvement.nhs.
uk/resources/clinical-negligence-and-litigation/
Nuremberg Code. (1947). Trials of War Criminals Before the Nuernberg [sic] Military Tribunals. Volume II. “The Medical
Case.” www.loc.gov/rr/frd/Military_Law/pdf/NT_war-criminals_Vol-II.pdf
Nursing and Midwifery Council. (2018). The Code: Professional standards of practice and behaviour for nurses,
midwives and nursing associates. www.nmc.org.uk/globalassets/sitedocuments/nmc-publications/nmc-
code.pdf
Ozdemir, B.A., Karthikesalingam, A., Sinha, S. et al. (2015). Research activity and the association with mortality.
PLoS ONE 10(2): e0118253.
Paramedicine Board Australia. (2018). Code of conduct (interim). www.paramedicineboard.gov.au/professional-
standards/codes-guidelines-and-policies/code-of-conduct.aspx
Pellegrino, E.D. (1988). For the Patient’s Good: The Restoration of Beneficence in Health Care. Oxford: Oxford University
Press
Public Health England. (2019). Measles: guidance, data and analysis. www.gov.uk/government/collections/
measles-guidance-data-and-analysis#epidemiology
Puddifoot, K. (2017). Dissolving the epistemic/ethical dilemma over implicit bias. Philosophical Explorations 20(1):
S73–S93.
Royal Pharmaceutical Society and Royal College of Nursing. (2019). Professional Guidance on the Administration of
Medicines in Healthcare Settings. www.rpharms.com/Portals/0/RPS%20document%20library/Open%20
access/Professional%20standards/SSHM%20and%20Admin/Admin%20of%20Meds%20prof%20guidance.
pdf?ver=2019-01-23-145026-567
Samanta, J. and Samanta, A. (2011). Medical Law. Basingstoke: Palgrave Macmillan.
Stewart, M. and Brown, J. (2001). Patient-centredness in medicine. In: Evidence-based Patient Choice (eds A.
Edwards and G. Elwyn). Oxford: Oxford University Press.
Stone, J. and Moskowitz, G.B. (2011). Non-conscious bias in medical decision-making: what can be done to reduce
it? Medical Education 45: 768–776.
Studdert, D.M., Mello, M.M., Sage, W.S. et al. (2005). Defensive medicine among high-risk specialist physicians in a
volatile malpractice environment. JAMA 293: 2609–2617.
Velasquez, M., Andre, C., Shanks, T. et al. (1988). Ethics and Virtue. www.scu.edu/ethics/ethics-resources/ethical-
decision-making/ethics-and-virtue/
Williamson, C. (2010). Towards the Emancipation Of Patients. Patients’ Experiences and The Patient Movement. Bristol:
Policy Press.

Further reading
Department of Health. (2012). Compassion in Practice. www.england.nhs.uk/wp-content/uploads/2012/12/
compassion-in-practice.pdf
Family Law Reform Act (1969). www.legislation.gov.uk/ukpga/1969/46
Health and Care Professions Council. (2016). Standards of conduct, performance and ethics. www.hcpc-uk.org/
globalassets/resources/standards/standards-of-conduct-performance-and-ethics.pdf
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). (2019). Clinical Guidelines. Bridgwater: Class
Professional Publishing.
National Institute of Health and Care Excellence (NICE). (2018). Guideline 109 Urinary tract infection (lower): antimi-
crobial prescribing. www.nice.org.uk/guidance/ng109
Chapter 3 Legal and ethical issues

Multiple-choice questions
1. Common law is also known as:
50 (a) Criminal law
(b) Case law
(c) Statute law
(d) All of the above.
2. Failure to act with reasonable care could result in a paramedic being held responsible
in which courts?
(a) Criminal court
(b) Civil court
(c) Civil and criminal court
(d) All of the above
3. What year did the Medicines Act become statute?
(a) 1966
(b) 1967
(c) 1968
(d) None of the above
4. Utilitarian theory considers:
(a) The greatest good for the greatest number
(b) Your duty of care takes priority over any other considerations
(c) How we ought to behave and seek relationships
(d) All of the above.
5. When adopting principle-based ethics to guide your decision making, where do you
need to gather the facts from?
(a) From all the stakeholders involved within the scenario
(b) From what is already known
(c) From other facts that are relevant from other scenarios’
(d) All of the above
6. Sensitive topics such as abortion can lead to the practitioner having _________
dilemma.
(a) Ethical
(b) Clinical
(c) Legal
(d) All of the above
7. Implicit means:
(a) Hidden
(b) Obvious
(c) Available
(d) Explicit.
8. Elements of implicit bias include:
(a) Stereotypes
(b) Prejudices
(c) Stereotypes and prejudices
(d) Impartialities.
9. Healthcare professionals harbour the ________ level of implicit bias as the general
population.
(a) Lower
(b) Higher
(c) Same
(d) None of the above
Legal and ethical issues Chapter 3

10. The influences of implicit bias on the practitioner’s professional behaviour include:
(a) Making the client feel uncomfortable
(b) Helping them access services
(c) Correct diagnoses and treatment
(d) Patient concordance. 51
11. What is the Bolam test?
(a) A test to assess patient capacity
(b) The opinion of a professional body as to whether the action was accepted practice
(c) An assessment of competency of a patient under 16
(d) All of the above
12. Shared decision making:
(a) Is an approach to care that increases patient engagement in treatment
(b) Improves patient engagement with care and treatment
(c) Reduces medico-legal claims
(d) All of the above.
13. What is distributive justice in relation to healthcare?
(a) The fair and equal distribution of health resources
(b) The ‘postcode lottery’
(c) An assessment of patient need
(d) All of the above
14. Why is research in healthcare so important?
(a) To test drugs for safety and efficacy
(b) To develop better treatments for patients
(c) To improve outcomes for patients
(d) All of the above
15. What must professionals do in order to abide by the ‘duty of candour’?
(a) Only tell the patient when a serious incident has occurred
(b) Inform patients and their families of everything related to the patient’s care at all
times
(c) Apologise to patients
(d) All of the above
Chapter 4
Medicines management
and the role of the paramedic
Annette Hand, Carol Wills and Paul Younger

Aim
The aim of this chapter is to provide the reader with an introduction to medicines management and
the role of the paramedic.

Learning outcomes
After reading this chapter the reader will:

1. Understand the term ‘medicines management’ and the role of the paramedic
2. Be able to appraise the paramedic’s role in managing medicines safely and effectively
3. Acknowledge the role of regulatory and advisory bodies in the management and optimisation of
medicines
4. Be able to apply the principles of medicine optimisation.

Test your knowledge

1. Which Act provides the legal framework governing the use of Controlled Drugs?
2. What do the 9Rs stand for?
3. What activities are included within medicines management?
4. What does the term PGD stand for?
5. How do you verify the identification of a patient prior to medicines administration?

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Medicines management and the role of the paramedic Chapter 4

Introduction
This chapter will support learning in relation to medicines management and the role of the para-
medic. Medicines are the most common intervention in healthcare and are vital in treating or manag-
ing many illnesses and conditions. As more people are taking more medicines, it is paramount, for
patients, healthcare professionals and organisations, that medicines are used appropriately.
Population growth and increases in the numbers of older people push up the volume of medicines 53
prescribed, partly due to older people being more likely to have long-term health conditions such as
cardiovascular problems, arthritis or diabetes (Duerden et al., 2013). Effective and safe medicines
management is a key responsibility for many paramedics, and it is important that individuals keep up
to date with new guidelines and regulations within this ever-expanding area of care.
Globally, health and care providers are regulated and monitored using different systems and
approaches. Understanding the various approaches that are used in the jurisdiction where you work
can help ensure that you are providing care that is legal, safe and patient centred. This chapter
focuses on those regulatory systems that are used across the UK and within the National Health
Service (NHS).
Currently all health and social care organisations in the UK are assessed and monitored by an
Independent Regulator of Health and Social Care to determine if they provide appropriate and safe
care; this includes the use of medicines. These regulators will inspect and assess the quality of care
and whether it is safe, effective, caring, responsive and well led. For example, the Care Quality
Commission (CQC) outlines Inspection Frameworks for NHS and independent ambulance services
which details the inspection guidance for Core Services of Emergency and Acute Care as well as Core
Services of Patient Transport Services. Each service is then rated as outstanding, good, requires
improvement or inadequate. Follow Clinical Consideration 1 to explore the rating of the service you
are currently working in. All health professionals have an important role in the provision of quality
services.

Clinical consideration 1
Visit your organisation’s website or the regulator’s website to access its latest inspection report. What
was the outcome of the report?

• Were any areas rated as good or requires improvement?

• What is/would your role be within this provision?

Medicines management
Medicines management involves the safe and cost-effective use of medicines in clinical practice,
maximising patient benefits while minimising potential harm. NHS spending on medicines was esti-
mated at £17.4 billion in 2016–17 and is said to be increasing at a rate of 5% each year (Ewbank
et al., 2018). This has been said to be unsustainable and all health professionals need to explore how
this can be managed. The human costs when things go wrong with medications include increased
use of health services, preventable admissions to hospital, serious harm and ultimately death. It is
estimated that 70% of errors are identified before they reach the patient and essentially all health-
care providers must minimise the risk and incidence of harm.
In the UK and other countries, laws and regulations exist to control medicines, from a number of
perspectives, such as the Medicines Act (1968), Human Medicines Regulations (2012), Prescription
Only Medicines (Human Use) Order (1997). These are in place to promote safe and effective medi-
cines management at each stage of the medicines journey. Essential elements of this journey include:

• Manufacturing and marketing

• Procurement and sale
• Selection
Chapter 4 Medicines management and the role of the paramedic

• Supply
• Prescribing
• Handling and administration
• Medicine optimisation
• Storage and disposal.
54
It is important to understand country-specific laws governing medicines management. Key elements
will be explored in the following sections.

Manufacturing, marketing, procurement

and sale
NHS medicine policies in the UK require that either the European Medicines Agency (the European
Union regulatory body) or the Medicines and Healthcare products Regulatory Agency (MHRA) (the
UK regulatory body) approves products and medical devices before they can be supplied to patients.
Safety, effectiveness and quality of the manufacturing process are assessed and must meet stringent
requirements before they are approved for sale and assigned a marketing authorisation. The market-
ing authorisation is assigned according to the licensed indication and degree of risk of the product,
the pack size and whether its supply needs to be supervised and monitored by a health professional.
The Medicines Act (1968) and subsequent Human Medicines Regulations (2012) allow the product to
then be available to the public as:

• a prescription-only medicine (PoM), meaning that the product can only be supplied by a
prescription from an appropriate health professional and issued by a pharmacist. A Controlled
Drug (CD) is also a prescription-only medicine
• a pharmacy (P)-only product which can be bought in the presence and under the supervision of
a pharmacist, e.g. chemist or in-store pharmacy within a supermarket
• a General Sales List product (GSL) which means it can be bought in a retail outlet, e.g. supermarket
or garage shop.

Pharmacy and GSL items are often referred to as ‘over-the-counter’ products, which is a general term
meaning they can be purchased in a retail outlet and do not need a prescription.
Following marketing approval, new products may be scrutinised for clinical and cost-
effectiveness by, for example, the National Institute for Health and Care Excellence (NICE) or the
Scottish Intercollegiate Guidelines Network (SIGN) to determine whether healthcare organisa-
tions will provide them. If NICE or SIGN approves them for use, commissioners must make them
available for patients. Many new products or changes in the use of a product will be assigned a
black triangle like this:

This alerts paramedics that there is limited experience in the use of this product so all suspected
adverse reactions must be reported to the MHRA. Not all products and devices require assessment by
NICE; some may be considered by NHS commissioners who can decide if they wish to make them
available to patients. This may then lead to the procurement or purchasing of products dependent
on a variety of factors which include local priorities, budgets and timeliness of NICE approval.
Procurement of medicines and medical devices for the NHS is undertaken by regional pharmacy
purchasing groups who aim to obtain the best price possible for the NHS and enter into contracts for
supply to NHS trusts and other organisations. These will be included in the national drug tariff (a list
of medicines and devices that can be prescribed within the NHS) and then agreed for purchase at a
local level, usually via drugs and therapeutic committees.
Independent organisations (e.g. non-NHS pharmacies, independent or private ambulance compa-
nies) may choose specific products that they wish to offer for sale to the general public. These are
restricted to pharmacy only and GSL products, depending on their status as discussed previously,
but also may have restrictions on the amount or dosage which can be sold. For example, the MHRA
Medicines management and the role of the paramedic Chapter 4

discourages large quantities of analgesia being sold; as an example, paracetamol can result in liver
damage if recommended dosages are exceeded. Shopkeepers thus limit purchase of these to 32 or
in some cases 16 tablets per pack.

Selection 55
Where there are many products or devices available to treat a condition, an NHS organisation, or your
employer, will decide which of these products are to be prescribed and included in the local formulary.
This ultimately means that some products will be available for supply in some parts of the UK but not
all. Selection will be based upon a range of measures including the evidence available to support the
product’s effectiveness and the cost of supplying the product in comparison to similar products.
The Product Licensing (PL) number is a unique code that is given to a pharmaceutical manufacturer
to produce a specific drug formulation. This code is unique to the manufacturer and not the drug.
Generic manufacturers may therefore produce drugs for various brands using the same PL number.
Some products which have been licensed for several years are often manufactured by several
companies with the result that an identical drug which is therapeutically equivalent has several pro-
prietary or trade names. An example of this is ibuprofen; this is its non-proprietary or generic name,
but it can also be supplied with a proprietary name of Brufen® or Nurofen®. Not only can this cause
confusion and possible medication errors, but it is generally more cost-effective for the NHS to sup-
ply or for the patient to buy a generic product. Compare the proprietary and non-proprietary forms
of ibuprofen in Clinical Consideration 2 to understand the differences in cost.

Clinical consideration 2
Nurofen Brufen Ibuprofen
Find out how much is a pack of 16 200 mg tablets of each
of these products in your local pharmacy or shop.
Check the product information on the packets; do they
contain the same amount of the same active ingredient?
What is the Product Licensing (PL) number? Are there any
that are the same?
Which is the cheapest?

The NHS Business Services Authority (NHSBSA) analyses prescribing trends and states that 81% of
all drugs in primary care are already prescribed generically which generates significant savings for
the NHS (NHSBSA, 2018). However, it also highlights that for medicines optimisation, there are fur-
ther savings that could be realised to help provide even better value care. This also includes the NHS
spending on products which can otherwise be bought by patients from a pharmacy or supermarket,
such as paracetamol. The NHS currently spends around £136 million a year on prescriptions for such
medicines (NHS England, 2018). Prescriptions are generally not issued for over-the-counter (OTC)
medicines which are used to treat a range of minor health conditions but there are those with chronic
ill health who may still have OTC medicines prescribed as part of their care pathway (e.g. paracetamol
for pain). All healthcare professionals have a responsibility to help the NHS to deliver an effective and
value-for-money service.

Supply
Medicines and medicinal products may be supplied to patients in a variety of ways. These are incor-
porated within legislation under the Medicines Act (1968), the Prescription Only Medicines (Human
Use) Order (1997) and subsequent changes to include patient-specific directions, prescriptions,
Patient Group Directions and exemptions.
Chapter 4 Medicines management and the role of the paramedic

Clinical Consideration 3 asks that you think about how patients are supplied with medicines/medical
devices in your current practice.

Clinical considerations 3
56 Are these provided through patient-specific directions, prescriptions or patient group directions?
1. Tick the boxes below that apply.
2. Give an example product or clinical situation for each process that you identify.

Patient-specific direction
Prescription
Patient Group Direction

Patient-specific directions
Patient-specific directions (PSD) are written instructions by a doctor, dentist or non-medical pre-
scriber for the supply and/or administration of medicines for a named patient. In paramedic practice,
this is most often seen in patients receiving palliative care who have been prescribed anticipatory
medication, also known as ’just in case’ or just in time’ medication, where the patient’s GP or hospital
doctor has left written instructions, often in the form of a Kardex, and the medication has been dis-
pensed from a pharmacy. As this medication has already been prescribed, it may be administered by
a paramedic as a registered healthcare professional, even though they cannot administer that drug
under an exemption, or Patient Group Direction (PGD).

Prescriptions
A prescription is a written instruction or order for the supply of a product by an appropriately quali-
fied healthcare professional to a named patient and must meet the legal requirements of the
Prescription Only Medicines (Human Use) Order (1997). You will be familiar with these if you have
been working in a primary care environment. Prescriptions may be handwritten or electronic.

Clinical consideration 4
• What is your organisation’s guidance on the administration of anticipatory (just in time or just in
case) medication?
• If you encountered a patient with a PSD for palliative medication, would you be confident to
administer it? Medication prescribed in a PSD for those receiving palliative care may be given for
symptom management that is not often encountered in paramedic practice.
• In palliative care opiates are given for analgesia. What else can they be prescribed for?
• Why would hyoscine butyl bromide be prescribed to a patient receiving palliative care?

Patient Group Directions

A Patient Group Direction (PGD) is a set of written instructions that allow some registered para-
medics to supply and/or administer specified medicines to a predefined group of patients, with-
out them having to see a prescriber first (such as a doctor or non-medical prescriber) (MHRA,
2017). Supplying and/or administering medicines under PGDs is reserved for situations in which
this offers an advantage for patient care, without compromising patient safety. PGDs are used
across a wide variety of healthcare settings. They are particularly useful in primary care for
immunisations (for example, the coronavirus vaccine), in sexual health clinics and emergency
care environments.
Medicines management and the role of the paramedic Chapter 4

Patient Group Directions are developed by multidisciplinary groups including a doctor, a pharmacist
and a representative of any professional group expected to supply the medicines under the PGD.
Legal requirements of a PGD are stated within the Human Medicines Regulations (2012). The legal
categories of medicines that can be supplied under a PGD are:

• Prescription only (PO) 57

• Pharmacy (P)
• General Sales List (GSL).
Unlicensed medicines, dressings, appliances and devices are not allowed to be supplied under a
PGD. However, a medication can be supplied under a PGD outside its Summary of Product
Characteristics, otherwise known as ‘off-label’, as long as it is justified by best clinical practice
(NICE, 2017). Each PGD will reference the area that it covers and provide clear parameters in which it
may be used.
Before using a PGD, paramedics should ensure that they:

• have undertaken the necessary initial training and continuing professional development
• have been assessed as competent and authorised to practise by the provider organisation
• have signed the appropriate documentation
• are using a copy of the most recent and in date final signed version of the PGD
• have read and understand the context and content of the PGD.
When supplying and/or administering a medicine under a PGD, paramedics should follow local
organisational policies and act within their code(s) of professional conduct and local governance
arrangements.
Patient Group Directions are a useful tool for use by paramedic-employing organisations to intro-
duce drugs into use for which there is no paramedic exemption. It can take several years for amend-
ments to be made in the Human Medicines Regulations (2012) for new drugs. Therefore, when a
change happens in practice requiring a drug to be administered by paramedics, PGDs allow that
practice to be introduced faster than waiting for the drug to be given an exemption. An example of
this is from the Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage 2 (CRASH 2)
trial (Shakur et al., 2010) where it was shown that there is an increased survival rate for major trauma
patients who receive tranexamic acid. There is no paramedic exemption for this drug but the results
of the trial led to ambulance services in the UK using a PGD to bring tranexamic acid into paramedic
practice. Although this study was published over a decade ago, and despite the drug being in wide-
spread use in UK paramedic practice, there still is no prescription exemption for paramedics to
administer tranexamic acid and a PGD must be used to administer this drug.

Exemptions
A range of healthcare professionals are permitted to administer specified licensed medicines under
the Human Medicines Regulations (2012 schedule 17 and amendments 2016). These include (within
occupational health schemes) paramedics, midwives and optometrists. Orthoptists, chiropodists
and podiatrists can undertake further training to undertake a wider range of exemptions. Schedule
19 of the Human Medicines Regulation (2012) also allows for certain drugs to be administered by
anyone in an emergency; for example, it is this schedule that allows non-healthcare professionals to
administer intramuscular (IM) glucagon to hypoglycaemic patients, and IM adrenaline 1:1000 to
those with anaphylaxis. It is also the mechanism by which paramedics are able to administer anti-
dotes to nerve agents in the prehospital environment. Other exemptions cover a range of situations
such as emergency use of asthma inhalers in schools and access to medicines in a pandemic. It is
important that you understand your organisation’s policies in respect to the administration of spe-
cific medicines to save a life in an emergency. Follow Skills in practice 1 to understand your role
within an emergency.
Paramedics registered with the HCPC can under the Human Medicines Regulations (2012 schedule
17 and amendments 2016) administer a number of drugs without a prescription to patients ‘only for
the immediate, necessary treatment of sick or injured persons and in the case of prescription only
medicine containing Heparin Sodium shall be only for the purpose of cannula flushing’.
Chapter 4 Medicines management and the role of the paramedic

Skills in practice 1
Referring to Schedule 17 and 19 of the Human Medicines Regulations (2012)

• Under which schedule(s) as a paramedic can you administer adrenaline 1:1000 IM to a patient with
58 anaphylaxis?
• Under which schedule(s) can you administer adrenaline to a patient in cardiac arrest?
• Under schedule 17 a paramedic can administer heparin sodium for which purpose?

The following prescription-only medicines can be administered via parenteral administration.

• Diazepam 5 mg per mL emulsion for injection.

• Succinylated modified fluid gelatin 4% intravenous infusion.
• Medicines containing the substance ergometrine maleate 500 mg per mL with oxytocin
5 international units per mL, but no other active ingredient.

The following prescription-only medicines containing one or more of the following substances, but
no other active ingredient, can be administered.

• Adrenaline acid tartrate

• Adrenaline hydrochloride
• Amiodarone
• Anhydrous glucose
• Benzylpenicillin
• Compound sodium lactate intravenous infusion (Hartmann solution)
• Ergometrine maleate
• Furosemide
• Glucose
• Heparin sodium
• Lidocaine hydrochloride
• Metoclopramide
• Morphine sulfate
• Nalbuphine hydrochloride
• Naloxone hydrochloride
• Ondansetron
• Paracetamol
• Reteplase
• Sodium chloride
• Streptokinase
• Tenecteplase
In October 2020, a public and patient consultation was launched by NHS England to propose an
increase in the drugs that paramedics can administer via exemption under the Human Medicines
Regulations (2012). The proposal was for the introduction of the following drugs to the paramedic
exception under Schedule 17 of the Regulations.

• Controlled Drugs:
• lorazepam (by injection)
• midazolam (by injection)
• Prescription-only medicines (POMs):
• dexamethasone
• magnesium sulfate
• tranexamic acid
• flumazenil
Medicines management and the role of the paramedic Chapter 4

Paramedics may also as part of their duties administer Pharmacy (P) only medication and hold a sup-
ply of these drugs as part of their practice (MHRA, 2014).

Student paramedic exceptions

The Human Medicines Regulations (2012) do not allow for paramedics to delegate their prescription
exemption under schedule 17 to others, nor does it allow student paramedics to administer drugs
59
under supervision. The task of the administration is solely held by the registered paramedic (College
of Paramedics, 2018). The only instance where a student may administer medication is where a pre-
scriber, including paramedic independent prescribers, directs a student paramedic to administer
prescribed medication.
Although schedule 19 of the Human Medicines Regulations allows any person to administer a list
of certain medications in an emergency, this is for circumstances where there is no other person
present to administer the medication. As students should be supervised at all times in practice, there
should be no need for a student to administer a schedule 19 medication.

Prescribing
Doctors and dentists are currently the only healthcare professionals who are able to prescribe on
registration. There are a range of healthcare professionals within the UK who have the right to
prescribe medications. Since 1992 non-medical prescribing has been permitted within the UK
(Cope et al., 2016). Multiple changes in legislation and professional regulation have enabled para-
medics, nurses, midwives, pharmacists, physiotherapists, chiropodists, podiatrists and diagnostic
radiographers to become independent prescribers, on successful completion of an accredited pre-
scribing programme and registration of their qualification with their regulatory body. This exten-
sion of prescribing responsibilities to other healthcare professional groups is likely to continue
where it is safe to do so and there is a clear patient benefit (Royal Pharmaceutical Society
(RPS), 2016). There are currently two forms of prescribing: independent prescribing and supple-
mentary prescribing.
An independent prescriber is a practitioner who is responsible and accountable for the assess-
ment of patients with undiagnosed or diagnosed conditions and can make prescribing decisions to
manage the clinical condition of the patient. Nurse independent prescribers can prescribe any medi-
cine or product listed within the British National Formulary (BNF) as well as unlicensed medicines and
any Controlled Drugs (within schedules II–V) if they are competent to do. For other healthcare profes-
sionals with prescribing rights, such as physiotherapists and paramedics, there are some restrictions,
particularly around the Controlled Drugs they can prescribe.
The Misuse of Drugs Act (1971) is the legislation which specifies which Controlled Drugs registered
paramedics can supply and administer as part of their duties. This Act works in combination with the
Human Medicines Regulations (2012) as to which Controlled Drugs paramedics can hold and admin-
ister as part of their exceptions. The only Controlled Drugs paramedics can supply and administer
using exemptions are:

• morphine sulfate (for injection and oral)

• diazepam emulsion (Diazemuls®).
Prior to 2019, paramedics and other prescribing allied health professionals only had their own spe-
cific ‘Standards for prescribing’ issued by the HCPC (2019). Due to the increasing number of health-
care professionals involved in medicines management, a more consistent approach was required,
that all healthcare professionals could follow. Since January 2019, all healthcare professionals are
required to follow the RPS (2018) ‘Professional guidance on the safe and secure handling of medi-
cines’ and the RPS (2019) ‘Professional guidance on the administration of medicines in healthcare
settings’. These guidance documents ensure consistent safe and effect medicine administration and
handling of medicines. Alongside this guidance, most local NHS trusts and other employers will also
have their own guidance or policies which employees should always check and follow when consid-
ering their actions related to medicines management.
Chapter 4 Medicines management and the role of the paramedic

Handling and administration

The online document ‘Professional guidance on the safe and secure handling of medicines’ (RPS
2018), accredited by NICE, provides details on the four core governance principles that underpin a
framework for the safe and secure handling of medicines. This guidance applies to all healthcare set-
tings and covers all pharmacists and other health professionals whose role involves handling medi-
60 cines. The document provides comprehensive guidance on obtaining medicines, their transport,
receipt, manufacture or manipulation and storage. It also includes information on the issuing of
medicines, and their removal or disposal. This guidance also helps organisations to ensure that they
adhere to regulations laid down by the Health and Safety Executive, to ensure prevention of work-
related death, injury and ill health of employees as some of these elements can expose healthcare
practitioners to the risk of harm.
Professional guidance on the administration of medicines in healthcare settings was copro-
duced by the Royal Pharmaceutical Society (RPS) and the Royal College of Nursing (RCN) (RPS,
2019). This document provides principles-based guidance to ensure the safe administration
and transcribing of medicines by registered healthcare professionals. The principles within
the guidance can also be applied in any healthcare setting by any person administering
medicines.
The guidance recommends that: ‘Those administering medicines are appropriately trained,
assessed as competent and meet relevant professional and regulatory standards and guidance’
(RPS, 2019, p.3, no. 8).
Employers will have their own policies and procedures for the medicines administration process,
which may differ slightly, so it is very important that you check these before administering any medi-
cation. An example of a medicine administration procedure is outlined in Box 4.1.
Your employing organisation will ensure that any risks associated with handling or adminis-
tration of medicines have been identified, and procedures should be in place to minimise any
risks. Your employing organisation should also ensure that any necessary equipment and
devices, required to aid the administration of medicines, are available and well maintained.
Follow Clinical Consideration 5 to understand the medicine administration procedure within
your organisation.

Box 4.1 Example of a medicine administration

procedure
This may include (but is not limited to) the following.

• Checking the identity of the patient.

• The prescription meets legal requirements, is unambiguous and includes where appropriate the
name, form (or route of administration), strength and dose of the medicine to be administered.
• That issues around consent have been adhered to.
• Allergies or previous adverse drug reactions have been checked and recorded.
• The directions for administration (e.g. timing and frequency of administration, route of adminis-
tration and start and finish dates where appropriate) are clear.
• Any ambiguities or concerns regarding the direction for administration of the medicine are raised
with the prescriber or a pharmacy professional without delay.
• Any calculations needed are double-checked where practicable by a second person and uncer-
tainties raised with the prescriber or a pharmacy professional.
• The identity of the medicine (or medical gas) and its expiry date (where available) have been
checked.
• That any specific storage requirements have been maintained.
• Confirm that the dose has not already been administered by someone else.
Medicines management and the role of the paramedic Chapter 4

Clinical consideration 5
Refer to your organisation’s policy or Standard Operating Procedure (SOP) on medicine administration
procedure. How does this compare with the example in Box 4.1?

61

Prior to administering a medicine, you should have an understanding of what the medication is
used for and how it works, the route of administration, potential side-effects and circumstances
when you should not give the medication. You need to be familiar with resources that will help you
to find out this information.
The correct medicine administration procedure must be followed to ensure the right patient gets
the right medication at the right time. To support this further, a systematic approach have been
developed for medicines administration, referred to as the 9Rs, or nine ‘rights’ of medication admin-
istration (Elliott and Liu, 2010).

1. Right patient: The identity of the patient must be verified by checking their name, address and
date of birth both with the patient and on their chart. Extra care needs to be taken for patients
who are unable to identify themselves, for example the unconscious patient or those with
cognitive impairment.
2. Right drug: Many drugs look the same, have similar names and even similar packaging. Without
careful checking, the wrong medication could be administered by mistake.
3. Right route: The same medicine is often available for administration using a variety of routes but
dose and onset of action can be different according to which route is used. The correct route of
medicine administration needs to be confirmed prior to giving it to the patient.
4. Right time: Medication needs to be given at the prescribed time in order to ensure stable levels of
drug within the body and avoid unwanted gaps in therapy. If a medication is ordered to be given
at particular time intervals, the paramedic should never deviate from this time by more than half
an hour (Galbraith et al., 2015). If administration occurs outside this 30-minute window,
bioavailability of the medication may be affected (Elliott and Liu, 2010). It is particularly important
that critical medications are administered at the prescribed time as a delay could cause potential
harm to the patient.
5. Right dose: The dose to be administered will be stated on the prescription. Best practice would
suggest that you check the dose of the medication in a pharmaceutical guide (see Chapter 2 of
this text) to ensure it is the correct dose. Some medications will require you to carry out a dose
calculation before administration. Variables such as age, weight, condition or specific biochemical
markers need to be considered to determine the dose that needs to be given.
6. Right documentation: It is very important that records of administration, or a medication being
withheld from or declined by the patient, is completed at the time, or as soon as possible
thereafter, and that all records are clear, legible and accurate (RPS, 2019). If a medication is not
administered, or has been refused, details of the reason why (if known) should be included in the
record and reported to the prescriber, or healthcare team, where appropriate. Look at Clinical
Consideration 6 and consider your actions.
7. Right action: Before you administer any medication, you must first ensure that it is prescribed for
an appropriate reason. This requires knowledge and understanding of the medical condition(s)
of your patient and the action of the drug(s) to be administered. Where possible, you should state
to the patient the action of the medication and the reason for which it is prescribed, as this may
help to avoid a medication error (Elliott and Liu, 2010).
8. Right form: Medications are available in different forms such as tablets, capsules, caplets, syrup,
suppositories and ampoules for intravenous administration. It is important that the route of
administration is clear (e.g. oral) and that the right form of medication is administered to avoid
harm to the patient. Specific instructions may need to be given to patients, for example not to
chew enteric-coated tablets as they are designed to dissolve in the alkaline environment of the
small intestine, and some drugs are enteric coated because the active ingredient will irritate the
stomach mucosa if they dissolve there (Adams and Koch, 2010).
Chapter 4 Medicines management and the role of the paramedic

9. Right response: Once a medication has been administered, patients should be monitored for any
side-effects, adverse effects or adverse reactions, which should be managed and documented
appropriately if they occur. It is also important to understand that some patients will need to be
monitored to ensure the intended effect or efficacy of the medication is achieved, for example
assessment of blood glucose level for the patient with diabetes or blood pressure monitoring for
62 patients with hypertension (Bruen et al., 2017).

If you are in any doubt about administering a medication consult the prescriber or pharmacy profes-
sional for further information or advice.

Clinical consideration 6
As a paramedic, you are called to see Mrs Doris Speed, a 64-year-old lady with a history of epilepsy. She
has been complaining of diarrhoea and vomiting for 2 days. The patient has declined to go to hospital
for assessment and has informed you that she has not been taking her prescribed medication. She
stopped taking her laxatives, stating she had moved her bowels four times that day already. Mrs Speed
has also declined to take her sodium valproate as she says it makes her feel sick.
In order to care effectively for Mrs Speed, what actions do you need to take for:

• the laxative?
• the sodium valproate?

Special consideration: Controlled Drugs and critical

medications
Some medications, due to their potential to be misused and the harm that this can cause, are classi-
fied as Controlled Drugs (CDs). There will be additional requirements that you must follow regarding
their use. The Misuse of Drugs Act (1971), and its associated regulations, detail the legal framework
governing the use of CDs. NICE has produced the guideline Controlled Drugs: Safe Use and Management
(NG46) (NICE, 2016a) which provides further details on the systems and processes that must be in
place in all healthcare environments (except care homes) for managing the use of CDs. Your trust/
employer may have additional policies/procedures related to controlled drugs that you will need to
follow.
Any medication should be administered in a timely manner, but there are some medications
that must not be omitted, or their administration delayed, as this has the potential to cause
harm to the patient. The NHS Specialist Pharmacy Service (2018) has updated the National
Patient Safety Agency (NPSA) Rapid Response Report ‘Reducing harm from omitted and delayed
medicines in hospital’ (February 2010). This document highlights the need for rapid access to
medications that are critical for patients, with the risks of delay, or omission, for each drug cat-
egorised using a traffic light system (Table 4.1). Medications that fall into the Risk 3 category are
classified as ‘critical medications’ due to the consequences to the patient if they are missed or
omitted.
‘Critical medicines’ include groups of medicines such as:

• antimicrobials
• anticoagulants
• antiepileptic agents
• anti-parkinsonian agents
• immunosuppressants
• insulin.
Any omission or delay in the administration of a critical medicine must be discussed with the pre-
scriber (or relevant physician) and reported as a patient safety incident.
Medicines management and the role of the paramedic Chapter 4

Table 4.1 The potential risks of missed medication.

Risk 1 Risk 2 Risk 3
Nil or negligible patient impact Significant short-term patient Significant or catastrophic long-term
with nil or minor intervention impact with moderate intervention patient impact with ongoing
required; no increase in length of required; increase in length of intervention required; long increase in
stay hospital stay possible length of stay possible 63
• There is no or negligible risk
of patient impact
• There is a risk of significant
short-term patient impact
• There is a risk of significant
long-term patient impact
• No or minor intervention
necessary
Subsequent moderate
intervention is required
• There is a risk of catastrophic
patient impact (i.e. death)
• There is no possibility of an
increase in the length of
• A resultant long increase
(1–15 days) in the length of
• Subsequent ongoing professional
intervention is required
hospital stay hospital stay is possible • Aincrease
resultant very long (>15 days)
in the length of hospital
stay is possible

Groups requiring special considerations

For women who are pregnant or breast feeding and for the older population, special care needs to
be taken in the medicines management process to ensure the safety of the patient.

Pregnancy and breast feeding

Administering medicines during pregnancy is complex and can have major consequences if not
managed with caution and expertise. It is important to establish whether someone of child-bearing
age may be pregnant prior to administration of any medicine. Careful consideration must be given to
the benefits and risks of taking medicines, both for the mother and the foetus. Within each edition of
the BNF (and online resource), there is an advice section on the specific medicine issues concerning
pregnancy and breast feeding. General advice is that drugs should only be prescribed if the benefit
for the mother is greater than the risk to the foetus, but all drugs should be avoided where possible
during the first trimester (BNF 80).
In life-threatening emergencies, such as cardiac arrest or anaphylaxis, Chu et al. (2020) recommend
that pregnant patients should be managed with the same algorithms and drug regimen as specified in
the advanced life support and anaphylaxis guidance from the Resuscitation Council (2015).
There is little information available for identifying the safety of medicines for women who are
breast feeding. This can cause confusion for health professionals offering information but also for the
breast-feeding woman who may cease breast feeding earlier than planned rather than expose her
child to unknown risks (McClatchey et al., 2017). The BNF identifies where it is known that medicines
are contraindicated or where caution is indicated during pregnancy and breast feeding.

Older people
Special care is required in managing medicines for older people. A large proportion of older people
within the UK have multimorbidity, and within this population the use of multiple medicines (polyp-
harmacy) is very common.
Polypharmacy occurs when an individual is taking four or more regular medicines (Patterson
et al., 2012). Taking multiple medications greatly increases the risk of drug interactions and adverse
reactions and can also affect compliance. It has been estimated that 30–50% of medicines taken for
long-term conditions are not taken as prescribed (NICE, 2016b). As a result of this, it is recommended
that older people’s medications are reviewed regularly and any medicine which is not of benefit
should be discontinued.
As an individual gets older, what the body does to a drug (pharmacokinetics) changes. The most
important effect of age is reduced renal clearance, meaning that older people excrete drugs more
slowly, increasing the risk of side-effects and adverse reactions (Shi and Klotz, 2011). The BNF state
the most common adverse reactions to monitor for are:
Chapter 4 Medicines management and the role of the paramedic

• confusion
• constipation
• postural hypotension and falls (BNF 80).
As a result of this, the BNF provides some general principles to be followed for the older person.
64
• Lower doses: Lower doses of medicines may be used (usually 50% of an adult dose) and only
increased if needed.
• Review regularly: Regular medication reviews should be undertaken to determine if the medication
is still appropriate/required. It may be necessary to reduce medications of some drugs as renal
function declines.
• Simplify regimens: Medications should only be given when there is a clear indication to do so (for
example, not prescribing antibiotics for a viral infection). If possible, medicines should only be
prescribed once or twice daily and confusing dosage intervals should be avoided.
• Explain clearly: Each medication should have clear instructions on how to take it with full directions
given (BNF 80).

These are some of the issues which need consideration for medicine management; can you think of
any more? Clinical Consideration 7 will help you to explore this further.

Clinical consideration 7
Having read this section, are there any other groups in your practice area that require further considera-
tion prior to administering medications under exception, or PGD?

Monitoring for side-effects

All medicines can have side-effects. The European Medicines Agency (EMA) (2017) defines an adverse
drug reaction (ADR) as ‘a response to a medicinal product which is noxious and unintended’. Part of
your role within medicines management is to understand, and identify, any ADR as some can occur
within minutes of administration, whereas others can present years after treatment (Ferner and
McGettigan, 2018).

Medicines optimisation
Medicines optimisation builds on medicines management, but encompasses all aspects of a patient’s
medicines journey from the initial prescription through to ongoing review and support. Medicines
optimisation is about ensuring that the right patients get the right choice of medicine, at the right
time. By focusing on patients and their experiences, the goal is to help patients to:

• improve their outcomes

• take their medicines correctly
• avoid taking unnecessary medicines
• reduce wastage of medicines
• improve medicines safety.
A multidisciplinary approach to medicines optimisation can encourage patients to take ownership of
their treatment (RPS, 2013). The RPS (2013) described four guiding principles for medicines manage-
ment in practice (see Box 4.2).
Medicines optimisation examines how patients use medicines over time. It may involve stopping
certain medicines as well as starting others, and considers opportunities for lifestyle changes and
non-medical therapies to reduce the need for medicines. By improving medicine safety, adherence
to treatment and reducing waste, the medicines optimisation approach ensures patients are sup-
ported to get the best outcomes from their medicines (NICE, 2015).
Medicines management and the role of the paramedic Chapter 4

Box 4.2 Four principles of medicines

management
Principle 1 Aim to understand the patient’s experience
Principle 2 Evidence-based choice of medicines 65
Principle 3 Ensure medicines use is as safe as possible
Principle 4 Make medicines optimisation part of routine practice

The key elements of medicines optimisation are that it:

• is patient centred and makes a difference to the patient’s outcomes

• is a partnership between healthcare professional and patient
• is about listening to the patient’s views and opinions, supporting adherence and self-care
• is the application of clinical and pharmaceutical expertise and understanding
• provides a personalised medication regimen for each patient
• encourages communication with other healthcare professionals to ensure continuity across care
settings
• encourages good governance, including safety, quality and better outcomes.
The paramedic therefore has a significant role in ensuring that patients/service users, and their car-
ers, are central to the shared decision-making process in managing their medicines with the ultimate
aim of improving health outcomes.

Safety in medicines management

A recent study found that an estimated 237 million medication errors occur in the NHS in England
every year (Elliott et al., 2018). These errors resulted in avoidable ADRs, causing 712 deaths and
contributing to 1708 deaths. Non-steroidal anti-inflammatory drugs (NSAIDs), anticoagulants
and antiplatelets caused over a third of hospital admissions due to avoidable ADRs. Gastrointestinal
bleeds were implicated in half of the deaths from primary care ADRs. The report also found that
older people were more likely to suffer avoidable ADRs. The cost to the NHS for these avoidable
ADRs was £98.5 million per year. This is a huge financial drain on the NHS but the harm and suf-
fering caused to patients and their families are immeasurable. The transfer of patients between
primary and secondary care is also an area for potential error where it is estimated that up to 70%
of patients may have an unintentional change or medication error (RPS, 2012a). Further risks of
errors were identified for people residing in care homes and recommendations for best practice
in managing polypharmacy, repeat prescribing and medication reviews as well as training for
staff are advised (RPS, 2012b). NHS England (2018) has since outlined guidance to support safe
and effective medicine management practices across primary, secondary and tertiary care, out-
lining the responsibilities of all professionals.
Medication errors are any Patient Safety Incident (PSI) where there has been an error in the process
of prescribing, preparing, dispensing, administering, monitoring or providing advice on medicines.
These PSIs can be divided into two categories:

• errors of commission (for example, wrong medicine or wrong dose)

• errors of omission (for example, an omitted dose or a failure to monitor).
The National Reporting and Learning System (NRLS) defines a ‘patient safety incident’ (PSI) as ‘any
unintended or unexpected incident, which could have or did lead to harm for one or more patients
receiving NHS care’.
The Central Alerting System (CAS) (managed by the MHRA) is a web-based cascading system for
issuing patient safety alerts, important public health messages and other safety-critical information
and guidance to the NHS and others, including independent providers of health and social care.
Alerts within this system include Medical Device Alerts (MDA) and Drug Alerts.
Chapter 4 Medicines management and the role of the paramedic

Storage and disposal

Medicines are used in all healthcare settings and the safe and secure handling of medicines is essential
to ensure patient safety. The Human Medicines Regulations (2012) outline the legal requirements to
support this process. Each medicine must be used and stored according to specific instructions
known as the Summary of Product characteristics (SPC or SmPC), details of which can be found in the
66 Electronic Medicines Compendium (www.medicines.org.uk/emc).
The RPS ‘Professional guidance on the safe and secure handling of medicines’ online document
(2018) advises that all individuals who handle medicines must be competent, legally entitled, appro-
priately trained and authorised to do the job. Medicines must be kept secure and safeguarded from
unauthorised access and stored at a level of security appropriate to their proposed use.
The Controlled Drugs used by paramedics from schedule 2 or 3 of the Misuse of Drugs Regulations
(2001), such as morphine sulfate, midazolam, or ketamine, must when not in use be stored in a metal
container or safe, attached to a wall or the floor as specified in the Misuse of Drugs (Safe Custody)
Regulations (1973). The Regulation also specifies that when CDs are being carried by a paramedic as
part of their practice, they must at all times (where possible) be kept in a locked container to which
only they, or someone authorised by them, have access.
Where products need to be stored at cooler temperatures, the cold chain must be maintained to
ensure the integrity of the product is maintained. For example, vaccines deteriorate at room tem-
perature and thus must be stored in a refrigerator and in cool conditions right until the moment they
are administered. Where this has been compromised, a risk assessment must be undertaken to deter-
mine whether the integrity of the product has been affected.
Safe handling and disposal of toxic substances such as cytotoxic drugs are governed by the Health
and Safety Executive (HSE) (2019) as they present significant risks for those who handle them. The
HSE offers practical guidance on meeting the Control of Substances Hazardous to Health Regulations
(COSHH) (2002) and how these substances should be safely handled and disposed of in all health and
social care environments, including the patient’s home.
Any unwanted or expired medicines in the community need to be returned to a pharmacy or
chemist for safe disposal. Inhalers contain gases which can be harmful to the environment so should
not be put in waste bins and must also be returned to a pharmacy/chemist where they can be recy-
cled. Pharmacies are obliged to accept any unwanted medicines from patients. The pharmacy must,
if required by NHS England or the waste contractor, sort them into solids (including ampoules and
vials), liquids and aerosols, and the local NHS England team will make arrangements for a waste con-
tractor to collect the medicines from pharmacies at regular intervals. Additional segregation is also
required under the Hazardous Waste (England and Wales) Regulations (2005). Ambulance providers
will have their own policy and procedure for their isolation from practice, and safe disposal of expired
medications. It is the responsibility of the practising paramedic to be aware of and follow their
employer’s medicines policies.

Conclusion
This chapter has explored the many strands to managing medicines to provide safe, efficient and
cost-effective care. Paramedics have a role in this process to ensure they understand and follow the
regulations, policies and practices which govern safe prescribing, administration and monitoring of
medicines. Medicines management should be a partnership between patients and all healthcare
professionals to ensure good patient-centred outcomes regardless of the health or social care
setting.
You must always ensure that you are working within your scope of practice and also adhere to
local and national policies and the appropriate aspects of the law so as to practise safely and
effectively.

References
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Bruen, D., Delaney, C., Florea, L. and Diamond, D. (2017). Glucose sensing for diabetes monitoring: recent develop-
ments. Sensors 17(8): 1866.
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Chu, J., Johnston, T.A., Geoghegan, J. and Royal College of Obstetricians and Gynaecologists. (2020). Maternal
Collapse in Pregnancy and the Puerperium: Green-top Guideline No. 56. British Journal of Obstetrics and
Gynaecology 127(5): e14–e52.
College of Paramedics. (2018). Practice Guidance for Paramedics for the Administration of Medicines under Exemptions
within the Human Medicines Regulations 2012. https://collegeofparamedics.co.uk/
Cope, L.C., Abuzour, A.S. and Tully, M.P. (2016). Nonmedical prescribing: where are we now? Therapeutic Advances
in Drug Safety 7: 165–172. 67
Duerden, M., Avery, T. and Payne, R. (2013). Polypharmacy and medicines optimisation: making it safe and sound.
www.kingsfund.org.uk/publications/polypharmacy-and-medicinesoptimisation
Elliott, M. amd Liu, Y. (2010). The nine rights of medication administration: an overview. British Journal of
Nursing 19(5): 300–305.
Elliott, R., Camacho, E., Cambell, F. et al. (2018). Prevalence and economic burden of medication errors in the NHS in
England. www.eepru.org.uk/prevalence-and-economic-burden-of-medication-errors-in-the-nhs-in-england-2/
European Medicines Agency (EMA). (2017). Guideline on good pharmacovigilance practices (GVP): Annex I -
Definitions(Rev4).www.ema.europa.eu/en/documents/scientific-guideline/guideline-good-pharmacovigilance-
practices-annex-i-definitions-rev-4_en.pdf
Ewbank, L., Omojomolo, D., Sullivan, K. et al. (2018). The rising cost of medicines to the NHS. www.kingsfund.org.uk/
sites/default/files/2018-04/Rising-cost-of-medicines.pdf
Ferner, R.E. and McGettigan, P. (2018). Adverse drug reactions. British Medical Journal 363: k4051.
Galbraith, A., Bullock, S., Manias, E., Hunt, B. and Richards, A. (2015). Fundamentals of Pharmacology: An Applied
Approach for Nursing and Health. Cambridge: Routledge.
Health and Care Professions Council (HCPC). (2019). Standards for prescribing. www.hcpc-uk.org/globalassets/
standards/standards-for-prescribing/standards-for-prescribing2.pdf
Health and Safety Executive. (2019). Control of Substances Hazardous to Health. www.hse.gov.uk/coshh/index.htm
Human Medicines Regulations. (2012). https://www.legislation.gov.uk/uksi/2012/1916/contents/made
McClatchey, A.K., Shield, A., Cheong, L.H., Ferguson, S.L., Cooper, G.M. and Kyle, G.J. (2017). Why does the need for
medication become a barrier to breastfeeding? A narrative review. Women and Birth 31(5): 362–366.
Medicines and Healthcare products Regulatory Agency (MHRA). (2014). Rules for the sale, supply and administra-
tion of medicines for specific healthcare professionals. www.gov.uk/government/publications/rules-for-the-
sale - supply- and- administration- of- medicines/rules- for- the - sale - supply- and- administration-
of-medicines-for-specific-healthcare-professionals
Medicines and Healthcare products Regulatory Agency (MHRA). (2017). Patient group directions: who can use
them. www.gov.uk/government/publications/patient-group-directions-pgds/patient-group-directions-who-
can-use-them
NHS Business Services Authority (NHSBSA). (2018). Medicines optimisation – generic prescribing. www.nhsbsa.nhs.
uk/epact2/dashboards-and-specifications/medicines-optimisation-generic-prescribing
NHS England. (2018). Responsibility for prescribing between primary and secondary/teriary care. www.england.nhs.
uk/publication/responsibility-for-prescribing-between-primary-and-secondary-tertiary-care/
NHS England. (2020). Consultation on proposed amendments to the list of medicines that paramedics are able to
administer under exemptions within the Human Medicines Regulations 2012 across the United Kingdom. www.
england.nhs.uk/wp-content/uploads/2020/10/paramedic-consultation-summary.pdf
NHS Specialist Pharmacy Service. (2018). Medicines Matters. www.sps.nhs.uk/wp-content/uploads/2018/10/
Medicines-Matters-september-2018-1.pdf
NICE. (2015). Medicines optimisation: the safe and effective use of medicines to enable the best possible outcomes
[NG5]. www.nice.org.uk/guidance/ng5
NICE. (2016a). Controlled drugs: safe use and management [NG46]. www.nice.org.uk/guidance/ng46
NICE. (2016b). Multimorbidity: clinical assessment and management [NG56]. www.nice.org.uk/guidance/ng56
NICE. (2017). Patient group directions. www.nice.org.uk/guidance/mpg2/chapter/Recommendations#training-
and-competency
Patterson, S.M., Hughes, C., Kerse, N., Cardwell, C.R. and Bradley, M.C. (2012). Interventions to improve the appro-
priate use of polypharmacy for older people. Cochrane Database of Systematic Reviews 5: CD008165.
Resuscitation Council. (2015). Adult advanced life support. www.resus.org.uk/resuscitation-guidelines/adult-
advanced-life-support
Royal Pharmaceutical Society (RPS). (2012a). Keeping patients safe when they transfer between care providers – get-
ting the medicines right: final report. www.rpharms.com/
Royal Pharmaceutical Society (RPS). (2012b). Improving pharmaceutical care in care homes. www.rpharms.com/
Royal Pharmaceutical Society (RPS). (2013). Medicines Optimisation. www.rpharms.com/Portals/0/RPS%20
document%20library/Open%20access/Policy/helping-patients-make-the-most-of-their-medicines.pdf
Royal Pharmaceutical Society (RPS). (2016). A Competency Framework for all Prescribers. www.rpharms.com/
Portals/0/RPS%20document%20library/Open%20access/Professional%20standards/Prescribing%20
competency%20framework/prescribing-competency-framework.pdf?ver=2019-02-13-163215-030
Chapter 4 Medicines management and the role of the paramedic

Royal Pharmaceutical Society (RPS). (2018). Professional guidance on the safe and secure handling of medicines.
www.rpharms.com/
Royal Pharmaceutical Society (RPS). (2019). Professional guidance on the administration of medicines in healthcare
settings. www.rpharms.com/
Shakur, H., Roberts, I., Bautista, R. et al., CRASH-2 trial collaborators. (2010). Effects of tranexamic acid on death,
vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2):
68 a randomised, placebo-controlled trial. Lancet 376(9734): 23–32.
Shi, S. and Klotz, U. (2011). Age-related changes in pharmacokinetics. Current Drug Metabolism 12(7): 601–610.

Further reading
Adam, M.P., Polifka, J.E. and Friedman, J.M. (2011). Evolving knowledge of the teratogenicity of medications in
human pregnancy. American Journal of Medical Genetics 157: 175–182.
Aronson, J.K. and Ferner, R.E. (2005). Clarification of terminology in drug safety. Drug Safety 28: 851–870.
Care Quality Commission. (2019). Issue 5: Safe management of medicines. www.cqc.org.uk/guidance-providers/
learning-safety-incidents/issue-5-safe-management-medicines
Clemow, B., Nolan, J.D., Michaels, D.L., Kogelnik, A.M., Cantrell, S.A. and Dewulf, L. (2015). Medicines in Pregnancy
Forum: proceedings on ethical and legal considerations. Ethic Special Section Meeting Report. Therapeutic
Innovaion and Regulatory Science 49(3): 326–332.
Department of Health. (2013). The Medicines Act 1968 and the Human Medicines Regulations (Amendment) Order.
London: Department of Health.
HMSO. (1973). The Misuse of Drugs (Safe Custody) Regulations 1973. London: HMSO.
HMSO. (1997). Prescription Only Medicines (Human Use) Order 1997. Statutory Instrument No. 1830. London: HMSO.
HMSO. (2001). The Misuse of Drugs Regulations 2001. London: HMSO.
Jones, S.W. (2009). Reducing medication administration errors in nursing practice. Nursing Standard 23: 40–46.
Murk, W. and Seli, E. (2011). Fertility preservation as a public health issue: an epidemiological perspective. Current
Opinion in Obstetrics and Gynecology 23: 143–150.
NHS. (2019). Medicines optimisation. www.england.nhs.uk/medicines/medicines-optimisation
NICE. (2009). Medicines adherence: involving patients in decisions about prescribed medicines and supporting adher-
ence [CG76]. www.nice.org.uk/guidance/cg76
Northern Ireland Department of Health. (2019). Medicines Management. www.health-ni.gov.uk/articles/
medicines-management
Nursing and Midwifery Council and Royal Pharmaceutical Society. (2019). Professional Guidance on the
Administration of Medicines in Healthcare Settings. www.rpharms.com/Portals/0/RPS%20document%20
library/Open%20access/Professional%20standards/SSHM%20and%20Admin/Admin%20of%20Meds%20
prof%20guidance.pdf?ver=2019-01-23-145026-567
Resuscitation Council. (2012). Emergency treatment of anaphylactic reactions: guidelines for healthcare providers.
www.resus.org.uk/library/additional-guidance/guidance-anaphylaxis/emergency-treatment
Rezaallah, B., Lewis, D.J., Zeilhofer, H.F. and Ber, B.I. (2019). Risk of cleft lip and/or palate associated with anti-
epileptic drugs: postmarketing safety signal detection and evaluation of information presented to prescrib-
ers and patients. Therapeutic and Regulatory Science 53(1): 110–119.
Royal College of Nursing. (2018). Medicines Management: prescribing in pregnancy. www.rcn.org.uk/clinical-topics/
medicines-management/prescribing-in-pregnancy
World Health Organization. (2007). Promoting Safety of Medicines for Children. Geneva: World Health Organization.

Multiple-choice questions
1. Medicines management could be best described as:
(a) Senior managers controlling medicines
(b) Safe, efficient and cost-effective use of medicines
(c) People managing to open their medicines.
2. A PoM is:
(a) The Price of the Medicine
(b) The Purpose of the Medicine
(c) A Prescription only Medicine.
3. Patient Group Directions are:
(a) Maps of the hospital to direct patents
(b) A list of medicines that can be given to a patient without a prescription
Medicines management and the role of the paramedic Chapter 4

(c) Written instructions directing registered health professionals to supply/

(d) administer specified medicines to a predefined group of patients.
4. Medicines are regulated by the:
(a) Medicines Regulatory Body
(b) Medicines and Healthcare products Regulatory Agency
(c) Regulatory Agency for Medicines. 69
5. A black triangle is applied to:
(a) Cheaper medicines
(b) Products where there is limited experience of use
(c) Medicines which should not be used.
6. A generic medicine is:
(a) A non-proprietary medicine
(b) A medicine which can be used for any condition
(c) A proprietary medicine.
7. The legal framework for medicines includes:
(a) The Human Medicines Regulations 2012
(b) The Medicines Law 2000
(c) The Regulations for Medical Use 2012.
8. Which of the following is a non-proprietary drug?
(a) Brufen
(b) Ibuprofen
(c) Nurofen
9. Critical medicines:
(a) Are important medicines
(b) Need special care
(c) Must not be omitted or delayed.
10. Before administering a medicine, the paramedic must:
(a) Consult with the prescriber for every patient
(b) Understand the medicine being administered and seek advice from the prescriber
or pharmacy professional if required
(c) Contact the pharmacist to check the prescription.
11. Which of the following Royal Pharmaceutical Society guidance should paramedics
adhere to for the administration of medicines?
(a) A competency framework for all prescribers
(b) Professional guidance for the administration of medicines in healthcare settings
(c) Professional guidance on the safe and secure handling of medicines
12. Common adverse reactions in older people include:
(a) Confusion, constipation, postural hypotension and falls
(b) Chest pain, headaches and constipation
(c) Earache, stomach pains and dizziness.
13. The Central Alerting System:
(a) Issues alerts to organisations about healthcare staff
(b) Alerts healthcare professionals about patients
(c) Issues patient safety alerts.
14. Which of the following bodies analyse the use of NHS medicines?
(a) The NHS Business Authority
(b) The NHS Medicines Authority
(c) The NHS Supply of Medicines Authority
15. Optimising medicines:
(a) Focuses on the medicine cost
(b) Focuses on the patient
(c) Focuses on the healthcare professional.
Chapter 5
Pharmacodynamics
and pharmacokinetics
Dan Davern

Aim
The aim of this chapter is to provide the reader with an introduction to pharmacokinetics and phar-
macodynamics as they relate to prehospital emergency care.

Learning outcomes
After completing this chapter the reader should be able to:

1. Define pharmacokinetics and pharmacodynamics

2. Explain the factors involved in medication absorption and distribution
3. Describe biotransformation
4. Explain how medications are eliminated from the body and factors that affect elimination.

Test your knowledge

1. Describe the phases of pharmacokinetics.
2. Describe first-pass metabolism.
3. Define pharmacodynamics.
4. Using an example from prehospital pharmacology, explain the term affinity.
5. List five common factors that affect elimination.

Introduction
This chapter explores the fundamentals of pharmacokinetics and pharmacodynamics as they apply
to prehospital emergency care.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Pharmacodynamics and pharmacokinetics Chapter 5

Professional regulatory council

The Health and Care Professions Council (HCPC) is the body responsible for protecting the public by
regulating 15 health and care professions in the UK, including paramedicine. There are other regula-
tory bodies globally which are also charged with the regulatuion and setting of standards for para-
medics. The HCPC approves programmes of education and training leading to registration in addition
to setting standards of proficiency for paramedics. These proficiency standards set out safe and effec-
tive practice for paramedics, to protect members of the public and provide appropriate care. These 71
threshold standards specify that paramedics must ‘understand relevant pharmacology and the
administration of therapeutic medications, including pharmacodynamics and pharmacokinetics’
(HCPC, 2014).

Programmes of education and training

Programmes of education and training leading to registration as a paramedic often involve a modu-
lar approach. This may include a specific module on pharmacology and therapeutics or integrate
pharmacological learning outcomes through several modules. Regardless of the delivery format,
pharmacology comprises an important part of paramedic education.
Paramedics administer medications to patients in order to produce a specific desired effect. Having
a detailed understanding of those medications, their effect on the body and the effect of the body on
the medication allows the paramedic to practise safely and provide the most appropriate care for
patients. The two most common terms paramedics must understand when studying pharmacology
are pharmacokinetics and pharmacodynamics.

Pharmacokinetics
Derived from two Greek words, pharmacon meaning ‘drug’ and kinesis meaning ‘movement’, put sim-
ply, pharmacokinetics is ‘what the body does to the drug’. Strictly defined, pharmacokinetics is the
study of the basic processes that determine the duration and intensity of a medication’s effect
(Bledsoe and Clayden, 2012). These four processes are absorption, distribution, metabolism (some-
times referred to as biotransformation) and elimination (Table 5.1).

Table 5.1 Four stages of pharmacokinetics.

1. Absorption of drugs into the body How does it get into the body?
2. Distribution of drugs to the tissues of the body Where does it go?
3. Metabolism (biotransformation) of drugs into the body How is it broken down?
4. Elimination of drugs from the body How does it leave?
Source: Young and Pritchard (2016).

The pharmacokinetic processes

The key aspects of pharmacokinetics are what the body does to the drug, how drugs are absorbed by
the body, how they are distributed to the body tissues, how drugs are metabolised (the liver is the
primary organ for biotransformation), and how the drug is eliminated by the body (primary excretion
organs are the kidneys and lungs).
Understanding pharmacokinetics is important to allow paramedics to determine the appropriate
route for medication administration (if required) or indeed to simply understand why medications
are administered via different routes. For example, why might a drug be administered orally (PO) or
intramuscularly (IM), or directly into the circulation by intravenous (IV) injection or by intraosseous
infusion (IO)?
Pharmacokinetics gives us an appreciation of the frequency of drug administration, for example
why some drugs are administered as a single bolus or why repeat administration is required in some
cases. With the liver, kidneys and lungs playing such a vital role, it is clear why diseased or aged
organs can have a significant effect on the metabolism of medications.
Chapter 5 Pharmacodynamics and pharmacokinetics

Oral Injectable (not IV)

Rectal Absorption Transdermal

72

Sublingual Topical

Distribution

IV
Metabolism
Excretion/
elimination

Figure 5.1 Stages of pharmacokinetics and medication administration routes. Source: Reproduced with
permission from Young and Pritchard (2016).

Figure 5.1 illustrates the four stages of pharmacokinetics and some common routes of medication
administration. It is worth noting that the IV route bypasses the absorption phase and first-pass
metabolism; we will discuss this further later in this chapter.

Phase 1: absorption
Medication absorption is the process encompassing a medication’s progress from the initial pharma-
cological dosage administered to a biologically available form which can pass through or across tis-
sues (Bledsoe and Clayden, 2012). It is suggested that drug absorption is determined by several
factors including:

• the drug’s physicochemical properties

• its formulation
• the route of administration, i.e. enteral or parenteral.
The dosage forms (e.g. tablets, capsules, liquid suspensions), consisting of the drug plus other ingre-
dients, are formulated to be given by a specific route; for example, glyceryl trinitrate (GTN) spray is
formulated to be administered via the sublingual route. Another example is midazolam prefilled
syringes for buccal administration.
Regardless of the route of administration, drugs must be in solution to be absorbed. Thus, solid
forms (e.g. tablets) must be able to disintegrate and disaggregate.
Unless administered directly to the circulatory system (IV/IO), A drug must cross or pass through
several semipermeable cell membranes before it reaches the systemic circulation. Cell membranes
act as gatekeepers that selectively admit or inhibit the passage of molecules; as such, the site of
absorption directly affects the rate at which the medication is absorbed. The area of the absorbing
Pharmacodynamics and pharmacokinetics Chapter 5

surface also determines the speed of absorption as medications are quickly absorbed from large
surface areas; for example, salbutamol administered via nebuliser for inhalation is distributed quickly
across the large pulmonary tissue area and is rapidly absorbed into circulation.
Finally, absorption is affected by the blood supply at the site of absorption. Some sites have a rich
blood supply while others do not. Medications administered to sites with a rich blood supply will
absorb much more quickly; for example, the sublingual route has a rich blood supply to the tissues
under the tongue and will absorb rapidly. Areas with a poor blood supply, such as the subcutaneous
layer (fatty tissue), will absorb medications much more slowly. 73
It is essential for paramedics to understand the various rates of absorption from each of the medi-
cation administration routes available to them. This enables the paramedic to determine the most
appropriate route of administration for specific medications to achieve the desired effect and prac-
tise safely.

Reflection – route selection

Epinephrine 1:1000 1 mg/1 mL standard ampoule presentation is a medication used by paramedics
for management of anaphylaxis. JRCALC guidelines indicate that the route for administration is intra-
muscular (IM). Why would paramedics not administer this medication via a quicker route such as
intravenous (IV)?

Physiology of transport
Active transport
Active transport requires energy to move a substance. This energy is achieved by the breakdown
of adenosine triphosphate (ATP), which is further broken down to adenosine diphosphate (ADP),
which releases a considerable amount of energy. An example of this active transport system can
be seen in the sodium potassium pump, which actively moves sodium ions into the cell and
potassium ions out. As this movement goes against the concentration gradient of the ions, it
must use energy. A simpler example of active transport would be a boat’s bilge pump, which
pumps water from the bottom of the boat back to the body of water; for this pump to work,
energy is required.
To be absorbed, orally administered medications must first withstand chemical and bacterial deg-
radation before they are absorbed from the gut. Absorption occurs via diffusion, or transport. Peptide
drugs (e.g. insulin) are particularly susceptible to degradation and are not given orally. Absorption of
oral drugs involves transport across membranes of the epithelial cells in the gastrointestinal (GI)
tract. Absorption is affected by:

• differences in luminal pH along the GI tract

• surface area per luminal volume
• blood perfusion
• presence of bile and mucus
• the nature of epithelial membranes.
The oral mucosa has a thin epithelium layer and is very vascular, both of which favour absorption;
however, contact is usually too brief for substantial absorption. A drug such as glucose gel or mida-
zolam placed in the buccal cavity (between the gum and cheek) or glyceryl trinitrate sublingually
(under the tongue) is retained longer, enhancing the absorption.
Active transport across the gut epithelium involves drug transporter systems similar to those
found in the liver and other organs. Gastrointestinal mucosal epithelium contains many of the meta-
bolic enzymes seen in the liver and other organs, and is the first site of biotransformation for many
ingested compounds before they reach the portal circulation. While the gut has a much lower overall
enzyme content compared with the liver, the enormous surface area and the obligatory exposure of
orally absorbed compounds result in small intestinal intrinsic clearance rates that may be 2–3 times
that of the liver.
Chapter 5 Pharmacodynamics and pharmacokinetics

The small intestine is the place where most orally ingested drugs are taken up. The epithelial cells
sit atop a basal membrane and are joined to each other by tight junctions; therefore, drug molecules
(and nutrients) have to be taken up across the cell membranes. Like the endothelial cells in the
blood–brain barrier, the intestinal epithelia express ABC transporters, which extrude some solutes
from the cells back into the gut lumen. Moreover, these cells also express specific enzymes, which
metabolise and inactivate many drug molecules (Bledsoe and Clayden, 2012).
Oral administration of drugs is the most common, because it is the most convenient for the patient.
74 However, the obstacles to uptake from the gut into the circulation are formidable; some drugs given
orally can fail entirely to be absorbed after administration; an example of this is insulin.
The second most common route of application is intravenous injection or infusion. In this case, the
absorption stage is bypassed altogether. This route is used with most protein drugs, as well as with
small molecules that fail to be taken up after oral ingestion. In clinical emergencies, intravenous
application is usually preferred even with drugs that are suitable for oral application in principle, in
order to ensure their rapid and quantitative uptake.

Passive transport
The primary means for drugs to cross the cell membrane is by passive diffusion. Passive transport
occurs when drug molecules move from an area of high concentration to an area of low concentra-
tion, down the concentration gradient. During this process, no energy is used. There are several fac-
tors that determine to what degree and how quickly drug molecules move by passive transport.

• The size of the drug molecules.

• Solubility of the drug molecules.
• The concentration of the drug molecules in various body compartments.
Drug molecules that use passive diffusion are typically small, predominantly lipid soluble and uncharged.
Absorption depends on the route of administration (Table 5.2), which can be classed as: (1) enteral,
entering the GI tract, either by oral administration or rectal suppositories, or (2) parenteral, not into
the GI tract, such as via injection (IV, IO, IM) or transdermal (Le, 2017).

Enteral
Medications which are given enterally are absorbed through the GI tract. Enteral medications are
taken orally (PO) or rectally (PR), which have several disadvantages in prehospital emergency care.
The patient must be conscious and co-operative to swallow oral medications. Medications which are
absorbed through the GI tract must first pass through the liver before distribution through the body.
Here, the drug can be partially metabolised, which in turn leads to a reduction in the amount of
medication available for distribution. This process is called first-pass metabolism. Medications admin-
istered via the enteral routes have other disadvantages including a variable absorption rate and irri-
tation of the stomach lining. However, there are advantages to enteral administration; it is considered
the safest route of administration and is the most common. Enteral administration often does not
require a sterile technique or equipment and its slow uptake to circulation often prevents rapid
changes in blood chemistry leading to adverse effects.

Parenteral
The term ‘parenteral’ is made up of two words – par meaning ‘beyond’ and enteral meaning ‘intestine’.
Hence, we can say that parenteral administration literally means introduction of substances into the
body by routes other than the gastrointestinal tract. Parenteral is the second most common route of
drug administration and is a significantly quicker route from administration to effect. Parenteral
routes of administration can be injectable (Figure 5.2), such as IV, IM, IO or subcutaneous (SC), or non-
injectable such as intranasal (IN), topical or inhalation. All of these routes are used routinely in pre-
hospital management.
There are several disadvantages to parenteral administration.
• An increased risk to the patient.
• Injectable routes are invasive and thus can cause pain, tissue damage and potential infection.
Pharmacodynamics and pharmacokinetics Chapter 5

Table 5.2 Factors that affect absorption of drugs.

Route Factors affecting absorption
Intravenous (IV) None: direct entry into the venous system
Intramuscular (IM) Perfusion of blood flow to the muscle
Fat content of the muscle
Temperature of the muscle: cold causes vasoconstriction and decreases
absorption; heat causes vasodilation and increases absorption. 75
Subcutaneous (SC) Perfusion of blood flow to the tissues
Fat content of the tissue
Temperature of the tissue: cold causes vasoconstriction and decreases absorption;
heat causes vasodilation and increases absorption.
Oral (PO) Acidity of the stomach
Length of time in the stomach
Blood flow to the gastrointestinal tract
Presence of interacting foods or drugs
Rectal (PR) Perfusion of blood flow to the rectum
Lesions in the rectum
Length of time retained for absorption
Mucous membranes Perfusion or blood flow to the area
(sublingual, buccal) Integrity of mucous membranes
Presence of food or smoking
Length of time retained in area
Topical (skin) Perfusion or blood flow to the area
Integrity of skin
Inhalation Perfusion or blood flow to the area
Integrity of lung lining
Ability to administer drug properly
Source: Reproduced with permission from Karch (2017).

Subcutaneous Intramuscular Intravenous Transdermal Implantation

Figure 5.2 Injectable routes of administration. Source: Reproduced with permission from MSD
Manuals: www.msdmanuals.com/home/drugs/administration- and- kinetics- of- drugs/drug-
administration

• The preparation time is increased and sterile techniques must be used.

• Training is required for use of the parenteral route.
There are several advantages to using a parenteral route. Parenteral routes are far more effective
with medications that absorb poorly or are unstable in the GI tract, such as insulin or heparin.
Parenteral routes can be used in unconscious patients or those actively vomiting who require emergency
Chapter 5 Pharmacodynamics and pharmacokinetics

treatment. The bioavailability of the drug is faster and much more predictable, in addition to avoiding
the interference by digestive enzymes or liver metabolism (Le, 2020).
See also Chapter 6 of this text for a more detailed discussion regarding drug formulas.

Phase 2: distribution
Once a drug is absorbed into the bloodstream, it is distributed throughout the body by the circula-
76 tory system. Distribution is the process by which a drug passes from the bloodstream to body tissues
and organs. It is how a drug moves from intravascular space, e.g. blood vessels, to extravascular
space, e.g. body tissues, as it is carried around the body by the circulatory system. Several factors can
affect the distribution of a drug.

• Cardiovascular function
• Regional blood flow
• Protein binding
• Physiological factors
Similar to absorption, distribution is dependent on cardiovascular function. When medications are
absorbed, they are initially distributed to more highly perfused areas of the body such as the brain,
heart, liver and kidneys. Distribution to the skin, muscles or GI tract is much slower. A patient in shock
or in congestive cardiac failure (CCF) will have a reduced cardiac output, which leads to a much
slower and more unpredictable distribution. Marked reduction of cardiac output can lead to negligi-
ble drug delivery in areas of minimal perfusion (Raj and Raveendran, 2019).
A variance in regional blood flow can also affect distribution. Patients in cardiogenic shock, for
example, will experience reduced blood flow to organs such as the kidneys; thus, medications such
as furosemide which act specifically on the kidneys may not reach the kidneys in a concentration to
be effective. In the JRCALC guidelines for paramedics, cardiogenic shock is a contraindication for the
administration of furosemide.

Protein binding
Binding to plasma proteins is both a help and a hindrance to the distribution of drugs through the body.
Transport in the bloodstream by binding to proteins helps drugs to reach regions remote from the site of
administration. When a drug is bound to a protein, it cannot readily leave the capillaries and affect the tar-
get tissues. However, the rate of distribution of a drug into the tissues will be controlled by the concentra-
tion gradient produced by the concentration of unbound unionised drug. Usually, it is the unbound drug
concentration that is considered to be active. The fraction of unbound drug can also influence the rate of
drug elimination. Binding does, therefore, affect both the duration and intensity of drug action. Some drugs
compete with others for the same protein-binding site, which will change the effectiveness of the drug or
cause toxicity when two or more drugs of the same group are administered together (Karch, 2017).

Blood–brain barrier
There are physiological barriers which affect distribution. The blood–brain barrier is an example of
this. These barriers inhibit the movement of certain molecules while allowing others to enter. The
blood–brain barrier is a collection of capillary endothelial cells within the brain. The make-up of these
cells does not allow entry to water-soluble medications, in addition to excluding the most ionised
molecules, for example dopamine. However, non-ionised and unbound molecules pass much more
easily and reach the central nervous system (CNS), in addition to drugs with a high lipid solubility. The
delivery of substances to the brain is limited by the blood–brain barrier, making it a protective mecha-
nism for the brain. A growing body of evidence supports a major role for the blood–brain barrier in the
ethology and pathogenesis of multiple vascular and neurodegenerative disorders (Pardridge, 2005).

Placental barrier
The placental barrier is another physiological example (Figure 5.3). The term ‘placental barrier’ is a
misnomer, as the placenta is not a true barrier for the transfer of most drugs and toxicants from
mother to fetus. The placenta has been characterised as ‘a lipid membrane that permits bidirectional
Pharmacodynamics and pharmacokinetics Chapter 5

Drug Drug Drug

Mother
Mother Mother

77
Placenta Placenta Placenta

Foetus Foetus Foetus

A Maternal target B Placental target C Fetal target

Figure 5.3 The placental barrier and drug administration.

transfer of substances between maternal and fetal compartments’ rather than as a barrier. In humans,
the placental barrier consists of the trophoblastic epithelium, covering the villi, the chorionic con-
nective tissue and the foetal capillary endothelium. Because medications must traverse the maternal
blood supply and cross capillary membranes into the foetal circulation, delivering medications to the
foetus requires them to be lipid soluble, non-ionised and non-protein bound.

Phase 3: metabolism (biotransformation)

Metabolism, sometimes referred to as biotransformation, is the recognition by the body that the
drug is present and the transformation of the drug into useable parts. Most drugs are metabolised in
the liver but other organs include the kidneys and intestines. The blood supply from the GI tract
intersects with the liver through the portal vein, so that all medications absorbed in the GI tract pass
through the liver. This first pass through the liver has the potential to partially or completely inacti-
vate medications. This first-pass effect is why paramedics may administer medications parenterally to
bypass the GI tract and avoid the first-pass hepatic metabolism.
Biotransformation can metabolise a drug into an active or inactive form. Some drugs are fully
metabolised before they are eliminated; lidocaine is one such example. Some drugs are partially
metabolised before being eliminated, while some are not metabolised at all prior to elimination
(Bledsoe and Clayden, 2012). Protein-bound medications cannot be biotransformed. Biotransformation
occurs immediately following the administration of the medication. Some medications are biotran-
formed rapidly while others are not. Epinephrine 1:10 000 is a common medication administered dur-
ing cardiac arrest which is active upon administration; this medication undergoes a rapid
biotransformation to an inactive form before it is eliminated. Because of this rapid biotransformation
to inactivity, the medication is repeated every 3–5 minutes as required. Some medications, however,
are inactive when administered but when absorbed are converted to their active form. Paramedics
administer several medications which must be converted to an active form before a therapeutic effect
is achieved. Diazapam is one such example.

Rates of reaction
To understand the processes of pharmacokinetics, the rates of these processes have to be consid-
ered. They can be characterised by two basic underlying concepts: a zero-order reaction and a first-
order reaction.
Chapter 5 Pharmacodynamics and pharmacokinetics

Zero-order reaction
Consider the rate of elimination of alcohol (A) from the body. We can say that the rate of decrease in
concentration is independent of concentration and depends only on the rate constant (k). So, in a
zero-order process, the same amount of drug will disappear in a given amount of time regardless of
how much drug is present. For example, if k = 2 mg/L/h, the concentration will decrease by 2 mg/L
every hour whether the starting concentration is 10 mg/L or 100 mg/L.
78 Drugs that have this type of elimination will show accumulation of plasma levels of the drug and hence
non-linear pharmacokinetics. Zero-order kinetics are rare and elimination mechanisms are saturable.

First-order reaction
First-order kinetics occur when a constant proportion of the drug is eliminated per unit of time. The
rate of elimination is proportionate to the concentration of drug in the body. Most drugs are elimi-
nated in this way and the elimination mechanisms are not saturable. In this reaction, the higher the
concentration of drug, the greater the amount eliminated each unit of time. For every half-life that
passes, the drug concentration is reduced by 50% (Hallare and Gerriets, 2021). For example, if 10 mg
of morphine is administered IV to a patient, after 2 h (approximate half-life of morphine) 5 mg will be
eliminated, another 2 h later a further 2.5 mg will be eliminated, after a further 2 h an additional 1.25
mg will be eliminated, and so on until the entire concentration is eliminated from the body.

First-pass metabolism
The first-pass effect is a phenomenon of drug metabolism whereby, specifically when administered
orally, the drug concentration is greatly reduced before it reaches the systemic circulation. It is the
fraction of drug lost during the process of absorption which is generally related to the liver and GI
wall. Notable drugs that experience a significant first-pass effect include morphine, midazolam, diaz-
epam and GTN. An example of this can be seen in Figure 5.4.

First Pass Metabolism 3

General (Systemic) Circulation

Drug
2

Liver Hepatic
Hepatic Portal Vein
metabolizes drugs! Portal
Capillary Network System

Lumen of GI Tract 1

The First Pass Process

1) The drug is absorbed by the GI Tract.

2) Drug absorbed from the gastrointestinal tract travels immediately to the liver
through the hepatic portal vein.
3) The first pass effect occurs at this stage. Hepatic first pass occurs when drug
absorbed from the gastrointestinal tract is metabolised by enzymes within the
liver to such an extent that most of the active agent does not exit the liver and,
therefore, does not reach the systemic circulation.
4) The remaining drug is distributed around the body within blood cells and
plasma.

Figure 5.4 First-pass metabolism.

Pharmacodynamics and pharmacokinetics Chapter 5

Hepatic first-pass effect

Drugs given by the oral route are absorbed from the stomach and the small intestine into the hepatic
portal vein, which goes directly to the liver. The process of biotransformation begins and the drug
will start to be metabolised in preparation for excretion from the body. The drug molecules in the
plasma move through the system. The molecules are now metabolised by the liver enzymes in the
normal fashion. This first-pass effect reduces the fraction of the dose administered, which then goes
on to reach the systemic circulation and become available for therapeutic effect. 79
For drugs administered orally, the amount of first-pass metabolism known to occur has been
factored into oral dosing regimens and guidelines. This means that the bioavailability, which is a
known factor, has been considered when dose and dose ranges are advised. It is important there-
fore for the paramedic to be aware of any hepatic dysfunction when administering oral drugs. If
there is compromised liver function or disease such as cirrhosis, then first-pass metabolism will
be compromised. This could lead to more active drug entering the systemic circulation due to the
reduced liver enzyme functionality and may cause side- effects, adverse effects or toxicity. Some
drugs are destroyed by liver enzyme systems at this first-pass stage and will not enter the general
systemic circulation. An example of such a drug is GTN, which is metabolised completely by the
liver and inactivated. Consequently, you will find GTNbeing administered via the sublingual route
to bypass this effect.
Not all oral drugs are destroyed by the liver at first pass, but many clinically significant drugs do
undergo an extensive first-pass effect. Therefore, the doses of some drugs are considerably higher
when given by the oral route compared to their dosing if given IV (Scott and McGrath, 2008).

Phase 4: elimination
Drugs are removed from the body by various elimination processes. Drug elimination refers to the
irreversible removal of drug from the body by all routes of elimination. Drug elimination is usually
divided into two major components: excretion and biotransformation. Drug excretion is the removal
of the intact drug. Non-volatile drugs are excreted mainly by renal excretion, a process in which the
drug passes through the kidney to the urinary bladder and ultimately into the urine (Figure 5.5).
Other pathways may include the excretion of drug into bile, sweat, saliva, milk (via lactation) or other
body fluids. Volatile drugs, such as gaseous anaesthetics, alcohol or drugs with high volatility are
excreted via the lungs into expired air. Excretion through the mammary glands is an area of concern
when breast-feeding mothers are administered medication.
The rate of elimination can vary depending on the medication and the state of the body. For exam-
ple, a patient in shock will experience poor perfusion to the kidneys. In these cases, medications
which are primarily excreted via the kidneys remain present in the body for a longer period of time.
The slower the rate of elimination, the longer the medication remains in the body.

Drug
Oxidation Conjugation
(Cytochrome P450’s) (Glucuronidation etc.)
Conjugation

Metabolite Stable Adducts

Polar Non-polar
Species Species

Renal Elimination Biliary Elimination

(Urine) (Stool)

Figure 5.5 Drug excretion process.

Chapter 5 Pharmacodynamics and pharmacokinetics

Example: pharmacokinetics of paracetamol

Paracetamol is commonly used in prehospital care for pain management and management of
pyrexia (a high temperature). It is typically used to relieve mild or moderate pain, such as head-
aches, strains or sprains, and reduce fevers caused by bacteria or viruses. Paracetamol is often rec-
ommended as one of the first treatments for pain, as it is safe for most people to take and side-effects
are rare. Paracetamol can be administered enterally or parenterally, and is available in tablet form,
80 suspension, rectal suppositories or soft pack for infusion. The pharmacokinetics of paracetamol can
be seen in Box 5.1.

Box 5.1 Pharmacokinetics of paracetamol

Absorption Following oral administration, it is rapidly absorbed from the gastrointestinal
tract, its systemic bioavailability being dose dependent and ranging from 70%
to 90%
Distribution It distributes rapidly and evenly throughout most tissues and fluids and has a volume
of distribution of approximately 0.9 L/kg; 10–20% of the drug is bound to red blood
cells
Metabolism Paracetamol is extensively metabolised (predominantly in the liver), the
major metabolites being the sulfate and glucuronide conjugates
Large doses of paracetamol (overdoses) cause acute hepatic necrosis as a
result of depletion of glutathione and binding of the excess reactive
metabolite to vital cell constituents. The plasma half-life ranges from 1.9 to
2.5 h and the total body clearance from 4.5 to 5.5 mL/kg/min. Age has little
effect on the plasma half-life, which is shortened in patients taking
anticonvulsants. The plasma half-life is usually normal in patients with mild
chronic liver disease, but is prolonged in those with decompensated liver
disease
Elimination In healthy subjects 85–95% of a therapeutic dose is excreted by the kidney in the urine
within 24 h, with about 4% appearing as unchanged paracetamol and its glucuronide,
sulfate, mercapturic acid and cysteine conjugates, respectively

Clinical considerations discussed below should be understood in relation to pharmacokinetics.

Clinical consideration: half-life

The half-life of medication is how long it takes for the medication to be reduced by half of its blood
concentration level. This is done through metabolisation. It can be affected by the individual’s ability to
metabolise, such as if the patient has renal failure and liver damage.

Clinical consideration: steady state

A steady state (SS) is when the amount of drug administered is equal to the amount of drug elimi-
nated within one dose interval, resulting in a plateau or constant serum drug level. Drugs with a
short half-life reach steady state rapidly, whilst drugs with a long half-life take as long as days to
weeks to reach a steady state.
Pharmacodynamics and pharmacokinetics Chapter 5

Clinical consideration: termination of action

A termination of action is when the medication has stopped its action at the site of requirement. This
may be seen in analgesic control; when the pain returns, the medication has stopped acting.

81
Clinical consideration: therapeutic range
A therapeutic range is similar to therapeutic index. It is the range area where the medication is effective
for the individual. Linking back to analgesic control, it is the period from when pain is blocked to when
it returns (Figure 5.6).
This can be seen with medication such as paracetamol, where you can repeat the dose of 1 g every
4–6 h. Greater dosages can be toxic as you have exceeded the therapeutic index.
The example of paracetamol and ibuprofen (subject to any contraindications) can be seen in
Figure 5.7 where to maintain a therapeutic level (black line), the two medications are used to comple-
ment each other, while not exceeding the recommended dose and thus therapeutic index.

Dose given Repeat Dose given

Theraputic level

Time ->

Figure 5.6 Therapeutic range.

Repeat Repeat
Paracetamol lbuprofen dose paracetamol dose lbuprofen dose
dose given given given given
Theraputic level

Time ->

Figure 5.7 Therapeutic level.

Pharmacodynamics
Pharmacodynamics is the study of the mechanisms by which specific medication dosages act to
produce biochemical or physiological changes in the body. Put simply, pharmacodynamics explores
what the drug does to the body, specifically, how the drug molecules interact within the body, what
they interact with and how they cause their effects. Medications act in four different ways They can:
1. bind to a receptor site
2. change the physical properties of a cell
3. combine chemically with other molecules
4. alter a normal metabolic pathway.

Medications predominantly operate by binding to a receptor. Almost all medication receptors are
proteins on the cell surface and are part of the body’s normal regulatory function. They can be stimu-
lated or inhibited by molecules which interact with them. Receptors are usually named in accordance
with the medication that stimulates them; for example, a receptor that is stimulated by an opiate is
called an opioid receptor. When a receptor is stimulated by multiple medications, the generic name
is used.
Chapter 5 Pharmacodynamics and pharmacokinetics

The force of attraction between a receptor and a medication is called their affinity. The greater the
affinity, the stronger the bond between the two. Different medications may bind to the same recep-
tor but the strength of the bond may vary.
The shape of the binding site determines its receptivity to molecules. The receptor sites are quite
specific; similar to a door lock, only a specific key will open it. In a similar way, non-opiate medications
generally will not affect an opiate receptor; however, a medication with a similar binding site will
occasionally cross-react.
82 One of the key challenges when studying pharmacodynamics is that drugs are affected by a
patient’s physiological changes such as disease, genetic mutations, ageing and/or by other
drugs. These changes are likely to alter the level of binding proteins or decrease receptor sensi-
tivity (Campbell and Cohall, 2017). It is important that paramedics recognise that some drugs
acting on the same receptor (or tissue) differ in affinity, the expected responses that they can
achieve (i.e. their ’efficacy’) and the amount of the drug required to achieve a response (i.e. their
’potency’). It is worth noting that the affinity and efficacy are not directly related. Constant expo-
sure of receptors or body systems to drugs sometimes leads to a reduced response, for example,
desensitisation.

Agonists and antagonists

Chemicals that stimulate receptor sites fall into two broad categories: agonists and antagonists. The
terms ‘agonist’ (a molecule that binds to a receptor causing activation and resultant cellular changes)
and ‘antagonist’ (a molecule that attenuates the action of an agonist) apply only to receptors
(Figure 5.8).

Agonist
An agonist is a drug that binds to a receptor, activating it and producing a biological response.
Agonists can be full, partial or inverse. Some drugs act on a variety of receptors. These are
known as non-selective and can cause multiple and widespread effects. A full agonist results
in a maximal response by occupying all or a fraction of receptors. A partial agonist results in less
than a maximal response even when the drug occupies all of the receptors (Scott and
McGrath, 2008).

Agonists and Antagonists

Agonists Drugs that occupy receptors and activate them.

Antagonists Drugs that occupy receptors but do not activate them,

Antagonists block receptor activation by agonists.

Agonist alone Agonist + antagonist Antagonist alone

Full activation Less activation No activation

Figure 5.8 Agonists and antagonists.

Pharmacodynamics and pharmacokinetics Chapter 5

The maximal effect or response an agonist can produce, abbreviated as Emax, is determined both by the
number of receptors bound to the agonist, which depends mainly on the amount of the agonist given, also
known as the dose, as well as its intrinsic activity, which is the ability of the agonist to fully or partially acti-
vate its receptors. So full agonists, upon binding to the receptor at high doses, are capable of producing a
maximal response of 100% Emax. This represents the point where all available receptors are bound to an
agonist. In contrast, partial agonists, even at very high doses, result in a smaller response, so their Emax will
be lower (Pleuvry, 2004). A full agonist is like a really well-made spare key that is just as effective as the origi-
nal, while a partial agonist is a poorly made spare key that could open the lock, but it takes longer. 83
An example of a widely used agonist is salbutamol, which is a beta-2 agonist. One easy way to
remember the location of beta-1 and beta-2 cells simply and quickly is that humans have 1 heart and
2 lungs. Beta-1 cells are mainly based around the heart (1 heart) and beta-2 cells are mainly based
around the lungs (2 lungs). Therefore, salbutamol, being a beta-2 agonist, would have its main effects
on the receptors based within the lungs. Beta-1 receptors, along with beta-2, alpha-1 and alpha-2
receptors, are adrenergic receptors primarily responsible for signalling in the sympathetic nervous
system. Beta agonists bind to the beta receptors on various tissues throughout the body. Beta-2
agonists are used for both asthma and chronic obstructive pulmonary disorder (COPD), although
some types are only available for COPD. Beta-2 agonists work by stimulating beta-2 receptors in the
muscles that line the airways, which causes them to relax and allows the airways to widen (dilate).
Hence why salbutamol is known as a bronchodilator.
Using opioids as an example, Table 5.3 gives examples of opioid by receptor binding.

Antagonists
In opposition to an agonist is an antagonist. An antagonist is a type of receptor ligand or drug that
blocks or dampens a biological response by binding to and blocking a receptor rather than activat-
ing it, like an agonist. They are sometimes called blockers; examples include alpha blockers, beta
blockers and calcium channel blockers.
Antagonists can be competitive or non-competitive.

• A competitive antagonist binds to the same site as the agonist but does not activate it, thus
blocking the agonist’s action.
• A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent
activation of the receptor (Pleuvry, 2004).

Clinical consideration: confidence in the drug

In clinical practice, all drugs have been tested through rigorous drug research trials prior to being made
available for safe administration through clinical practice guidelines. These drugs are licensed for use
within a recommended dose range. This ensures that patients achieve a good response to the medica-
tion administered and remain safe during care. Practitioners should always consider the contraindica-
tions and the patient’s state prior to drug administration to ensure no additional harm is caused.

Table 5.3 Examples of opioid by receptor binding.

Antagonist
Full agonist Partial agonist Mixed agonist (also known as blockers or reversals)
Codeine Buprenorphine Buprenorphine Naloxone
Fentanyl Butorphanol Butorphanol Naltrexone
Heroin Pentazocine Nalbuphine
Hydrocodone Tramadol Pentazocine
Hydromorphone
Levorphanol
Meperidine
Methadone
Morphine
Oxycodone
Oxymorphone
Chapter 5 Pharmacodynamics and pharmacokinetics

Episode of care: adult suffering an opiate

overdose
Ms Murphy is a 24-year-old female with a past medical history of substance use and depression.
Ms Murphy has been a heroin user since the age of 17. She was arrested a year ago for assault and theft
and sentenced to 1 year in prison. Ms Murphy was released 2 weeks ago and has been living in tempo-
84 rary accommodation since her release. During her incarceration, she suffered withdrawal symptoms
but has been off heroin for 8 months and is currently prescribed methadone daily. One month into her
stay, staff find Ms Murphy unconscious with respiratory depression and pinpoint pupils following an
opiate overdose. She is administered naloxone by the staff and quickly recovers prior to the arrival of
the ambulance crew. Ms Murphy admits to injecting heroin that morning but ‘no more than I would
usually take’. She is refusing further care and transport to hospital.

Clinical considerations
A significant clinical consideration in cases such as this is the body’s tolerance to medications. Tolerance
happens when a person no longer responds to a drug in the way they did at first. So it takes a higher
dose of the drug to achieve the same effect as when the person first used it. This is why people with
substance use disorders use more and more of a drug to get the ‘high’ they seek. However, when the
body has gone through withdrawal, such as during a period of incarceration, the level of tolerance is
not what it was prior to incarceration as such the dose required for overdose may be less than the nor-
mal dose used prior to withdrawal. Evidence shows former prisoners are at a much higher risk of opiate
overdose following release (Binswanger, 2007).
The second clinical consideration in the case of Ms Murphy is the potential for reoccurrence of res-
piratory depression and overdose symptoms.
Naloxone is a synthetic derivative that antagonises opioids. It has been postulated to antagonise the
three different opioid receptors in the brain. The drug onset is related to its rapid entry into the brain,
which is affected by the 12–15 times greater brain to serum ratio compared to morphine, primarily due
to its high lipophilicity. The distribution half-life for naloxone has been reported to be 4.7 minutes while
the elimination half-life averages 65 minutes. Naloxone competitively inhibits most opioids rapidly. The
short duration of activity of naloxone may play a role in the reoccurrence of toxicity and respiratory
depression due to the high dose of heroin self-administered and its longer half-life. For example, in a
study, 16 healthy volunteers received intravenous morphine at 0.15 mg/kg and were reversed with
low-dose naloxone (0.4 mg). Interestingly, there was a return to severe respiratory depression within
30 minutes. Paramedics should consider the potential for a return of respiratory symptoms in such
patients and ensure an appropriate management plan is instigated.

Drug potency and efficacy

Potency is the concentration or dose of a drug required to produce 50% of that drug’s maximal effect.
Efficacy is the maximum effect which can be expected from this drug (i.e. when this magnitude of
effect is reached, increasing the dose will not produce a greater magnitude of effect) (Figure 5.9).
Intrinsic activity is the drug’s maximal efficacy as a fraction of the maximal efficacy produced by a full
agonist of the same type acting through the same receptors under the same conditions.

Therapeutic index
The therapeutic index is classified as the margin of safety that exists between the dose of a drug that
produces the desired effect and the dose that produces unwanted and possibly dangerous side-
effects. This relationship is defined as the ratio LD50:ED50, where LD50 is the dose at which a drug kills
50% of a test group of animals and ED50 is the dose at which the desired effect is produced in 50% of
a test group. In general, the narrower this margin, the more likely it is that the drug will produce
unwanted effects. The therapeutic index has many limitations, notably the fact that LD50 cannot be
measured in humans and, when measured in animals, is a poor guide to the likelihood of unwanted
Pharmacodynamics and pharmacokinetics Chapter 5

Drug A Drug B

85
Effect

Dose

Figure 5.9 Drug potency and efficacy. Both Drug A and Drug B achieve the same maximum effect,
i.e. they have equal efficacy. However, drug A achieves this effect at a lower dose. Thus, Drug A has
higher potency than Drug B.

effects in humans. Nevertheless, the therapeutic index emphasises the importance of the margin of
safety, as distinct from the potency, in determining the usefulness of a drug (Raj and Raveendran, 2019).
Narrow therapeutic index (NTI) drugs are defined as those drugs where small differences in dose
or blood concentration may lead to dose- and blood concentration-dependent, serious therapeutic
failures or adverse drug reactions. Serious events are those which are persistent, irreversible, slowly
reversible or life-threatening, possibly resulting in hospitalisation, disability or even death. Some
examples of drugs that are known to have an NTI can be seen in Table 5.4. Slight changes in medica-
tion dose or blood concentration level can be dangerous.

Adverse drug reactions

An adverse drug reaction (ADR, or adverse drug effect) is a broad term referring to unwanted,
uncomfortable or dangerous effects that a drug may have (IUPHAR, 2019) (Table 5.5 and Box 5.2).
Adverse drug reactions can be considered a form of toxicity; however, toxicity is most commonly

Table 5.4 Narrow therapeutic index examples.

Drug Description
Warfarin A vitamin K antagonist used to treat venous thromboembolism, pulmonary embolism,
thromboembolism with atrial fibrillation, thromboembolism with cardiac valve replacement and
thromboembolic events post myocardial infarction
Digoxin A cardiac glycoside used in the treatment of mild-to-moderate heart failure and for ventricular
response rate control in chronic atrial fibrillation
Lithium A medication used to treat manic episodes of bipolar disorder
Phenytoin An anticonvulsant drug used in the prophylaxis and control of various types of seizures
Heparin An anticoagulant indicated for thromboprophylaxis and to treat thrombosis associated with a
variety of conditions such as pulmonary embolism and atrial fibrillation
Vancomycin A glycopeptide antibiotic used to treat severe but susceptible bacterial infections such as
methicillin-resistant Staphylococcus aureus (MRSA) infections
Amiodarone A class III antiarrhythmic indicated for the treatment of recurrent haemodynamically unstable
ventricular tachycardia and recurrent ventricular fibrillation
Amitriptyline A tricyclic antidepressant indicated in the treatment of depressive illness, either endogenous or
psychotic, and to relieve depression-associated anxiety
Source: Drugsbank 2021.
Chapter 5 Pharmacodynamics and pharmacokinetics

Table 5.5 Physiological changes in older patients and pregnant/lactating patients (Bledsoe and
Clayden, 2012)
Older patients Pregnant/lactating patients
Decreased cardiac output Increased cardiac output
Decreased renal function Increased heart rate
Decreased brain mass Increased blood volume
86 Decreased body fat Decreased protein binding
Decreased serum albumin Decreased hepatic metabolism
Decreased respiratory capacity Decreased blood pressure
These changes can lead to altered pharmacokinetics These anatomical and physiological changes must be
and pharmacodynamics for many medications. The considered prior to administering medications or fluids. In
rate of metabolism and elimination can be decreased addition, the potential of medications crossing the
and there can be an increase in relevant potency of placental barrier and affecting the foetus must be
medications. In a clinical scenario, for example considered. As such, medications should be administered
managing a CCF patient who also has renal failure, in pregnancy only when the potential benefits outweigh
this may require an increased dose of furosemide and the risks. As with pregnancy, the same risk–benefit
a reduced dose of morphine approach should be applied with breast-feeding mothers
due to the excretion of some medications into breast milk

Box 5.2 Factors altering medication response.

Different patients may have a different response to the same medication. Factors that alter standard
medication response include the following.
Age
The liver and kidneys in infants are not fully developed, so their response to medications may be
altered. Also, with age, the function of these organs deteriorates. Therefore, infants and geriatric
patients are most susceptible to having an altered response to a medication.
Body mass
Drug doses often need adjustment in obese patients. Paramedics should consider the patient’s body
composition when calculating doses. Drug clearance is greater in obesity and correlates with lean body
weight. Body size metrics help guide dose selection, but there are advantages and disadvantages to all
of them.
The clinical issue is that calculating drug doses using each body size descriptor will result in a differ-
ent weight. Consider dosing a 150 kg man who is 170 cm tall. Rounded to the nearest 5 kg, his body size
descriptors are:

• total body weight = 150 kg

• lean body weight = 80 kg
• ideal body weight = 65 kg.
Obviously, large variations exist for mg/kg dosing depending on which metric is used. Estimating the
optimal dose for obese patients is difficult and, in many cases, ill defined. Basing maintenance doses on
total body weight is unlikely to result in a comparable drug response across different body sizes and
generally increases the risk of adverse events. Individualised dosing based on the patient’s lean body
weight is recommended, with accompanying therapeutic drug monitoring and monitoring of the
patient’s clinical response.
Pathological state
Several disease states alter the medication response relationship. The most common are hepatic and
renal dysfunctions. The most common issue with both is the accumulation of medications in the body.
Renal failure will probably decrease the elimination of medications, while hepatic failure can inhibit or
decrease metabolism and prolong the duration of action.
Genetic factors
Genetic factors such as a specific enzyme deficiency or a lower metabolic rate can alter the absorp-
tion and biotransformation of a medication, in turn modifying the response of the patient.
Pharmacodynamics and pharmacokinetics Chapter 5

applied to effects of overingestion (accidental or intentional) or to elevated blood levels or

enhanced drug effects that occur during appropriate use (e.g. when drug metabolism is tempo-
rarily inhibited by a disorder or another drug). You can read more about adverse drug reactions in
Chapter 7 of this text.

Conclusion 87
A fundamental understanding of pharmacokinetics and pharmacodynamics is essential for para-
medics and prehospital providers. Anticipating the desired effects as well as potential adverse effects
is required to ensure patient safety. Factors such as absorption, distribution, biotransformation and
elimination in addition to the therapeutic concentration and toxicity should be considered with the
administration of all medications.

References
Binswanger, I.A., Stern, M., Deyo, R. et al. (2007). Release from prison – a high risk of death for former inmates. New
England Journal f Medicine 356(2): 157–165.
Bledsoe, B.E. and Clayden, D.E. (2012). Prehospital Emergency Pharmacology, 7th edn. New York: Pearson.
Campbell, J.E. and Cohall, D. (2017). Pharmacodynamics – a pharmacognosy perspective. In: Pharmacognosy:
Fundamentals, Applications, and Strategies (eds S. Badal and R. Delgoda). St Louis: Elsevier Inc.
Hallare, J. and Gerriets, V. (2021). Half Life. Treasure Island: StatPearls Publishing.
Health and Care Professions Council. (2014). Standards of proficiency. www.hcpc-uk.org/globalassets/resources/
standards/standards-of-proficiency---paramedics.pdf?v=637106257480000000
International Union of Basic and Clinical Pharmacology (IUPHAR). (2019). Pharmacodynamics. www.
pharmacologyeducation.org/pharmacology/pharmacodynamics
Karch, A. (2017). Focus on Nursing Pharmacology, 7th edn. Philadelphia: Wolters Kluwer.
Le, J. (2020). Drug Metabolism. www.msdmanuals.com/en-gb/professional/clinical-pharmacology/pharmacokinetics/
drug-metabolism
Le, J. (2017). Drug Absorption. www.msdmanuals.com/en-gb/professional/clinical-pharmacology/pharmacokinetics/
drug-absorption
Pardridge, W.M. (2005). The blood–brain barrier: bottleneck in brain drug development. NeuroRx 2(1): 3–14.
Pleuvry, B. (2004). Pharmacology: receptors, agonists and antagonists. Anaesthesia and Intensive Care Medicine
5(10): 350–352.
Raj, G. and Raveendran, R. (2019). Introduction to Basics of Pharmacology and Toxicology Volume 1: General and
Molecular Pharmacology: Principles of Drug Action. Singapore: Springer Nature.
Scott, W. and McGrath, D. (2008). Nursing Pharmacology Made Incredibly Easy. Philadelphia: Wolters Kluwer Health/
Lippincott Williams and Wilkins.
Young, S. and Pritchard, B. (2016). Medicines Management for Nurses at a Glance. Oxford: Wiley.

Further reading
Bickly, L. (2017). Bates’ Guide to History Taking and Physical Examination, 12th edn. Philadelphia: Wolters Kluwer.
BNF and NICE. (2019). Amitriptyline. https://bnf.nice.org.uk/drug/amitriptyline-hydrochloride.html
BNF and NICE. (2019). Phenelzine. https://bnf.nice.org.uk/drug/phenelzine.html
Hale, T.W. (2012). Medication and Mother’s Milk, 15th edn. Amarillo: Hale Publishing.
Health Education England. (2017). Advisory Guidance: Administration of Medicines by Nursing Associates. www.hee.
nhs.uk/sites/default/files/documents/Advisory%20guidance%20- %20administration%20of%20
medicines%20by%20nursing%20associates.pdf
Kwatra, S., Taneja, G. and Nasa, N. (2012). Alternative routes of drug administration – transdermal, pulmonary and
parenteral. Indo Global Journal of Pharmaceutical Sciences 2(4): 409–426.
NHS. (2018). Antidepressants. www.nhs.uk/conditions/antidepressants/
NHS. (2018). Stevens–Johnson syndrome. www.nhs.uk/conditions/stevens-johnson-syndrome/
Royal Pharmacological Society and Royal College of Nursing. (2019). What is Pharmacology? www.bps.ac.uk/
about/who-we-are-(2)/history-of-the-society
Talevi, A. and Quiroga, P. (2018). ADME Processes in Pharmaceutical Sciences: Dosage, Design, and Pharmacotherapy
Success. Basel: Springer.
Chapter 5 Pharmacodynamics and pharmacokinetics

Multiple-choice questions
1. An accurate definition of pharmacodynamics is:
(a) The study of how a certain concentration of a drug produces a biological effect by
interacting with specific targets at its site of action
(b) The study of how the body affects the given drug
88 (c) The study of how a drug affects the body.
2. Tolerance develops because of:
(a) Diminished absorption
(b) Rapid excretion of a drug
(c) Both of the above
(d) None of the above.
3. Which of the following is considered a parenteral route?
(a) Oral
(b) Rectal
(c) Intravenous
4. What is meant by medications that have a narrow therapeutic index?
(a) The gap between effective and toxic effect is large
(b) The gap between effective and toxic effect is small
(c) The gap between effective and toxic effect is insignificant
5. Pharmacokinetics is the study of drugs and their corresponding pharmacological,
therapeutic, or toxic responses in humans and animals. Is this:
(a) True?
(b) False?
6. Which route of drug administration is most likely to lead to first-pass effect?
(a) Sublingual
(b) Intravenous
(c) Intramuscular
(d) Oral
7. Absorption and distribution are processes of:
(a) Pharmacodynamics
(b) Pharmacokinetics
(c) Pharmacovigilance
(d) Pharmacotherapeutics.
8. The two principal organs responsible for drug elimination are:
(a) The spleen and the respiratory system
(b) The kidneys and the bowel
(c) The spleen and the bowel
(d) The kidney and the liver.
9. A drug that may change the acidity of the stomach acid is likely to affect a drug that is
dissolved in the stomach.
(a) True
(b) False
10. Active transports uses energy (ATP) to transfer molecules and ions in and out of the cell.
(a) True
(b) False
11. Drug potency is an expression of:
(a) How much alcohol is used within the drug
(b) The activity that judges the therapeutic effectiveness of the drug in humans
(c) The activity of a drug in terms of the concentration or amount of the drug required
to produce a defined effect.
Pharmacodynamics and pharmacokinetics Chapter 5

12. Clinical efficacy:

(a) Judges the therapeutic effectiveness of the drug in humans
(b) Is the activity of a drug in terms of the concentration or amount of the drug
required to produce a defined effect
(c) Is how ethical it is to administer the drug.
13. Naloxone is an example of an antagonist.
(a) True 89
(b) False
14. Another name for biotransformation is:
(a) Administration
(b) Distribution
(c) Metabolism
15. Drugs that are not lipid soluble:
(a) Are not able to pass the blood–brain barrier
(b) Can pass the blood–brain barrier.
Chapter 6
Drug formulations
Sarah Dineen-Griffin and Barbara C. Wimmer

Aim
The aim of this chapter is to review different drug formulations and the points to consider for the
administration of medicines to patients via various routes of delivery.

Learning outcomes
1. Identify the different formulations of medicines that are commonly available and used by the
paramedic.
2. Understand the administration of medicines via different routes, including potential advantages
and disadvantages of these routes.
3. Understand the reasons why a certain drug formulation may be selected.
4. Identify the risks and considerations regarding altering medicine dose form, for instance, by
crushing.

Test your knowledge

1. Why are the specific formulations of a medicine important and what implications does this have in
the healthcare setting?
2. What are the key issues a paramedic should think about when considering the route of drug
administration?
3. What are the benefits and rationale for sublingual drug administration and when would this route
be used in practice?
4. What specific oral formulations must not be chewed or broken?
5. Which populations may have problems swallowing conventional oral formulations such as tablets
or capsules?

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Drug formulations Chapter 6

Introduction
This chapter explores the different formulations of medicines, includes discussion about the admin-
istration of medicines via different routes (such as parenteral and enteral) and gives examples of their
use and administration in paramedic practice, clinical considerations and implications.
The therapeutic nature of a medicine determines the route of administration. For example, for
most gastrointestinal (GI) diseases, oral drug delivery is a logical option. The choice of route will
depend on the physicochemical and therapeutic properties of a drug. For example, transdermal drug
delivery has several criteria that must be met by the drug in order to be delivered via this route, such 91
as high potency and ready permeability.

Routes of drug administration

A route of administration is defined as the path by which a medicine or other substance is taken
into the body (MSD Manual, 2020). Routes may be classified by the location to which they are
administered or applied, or by the site of action. Intravenous (IV) and oral administration are com-
mon examples. Administration may also be enteral (delivered through the GI tract for a system-
wide effect, topical (local) or parenteral (delivered via routes other than the GI tract for a systemic
effect) (Figure 6.1).
Medicines are introduced via the following routes.

• Taken by mouth (orally).

• Placed under the tongue (sublingually) or between the gums and cheek (buccally).
• Inserted in the rectum (rectally) or vagina (vaginally).
• Applied to the skin (cutaneously) for a local or systemic effect.
• Delivered through the skin by a patch (transdermally) for a systemic effect.
• By injection into a vein (IV), into a muscle (intramuscularly [IM]), into the space around the spinal cord
or into the space between layers of tissue around the brain (intrathecally), directly into the marrow of
a bone (intraosseous), beneath the skin (subcutaneously [SC]) or into the dermis (intradermal).

Administration Absorption and distribution Elimination

Bile

Portal
Liver Kidney Urine
system Metabolites
Oral or rectal Gut Faeces

Percutaneous Skin

Milk,
Intravenous PLASMA Breast, sweat glands
sweat

Intramuscular Muscle
Brain

Placenta
lntrathecal CSF

Fetus
Expired
lnhalation Lung air

Figure 6.1 The main routes of drug administration and elimination. Source: Reproduced with permission
from Rang (2016).
Chapter 6 Drug formulations

• Applied to the eye (ocular) or the ear (otic).

• Sprayed into the nose and absorbed through the nasal membranes (nasally).
• Breathed into the lungs, through the mouth (by inhalation) or mouth and nose (by nebulization).
The choice of route of drug administration is governed by various factors including:

• physicochemical properties of a medicine, e.g. physical (solid, liquid and gas) and chemical
(solubility, stability, pH, irritancy) properties
92 • desired site of action
• rate of absorption of the drug from different routes
• drug metabolism
• condition of the patient.
In acute situations, for example, medicines are most often given IV. The absorption of medicines from
the GI tract and tissues can often be unpredictable in acutely ill patients due to altered blood flow or
bowel motility.

Parenteral administration
Parenteral administration refers to any routes of administration that do not involve drug absorption
via the GI tract (including IV, IM, SC, intrathecal, intradermal or intraosseous). Reasons for selecting
the parenteral route over the oral route may be due to low oral bioavailability of a drug, the need for
immediate effect (e.g. in an emergency situation), for patients who are unable to take the drug by
mouth, or if there is a need to control the rate of absorption and duration of effect. There are a num-
ber of advantages to parenteral administration. These include:

• drugs that are poorly absorbed, inactive or ineffective if given orally, can be given by this route
• the IV route provides a rapid onset of action
• the IM and SC routes can be used to achieve slow or delayed onset of action
• patient compliance issues are largely avoided.
Disadvantages of parenteral administration include cost, pain, appropriately prepared staff to administer
and a potential need for supporting equipment, for example, infusion devices.

Intravenous administration
Specific medicines must be given by an IV injection or infusion and are delivered directly into the
vein. The IV route is most frequently used. This is because it is flexible regarding the rate of dosing
and injection volume (Riebesehl, 2015). However, infusions allow for controlled or constant plasma
profiles (Riebesehl, 2015). A drug given by the IV route, however, tends to have a shorter duration of
action. As such, some medicines may be administered by continuous infusion. This method over-
comes repetitive injections, prevents delays in drug administration and allows for more precise titra-
tion and extended duration of effect (McGrath and Brown, 2009; Sinatra, 2003). During an infusion, a
solution is moved by an infusion pump or by gravity, through thin tubing and cannula, which is
inserted into a vein (MSD Manual, 2020). An IV ‘push’ or ‘bolus’ is the rapid administration of a drug in
a bolus (a single, large dose of a drug). A bolus injection may be necessary if a patient requires a par-
ticular medicine immediately.

Episode of care
Ms Smith is a 59-year-old female with chronic obstructive pulmonary disease (COPD). You are treating
her for severe shortness of breath (SOB) associated with an exacerbation, and IV dexamethasone is
administered. Are there any adverse effects of dexamethasone when it is used like this? What if it was used
on a daily basis? What else can dexamethasone be used for?
Drug formulations Chapter 6

Dexamethasone may cause adverse effects including headache, oedema, vertigo, fluid retention,
nausea, hypertension, hyperglycaemia and congestive heart failure (Australian Medicines Handbook,
2020; Joint Formulary Committee, 2020). Adverse effects are more common with prolonged administra-
tion, and include Cushing syndrome (euphoria, fat redistribution around the mid-section and upper
back, between the shoulders, moon face, muscle wasting, thinning of the skin, poor wound healing,
hypertension, obesity, osteoporosis and increased susceptibility to infections). In an emergency setting,
dexamethasone can be used for severe asthma and COPD exacerbations, suspected croup and severe
sepsis (Australian Medicines Handbook, 2020; Joint Formulary Committee, 2020). In other settings, dexa- 93
methasone can be used for cerebral oedema due to malignancy or postoperative or chemotherapy-
induced nausea and vomiting (Australian Medicines Handbook, 2020; Joint Formulary Committee, 2020).

Subcutaneous administration
The administration of a SC injection is into the fatty tissues (SC tissue) between the muscle and
skin. The SC tissue has small blood vessels (capillaries), which allows a medicine to be more slowly
absorbed than if administered via the IV route (Case-Lo, 2018; Shepherd, 2018). The advantages
of administering medicines via the SC route are that they are less expensive, sometimes more
effective when administering specific drugs, beneficial for medicines that have low oral bioavail-
ability (e.g., insulin) or medicines that require continuous absorption (e.g., heparin) (Case-Lo,
2018; Shepherd, 2018). Solutions are not appropriate to be delivered via the SC route as it is irri-
tating to the tissue and may result in necrosis of the skin. A 16mm long and 25–27 gauge needle
is generally used to administer medicines via this route (Department of Health, 2020; Public
Health England, 2020). Areas for injection include (1) the abdomen, about 2 inches from the
navel, (2) back or side of the upper arm, (3) top of the thigh, or (4) top of the buttocks (Figure 6.2).
The site of injection may vary for individuals as each patient has different levels of SC tissue.
Separating the SC fat from the muscle underneath by lifting the skin fold may be required
(Shepherd, 2018). For those patients requiring frequent injections, the injection sites should be
rotated (Villines, 2018).

Intramuscular administration
The IM route is preferred to the SC route when larger volumes of a medicine are required. IM injec-
tions are limited to volumes of up to 5 mL. A longer needle is used because the muscles lie below the
skin and fatty tissues. Medicines can be injected into the upper arm, thigh or buttock.

9 mm (2-18)
15 mm (4-30)

14 mm (2-30) 23 mm (6-58)
28 mm (18-40)
36 mm (28-44)

7 mm (2-22) 14 mm (5-34)

Figure 6.2 Subcutaneous injection sites and the average thickness of the subcutaneous fat.
Chapter 6 Drug formulations

Drug absorption is influenced by factors (e.g. exercise) that alter blood flow to the muscle. A medi-
cine will be absorbed more quickly where there is greater blood supply. Slower absorption may be
achieved by altering the drug vehicle. For example, slower release of a drug can be achieved by using
a depot IM injection. Within paramedic practice, glucagon, benzyl penicillin, hydrocortisone and
adrenaline are examples of medicines administered via the IM route.

94 Skills in practice: administration of adrenaline

auto-injector (e.g. EpiPen® or EpiPen Jr®)
for anaphylaxis or severe allergic reaction
The EpiPen or EpiPen Jr adrenaline auto-injector is a disposable, pre-filled automatic injection device
capable of administering adrenaline in the event of anaphylaxis or severe allergic reaction. The emer-
gency administration of adrenaline will assist with relaxing the muscles in the airways to improve
breathing and reverse rapid and dangerous decreases in blood pressure (Queensland Ambulance
Service, 2019a).
Procedure for administration
1. Lay person flat – do not allow them to stand or walk. If unconscious, place in recovery position. If
breathing is difficult, allow them to sit.
2. Remove the EpiPen or EpiPen Jr auto-injector from the carrier tube. Inspect and confirm it is within
the expiry date and the solution is clear. If it is discoloured, discard and use an alternative device.
3. Form fist around the EpiPen with orange tip pointing downwards and remove blue safety cap by
pulling upwards (do not bend or twist).
4. Hold leg still and push the orange tip firmly into the patient’s mid-outer thigh (with or without
clothing) until a click is heard or felt.
5. Hold onto the patient’s thigh for 3 seconds.
6. Remove from the patient’s thigh – the orange needle cover will automatically extend to cover the
injection needle.
7. Dispose of the auto-injector immediately into a sharps container.
Additional practice points
If required, the EpiPen or EpiPen Jr auto-injector may be injected through the patient’s clothing.
When administering an auto-injector to a child, hold the child’s leg firmly to minimise risk of injury
(e.g. lacerations) to the child or the person giving the dose.
The following doses are recommended by organisations such as the Australasian Society of Clinical
Immunology and Allergy (Australian Medicines Handbook, 2020). A repeat dose may be administered
if there is no response after 5 minutes.
Adult, child >20 kg – IM 0.3 mg
Child 7.5–20 kg, IM 0.15 mg

Clinical consideration: administration

of adrenaline
The IM route is preferred over IV for the administration of adrenaline (Australian Medicines Handbook,
2020). IV administration may be necessary if repeated IM doses of adrenaline do not produce the
desired clinical response. IV administration should only be by those experienced in its use. Blood pres-
sure, pulse oximetry and ECG should be continuously monitored. SC administration is not recom-
mended in anaphylaxis as absorption is erratic (Australian Medicines Handbook, 2020).
Drug formulations Chapter 6

Vastus lateralis
Deltoid and rectus femoris

Acromial process
Greater trochanter
Deltoid muscle of femur
Scapula Rectus femoris
Deep brachial 95
artery Vastus lateralis

Radial nerve Vastus medialis

Humerus

Dorsogluteal Ventrogluteal
Posterior superior
Iliac crest
iliac spine
Anterior superior
Gluteus medius iliac spine
Gluteus maximus Gluteus medius
Greater trochanter Greater trochanter
of femur of femur
Sciatic nerve

Figure 6.3 Sites identified for IM injection.

Known sites identified for IM injections include ventro-gluteal, deltoid, dorso-gluteal, rectus femoris
and vastus lateralis (Figure 6.3) (Kirk, 2018). The Joint Royal Colleges Ambulance Liaison Committee
(JRCALC) primarily recommends the anterolateral aspects of the thigh or upper arm for administra-
tion for their ease of access and rapid absorption (JRCALC, 2019).

Intraosseous administration
Intraosseous administration is the process of injecting directly into the marrow of a bone and pro-
vides a non-collapsible entry point into the systemic venous system. This is an effective route for
fluid resuscitation and drug delivery when IV access is not available or not feasible. Intraosseous
administration allows for the administered medications and fluids to go directly into the vascular
system.

Intrathecal administration
Intrathecal administration is when a needle is inserted into the subarachnoid space (between two
vertebrae in the lower spine and the space around the spinal cord), and a medicine is delivered to the
cerebrospinal fluid (ScienceDirect, 2008). Intrathecal administration produces rapid or local effects
on the brain, spinal cord and meninges (MSD, 2020). Anaesthetics and analgesics (such as morphine)
can be administered via this route.

Intradermal administration
Intradermal (ID) injections are shallow or superficial injections of a drug into the dermis, located
below the epidermis. This route is relatively rare compared to injections via the SC or IM route. Due to
the more complex technique, ID injections are not the preferred route of administration for injec-
tions (Shrestha and Stoeber, 2018), and therefore are used for certain therapies only. ID injections are
used for sensitivity tests, such as for allergies, whereby a small and very thin needle is used to inject
Chapter 6 Drug formulations

a diluted allergen just below the skin surface. The advantage of these tests is that it is easy to visualise
the body’s response and the degree of reaction can be assessed.

Skills in practice
Different syringes and needles may be desired for different procedures and should be chosen carefully
according to the type of procedure and injection to be administered. It is important to consider the
length and gauge of a needle, in addition to, the type of syringe appropriate for the volume of a medi-
96 cine to be delivered, viscosity and the injection site. The size, age and condition of the person receiving
the injection are also important to consider. Site selection and consideration of the appropriate degree
of entry are requirements for successful and comfortable administration (Figure 6.4).

Intramuscular Subcutaneous
90° 45°

Intravenous
25°
Intradermal

10° - 15°

Epidermis

Dermis

Subcutaneous
tissue
Muscle

Angle of injections

Intramuscular Subcutaneous Intravenous Intradermal

Figure 6.4 Needle insertion angles for IM, SC, IV and ID injections.

It is important for paramedics to evaluate their patient’s specific body composition and select the
best needle gauge and length accordingly. Becoming familiar with the various injection techniques
and developing a positioning approach that works well for both the patient and paramedic will pro-
Drug formulations Chapter 6

mote optimal outcomes. Regardless of classification, injections require sterile environments and pro-
cedures to minimise the risk of introducing pathogens into the body.

Formulations
Localised versus long-acting injectable formulations
Localised injectables 97
Injections may be administered to produce a local effect and avoid undesirable side-effects if sys-
temically administered. Medicines can be injected directly into the vitreous humour of the eye
(known as intravitreal injections) for conditions such as macular degeneration (American Society of
Retina Specialists, 2017). Intra-articular injections can also be administered (that is, into the articular
space around a joint). As an example, intra-articular corticosteroids can be used for inflammation and
pain in osteoarthritis. Evidence suggests that most people, immediately after receiving intra-articular
corticosteroids, will experience a significant decrease in pain rating scores (McAlindon et al., 2017).
However, while these injections may work to relieve inflammation and pain, the benefits are only
short term. Evidence has shown that further damage to the joint cartilage and acceleration of the
development of osteoarthritis may result following administration of intra-articular corticosteroids
(McAlindon et al., 2017).

Long-acting injectables
Long-acting injectable formulations release medication at a predictable rate over a long period and
are not intended to have a rapid effect. Long-acting injectables are often used to increase adherence
to a medicine by reducing the frequency of administration. Depot injections are usually oil based or
an aqueous suspension and allow for an active drug to be released consistently and gradually
absorbed over a long period. For example, depot antipsychotics (e.g. haloperidol decanoate) may be
prescribed for patients with a history of non-adherence to oral antipsychotics (Lehman et al., 2003;
West et al., 2008).

Topical formulations
Topical administration involves application of the drug primarily to elicit local effects at the site of
application and to avoid systemic effects (Bardal et al., 2011). Examples include drugs adminis-
tered to the eye (e.g. beta-blockers for the treatment of glaucoma [Brooks and Gillies, 1992]), the
nasal mucosa or the skin (e.g. topical steroids in the management of dermatitis [Gabros
et al., 2020]). There are advantages of topical administration in the management of localised dis-
ease including that the drug is able to work predominantly at the intended site of action and a
reduction in systemic side effects.

Ocular
Medicines for eye disorders (such as conjunctivitis or glaucoma) may come in the form of a
liquid, gel or ointment so they can be applied to the eye. They are almost always used for their
local effects. There are advantages and disadvantages. For example, liquid drops may run off
the eye before being absorbed however, they are relatively easy to use. Ointments remain in
contact with the surface of the eye longer, however, may cause blurry vision. Solid inserts may
be hard to put in and keep in place, however, they release a drug continuously and slowly.
Some examples of eye drops produce a local effect (acting directly on the eyes) including arti-
ficial tears for dry eyes, acetazolamide and betaxolol for glaucoma, or phenylephrine used to
dilate pupils.
Chapter 6 Drug formulations

Clinical consideration: topical beta-blockers

Topical beta-blockers reduce the intraocular pressure (IOP) by blockade of sympathetic nerve end-
ings in the ciliary epithelium, causing a fall in aqueous humour production. Two types of topical
beta-blockers are available for use in glaucoma: non-selective, which block both beta-1 and beta-2
adrenoceptors, and cardioselective, which block only beta-1 receptors (Brooks and Gillies, 1992). As
topical beta-blockers can be absorbed systemically, there is potential for cardiovascular and respira-
tory effects (Australian Medicines Handbook, 2020; Joint Formulary Committee, 2020). Topical beta-
98 blockers are contraindicated in bradyarrhythmia, second- or third-degree atrioventricular block or
uncontrolled heart failure (Australian Medicines Handbook, 2020). Care should be taken when treat-
ing with other drugs that cause bradycardia as this may further decrease heart rate (Australian
Medicines Handbook, 2020). As topical beta-blockers may precipitate bronchospasm, they are gen-
erally contraindicated in asthma (Australian Medicines Handbook, 2020; Joint Formulary
Committee, 2020).

Otic
Ear inflammation and infection can be treated using medicines which are directly applied to the
affected ears. Ear drops, as solutions or suspensions, are generally applied to the outer ear canal.
Systemic effects are absent or minimal if drugs are given by the otic route, which means little to no
drug enters the blood stream. However, systemic effects may be seen if applied too frequently or
used for long periods. Examples include ciprofloxacin (for ear infection), benzocaine (to anaesthe-
tise the ear) and hydrocortisone (for ear inflammation).

Nasal
Drug administration via the nasal cavity yields rapid drug absorption and therapeutic effects. If a
drug is to be inhaled via the nose and absorbed through the thin membranes of the nasal passages,
it must be transformed into tiny droplets in air (atomised). Once absorbed, the drug enters the blood-
stream. Drugs that can be administered by the nasal route include sumatriptan (for migraine head-
aches [Derry et al.,, 2012]), and corticosteroids (for allergies [Chong et al., 2016]). Some peptide
hormone analogues (e.g. antidiuretic hormone and gonadotropin-releasing hormone) can also be
administered as nasal sprays.

Clinical consideration: topical medications

Paramedics may be called to administer topical medications and creams to patients. As described in
this chapter, topical medications come in varying forms depending on patient needs. Topical medica-
tions are designed to act locally on the affected area through absorption of the skin. It is therefore
required that all health professionals wear gloves when administering topical treatments to prevent
the absorption of the medication through their hands. Following hand hygiene techniques and using
clean gloves is important when in contact with broken skin to prevent the transmission of micro-
organisms. At all times, the paramedic must adhere to local policies and procedures.

Transdermal
Transdermal administration is effective for introducing drugs into the systemic circulation through
the skin. For example, glyceryl trinitrate may be used for the prophylaxis of angina (Yellon et al.,
2018), fentanyl for the treatment of chronic pain (Taylor, 2020), oestrogens for hormone replacement
(Beck et al., 2017) or nicotine for smoking cessation (Wadgave and Nagesh, 2016). A drug must be
highly lipophilic and may be mixed with a chemical (such as alcohol) to enhance penetration through
the skin into the bloodstream.
Drug formulations Chapter 6

There are many advantages of transdermal administration including avoiding GI drug absorption,
first-pass effects and replacement of oral administration. Patches are beneficial for drugs which are
quickly eliminated and may be delivered slowly and continuously for many hours or days to produce
long-lasting effects. Disadvantages include local skin reactions, irritation of the skin and issues with
adhering the system to the skin. Transdermal delivery systems also require relatively potent drugs for
administration in this manner.

Vaginal formulations 99
Certain medicines may be administered vaginally to women as a solution, cream, gel, pessaries (a
tablet inserted into the vagina) or intravaginal rings (soft plastic rings inserted into the vagina).
Administering a drug vaginally has the potential advantage of exerting effects primarily in the vagina
with limited systemic adverse effects compared to other routes of administration. Medicines primar-
ily delivered via the intravaginal route include oestrogens and progestogens, antibacterials to treat
bacterial vaginosis or antifungals to treat vaginal candidiasis. For example, intravaginal hormone
replacement therapy (HRT) creams containing the hormone estriol (an oestrogen) can be used in
postmenopausal women for relief of symptoms (such as dryness, soreness and redness) occurring
after menopause.

Inhaled formulations
Inhalation
The lungs are an effective route of administration. The alveolar epithelium is very thin (approximately
0.1–0.5 mm thick) which permits rapid and complete drug absorption (Colombo et al., 2012). The
pulmonary alveoli represent a large surface area. This, in addition to, blood flow to the lungs provides
for rapid exchange of drugs and rapid adjustment of plasma concentration. Local (e.g. bronchodila-
tors in the treatment of asthma) and systemic (e.g. inhaled general anaesthetics) effects may be
intended.
Inhaled drugs must be atomised into smaller droplets to ensure the drug can pass through the
trachea and into the lungs. This results in an increase in the amount of drug absorbed. For example,
glucocorticoids such as beclomethasone dipropionate (Singh et al., 2016) and bronchodilators such
as salbutamol (Ullmann et al., 2015) are administered to limit systemic effects and achieve high local
concentrations. However, drugs are partly absorbed following inhalation and therefore may result in
side effects. As an example, tremor may follow salbutamol use (Australian Medicines Handbook,
2020; Joint Formulary Committee, 2020). The process of delivering drugs to the lung is not simple
and is related to many factors associated with the inhaled product and the patient.
The lung is a desirable target for drug delivery given that it provides direct access to deliver drugs
to the disease site while limiting systemic adverse effects. Local drug delivery through the lung also
has the advantage of bypassing absorption in the GI tract and first pass metabolism. Furthermore,
the large surface area of the lung can be utilised for the systemic absorption of certain medications,
from small molecules to large proteins (Patton et al., 2004). Systemic drug delivery to the lung is
non-invasive.

Episode of care: methoxyflurane

You are dispatched to a local park to attend to a 34-year-old male who has fallen down while running.
He has injured his ankle and cannot bear any weight on it. He requires pain relief and you offer him
methoxyflurane.
Describe the mechanism of action of methoxyflurane. What are its adverse effects? How is it administered?
Methoxyflurane is a general anaesthetic, mainly used for immediate, short-term pain relief in the
prehospital setting, e.g. by a paramedic crew. Its overall effects are to enhance the transmission of
Chapter 6 Drug formulations

inhibitory neurotransmitters (e.g. GABA) and inhibit the transmission of excitatory neurotransmitters
(e.g. glutamate) (Porter et al., 2018). Methoxyflurane has low blood solubility, meaning it doesn’t take
long to saturate the blood. It has a fast onset of action and short duration. Onset of pain relief is
achieved after 6–10 breaths and continues for several minutes after stopping. It has high lipid solubil-
ity, meaning that it is highly potent because it easily crosses the blood–brain barrier to exert its effects.
Therefore, low doses are required. Adverse effects include drowsiness, confusion, nausea, headache,
decreased heart rate and blood pressure. Methoxyflurane is administered via an inhalation device, as
follows (Queensland Ambulance Service, 2019b).
100
1. Tilt the inhaler to a 45° angle and pour the contents of one 3 mL bottle into the base whilst
rotating.
2. Instruct the patient to inhale and exhale gently through the mouthpiece.
3. If stronger analgesia is required, the patient may be instructed to temporarily cover the dilution hole
with their own finger to increase concentration.

Nebulisation
A drug must be aerosolised into small particles to reach the lungs if given by nebulisation. Examples
of drugs that can be nebulised include tobramycin for cystic fibrosis (NPS MedicineWise, 2019) and
salbutamol for symptom-relief associated with an asthma exacerbation (EMC, 2020; Queensland
Ambulance Service, 2020). Adverse effects may occur if the drug is deposited directly in the lungs
and may include shortness of breath or lung irritation. Importantly, the amount of drug delivered to
the lungs will be maximised with proper use of the nebuliser. When the device is reused and inade-
quately cleaned, contamination may also occur.

Episode of care
You are dispatched for a 40-year-old male having difficulty breathing. On arrival, you find the
patient sitting on the deck and are met by a 35-year-old female. The patient is flushed and
anxious and is only able to speak short sentences. The male reports a history of asthma which is
aggravated by dust, pollen and exercise. He mentioned to you that he suddenly felt chest constric-
tion while mowing the lawn. He normally uses his salbutamol inhaler, however, couldn’t find an
inhaler when needed. His asthma has been controlled over the last few years with regular use of
preventer and symptom controller inhalers. He advises he has never experienced an asthma attack
this severe.
How would you initially treat this patient? Describe how the patient’s inhaler (salbutamol) works. What
are the roles of preventers and symptom controllers in the management of asthma?
This patient appears to be suffering from an acute asthma exacerbation. The patient would initially
be treated with salbutamol (via an inhaler or nebuliser with oxygen). Additional treatment options
(depending on response, severity and drug availability) include ipratropium, dexamethasone and
adrenaline. Salbutamol is a beta-2 receptor agonist (Ullmann et al., 2015). It causes relaxation of bron-
chial smooth muscle and bronchodilation (as a ‘reliever medication’ – to be used only when required).
Preventers are used on a regular basis to control the underlying inflammation in asthma and prevent or
reduce the occurrence of asthma exacerbations. Symptom controllers can be used on a regular basis
with preventers to keep the airways open. As long as they are used in conjunction with preventers, they
can reduce the occurrence of asthma exacerbations. However, if used without a preventer, they may
mask underlying inflammation and may increase the risk of an asthma exacerbation.
Drug formulations Chapter 6

Enteral formulations
Enteral administration involves absorption of the drug via the GI tract and includes oral, gastric or
duodenal (e.g. feeding tube) and rectal administration. Furthermore, other locations often classified
as enteral include sublingual (under the tongue) and buccal (between the cheek and gums/
gingiva).

Oral
Oral (PO) administration is the most frequently used route of administration. Drugs administered 101
orally include tablets or chewable tablets, capsules and liquids (MSD Manual, 2020). There are many
advantages of oral administration. It is inexpensive and offers convenience and simplicity, all of
which improve patient compliance. Tablets and capsules have a high degree of drug stability which
allows for accurate dosing. For patients who cannot tolerate tablets and capsules, such as children
or older patients who have difficulty swallowing, the use of liquids or soluble formulations is
beneficial.
The oral route is nevertheless problematic because of the unpredictable nature of GI drug absorp-
tion. Food may impact how rapid a drug is absorbed and how much of a drug is absorbed in the GI
tract. Some medicines taken orally are to be taken with food or alternatively, on an empty stomach.
Similarly, drugs taken concomitantly may interact or affect how much and how fast the drug is
absorbed (MSD Manual, 2020). Additionally, the formulation impacts how quickly the medication is
absorbed and gets into the systemic circulation (Figure 6.5).
If a patient is vomiting or is unable to swallow, oral administration is less desirable. Drugs delivered
via the oral route need to be stable in gastric acid, otherwise they may be destroyed by acid and
digestive enzymes in the stomach and may be poorly or erratically absorbed (World Health
Organization, 2011a, b). If the oral route is not suitable (for example, if a patient is nil by mouth, if
rapid onset of action is required, or if a drug is poorly absorbed), other routes of administration
should be used.

Tablets
Immediate release
Immediate-release medications quickly disintegrate and release the drug rapidly (Maiti and
Sen, 2017). This is particularly important in situations where a quick onset of action is required (e.g.
sumatriptan, a triptan medication, is a fast-disintegrating tablet indicated for the treatment of acute
migraine).

Solutions
Suspensions
Caps/Tabs
Coated Tabs
Conc

Controlled-
release

Time

Figure 6.5 Speed of absorption depending on the formulation of oral medications.

Chapter 6 Drug formulations

Controlled release
Controlled-release formulations deliver a drug at a predetermined rate over a specified period of
time, achieving a constant drug plasma concentration (Wen and Park, 2010). This may also be termed
modified release, sustained release, extended release or long-acting. The main advantage for indi-
viduals taking controlled-release dosage forms is that doses usually only need to be taken once or
twice daily. Damage to the release-controlling mechanism, for example, by chewing or crushing a
controlled-release tablet, can result in the full dose of drug being released at once rather than over a
number of hours. This may increase the risk of toxicity and adverse events, or the medication may not
102 be absorbed at all, leading to suboptimal treatment. Therefore, controlled-release preparations gen-
erally must not be crushed or broken at the point of administration.
There are some exceptions, however, such as controlled-release medications that are scored. For
example, gliclazide controlled-release scored 60 mg tablets (indicated for type 2 diabetes) have a
score line and may be administered as whole or half tablets. To ensure that the controlled-release
properties of the product are maintained, the tablets should not be chewed or crushed.

Skills in practice: controlled-release

medications
Controlled-release medications should not be used to treat acute conditions requiring rapid onset or
quick and safe titration.

Enteric coated
Some medications are not stable in the acidic stomach environment. An enteric coating is a polymer
barrier applied to oral medication that prevents its dissolution or disintegration in the gastric envi-
ronment. Medications with enteric coating pass safely through the acidic stomach environment and
disintegrate later in the GI system, generally in the small intestine (World Health Organization, 2011a, b).
Broadly speaking, there are two forms of enteric-coated tablets: tablets that are coated on their out-
side and tablets that contain small enteric-coated pellets.

Enteric-coated tablets and patients with

swallowing difficulties
Generally, tablets with enteric coating must not be chewed or crushed and should be swallowed as a
whole. Breaking the integrity of the tablet would bring the contents in contact with the stomach acid
which may destroy the active ingredient(s). Dispersible tablets that contain enteric-coated pellets
may be dispersed in water or fruit juice. For example, omeprazole magnesium dispersible tablets can
be placed in half a glass of non-carbonated water or fruit juice, should be stirred until the tablet dis-
perses into little pellets, and consumed immediately or within 30 minutes (Australian Medicines
Handbook, 2020; EMC, 2021).

Dispersible (soluble/effervescent)
Before an oral medication can be absorbed in the GI tract to exert its effect, it needs to disintegrate
into a solution. In the case of dispersible, soluble or effervescent tablets, this process is speeded up
and the medication exhibits a quicker effect than conventional tablets. Dispersible or soluble tablets
dissolve in water to produce a clear or slightly opalescent solution (World Health Organization, 2011a, b).
Effervescent tablets need to be dispersed in water prior to use as they react quickly in water, releas-
ing carbon dioxide.
Drug formulations Chapter 6

Chewable
Chewable tablets are usually uncoated and are intended to be processed by chewing to facilitate
release of the active ingredient(s) (World Health Organization, 2011a, b). The release of drug happens
quicker than with a conventional tablet when swallowed as a whole. Chewable tablets are a versatile
dosage form offering several advantages including oral drug delivery without the need for water,
ease of swallowing and the stability advantages of solid dosage forms. An example of a dispersible/
chewable medication is lamotrigine which is indicated for the treatment of epilepsy and bipolar
disorder.
103
Capsules
Immediate release
Immediate-release capsule formulations need to be swallowed whole and are designed to dissolve
as quickly as possible so that the medication can get into solution and be absorbed without delay
(Maiti and Sen, 2017). Immediate-release formulations are used when a fast onset of action is
desirable.

Controlled release
Controlled-release capsules can have a hard or a soft shell and exhibit a controlled rate of release of
their active ingredient(s) in the GI tract. Similar principles apply as with controlled-release tablets –
crushing or chewing them could release all the content at once and cause potential overdose or it
could lead to the medication not being absorbed and reduced effect.

Enteric coated
Similar principles as for enteric-coated tablets apply here (World Health Organization, 2011a, b). With
enteric-coated capsules, either the capsule itself is coated, and therefore protected from the acidic
environment, or capsules contain small pellets with individual enteric coating (multi-unit pellet sys-
tems [MUPS]). Both capsules and pellets must not be crushed or chewed. In the case of capsules
containing individual enteric-coated pellets, the capsule contents may be mixed with a spoonful of
yoghurt or apple puree. This option is suitable for people with swallowing difficulties.

Liquid formulations
Solutions/suspensions
Solutions are homogeneous mixtures of two or more components. A suspension is a heterogeneous
mixture in which particles do not dissolve but rather remain suspended. That means that particles
may still be seen with the naked eye. Solutions and oral liquid suspensions can be very useful particu-
larly for patients with dysphagia, children or older people.

Skills in practice
Suspensions
Suspensions need to be shaken well before each use. This is important to ensure the uniformity of the
dose at the time of administration. If a suspension is not shaken well and particles (active ingredient)
have settled, the suspension when administered could potentially be less concentrated than expected
while the remainder of the stock suspension would then be more highly concentrated.

Oral formulations of morphine

Morphine, an opioid analgesic indicated for severe pain, is an example of a medication with various oral
formulations including conventional (immediate-release) tablets, conventional oral liquids, controlled-
release tablets (12-h), controlled-release oral liquids (granules, 12-h) and controlled-release capsules
(12- or 24-h). Different oral formulations and combinations of immediate- and controlled-release forms
can be used to achieve optimal control in acute and chronic pain.
Chapter 6 Drug formulations

Recommendations for the different oral formulations of morphine

• Controlled-release tablets must be swallowed whole, not crushed or chewed.
• Controlled-release capsules may be opened, pellets sprinkled on soft food or mixed with 30 mL of
liquid, and taken within 30–60 minutes depending on the brand used. Pellets must not be crushed
or chewed.
• For controlled-release suspension, the contents of the sachet should be added to the recom-
mended amount of water, mixed thoroughly and taken immediately (Australian Medicines
104 Handbook, 2020).

Sublingual and buccal formulations

Buccal and sublingual medications are available in the form of tablets, wafers, films or sprays.
Sublingual administration is undertaken by placing the drug under the tongue. Drugs can be rapidly
absorbed through the sublingual mucosa, given its high permeability and supply of blood vessels.
Peak blood drug levels are usually achieved 3–10 times faster than via the oral route. Glyceryl trini-
trate, indicated for the treatment of acute angina, is an example of a drug that is administered sublin-
gually. ‘Wafer’-based versions of tablets are also available which dissolve rapidly under the tongue.
Rizatriptan, indicated for the acute treatment of migraine, is an example of a drug administered as a
wafer. Additionally, wafers may be used where low medication adherence is suspected. Olanzapine,
indicated for schizophrenia, is available as a wafer formulation.
Buccal administration is undertaken by placing the drug between the inner lining of the cheek
and gums. Buccal tissue is less permeable than sublingual tissue and results in slower
absorption.

Skills in practice: glyceryl trinitrate

You are dispatched to an office building for a 49-year-old male patient experiencing chest pain. Upon
arrival, you are greeted by a female co-worker. She tells you that the patient took his heart medication,
but is still in a lot of pain. You find the patient sitting in a chair. He has a fearful look, is clenching his fist
against his chest and is noticeably diaphoretic (sweating). After initial assessment, you determine his
pulse to be 75 beats per minute, his blood pressure 134/84 mmHg, his cardiac rhythm and oxygen satu-
ration level normal. His regular medications include atenolol and glyceryl trinitrate (GTN). He has a
history of hypertension and angina. GTN is a sublingual medication, which comes in both tablet and
spray form and is used to treat acute chest pain, commonly brought on by angina, or by patients expe-
riencing myocardial infarction (MI). GTN is a potent coronary vasodilator, which reduces venous return
due to its vasodilating properties, therefore reducing left ventricular load and resulting in pain relief for
the patient, if the chest pain is coronary in origin. Advantages of sublingual GTN include that it is rapid
acting and provides almost immediate relief of symptoms. Disadvantages are the side-effects, which
can be severe in some patients such as hypotension or severe headache.
The following steps should be followed for the administration of sublingual GTN spray (Queensland
Ambulance Service, 2019c).

1. Position the patient in a sitting or semi-reclined position.

2. Remove the plastic cover from the GTN spray bottle, thoroughly wipe the entire container, including
the nozzle, with an alcohol swab and allow it to dry.
3. If using a new bottle, prime the pump by holding the bottle upright, facing away from the
patient, and depress the nozzle five times (do not shake the bottle). If first use for the day, prime
by spraying once.
Drug formulations Chapter 6

4. Instruct the patient to open their mouth wide and lift their tongue to the roof of their mouth (some
patients may have difficulty and may require demonstration).
5. Bring the bottle approximately 3-4 cm from the patient’s mouth (without contact) with the nozzle
aimed directly under the tongue and steadily depress the nozzle once.
6. After the last administration, thoroughly wipe the entire bottle, including the nozzle, and inside of
the cap using an alcohol swab.
7. Recap the bottle.
105

Rectal formulations
The rectal route is an effective route of administration. Rectal preparations may include creams, oint-
ments, suppositories and enemas. This route allows for rapid and effective absorption given the rec-
tal mucosa is highly vascularised. Medications may be delivered to the distal one-third of the rectum
with the aim of partially avoiding first-pass metabolism. This allows for greater bioavailability than
some medications which are delivered orally.
A suppository is a solid dosage form for rectal administration. A suppository may be beneficial for
patients who are unable to take a medicine orally (for example, in patients who are nil by mouth or
are unable to swallow). Paracetamol, diazepam and laxatives are examples of medicines that can be
administered rectally. A disadvantage of this route is patient acceptability.

Clinical consideration: dosage differences

across formulations
Paracetamol is an analgesic medication commonly utilised as first-line pain relief. Paracetamol is avail-
able in different formulations including rectal suppositories, oral tablets, oral liquid and IV. It is there-
fore vital that paramedics understand the differences in drug dosages across formulations. For example,
a standard and maximum adult dose of paracetamol administered orally in tablet form is 1 g every 4–6 h,
up to four times daily. However, for adults who weigh less than 50kg, the maximum IV dose is 15 mg/kg
every 4–6 h. For adults who weigh over 50 kg, the dose remains the same as oral recommendations.
Recommendations are also in place for patients with known hepatic disorders or those at risk of hepa-
totoxicity. For example, a maximum daily dose of 3 g can be administered to this patient group. Clinical
judgement should be exercised if a patient is deemed at risk of toxicity and the dosage adjusted
accordingly. It is also important to check a patient’s cumulative paracetamol dose over the previous 24
h, prior to administering the next dose of paracetamol, and to seek guidance on dosages where unsure.
Adhere to local policy and procedure.

Conclusion
This chapter provides details of different formulations of medication available and their uses. The
reader has been provided with knowledge and guidance concerning the various formulations of
drugs, how to administer these safely and correctly and when to consider alternative formulations,
and now will have a wider understanding when entering into practice.
Chapter 6 Drug formulations

Find out more about these conditions

The following is a list of conditions requiring a variety of medications to be administered via a variety of routes
using different drug preparations. Take some time to test your knowledge and write some notes about each
condition. Think specifically about the different medications, treatments or therapies a patient may require and
how these might be administered.

Condition Notes
Nausea and vomiting
106 Epilepsy
Angina
Atrial fibrillation
Opioid overdose

Glossary
Bioavailability The degree to which a medication is absorbed into the circulatory system.
Digestion The breakdown of material in the alimentary canal into substances that
can be absorbed by the body.
Plasma concentration Concentration of a medication or other substance measured in the
patient’s blood plasma.
Systemic absorption The process of a medication being directly absorbed through the body
for therapeutic effect.
Topical application Application to body surfaces such as the skin or mucous membranes.

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Riebesehl, B.U. (2015). Drug delivery with organic solvents or colloidal dispersed systems. In: The Practice of
Medicinal Chemistry, 4th edn (eds C. Wermuth, D. Aldous, P. Raboisson and D. Rognan). Philadelphia: Elsevier,
699–720.
ScienceDirect. (2008). Intrathecal Drug Administration. www.sciencedirect.com/topics/medicine-and-dentistry/
intrathecal-drug-administration
Shepherd, E. (2018). Injection Technique 2: administering drugs via the subcutaneous route. Nursing Times 114(9).
www.nursingtimes.net/clinical- archive/assessment- skills/injection- technique- 2- administering-
drugs-via-the-subcutaneous-route-28-08-2018/
Shrestha, P. and Stoeber, B. (2018). Fluid absorption by skin tissue during intradermal injections through hollow
microneedles. Scientific Reports 8(1): 13749.
Sinatra, R. (2003). Pain, Postoperative. In: Encyclopedia of the Neurological Sciences (eds R. Daroff and M. Aminoff ).
St Louis: Elsevier.
Singh, A., Nandan, D., Dewan, V. and Sankar, J. (2016). Comparison of clinical effects of beclomethasone dipropi-
onate and budesonide in treatment of children with mild persistent asthma: a double-blind, randomized,
controlled study. Indian Journal of Medical Research 144(2): 250–257.
Taylor, K.P. and Goyal, A. (2020). Fentanyl Transdermal. Treasure Island: StatPearls Publishing.
Ullmann, N., Caggiano, S. and Cutrera, R. (2015). Salbutamol and around. Italian Journal of Pediatrics 41(Suppl 2):
A74.
Villines, Z. (2018). Is a subcutaneous injection painful? www.medicalnewstoday.com/articles/322710
Wadgave, U. and Nagesh, L. (2016). Nicotine replacement therapy: an overview. International Journal of Health
Science 10(3): 425–435.
Wen, H. and Park, K. (2010). Introduction and overview of oral controlled release formulation design. In: Oral
Controlled Release Formulation Design and Drug Delivery: Theory to Practice (eds H. Wen and K. Park). Hoboken:
John Wiley & Sons, 1–20.
West, J., Marcus, S., Wilk, J., Countis, L., Regier, D. and Olfson, M. (2008). Use of depot antipsychotic medications for
medication nonadherence in schizophrenia. Schizophrenia Bulletin 34(5): 995–1001.
World Health Organization. (2011a). Revision of monograph on tablets. (www.who.int/medicines/publications/
pharmacopoeia/Tabs-GeneralMono-rev-FINAL_31032011.pdf
World Health Organization. (2011b). Revision of monograph on capsules. www.who.int/medicines/publications/
pharmacopoeia/Caps-GeneralMono-rev-FINAL_31032011.pdf
Yellon, D.M., He, Z., Khambata, R., Ahluwalia, A. and Davidson, S.M. (2018). The GTN patch: a simple and effective
new approach to cardioprotection? Basic Research in Cardiology 113(3): 20.
Chapter 6 Drug formulations

Further reading
eTG complete. Melbourne: Therapeutic Guidelines Limited. www.tg.org.au
Maria, S., Colbeck, M. and Caffey, M. (2020). Paramedic and Emergency Pharmacology Guidelines, 2nd edn.
Melbourne: Pearson Australia Group.
National Institute for Health and Care Excellence (NICE). British National Formulary (BNF). Available from: https://
bnf.nice.org.uk/

108 Multiple-choice questions

1. Enteric-coated tablets:
(a) Disintegrate in the stomach
(b) Take longer to dissolve and take effect than regular tablets
(c) Can be crushed
(d) Are suitable for patients who have difficulty in swallowing.
2. Modified-release medications:
(a) Are suitable for crushing/dissolving
(b) Require less frequent dosages
(c) Are not suitable for the treatment of chronic pain
(d) Should be used to treat acute conditions requiring rapid onset.
3. Sublingual GTN spray:
(a) Is an ineffective treatment for acute angina
(b) Is a potent vasoconstrictor
(c) Is suitable for hypovolaemic patients
(d) Can cause vasodilatory side-effects such as headache, flushing and orthostatic
hypotension.
4. Patients unable to absorb oral medications, due to gut ileus:
(a) Should be given their tablets anyway on the off-chance that they may absorb
them
(b) Should receive the equivalent intravenous preparation for all essential medications
(c) Do not require any further investigation or monitoring
(d) Should be advised to crush or chew their tablets.
5. Suppositories can be used for what effect?
(a) Analgesia
(b) Bowel preparation
(c) Local treatment, such as haemorrhoids
(d) All of the above.
6. What is the recommended time interval between eye drops to ensure maximum effect?
(a) 30 seconds
(b) 3 minutes
(c) 5 minutes
(d) 60 seconds
7. Oral liquid suspensions should be considered for:
(a) Patients with dysphagia
(b) Children
(c) The elderly
(d) All of the above.
8. Topical beta-blockers:
(a) Increase intraocular pressure by blockade of sympathetic nerve endings
(b) Are not absorbed systemically, and therefore there is no potential for cardiovascular
effects
(c) Are indicated for the treatment of glaucoma
(d) Are generally safe to use in asthmatic patients.
Drug formulations Chapter 6

9. Methoxyflurane:
(a) Is mainly used for immediate, short-term pain relief in the prehospital setting, e.g.
by ambulance personnel
(b) Produces pain relief after 12–20 breaths which continues for several minutes after
stopping
(c) Has high blood solubility
(d) Has a long duration of action.
10. Which of the following statements is incorrect? 109
(a) A depot injection deposits a drug in a localised mass, called a depot, from which it
is gradually absorbed by surrounding tissue.
(b) Depot antipsychotics are used as a maintenance treatment for patients with a
history of non-adherence with oral antipsychotics.
(c) Long-acting injectable formulations are intended to have a rapid effect.
(d) Injections may be used to insert a solid object (or implant) into the body which
releases a medication slowly over time.
11. Which of the following statements is incorrect?
(a) Intrathecal administration penetrates the subarachnoid space to allow access of
the drug to the cerebrospinal fluid of the spinal cord.
(b) Intradermal injections are shallow or superficial injections of a drug into the
dermis, located below the epidermis.
(c) A subcutaneous injection is one into the fatty tissues (subcutaneous tissue)
between the skin and the muscle.
(d) Subcutaneous administration is beneficial for drugs that have high oral
bioavailability (e.g. insulin).
12. Which of the following statements is incorrect regarding dexamethasone?
(a) Adverse effects are more common with prolonged administration.
(b) Dexamethasone can be used for severe asthma and COPD exacerbations,
suspected croup and severe sepsis.
(c) Dexamethasone may cause hypoglycaemia.
(d) Dexamethasone increases the risk and severity of infections.
13. Which of the following statements is correct?
(a) Intramuscular injections are limited to volumes of up to 5 mL.
(b) An intramuscular injection must be administered at a 45° angle.
(c) The appropriate degree of entry does not play a role in the successful and
comfortable administration of injections.
(d) The IV route provides delayed onset of action.
14. Which of the following statements is incorrect?
(a) Rectal mucosa is highly vascularised tissue that allows for rapid and effective
absorption of medications.
(b) Buccal administration is achieved by placing the medication between the gums
and the inner lining of the cheek.
(c) Buccal tissue is more permeable than sublingual tissue.
(d) Peak blood drug levels with sublingual administration are usually achieved 3–10
times faster than via the oral route.
15. Which of the following statements is incorrect regarding local drug delivery to the lung?
(a) Undergoes first-pass metabolism in the liver.
(b) Delivers high concentration directly to the disease site, minimising risk of systemic
side-effects.
(c) Achieves rapid clinical response.
(d) Achieves a similar or superior therapeutic effect at a fraction of the systemic dose.
Chapter 7
Adverse drug reactions
Matt Dixon

Aim
The aim of this chapter is to equip the reader with an understanding of what adverse drug reactions
are and how they are relevant to clinical practice.

Learning outcomes
After reading this chapter, the reader will be able to:

1. Understand what an adverse drug reaction is and how it is relevant to clinical practice
2. Understand the different types of adverse drug reaction
3. Recognise the signs and symptoms of adverse drug reactions
4. Understand which patient groups are more likely to experience an adverse drug reaction
5. Understand the professional duties around identification and reporting of adverse drug reactions.

Test your knowledge

1. How would you define an adverse drug reaction?
2. Describe how you would recognise an adverse drug reaction.
3. Are adverse drug reactions a common occurrence?
4. Name the patient groups more likely to experience an adverse drug reaction.
5. What actions should be taken when dealing with a suspected adverse drug reaction?

What is an adverse drug reaction?

Originally defined in 1972 by the World Health Organization, and then adopted in the UK by the
Medicines and Healthcare products Regulatory Agency, an adverse drug reaction (ADR) is ‘any
response to a drug which is noxious and unintended and which occurs at doses normally used in
man for prophylaxis, diagnosis or therapy’.
This has been expanded upon more recently by the National Institute of Health and Care Excellence
(NICE, 2017) which states in addition to the above that an ADR is ‘an unwanted or harmful reaction

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Adverse drug reactions Chapter 7

which occurs after administration of a drug or drugs, and is suspected or known to be due to the
drug’. This definition is important, especially with newer drugs, in including the fact that only suspi-
cion is needed to be able to label a response an ADR.
The National Institute of Health and Care Excellence recommends also that care is taken to distin-
guish the term ‘adverse drug reaction’ from ‘adverse effect’, the latter being preferable to but inter-
changeable with ‘side-effect’ and ‘toxic effect’. This subtle difference in terminology reflects the fact
that a drug can cause an adverse effect, whereas a patient experiences an adverse reaction. The term
‘adverse effect’ is preferred above others because alongside adverse drug reaction, these terms
encompass all unwanted effects. They are unambiguous, make no assumption about mechanism
and avoid the risk of misclassification. 111

Classification of adverse drug reactions

Adverse drug reactions are commonly broken down into two categories, Type A and Type B, although
there are further subtypes beyond these which provide more accurate classification: Type C, Type D
and Type E (MHRA, 2015).
Type A (Augmented) reactions are due to exaggerated but normal pharmacological effects at normal
doses. They are dose dependent and therefore readily reversible when reducing the dose or withdraw-
ing the drug. An example of a Type A reaction would be respiratory depression following administra-
tion of morphine, which is predictable based on the pharmacology of the drug and would be commonly
encountered at higher doses. It would be expected to resolve with cessation or reversal of treatment or
reduction in dose. Type A reactions account for approximately 80% of all adverse drug reactions.
Type B (Bizarre) reactions are idiosyncratic and not predictable given the pharmacological nature
of the drug. An example of a Type B reaction would be anaphylaxis as a result of penicillin administra-
tion. This is uncommon, is not predictable based on the pharmacology of the drug, and will require
more intervention to manage beyond moderating the original drug treatment. Type B adverse drug
reactions account for approximately the remaining 20% of reactions.
Beyond Type A and B reactions there are the more nuanced C, D and E reactions.
Type C (Continuing) reactions are a subset of Type A and are relatively long-lived. An example of
this would be osteonecrosis of the jaw associated with the use of bisphosphonates, which are used
to slow the rate of bone turnover in order to help treat certain bony conditions such as osteoporosis
(Longmore et al., 2010).
Type D (Delayed) reactions are those which only become apparent some time after the beginning
of administration of a drug, and are again a subset of Type A. An example is the onset of leucopenia
(reduction in white blood cells) which can be provoked up to 6 weeks after a dose of the anticancer
drug lomustine.
Type E (End-of-use) reactions are associated with withdrawal of treatment. Examples include the
development of anxiety and fatigue when withdrawing the antidepressant sertraline too quickly.
This may be moderated or eliminated by careful tapering of drugs known to cause withdrawal effects.

How prevalent are adverse drug reactions?

Depending on reporting, it may be difficult to accurately quantify the prevalence of ADRs but in the
UK a systematic review by Howard et al. (2007) found that 3.73% of all hospital admissions were as a
result of ADRs. In a suite of evidence from the UK, NICE (2017) estimates that adverse drug reactions
may account for 6–7% of admissions. NICE (2017) goes on to suggest that ADRs occur in 10–20% of
hospital inpatients and that 2% of patients admitted with an ADR died. In total, ADRs are believed to
contribute to around 1700 deaths and are directly responsible for around 700 potentially avoidable
deaths per year in the UK.
Awareness of the prevalence of ADRs is important as the cost burden they place on healthcare
systems is considerable. Pirmohamed et al. (2004) calculated that the annual cost to the NHS was
£466M, which when adjusted for inflation reflects in 2020 an annual cost of nearly £0.75B. Hidden
within this price is considerable morbidity and mortality, an estimated resource burden of 4 in 100
hospital bed-days, as well as costs associated with litigation and insurance coverage. For interna-
tional context, the estimated cost of medication-related problems was estimated by the
Pharmaceutical Society of Australia (2019) to be $AUD 1.4 Billion (~£800M).
Chapter 7 Adverse drug reactions

The surveillance of ADRs, especially those related to newer medications and those more likely to
be experienced by vulnerable groups, is an important area of work for government regulators, given
the significant associated costs, both financial and in terms of morbidity and mortality.
The knowledge that around 80% of ADRs are predictable based upon the drug’s pharmacology is
an important factor in trying to reduce the incidence of adverse reactions. Indeed, the ability to rec-
ognise and report adverse reactions is a required element within the College of Paramedics (2018)
Practice Guidance for Paramedics. This is mirrored in guidance for other professions across the NHS
(NICE, 2017).

112
Who is more likely to experience adverse
drug reactions?
Adverse drug reactions are more likely to be experienced amongst certain patient groups (Table 7.1),
and when certain classes of medications are involved (Table 7.2).

Table 7.1 Patient characteristics which predispose to adverse drug effects.

Characteristic Remarks
Age Patients at the extremes of age are especially susceptible to adverse reactions. Children and
neonates in particular are at greater risk of experiencing adverse reactions due to physiological
immaturity and variable responses to medications. Extremely small children are at greater risk
of calculation errors where drug doses and volumes can be very small. At the upper limit of age
patients are once again more vulnerable to adverse reactions due to changes in physiology
which affect the ADME processes, as well as potentially lacking physiological reserves to
adequately respond to stressors. Absorption may be decreased by slowed gastric transit; the
distribution of medications may be affected by increased body fat as well as reduced body
water content. A lipid-soluble drug will accumulate in adipose tissue and be less available for
metabolism, lengthening its duration of action. Conversely, water-soluble drugs will be found
in greater concentrations in the extracellular fluid, including plasma. Drug metabolism can be
adversely affected by declining hepatic function and drug and metabolite excretion can be
impaired by reduced renal function, both increasing the risk of higher levels of drug and
therefore adverse effects. The upper limits of age are also compounded by the increased
likelihood of comorbid conditions and polypharmacy
Gender Physiological and anatomical variations based on gender can affect the pharmacokinetics of
many drugs and hence the risk of adverse reactions. Body composition and weight, along with
hepatic function, renal function and gastric motility can all vary with gender. Females tend to
have a lower body weight and smaller organs, with an increased proportion of adipose tissue,
lower glomerular filtration rate and different gastric motility, all of which can leave women at
greater risk of adverse reactions. Other gender-related factors such as hormonal and
immunological status may contribute to an increased risk of adverse reactions in females
Ethnicity Ethnic background can have an effect on risk of adverse drug reactions, primarily due to
genetic differences. The frequency of some drug reactions can differ greatly between ethnic
groups because of variations in the hepatic CYP450 enzymes, for example. One important and
notable difference in these metabolising enzymes exists in the gene encoding for the CYP2D6
enzyme which is an important step in the metabolism of codeine to its active metabolite
morphine, among many other important metabolic reactions. Some 10% of Caucasian people
may have little or no CYP2D6 function, and are classified as poor metabolisers, who are less
likely to experience a therapeutic effect from a normal dose of codeine due to slower
production of the active metabolite. This variant occurs less frequently in people of Asian and
African origin, although there is a greater prevalence of ultra-rapid metabolisers among this
population, which increases risk of adverse effects and opiate toxicity (Holmquist, 2009).
Another example of this is the antidepressant duloxetine, which is metabolised by the CYP2D6
enzyme from the active form to its inactive metabolites; hence in a poor metaboliser there is
increased exposure to the active drug and greater chance of adverse reaction
Adverse drug reactions Chapter 7

Table 7.1 (Continued)

Characteristic Remarks
Environmental Environmental factors can be hard to quantify but some have a well-defined effect on risk of
factors drug reactions. Tobacco smoking is a powerful inducer of the CYP1A2 enzyme (van der Weide
et al., 2003) resulting in more rapid metabolism of drugs that are metabolised by this enzyme.
Alcohol, diet and other factors may influence the pharmacokinetics of a drug and hence the
risk of adverse reaction. A gastric ulcer caused by excessive alcohol intake may impair the
absorption of a drug, and a cirrhosed liver due to alcoholism is less capable of the metabolism
of drugs
Polypharmacy Polypharmacy, the term used to describe patients taking multiple drug therapies, is an
113
important factor in assessing for risk of adverse reactions. Those on multiple medications are
more likely to experience drug-to-drug reactions when treatments are initiated or changed
(Royal Pharmaceutical Society, 2020)
Pregnancy Pregnancy is a well-known risk factor for increased incidence of adverse drug reactions, as
changes in the body, such as increased fluid volume, diluted plasma proteins, cardiac output
and renal blood flow increases as well as reduced gastric motility, can all affect a drug’s
pharmacokinetics. Gastric changes may impair absorption, altered body fluid volumes can
affect distribution, and increased renal blood flow will increase the excretion rate. In pregnancy
and also in nursing mothers, a potential developmental effect upon the foetus or infant must
be considered. While the evidence is limited due to the ethics of such studies, the thalidomide
disaster illustrates the potential harm that drugs used by a pregnant mother can cause. More
common drugs such as warfarin and ibuprofen are contraindicated in pregnancy due to known
concerns about birth defects. Drugs excreted in breast milk can also be passed on the infant,
along with the risk of an adverse reaction. The risk of harm to the infant when giving a
breast-feeding mother medications must also be carefully considered (McKay et al., 2010)
Host factors Host disease may predispose to a particular adverse reaction. For example, the antibacterials
amoxicillin and ampicillin can cause a rash in patients with glandular fever (infectious
mononucleosis)
Patient health A patient’s individual health status can also alter the risk of adverse drug reactions. A patient
and with chronic kidney disease will excrete medications more slowly, resulting in higher drug
comorbidities levels and potential for accumulation and hence adverse effects. Patients with liver disease may
be less able to metabolise drugs and hence unwanted effects may again be more likely. Age,
external factors, comorbid conditions and polypharmacy are closely linked, as an older person
is more likely to have age-related physiological changes and comorbidities, which increase the
likelihood of polypharmacy, all of which compound and increase risk of adverse drug reactions
ADME, absorption, distribution, metabolism and excretion.

Table 7.2 The most common causative medications, ranked by percentage of ADRs.
Drug class Percentage of ADRs
Non-steroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen) 29.6%
Diuretics (e.g. furosemide) 27.3%
Warfarin 10.5%
Angiotensin-converting enzyme inhibitors (e.g. ramipril) 7.7%
Antidepressants (e.g. sertraline) 7.1%
Beta-blockers (e.g. propranolol) 6.8%
Opiates (e.g. morphine) 6.0%
Digoxin 2.9%
Prednisolone 2.5%
Clopidogrel 2.4%
Source: Adapted with permission from Pirmohamed et al. (2004).
Chapter 7 Adverse drug reactions

Recognising signs and symptoms of adverse

drug reactions
Adverse drug reactions range from life-threatening to functionally benign and the entire spectrum
between. The most clinically important adverse drug reaction would be the anaphylactic reaction.

Anaphylaxis
Anaphylaxis is a severe generalised immunological response to a foreign substance; its onset is gen-
114 erally within minutes of exposure to the stimulus and it commonly involves severe and possibly life-
threatening symptoms. Anaphylaxis is most commonly caused by drugs such as antibiotics, in
particular penicillins, non-steroidal anti-inflammatories, aspirin and some vaccines. It can also be
caused by exposure to any allergen and can occur as a result of exposure to bee or wasp stings, latex
and foods such as nuts or shellfish in sensitive individuals.
The common symptoms of anaphylaxis are:
• oedema to the lips, tongue, pharynx and epiglottis with associated risk of airway obstruction
(Figures 7.1 and 7.2)
• dyspnoea, wheezing, chest tightness, hypoxia and tachypnoea

Figure 7.1 Anaphylaxis lips. Source: BBC News.

Figure 7.2 Anaphylaxis tongue. Source: James Heilman, MD/Wikimedia Commons.

Adverse drug reactions Chapter 7

• circulatory collapse (anaphylactic shock) accompanied by tachycardia (as a response to the drop
in blood pressure)
• confusion, dizziness, reduced level of consciousness
• erythema, urticaria, angio-oedema
• nausea, vomiting, abdominal pain.
If faced with a patient experiencing an anaphylactic or suspected anaphylactic reaction, it is
imperative for the paramedic to act quickly. If known, the stimulus should be removed or its
administration stopped. The patient should be treated with high-flow oxygen and airway and
ventilation should be supported where needed (noting that in the case of potential airway occlu- 115
sion, senior help from a hospital emergency department or critical care team will be needed).
Pharmacological treatment includes 500 mg intramuscular adrenaline, intravenous steroids such
as hydrocortisone (100 mg) and antihistamines, such as chlorphenamine (10 mg) as well as fluid
boluses to correct any hypotension. If the patient is experiencing lower airway symptoms such as
wheezing or tightness in the chest then bronchodilators may be required, with inhaled salbuta-
mol added to oxygen therapy. The ultimate possible consequence of anaphylaxis could be car-
diac arrest, for which treatment is as per standard advanced life support algorithms (Resuscitation
Council UK, 2020).

Clinical consideration
Benzylpenicillin is used in paramedic practice to treat suspected meningococcal septicaemia. It is com-
mon for patients to report they are allergic to penicillin when in fact they experienced common side-
effects only, such as a rash or diarrhoea. In situations where ‘allergy’ is reported by the patient, the
paramedic should establish what the symptoms were, and if they were in fact likely to be side-effects.
Unless the patient experienced a true anaphylaxis or a clearly severe allergic reaction, the risk/benefit
analysis is likely to be in favour of giving the benzylpenicillin to treat a life-threatening infection, rather
than waiting (JRCALC, 2020).

Rashes and skin eruptions

It is common to see a rash as a result of an ADR. This can be an urticarial rash driven by an allergic
process or a non-allergic process, such as the erythematous rash often experienced by those taking
ampicillin (Figure 7.3).
A fixed drug eruption is another form of cutaneous adverse reaction. This takes the form of well-
defined round or oval patches of redness and swelling in the skin, sometimes blistering. In time it will
fade to a darker colour and may slough off before healing. The most common sites are hands and
feet, lips, eyelids and genitalia. The lesion will predictably appear following administration of the
causative agent and fade over time, usually returning upon subsequent dosing (Burge et al., 2016).

Serum sickness
This is a specific type of hypersensitivity reaction to animal proteins in serum and, less commonly,
medication. It usually manifests 5–10 days following exposure to the proteins and causes a constel-
lation of symptoms, including rashes (Figure 7.4), itching, small joint arthralgia, fever, malaise, lym-
phadenopathy and proteinuria. It can be treated on a symptomatic basis if needed but will
spontaneously resolve within a week of stopping treatment with the causative agent (Nguyen and
Miller, 2017).

Renal disorders
Some classes of drugs are especially prone to causing renal failure, non-steroidal anti-inflammatories
(NSAIDs) and angiotensin-converting enzyme inhibitors (ACEi) being two classes that are often
implicated in acute renal failure. Acute renal injury can also be produced by antimicrobials such as
the penicillins and aminoglycosides (e.g. gentamicin).
Chapter 7 Adverse drug reactions

116

Figure 7.3 Urticarial drug rash.

Figure 7.4 Serum sickness rash. Source: Brad Sobolewski, MD, MEd.

Geriatric syndrome
Identification of adverse reactions in the elderly can be difficult as these often manifest as symptoms
which are already common in this age group. Dizziness, falls and confusion (the geriatric syndrome)
may be the only indication of an ADR and should prompt the clinician to consider this possibility as
well as looking for other possible causes (Lane et al., 2019).
When suspicious that a patient is experiencing an ADR, it is important for the clinician to either
investigate and manage the situation themselves or, if not able to do so, to escalate the concerns to
another clinician, such as the patient’s general practitioner or hospital doctor, so that further investi-
gation and management can be carried out. It is important to remember that while ADR may present
overtly, in the form of anaphylaxis for example, a rash, deterioration in renal function or fall in an
elderly patient may be the only indication of a problem. Without considering the potential for an
adverse reaction to a medication, it can be easy to miss.
Adverse drug reactions Chapter 7

Idiosyncratic reactions
Certain adverse reactions present as idiosyncratic, being unexplainable by the drug’s pharmacol-
ogy. Examples would be Achilles tendinopathy secondary to quinolone antibiotics, aplastic anae-
mia secondary to the antibiotic chloramphenicol or toxic epidermal necrolysis caused by
allopurinol.

Preventing adverse drug reactions

Considering the burden and prevalence of ADRs, the preferable course of action will always be to pre-
vent their occurrence rather than treat and mitigate after they have occurred. The risk of ADRs can be 117
reduced by the use of prescribing strategies which include a comprehensive health and medication
history, including use of non-prescription, herbal, alternative and recreational medications. Regular
medication reviews, taking into account therapeutic aims, comorbidities and polypharmacy, are impor-
tant, as is ensuring that the patient is able to take the medication correctly. Cognitive impairment, poor
dexterity, poor vision or poorly explained medication regimens can all play a role in incorrect self-
administration of medication which may lead to ADRs. Prescribing tools such as the STOPP START tool
(Gallagher et al., 2014), which is designed to reduce polypharmacy and optimise prescribed medication
use in the elderly, can reduce risk of ADRs.
Once an adverse reaction has occurred and been identified, the next action to take will be to man-
age it acutely and try to avoid any recurrence.
Questions that can be included in a drug history and when considering starting or changing medi-
cation can include the following.

• Have you had this (or similar) medication before and experienced an adverse reaction that you
are aware of?
• Did any reaction occur after the drug was started?
• Did anything else happen at the time that might have been contributory? Were you started on
another treatment or did your condition change? (Coleman and Pontefract, 2016)

Clinical consideration
When treating a male patient with GTN, the paramedic should ensure they have taken a full medicines
history. This is due to a potentially severe interaction between GTN and drugs used to treat erectile
dysfunction (Viagra® (sildenafil), Cialis® (tadalafil)). Most erectile dysfunction drugs work by increasing
vasodilation in the penis. While this effect is primarily seen locally, there may be more systemic vasodi-
lation and hence hypotension. Thus, if a patient who has recently taken their ED medication is given
GTN (which is also a vasodilatory drug), there is a risk of compounding the effects of both and resulting
in profound hypotension (JRCALC, 2020).

Managing adverse drug reactions

While every effort should be made to avoid ADRs, given their prevalence it is essential to be able to
manage them when they do occur. If the patient is presenting with an anaphylactic reaction then
they should be treated as per the protocol on page XX, but if the patient’s symptoms are less severe,
then less immediate action may be called for. However, once an ADR of any severity is suspected,
then it must be investigated and managed appropriately.
Because the signs and symptoms can range from subtle and idiosyncratic to overt, it is essential
that the paramedic and indeed all healthcare professionals are aware of the potential for adverse
reactions and confident to raise concerns about them where suspected (Montané and
Santesmases, 2020).
Presuming that the adverse reaction does not require emergency action or resuscitative measures
as these have been covered previously, there are still several measures that should be considered. If
possible, administration of the drug suspected of causing the reaction should be ceased.
Chapter 7 Adverse drug reactions

Clinical consideration
Morphine and other opiates are commonly used in paramedic practice to provide analgesia; a common
side-effect of opiate medication, especially by the intravenous route, is hypotension. The paramedic
may find that their patient experiences a drop in blood pressure following administration of morphine,
and then would need to counter this by stopping the administration of the drug, or in extremis revers-
ing the effect with an opiate antagonist.
Similarly, patients may experience stinging or burning when given intravenous hydrocortisone too
rapidly, which may be countered by pausing administration or slowing the rate of administration.
118

In some situations cessation of treatment may be all that is needed to mitigate the risk and end the
adverse reaction, and in all cases appropriate communication with the patient and other healthcare
professionals, including their GP, in order to log the adverse reaction, is essential.
Some adverse reactions may need longer-term care and treatment, for example, physiotherapy for
quinolone-induced Achilles tendinitis or inpatient care of an acute kidney injury due to NSAID use in
a vulnerable patient. In these cases, the paramedic will need to refer the patient on for care by their
own GP or an admission to hospital, depending on the circumstances. Advice can be obtained from
the patient’s GP or senior clinician if unsure.
A useful method for helping to identify ADRs produced by medications which the paramedic
administers is to educate the patient on the common adverse effects of any drug given, so they are
better placed to recognise a problem and seek help at an earlier stage.
Once any immediate intervention has been made and treatment stopped, the patient should be
reviewed with the following considerations.

• Review treatment options. This could include stopping further administration of the suspected
causative agent if significant harm has occurred or if the patient requests it.
• If the patient still needs treatment for the underlying condition then an alternative drug should
be considered.
• If the drug that caused the adverse reaction is the only one that is suitable then a review of the
dose is necessary, for example opiate toxicity in palliative care.
• Temporary cessation of treatment may be adequate, for instance if a patient experienced a kidney
injury by taking metformin during a dehydrating illness. This action may be taken retrospectively
to treat a kidney injury that has already occurred or prophylactically to reduce the risk of one. The
sick day rules provide a useful reference for pre-emptively suspending treatment during minor
dehydrating illness (NHS England, 2020).
• Pharmacological management of the adverse reaction may be needed. This could be immediate
treatment such as reversal of opioid effects with an opioid antagonist, or it may be the prescribing
of a new treatment, although best practice should be to try and avoid prescribing a medication
to treat the side-effects of another, given the well-established risks of polypharmacy.
• The adverse reaction should be recorded in the patient’s notes such that it is accessible to anyone
accessing their shared care record, and should be reported using the Yellow Card system or local
incident reporting system if this is not available.

Clinical consideration
Opioid drugs can be used in significant doses in palliative care which may lead to opioid toxicity; the
symptoms include confusion, stupor, constricted pupils, nausea, vomiting, constipation, loss of appe-
tite, and in more severe cases circulatory and respiratory depression. While opioid toxicity can be
reversed with an opioid antagonist, extreme care should be taken in a palliative care situation, as
acute reversal of opiate medication may result in significant pain and distress to the patient and their
relatives. The appropriate action is likely to be omission of future doses or dose reduction rather than
acute reversal.
Adverse drug reactions Chapter 7

Skills in practice: adrenaline dosing

in anaphylaxis
A fundamental part of paramedic practice is the ability to manage high-acuity patient presentations,
including anaphylaxis. Doses of drugs for emergency use should be memorised, and then checked
prior to administration. Table 7.3 presents the adrenaline dosing for anaphylaxis.

Table 7.3 Adrenaline dosing guidance.

Age Dose Repeat dose Dose interval Maximum dose 119
12 years and over 500 mg 500 mg 5 minutes No max. dose
6–11 years 300 mg 300 mg 5 minutes No max. dose
Birth to 5 years 150 mg 150 mg 5 minutes No max. dose
Source: JRCALC (2020).

The management of anaphylaxis is likely to involve multiple drug therapies via several administra-
tion routes. Adrenaline must only be given by the intramuscular (IM) route when treating anaphy-
laxis, as rapid administration of concentrated adrenaline intravenously can cause significant
side-effects such as chest pain and tachycardia. There is also a risk of local vasoconstriction and tissue
necrosis if the IV access is peripheral (McLean-Tooke et al. 2003).

Reporting adverse drug reactions

All healthcare professionals must act in the best interests of their patient, which places a duty of care
upon the paramedic to consider the possibility of ADRs as a possible cause of illness when clinically
relevant, and to report them without delay (HCPC, 2020).
The reporting of ADRs is an essential part of the process of pharmacovigilance, the scientific
method for monitoring, detecting, evaluating and preventing incidences of ADRs and any other
medicine-related problem (European Medicines Agency, 2020).
In the UK, ADRs are reported to, and monitored by, the Medicines and Healthcare products
Regulatory Agency (MHRA), using the Yellow Card system. Introduced in 1964, following the seri-
ous adverse effects identified in the children of pregnant mothers given thalidomide in the 1950s
(Coleman and Pontefract, 2016) to identify, monitor and prevent similar situations recurring, this
was initially a paper form found in the back of all copies of the British National Formulary to be
filled out by hand but is now accessible in digital formats and reports can be made physically, by
phone or online (MHRA, 2020a). Through the Yellow Card system, the MHRA collects data on all
suspected ADRs, including those involving alternative therapies, recreational drugs and medical
devices, in adults and children. In Australia, a similar system, known as the Adverse Drug Reactions
Advisory Committee (ADRAC) Blue Card system, has been in operation since 1964 (Australian
Government, 2021).
The National Institute for Health and Care Excellence (2017) states that a Yellow Card should be
submitted to report any suspected or proven adverse reaction in the following circumstances.

• All ADRs in adults and children which are serious, medically significant, or result in harm.
• Any ADR associated with a black triangle product, whether considered harmful or not.
N.B. A black triangle product is a new medicine or vaccine which is under additional monitoring.
These medicines are denoted in the BNF, Summaries of Product Characteristics, patient information
leaflets and technical literature with an inverted black triangle symbol (▼). Any new medicine,
including vaccines, is always monitored more closely, because the clinical trials conducted prior to
making a drug available involve a limited number of subjects. Once available to the public, a drug is
likely to be used by a much larger and more diverse patient population, so previously unidentified
Chapter 7 Adverse drug reactions

adverse effects may come to light. Sometimes adverse reactions associated with a drug may not
become apparent for some time after it has become widely available hence the need for more inten-
sive monitoring when new (MHRA, 2020b).
The MHRA is especially interested in any adverse reactions which:

• occur in children
• occur in anyone aged over 65
• involve biological medicines and vaccines
• involve defective or substandard medicines or devices
120 • involve fake or counterfeit medicines or devices.
• involve complementary remedies
• produce congenital defects.
Skills in practice: completing a Yellow Card
Reporting of ADRs, either suspected or confirmed, is via the Yellow Card system in the UK (Figure 7.5).
It should be carried out as soon as possible once there is suspicion of an adverse reaction. These reports
can be made in the following ways.

• Electronically via the MHRA Yellow Card website (https://yellowcard.mhra.gov.uk/).

• Using the yellowcard mobile app.
• By completing the Yellow Card form found in BNFs and posting it to the MHRA.
• By emailing [email protected].
• By calling the national Yellow Card information service (0808 100 3352). ]

A Yellow Card reporting form

produced by the MHRA.
This is a standard form used
by healthcare professionals
to report ADRs. There is also
It is important to note the
a version that is available for
use of the word ‘suspected’.
members of the public to use.
You do not need to be
certain of the nature of the
ADR or if the drug is
definitely to blame.

Figure 7.5 The Yellow Card. Crown copyright. Source: Reproduced under OGL 3.0/Public Domain.
Adverse drug reactions Chapter 7

In addition to reporting an adverse reaction, the clinician must make sure it is documented in the
patient’s notes and ideally the patient or their carer should be made aware as well.
Once the MHRA has been notified of an adverse reaction, it will assess the date and collate it with
any other information in order to produce a report on the medicine, and this will then be published
and disseminated widely in order that action to mitigate further potential harm can be taken
(Kaufman, 2016).
Actions that may be taken by the MHRA include:

• restricting the use of a medicine or device

• changing the legal status of the medicine or device (from over the counter to prescription only) 121
• amending the medicine’s or device’s warning information
• removing the marketing authorisation for the medicine or device and banning its use in the UK.
When reporting an adverse reaction via the Yellow Card system, the following information will be
needed (MHRA, 2020a).

• The name and address of the reporter. This can be the clinician who started the treatment
suspected of causing the reaction, the clinician who suspected the adverse reaction, or the
patient themselves.
• As much information as possible about the patient; this would include initials, sex, age, ethnicity,
pregnancy status and an NHS or hospital number.
• Information about the drug suspected of causing the adverse reaction, including, where possible,
name, brand, batch, route, dose, start and end dates and the indication it was given for.
• The nature of the suspected reaction, the outcome and severity of the reaction and any treatment
given for it.
• Details (if known) of any other drugs the patient was taking within the 3 months prior to the
reaction, including over-the-counter and complementary therapies.
• Any other relevant information, which may include medical and drug history, investigation and
test results. For example, if the adverse reaction occurred during pregnancy, specific information
relating to all other concurrent treatments and clinical information about the pregnancy should
be included.

It must be kept in mind that without adequate reporting, the process of pharmacovigilance and the
subsequent reduction in incidence and harm caused by adverse reactions will be less effective. While
spontaneous notification is the most common method of identifying adverse reactions, its efficacy is
significantly limited by under-reporting (Montané and Santesmases, 2020), with some authors sug-
gesting that only around 5% of adverse reactions are actually reported (Coleman and Pontefract, 2016).
This should further prompt the clinician to remain alert to the potential for ADRs and to report them
whenever they are suspected.

Episode of care
While working as a paramedic on an ambulance, you are called to Harriet, an 85-year-old resident in a
nursing home. She is frail, weighs only 53 kg, and has recently been suffering from a bout of gastroen-
teritis, leaving her dehydrated and feeling dizzy. The dizziness causes her to fall in her room when get-
ting up from her chair. She is found by one of the nurses, who calls an ambulance when Harriet
complains of new hip pain.
Upon your arrival, you observe that she is showing signs of pain in the right hip, and the right leg is
shorter and rotated externally. You suspect she has fractured the neck of her femur. Harriet is cannu-
lated and given 1 g of paracetamol injection to treat her pain, but this only reduces her pain from 8 to
6 and she is still too uncomfortable to be moved. Following a stepwise approach, you give the patient
5 mg of morphine intravenously which reduces her pain. However, within 5 minutes you note that she
has become drowsy, and her previously healthy blood pressure of 140/89 mmHg has dropped to 75/40
mmHg; her respiratory effort remains adequate.
Chapter 7 Adverse drug reactions

You consider the morphine the likely cause of the drop in blood pressure based on the known
actions of morphine and other opioids. You consider reversing the effects of the morphine using nalox-
one but you are aware this would result in return of the patient’s pain. Harriet’s blood pressure is stable
albeit low and she is still making a good respiratory effort. You decide that giving a fluid bolus to coun-
teract the low blood pressure is an appropriate action which will not affect pain control.
After a bolus of 250 mL 0.9% normal saline (sodium chloride solution), Harriet’s blood pressure
increases to 135/80 mm Hg and her level of consciousness improves. You discuss what you suspect
is an adverse effect of morphine with your clinical supervisor and decide that in future, with frail
older patients, a better course of action would be to start with a lower dose of morphine and titrate
122 up gradually. When a similar scenario arises, you are able to mitigate the risk of adverse effects by
giving the patient 2.5 mg morphine initially, increasing this gradually, rather than giving a single
larger initial dose.

Conclusion
Adverse drug reactions have been discussed in this chapter, including those patient groups more
prone to experiencing them, common signs and symptoms, management and reporting. The aware-
ness of ADRs and their consequences is important as the significant prevalence and cost associated
with them represent a large burden on the health service.
It is important to understand the types of ADRs and be able to report them but, more importantly,
a knowledge of ADRs is essential to underpin medications administration decisions and decisions to
treat patients, taking into account their risk factors for adverse reactions. This should assist the para-
medic in making informed decisions.

References
Australian Government, Department of Health Therapeutic Goods Administration. (2021). Blue card adverse reac-
tion reporting form. www.tga.gov.au/form/blue-card-adverse-reaction-reporting-form
Burge, S., Matin, R. and Wallis, D. (2016). Oxford Handbook of Medical Dermatology, 2nd edn. Oxford: Oxford
University Press.
Coleman, J.J. and Pontefract, S.K. (2016). Adverse drug reactions. Clinical Medicine 16(5): 48485.
College of Paramedics. (2018). Practice Guidance for Paramedics for the Administration of Medicines Under
Exemptions within the Human Medicines Regulations. www.collegeofparamedics.co.uk/COP/Professional_
development/Medicines_and_Independent_Prescribing/COP/ProfessionalDevelopment/Medicines_and_
Independent_Prescribing.aspx?hkey=04486919-f7b8-47bd-8d84-47bfc11d821a
European Medicines Agency. (2020). Pharmacovigilance: overview. www.ema.europa.eu/en/human-regulatory/
overview/pharmacovigilance-overview
Gallagher, P., Ryan, C., O’Connor, Mm, Byrne, S., O’Sullivan, D. and O’Mahoney, D. (2014). STOPP (Screening tool of
older persons prescriptions)/START (Screening tool to alert doctors to right treatment) criteria for potentially
inappropriate prescribing in older people version 2. Age and Ageing 44(2): 213–218.
Health and Care Professions Council (HCPC). (2020). Standards of conduct, performance and ethics. www.hcpc-uk.
org/standards/standards-of-conduct-performance-and-ethics/
Holmquist, G. (2009). Opioid metabolism and effects of cytochrome P450. Pain Medicine 10(s1): S20–S29.
Howard, R., Avery, A. and Slaensburg, S. (2007). Which drugs cause preventable admissions to hospital? A system-
atic review. British Journal of Clinical Pharmacology 63(2): 136–147.
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). (2020). Clinical Practice Guidelines. Bridgwater: Class
Professional Publishing.
Kaufman, G. (2016). Adverse drug reactions: classification, susceptibility and reporting. Nursing Standard 30(50):
53–56.
Lane, N., Stukel, T. and Boyd, C. (2019). Long-term care residents geriatric syndromes at admission and disable-
ment over time: an observational cohort study. Journal of Gerontology 74(6): 917–923.
Longmore, M., Wilkinson, I., Davidson, E., Foulkes, A. and Mafi, A. (2010). Oxford Handbook of Clinical Medicine, 8th
edn. Oxford: Oxford University Press.
McKay, G., Reid, J. and Walters, M. (2010). Clinical Pharmacology and Therapeutics, 8th edn. Oxford: Wiley Blackwell.
McLean-Tooke, A., Bethune, C., Fay, A. and Spickett, G. (2003). Adrenaline in the treatment of anaphylaxis: what is
the evidence? BMJ 327(7427): 1332–1335.
Adverse drug reactions Chapter 7

Medicines and Healthcare products Regulatory Agency (MHRA). (2015). Guidance on adverse drug reactions.
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/
file/949130/Guidance_on_adverse_drug_reactions.pdf
Medicines and Healthcare products Regulatory Agency. (2020a). About Yellow Card. https://yellowcard.mhra.gov.
uk/the-yellow-card-scheme/
Medicines and Healthcare products Regulatory Agency. (2020b). Black triangle scheme – new medicines and vac-
cines subject to EU-wide additional monitoring. www.gov.uk/guidance/the-yellow-card-scheme-guidance-
for-healthcare-professionals#black-triangle-scheme
Montané, E. and Santesmases, J. (2020). Adverse drug reactions. Medicina Clinica (English Edition) 154(5): 178–184.
National Institute for Health and Care Excellence (NICE). (2017). Adverse drug reactions. https://cks.nice.org.uk/
topics/adverse-drug-reactions/ 123
Nguyen, C. and Miller, D. (2017). Serum sickness-like drug reaction: two cases with a neutrophilic urticarial pat-
tern. Journal of Cutaneous Pathology 44(2): 177–182.
NHS England. (2020). Sick day rules: how to manage type 2 diabetes if you become unwell with coronavirus and what
to do with your medication. www.england.nhs.uk/london/wp-content/uploads/sites/8/2020/04/3.-Covid-19-
Type-2-Sick-Day-Rules-Crib-Sheet-06042020.pdf
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PSA-Medicine-Safety-Report.pdf
Pirmohamed, M., James, S., Meakin, S. et al. (2004). Adverse drug reactions as cause of admission to hostpial: pro-
spective analysis of 18820 patients. BMJ 329(7456): 9–15.
Resuscitation Council UK. (2020). Guidance: anaphylaxis. www.resus.org.uk/library/additional-guidance/
guidance-anaphylaxis
Royal Pharmaceutical Society. (2020). Polypharmacy: getting our medicines right. www.rpharms.com/recognition/
setting-professional-standards/polypharmacy-getting-our-medicines-right
Van der Weide, J., Steijins, L. and van Weelden, M. (2003). The effect of smoking and cytochrome P450 CYP1A2
genetic polymorphism on clozapine clearance and dose requirement. Pharmacogenetics 13(3): 169–172.

Further reading
Blaber, A., Collen, A. and Ingram, H. (2018). Independent Prescribing for Paramedics. Bridgwater: Class Publishing.
Ferner, R. and McGettigan, P. (2018). Adverse drug reactions. BMJ 363: k4051.
Ritter, J., Flower, R., Henderson, G., Loke, Y., MacEwan, D. and Rang, H. (2019). Rang and Dale’s Pharmacology, 9th
edn. St Louis: Elsevier.
United Kingdom Teratology Information Service. (2021). BUMPS: best use of medicines in pregnancy. www.
medicinesinpregnancy.org/

Multiple-choice questions
1. Which category of adverse drug reaction is most common?
(a) D
(b) A
(c) B
(d) E
2. How do you report a suspected adverse drug reaction?
(a) MHRA yellowcard scheme
(b) Local organisational event reporting system
(c) Both
3. What is the approximate percentage of hospital admissions related to adverse drug
reactions?
(a) 1%
(b) 6%
(c) 12%
(d) 20%
4. What is the estimated cost per year in the UK of adverse drug reactions?
(a) £168M
(b) £412M
(c) £750M
(d) £900M
Chapter 7 Adverse drug reactions

5. Pregnancy is a risk factor for increased chance of an adverse drug reaction.

(a) True
(b) False
6. Which of these drugs is most likely to cause a Type E, or end of treatment, reaction?
(a) Paracetamol
(b) Sertraline
(c) Ramipril
(d) Morphine
7. Anaphylaxis (a Type B reaction) is likely to occur shortly after drug administration.
124
(a) True
(b) False
8. Which of these drugs is least likely to cause an adverse drug reaction?
(a) Ibuprofen
(b) Warfarin
(c) Benzylpenicillin
(d) Oxygen
9. Who has responsibility for reporting adverse drug reactions?
(a) Paramedics
(b) Patients
(c) Doctors
(d) All of the above
10. Patients on multiple drugs are at greater risk of adverse drug reactions. What is the
term used to describe treatment with multiple drugs?
(a) Polypharmacy
(b) Polymyalgia
(c) Pharmacology
(d) Pharmacokinetics
11. Adverse drug reactions can be produced by alternative therapies, including herbal
remedies.
(a) True
(b) False
12. What percentage of adverse drug reactions can be predicted based on the
pharmacology of the drug?
(a) 80%
(b) 12%
(c) 55%
(d) 68%
13. What is the suggested dose of adrenaline to treat anaphylaxis in adults?
(a) 500 mg
(b) 1 mg
(c) 500 μg
(d) 1 g
14. How many people per 100 000 die as a result of adverse drug reactions per year?
(a) 0.9
(b) 2.0
(c) 2.5
(d) 3.9
15. Why is reducing adverse drug reactions important?
(a) To reduce heathcare costs
(b) To reduce preventable deaths
(c) To shorten inpatient stays
(d) All of the above
Chapter 8
Analgesics
Tom Mallinson

Aim
This chapter will provide an introduction and overview to medications commonly used to treat pain,
with a focus on those applicable to acute pain in a prehospital setting. Consideration will be given
to these medications’ pharmacological mechanisms of action and how they can be used synergisti-
cally as part of a multimodal approach to analgesia.

Learning outcomes
After reading this chapter the reader will:
1. Understand the mechanism of action of common classes of analgesic drugs
2. Be able to discuss the benefits and limitations of specific drugs or classes of drug
3. Have a greater awareness of the need for a multimodal approach to analgesia
4. Be able to consider appropriate drug choices for a range of conditions.

Pain and analgesia

Assessing pain can be challenging, and discomfort can be experienced due to any number of causes.
The provision of analgesia can also be a complex process, requiring a good working knowledge of
the pharmacological properties of the medicines being used to facilitate safe and effective polyp-
harmacy. To fully address a patient’s pain, we must first understand how and why they are experi-
encing it and ideally be able to quantify the extent of their discomfort.

Understanding and assessing pain

Pain is a feature of inflammation and injury, these features being calor (Heat), dolor (Pain), rubor
(Erythema/Redness), tumor (Swelling), et functio laesa (Loss of Function), with the functional limita-
tions described possibly also being due to pain.
A widely accepted definition of pain is: An unpleasant sensory and emotional experience which is
associated with actual (or potential) tissue damage, or that is described in terms of such damage. While
this definition is useful, it has some limitations. Most notably, it includes reference to how a sensation
is described, yet clearly even if one were unable to articulate a description of pain, that pain would
still be experienced. This is especially relevant when we consider the care of those who cannot effec-
tively communicate verbally and any pain assessment tool must take this into consideration.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 8 Analgesics

Why do we treat pain?

There are many reasons to treat pain, not least because it is unpleasant and from a humanitarian
point of view we should seek to reduce suffering whenever possible. Indeed, humanitarian consid-
erations are also a recognised indication for prehospital anaesthesia, where this is felt to be the only
option for providing appropriate and safe analgesia. Another core reason to provide appropriate
analgesia is to reduce the physiological response to pain which can be detrimental to healing and
worsens morbidity (Page, 2013; Tsui et al., 1997) and to mitigate the unwanted psychological seque-
lae of experiencing a painful event.

Psychology of pain
126 Experiencing pain is unpleasant. It has both psychological and emotional impact, as well as the
physiological response discussed later. Episodes of severe acute pain can precipitate and lead to
long-term sequelae such as post-traumatic stress disorder (PTSD), while the presence of PTSD wors-
ens the experience of any subsequent pain. We know that fear and anxiety will heighten psychologi-
cal arousal and increase the intensity of pain, and many of the non-pharmacological interventions
are targeted at reducing such concerns (see Table 8.1).
In relation to chronic pain, pharmacological interventions may be inadequate to offer adequate
relief, and as clinicians we may need to look to social or psychological interventions to allow a patient
to better manage their pain and facilitate a return to normality. One of the most promising psycho-
logical interventions is cognitive behavioural therapy, which is widely used for pain, depression, anxi-
ety and many other conditions. Such interventions require a truly multidisciplinary approach to be
successful, and it is important that as clinicians, we understand and respect the beneficial effects of
such non-pharmacological interventions (Parkinson, 2015; Russell et al., 2014).
For many patients, psychological distress can severely exacerbate pain, and can make an upsetting
experience truly terrifying. This is especially true of those at the extremes of age and other vulnerable
groups. In such cases, non-pharmacological interventions to address distress and pain are vitally
important. Such non-pharmacological interventions, both psychological and physical, are repre-
sented by the TWEED SASH mnemonic (Table 8.1).

Table 8.1 Non-pharmacological interventions to relieve distress and pain (TWEED SASH).
Psychological analgesia:
Therapeutic Touch (e.g. hand-holding)
Warn about any painful interventions
Explain what is happening or about to happen
Establish Eye contact
Defend patient Dignity

Physical interventions:
Stabilise fractures
Apply dressings to burns
Soft surface (early removal from rigid stretchers)
Hypothermia avoidance (hypothermia increases perceived pain intensity)
Analgesics Chapter 8

Table 8.2 Physiological manifestations of pain.

Body system Effect of pain
Cardiovascular • Tachycardia
• Hypertension
• Vasoconstriction
• Increased myocardial oxygen consumption
Respiratory • Tachypnoea
Neurological • Mydriasis (pupillary dilation)
• Increased sympathetic tone
Endocrine • Increased serum glucose 127
• Increased serum cortisol
Gastrointestinal • Reduced gastric emptying
• Reduced intestinal motility
• Nausea and vomiting
• Constipation
• Inappetence or anorexia
Urinary • Sodium retention
• Fluid retention
Musculoskeletal • Hyper-reflexia
General • Increased oxygen demand
• Piloerection
• Diaphoresis
• Immunosuppression

Physiology of pain
Experiencing pain is not only psychologically unpleasant but can be detrimental to health and heal-
ing (Swift, 2018). Pain can cause significant derangement of physiology separately from the illness
or injury causing the pain (Table 8.2). This is detrimental for a number of reasons: such deranged
physiology may mask or confuse underlying pathology, making diagnosis more challenging, and
many of these effects can also lead to further morbidity themselves. Increased myocardial oxygen
demand could cause angina, hypertension and tachycardia can contribute to increased blood loss
and atelectasis can lead to pneumonia. It is important to remember these detrimental effects of pain
when considering the provision of analgesia to our patients, and also when attempting to assess
pain in those who cannot clearly communicate with clinicians, such as children, those with signifi-
cant intellectual disability and anaesthetised patients.
Pain, however, also has an evolutionary benefit, in that it facilitates avoidant and protective behav-
iours to either stop ongoing injury or tissue damage or promote healing through resting or protect-
ing an injured part of the body. The increase in sympathetic tone seen as a result of pain is also part
of the fight or flight mechanism, intended to aid survival.

Pain transmission
In normal physiology, the sensation of pain is perceived when specific nerve impulses reach the
brain. The main sensors of painful stimuli are the endings of myelinated A delta and unmyeli-
nated C primary sensory neurons, which detect damaging or potentially damaging (noxious)
stimuli. Other sensory receptors and nerve fibres are responsible for touch and proprioception
(Table 8.3).
Such stimuli are transmitted through the peripheral (primary) sensory fibres to the spinal
cord. Here, they terminate in the dorsal horns and form synapses with secondary neurons which
transmit the nerve impulses to the cerebral cortex (this is known as an ascending pathway),
where the stimuli are consciously perceived as pain and can trigger avoidant behaviour. Once
these nerve impulses reach the brain, they cause activation of multiple regions of the brain
including the somatosensory cortices, thalamus, anterior cingulate cortex, motor regions,
Chapter 8 Analgesics

Table 8.3 Features of sensory nerve fibres.

Conduction speed
Nerve fibre type Myelin sheath (metres per second) Sensory modality
A alpha Yes 120 Proprioception (muscle length and stretch)
A beta Yes 75 Stretch, skin touch and pain
A delta Yes 30 Acute pain, pressure and cold
C No 2 Pain and warmth

128

Somatosensory
Motor and cortex
premotor A
A cortices
Anterior
cingulate B
cortex C
Thalamus

Cerebellum F

G
D
X

Figure 8.1 The pain matrix.

premotor cortex and cerebellum, collectively known as the ‘pain matrix’ (Figure 8.1). In response
to a stimulus from these ascending pathways, descending modulating pathways will become
active.

Pain modulation
A number of theories have been put forward to better understand the modulation of pain. One of
the most famous, the gate control theory, suggests that concurrent tactile stimulation of the A beta
fibres (for example, by rubbing the skin) near the location of a painful stimulus results in presynaptic
inhibition within the spinal cord, thus blocking transmission of pain signals through the slower A
delta and C fibres. Another means of pain modulation is the descending modulatory pathways
(Figure 8.2). These pathways originate in the midbrain and medulla in areas with high concentra-
tions of opioid receptors and carry impulses from the brain down to the dorsal horn, where they
inhibit ascending transmission or pain signals. This interaction within the dorsal horn is regulated by
the neurotransmitters serotonin and noradrenaline. In addition to their actions in the midbrain and
medulla, endogenous endorphins and enkephalins interact with opioid receptors in the spinal cord
to inhibit and modulate pain transmission (Bannister, 2019).
Analgesics Chapter 8

3
The perception of the pain
signals in the somatosensory
cortex can be influenced by
psychological, physical and
social factors.

4
Descending efferent pathways
2
Primary sensory neurons carry
send signals to the dorsal horn, 129
activating neurotransmitters to
impulses via afferent A-delta and
release noradrenaline, serotonin
C fibres, which terminate in the
and endorphins which inhibit
dorsal horn of the spinal cord.
ascending pain signals.
Secondary neurons carry the
signal from the spinal cord to
the brain.

1
Stimulation of nociceptors by
chemicals (histamine and
prostaglandins) released when
tissue injury or irritation occurs
(i.e. heat, cold, chemicals).

Figure 8.2 The pain pathway.

Clinical consideration
A number of abnormal pain syndromes exist where benign, mild or normally imperceptible stimulation
results in increased pain perception. Such conditions can give rise to allodynia (pain from light touch),
hyperalgesia (extreme pain from mild noxious stimuli), hyperesthesia (increased sensitivity to mild stim-
uli) or a host of other abnormal responses.
The condition of phantom limb pain can even cause apparent pain in an arm or leg that has been
amputated. These conditions are challenging to manage and require a combination of pharmacologi-
cal and psychological interventions.

Types of pain
A wide variety of terminology is used when discussing pain and the provision of analgesia. Having
an understanding of the types of pain people may experience informs a clinician’s choice of analge-
sia and to some extent may predict which agents may be most effective. Pain sensations can be
classified as either nociceptive or neuropathic (or mixed), with these two types responding to differ-
ent analgesic approaches (Figure 8.3)
The perception of nociceptive pain (from the Latin nocere meaning harm) results from damage, or
threatened damage, to body tissue. Such insult is signalled by intact and functioning pain nerve
fibres which transmit this information to the brain, as opposed to neuropathic pain, discussed below.
Chapter 8 Analgesics

Pain

• Temperature
• Vibration Nociceptive Neuropathic
• Stretch
• Chemical exposure
• Trauma to nerve fibres
• Neurological dysfunction
Visceral Somatic
130

Figure 8.3 Categorisation of pain.

Lung and
diaphragm
Liver and Liver and
Heart
gall bladder gall bladder
Small Stomach
intestine Pancreas
Appendix Ovary
(female)
Colon
Kidney
Ureter
Urinary
bladder

Figure 8.4 Common sites of referred pain.

The sensory fibres involved in this pathway are called nociceptors, and are able to sense and trans-
duce a range of noxious stimuli, including extremes of temperature, vibration, stretch and chemical
exposure. This includes exposure to inflammatory mediators which both excite and sensitise
nociceptors.
Nociceptive pain can be further divided into somatic or visceral pain, depending on where the
pain originates. Somatic pain arises from the soma (skin, skeletal muscle and bone) and is often well
localised. Visceral pain results from injury or insult to the viscera (internal organs such as the liver,
bowel, heart, etc). This is less well localised and may be referred to other adjacent structures
(Figure 8.4). Examples include experiencing pain in the shoulder tip as a result of diaphragmatic irri-
tation (for example, due to liver pathology), probbly due to a shared innervation of the diaphragm
and shoulder tip (C4 nerve root), or pain in the left arm and jaw as a result of myocardial ischaemia or
infarction. The causes behind all cases of referred pain are not fully understood, but some are thought
to arise from a convergence of nerve fibres from different organs along the pain pathway.
Neuropathic pain, on the other hand, occurs as a result of damage or irritation to the pain fibres
themselves. It occurs acutely in traumatic injuries such as amputations or non-freezing cold injuries
and can be the cause of significant ongoing morbidity. In many cases, neuropathic pain is harder to
diagnose and treat than nociceptive pain.
Analgesics Chapter 8

Clinical considerations
An understanding of nociception and relevant anatomy facilitates accurate testing of specific nerves.
When undertaking cranial nerve testing, for example, cranial nerve I, the olfactory nerve (sense of smell),
must be tested with an innocuous/benign scent (e.g. lemon peel/coffee) as any noxious stimuli such as the
isopropyl alcohol from a preinjection swab or the ammonia in smelling salts would result in stimulation of
intranasal trigeminal pain nerve fibres, thus bypassing a potentially damaged olfactory nerve.

131

Some injuries create intense pain which appears out of keeping with clinical findings or visible tissue dam-
age. Three important examples are high-voltage electrical burns, high-pressure injection injuries from
hydraulic lines and compartment syndrome, all of which require emergency assessment and treatment.

Assessment of pain
It is valuable to be able to quantify the severity of pain, as this allows not only appropriate selection
of drug and dosages, but also reassessment of pain levels after interventions have been made
(JRCALC, 2019). Commonly used scales include the verbal numerical pain scale/visual analogue scale,
the Wong–Baker Scale and the FLACC score, each of which has its benefits and limitations. The verbal
numerical pain scale and visual analogue scale are both validated for use in acute pain, can be used
to report a quantifiable measure of pain, and are simple to administer with minimal training (Jennings
et al., 2009; JRCALC, 2019). The two methods should not be used interchangeably as, despite their
commonalities, they are not validated to be used in this way. The Wong–Baker face scale is also vali-
dated in acute care, but does require a patient to be able to see the faces on the score chart (Baker
and Wong, 1987). It may be a highly useful score to use in children, and it overcomes language differ-
ences and perhaps some cultural differences, although the faces may be misconstrued as represent-
ing other emotions such as fear, sadness or anxiety. The Wong–Baker scale should be used in black
and white, as the inclusion of colour invalidates the tool and may make it less accurate.
The Face, Legs, Activity, Cry and Consolability (FLACC) score has been utilised in paediatric patients
(>2 months old) and also in critically ill adults (JRCALC, 2019; Merkel et al., 1997; Voepel-Lewis et al.,
2010). It utilises a combined scoring system with five components. Scores range from 0 to 10, with
10 indicating the most intense pain (Table 8.4).

Table 8.4 FLACC Score.

Criterion Score 0 Score 1 Score 2
Face No particular expression Occasional grimace or frown, Frequent to constant
or smile withdrawn, uninterested quivering chin, clenched jaw
Legs Normal position or Uneasy, restless, tense Kicking, or legs drawn up
relaxed
Activity Lying quietly, normal Squirming, shifting, back and forth, Arched, rigid or jerking
position, moves easily tense
Cry No cry (awake or asleep) Moans or whimpers; occasional Crying steadily, screams or
complaint sobs, frequent complaints
Consolability Content, relaxed Reassured by occasional touching, Difficult to console or
hugging or being talked to, comfort
distractible
Source: Adapted from Merkel et al. (1997) and Voepel-Lewis et al. (2010).
Chapter 8 Analgesics

In cases of complex or chronic pain, it is important to remember that pain is a biopsychosocial

phenomenon, and a broad history must be obtained to fully understand the patient’s experience.
The simple mnemonics of SOCRATES or OPQRSTA can sometimes be a useful starting point for
understanding a patient’s experience of pain (Gregory and Mursell, 2015; JRCALC, 2019). In the
OPQRSTA mnemonic, you ask about the Onset of the pain, in relation to when it was first noticed,
what they were doing at the time and also the nature of its onset and progression. Next, you ask
about any Provoking and relieving factors in relation to the pain; for example, a headache which is
exacerbated by a change in posture may be due to raised intracranial pressure. The Quality of the
pain is also useful to explore; chest pain described as burning or stinging may indicate a neuropathic
cause such as shingles or cord compression, while a dull, heavy or crushing chest pain may point
towards ischaemia. Radiation is also important to elicit; for example, lower back pain with pain radiat-
132 ing down both legs (bilateral sciatica) would be considered a red flag, while back pain without such
radiation may be benign. An assessment of Severity is useful in both providing an insight into the
patient’s experience and assessing the efficacy of any treatments given. The tools discussed previ-
ously may assist with such quantification. Timing reminds you to clarify the time of pain onset,
whether it has occurred at other times, and when the pain subsided, if it is no longer present. Asking
about Associated symptoms is also valuable in putting the pain into a wider context, and forming
your differential diagnosis. A headache with associated unilateral temporal artery tenderness would
prompt you to consider temporal arteritis, while associated amaurosis fugax would make you con-
sider a significant ischaemic insult and associated photophobia with neck stiffness would indicate
meningism. In addition, gaining a full social history will provide an insight into complex personal
circumstances, and allow you to put the pain symptom into a wider patient context.

Approach to analgesia
Using a combination of pharmacological and non-pharmacological methods can be an effective
approach to the provision of effective analgesia (Thies et al., 2018). Multimodal analgesia, the use of
multiple pharmacological agents acting via different mechanisms to control pain, is advocated in
current clinical guidelines (JRCALC, 2019). In many cases it is most beneficial to give analgesics from
various drug families/classes as they will have a synergistic effect and the patient is less likely to
experience as great a side-effect burden compared to using a sole agent at higher doses. In
Figure 8.5. At a more advanced level, these may be augmented or replaced with different agents or
modalities, such as fentanyl, ketamine or regional anaesthesia techniques. The core UK paramedic

Paracetamol

Multimodal
Morphine Ibuprofen
analgesia

Penthrox
or
Entonox

Figure 8.5 Example of multimodal analgesia provision.

Analgesics Chapter 8

analgesic pharmacopoeia will be discussed below (paracetamol, NSAIDs, inhalational analgesia,

opioids). These agents can be combined in paramedic practice to provide multimodal analgesia
during the prehospital phase. This will be followed by some additional agents which are used by
advanced practitioners or doctors.

Find out more

The anatomy, physiology and pharmacology of pain is a huge area, and one which is acutely relevant
to paramedic practice. While there are many avenues for further learning, the Faculty of Pain Medicine
of the Royal College of Anaesthetists has provided the ePAIN learning platform which is an extremely
valuable resource: 133
https://fpm.ac.uk/faculty-of-pain-medicine/e-pain
The Royal College of Anaesthetists has also produced a separate suite of e-learning resources covering
topics related to analgesia and anaesthesia more broadly, which is a useful source of further reading:
https://rcoa.ac.uk/e-learning-anaesthesia
Both of these are available through the e-Learning for Health website:
https://portal.e-lfh.org.uk/

Paracetamol
Paracetamol (acetaminophen) is an analgesic with a poorly understand and complex mechanism of
action. It inhibits prostaglandin synthesis and modulates serotonergic and cannabinoid pathways,
acting both centrally and peripherally (Przybyla et al., 2021). Paracetamol can be administered orally,
intravenously or rectally. It is a powerful analgesic and should be administered early in a patient’s
clinical journey for them to gain maximum benefit. It is used internationally in civilian and military
prehospital care (Committee on Tactical Combat Casualty Care, 2020). It has a key benefit over the
NSAIDs in that it does not cause gastric irritation (Table 8.5).

Paracetamol overdose
The majority of ingested paracetamol (around 90–95%) is conjugated in the liver to a non-toxic metabolite,
in a process called glucuronidation, and excreted in the urine. The remaining paracetamol is oxidised
by the cytochrome P450 enzyme, producing a hepatotoxic metabolite called N-acetyl-p-benzoquinone
imine (or NAPQI for short), which when taken at therapeutic doses is deactivated through conjugation
with glutathione. In overdose, however, the liver’s supply of glutathione is exhausted and NAPQI accu-
mulates and can lead to fulminant hepatic failure and death. The antidote to paracetamol overdose,
N-acetylcysteine (NAC), replenishes the body’s supply of glutathione, allowing metabolism of NAPQI.

Non-steroidal anti-inflammatory drugs

The term non-steroidal anti-inflammatory (NSAID) can be used to describe a wide range of medica-
tions (see Table 8.5). They are widely used in healthcare for both chronic and acute pain, but in
general ibuprofen is the only one frequently administered by paramedics. These drugs act by inhibi-
tion of the cyclo-oxygenase enzymes, resulting in decreased production of inflammatory mediators,
specifically the proinflammatory prostaglandins. Their analgesic effect is secondary to inhibition of
the inflammatory response. They also have an antiplatelet effect through reducing the synthesis of
thromboxane (Figure 8.6).
The NSAIDs may produce an unwanted direct toxic effect on the kidneys, leading to acute kidney
injury (AKI) through a combination of acute tubular necrosis and acute interstitial nephritis, and are
the cause of around 1 in 8 cases of acute drug-induced renal failure. This risk is exacerbated in the
dehydrated or elderly. They can also lead to unwanted gastric irritation due to reduced protection of
Chapter 8 Analgesics

Table 8.5 Comparison of common non-opioid analgesics.

Maximum Time to
24-hour dose peak plasma Half-life Gastric
Drug (in adults >70 kg) concentration (h)a (h) irritation
Paracetamol 4g 0.5–1 2–4 -
NSAIDs Aspirin 4g 1–2 Variable +++
Ibuprofen 1.2 g 0.5–1.5 2–3 ++
Naproxen 1g 1–2 12–17 ++++
Diclofenac 150 mg 1–2 1–2 ++++
134
Ketorolac 60–90 mg 1 5–6 ++
Meloxicam 15 mg 2 15–20 +
Celecoxib 400 mg 2–3 10–12 +
a
When given orally.

Arachidonic
Acid

Cyclo-oxygenase 1 Cyclo-oxygenase 2 5-Lipoxygenase

(COX-1) (COX-2) (5-LOX)

Homeostasis Inflammatory Inflammatory

Prostaglandins Prostaglandins Leukotrienes
Prostacycline
Thromboxane A2

Figure 8.6 Role of the COX and LOX enzymes.

gastro-protective prostaglandins. Such irritation can be mild or may lead to fatal haemorrhage from
perforated gastric ulceration. Therefore, concurrent administration of proton pump inhibitors such
as omeprazole is often used when a course of NSAIDs is prescribed.

Salicylates
The salicylates include derivatives of acetylsalicylic acid, which gain their name from the white wil-
low tree (Salix alba), from the bark of which the active ingredient salicin was identified. Aspirin is the
most common example. It acts through irreversible inhibition of the COX-1 enzyme, and thus
reduced thromboxane A2 production with subsequent reduced platelet aggregation, and through
modifying the activity of the COX-2 enzyme (see Figure 8.6). Aspirin is metabolised to salicylic acid,
itself an active anti-inflammatory. Aspirin is, in general, contraindicated in children due to the occur-
rence of Reye syndrome, a notable exception being in cases of Kawasaki disease. In overdose, aspirin
causes a metabolic acidosis, tinnitus, deafness, dizziness and in severe cases cerebral oedema,
hyperpyrexia, seizures and death.

Find out more

Aspirin is also linked to a phenomenon called Samter’s triad. This is the association between nasal
polyps, asthma and respiratory symptoms triggered by aspirin or NSAIDs.
You can read more at: www.samterssociety.org/
Analgesics Chapter 8

Propionic acid derivatives

The proprionic acid derivatives include ibuprofen, naproxen and ketoprofen. Ibuprofen is widely
used by the topical and oral routes, and is available to many paramedics as part of their approach to
multimodal analgesia. These medications are extremely useful for musculoskeletal pain, but have an
associated risk of gastric irritation and if administered long term may worsen renal function. Naproxen
is often preferred due to its twice-daily dosing but it confers a greater risk of gastric irritation.

Acetic acid derivatives

This class of NSAID includes diclofenac and ketorolac. Diclofenac is a commonly used analgesic agent
available over the counter. It is often used as a topical gel or in tablet form. Diclofenac is also believed
to inhibit both the COX and LOX enzymes, giving a dual anti-inflammatory effect (see Figure 8.6). 135
Ketorolac is an injectable NSAID used worldwide both in and out of hospital for numerous causes
of pain. It can be delivered by the intravenous or intramuscular routes, making it a useful adjunct in
acute pain for patients who are ‘nil by mouth’.

Enolic acid derivatives

This group of NSAIDs, also known as the oxicams, contains the drugs piroxicam and meloxicam, and a
number of others. Meloxicam is a favoured analgesic in military or remote settings due to its effective-
ness, reduced platelet inhibition, low gastrointestinal risk and once-daily administration due to its long
half-life (Committee on Tactical Combat Casualty Care, 2020; Wedmore and Butler, 2017). Many enolic
acid derivatives are non-selective COX-1 and COX-2 inhibitors, but meloxicam is selective for COX-2.

Selective COX-2 inhibitors

These drugs, also known as the coxibs, selectively inhibit the COX-2 enzyme (see Figure 8.6). They have
the benefit over many other NSAIDs that they only require once- or twice-daily dosing, due to their
long duration of action. The risk of gastrointestinal bleeding and platelet dysfunction with COX-2 inhib-
itors is also less than many other NSAIDs. However, concerns have been raised about their cardiovas-
cular safety profile, as their use seems to correlate with an increased risk of ischaemic cardiac events
(Antman et al., 2007). Newer drugs are being developed which are dual COX-2 and 5-LOX inhibitors,
which it is hoped will provide additional benefit by reducing leukotriene synthesis. 5-LOX inhibitors are
found in small amounts in a number of plants, including St John’s wort, used to treat depression.

Find out more

It is challenging to clearly delineate which of the non-opioids is better or stronger or more effective,
and there is certainly significant individual variation between patients. The closest resource we have to
answer this is probably the Oxford league table of analgesics. This is based on the drug’s number
needed to treat (NNT) in order to achieve a 50% reduction in pain when compared to a placebo. The
lower the NNT number, the greater the efficacy of the analgesic in question.
While various similar tables are available in the literature, the table provided by the Bandolier team
on its Oxford Pain Site is a useful place to start:
www.bandolier.org.uk/booth/painpag/Acutrev/Analgesics/Leagtab.html

Episode of care
Forty-year-old Emily calls an ambulance for severe back pain and pain down the back of one thigh. She
relates a history of lower back pain for around 2 weeks, after lifting a lot of boxes when she moved house.
She has none of the red flags for serious pathologies, but is in enough pain to severely limit her abil-
ity to move. The attending crew feel she could safely be discharged on scene, but want to provide
Chapter 8 Analgesics

appropriate analgesia. They administer 1 g of oral paracetamol and 400 mg of oral ibuprofen and dis-
cuss non-pharmacological interventions like gentle stretching and mobilisation. They also provide
safety netting advice, especially discussing the red flags for back pain.
Before they leave, the crew contact Emily’s GP to enquire about other analgesic options. The duty
doctor phones Emily back later that day and undertakes a telephone consultation. They then prescribe
amitriptyline and opt to continue the ibuprofen but add in regular omeprazole for gastric protection.
They provide further safety netting advice and will phone the patient back in a week’s time.

136 Inhalational analgesia

Nitrous oxide
There are two main inhalation anaesthetics which are known to have analgesic properties along
with their anaesthetic actions, and these are in frequent prehospital use at subanaesthetic doses, for
analgesia. The first is nitrous oxide, which is administered in a mixture with 50% oxygen (JRCALC,
2019). The use of such a nitrous oxide:oxygen mixture has a number of drawbacks.
First, the two gases will separate at low temperatures (anything below around 5–10 °C), resulting
in the administration of a high concentration of oxygen or an increasingly hypoxic concentration of
nitrous oxide. Therefore, cold cylinders should be rewarmed and then inverted a number of times
before use. Second, nitrous oxide diffuses into any gas-filled cavity within the body, potentially dis-
tending that space. Therefore, it should be avoided in conditions where this may cause significant
harm, such as bowel obstruction, pneumocephaly, bullous emphysema or for patients who have
recently been diving. Entonox use also raises intracranial pressure by increasing cerebral blood flow
and should be avoided in head injuries.
Prolonged or repeated use of nitrous oxide can lead to the symptoms of vitamin B12 deficiency,
due to its ability to oxidise and inactivate cobalamin (B12). These symptoms include sensory neu-
ropathy, myopathy and encephalopathy, and it would be prudent to avoid its use in patients with
known B12 deficiency or peripheral neuropathies. It is also unsuitable in a number of concurrent
conditions and it is vital to be familiar with its specific contraindications (Box 8.1).

Methoxyflurane
The second most widely used inhalational agent is methoxyflurane (Penthrox®) which is a fluori-
nated hydrocarbon anaesthetic agent. When used for acute pain, however, it is being used at anal-
gesic, rather than anaesthetic doses.
Methoxyflurane’s analgesic effects occur through action in both the brain and spinal cord. It has this
effect through interaction with various receptors including GABA receptors, potassium channels, gluta-
mate and glycine receptors. It also interacts directly with components of second messenger systems.

Box 8.1 Contraindications to nitrous

oxide:oxygen (50:50 mix) administration
• Decompression sickness a

• Head injuries
• Impaired consciousness
• Pneumothorax a

• Pneumocephalus a

• Pneumoperitoneum a

• Violent psychiatric patients

• Intraocular gas injection in preceding 8 weeks a

• Suspected bowel obstruction a

a
Related to its diffusion into and distension of gas-filled spaces.
Analgesics Chapter 8

These functions lead to reduced transmission across synapses and conduction within neurons. Unlike
some other analgesics, it produces little in the way of euphoria and does not appear to have an effect
on the circulating levels of dopamine, serotonin or endogenous opioids. In prehospital care, it is inhaled
as a vapour using the Green Whistle device, and produces an analgesic effect within 6–10 breaths, with
one dose (3 mL) providing around 30 minutes of analgesia. It has been used successfully to provide
analgesia for painful procedures and as a prehospital analgesic (Forrest et al., 2019).
Methoxyflurane does, however, have a number of contraindications and limitations related to its
chemical nature and metabolism. The most significant of these is its contraindication in patients with
a history of malignant hyperthermia from any cause, including other anaesthetic vapours, as it can
trigger this condition (Box 8.2).
137
Box 8.2 Contraindications to
methoxyflurane administration
• Malignant hyperthermia (in patient or family)
• Allergy/adverse reaction to anaesthetic vapours
• Impaired consciousness
• Significant head injuries
• Cardiovascular instability
• Renal impairment
• Ventilatory compromise

Skills in practice: Penthrox preparation

and administration
1. Insert the activated charcoal chamber into the dilutor hole on the top of the green whistle.
2. Open the bottle of methoxyflurane, either by hand or using the base of the green whistle to
loosen it.
3. Hold the green whistle at a 45° angle and pour the contents of the bottle into the base of the
whistle.
4. Allow the patient to hold the device, and coach them to inhale through the mouthpiece.
5. Advise the patient to take a few small breaths initially to get used to the taste and smell.
6. Encourage the patient to inhale through the green whistle, which allows the activated charcoal
chamber to absorb exhaled methoxyflurane.
7. Intermittent periods of inhalation through the device may be enough to provide analgesia, but
continuous use of the device is also possible.
8. If a higher concentration of inhaled methoxyflurane is required, the hole on top of the activated
charcoal chamber can be occluded, which reduces the entrainment of extra diluting air.
9. Once treatment is completed, dispose of the green whistle and methoxyflurane bottle in
accordance with local policy.
10. If required, a second green whistle can be used for the same patient.

Opioids
Agonists
The opiates and opioids are drugs with active contents related to the chemicals found in the opium
poppy (Papaver somniferum). Opiates are those medications which are directly related to the natural
compounds found in such poppies, while opioids are synthetic compounds which have similar
action to the natural opiates.
Chapter 8 Analgesics

Opioid medications exert their action through binding with opioid receptors, which are predomi-
nantly located in the central nervous system but are also present in peripheral sites, such as the
intestines. In this regard, the opioids we administer are activating intrinsic modulatory pathways
which utilise endorphins and enkephalins. Unfortunately, one of these central locations is the chem-
oreceptor trigger zone on the surface of the medulla oblongata, which contains mu opioid receptors,
resulting in nausea and vomiting with opioids.
The different subtypes of opioid receptors lead to different clinical effects when bound by an ago-
nist (Table 8.6). Opioid agonists also share a common group of side-effects (Figure 8.7), with each
individual drug having a slightly different side-effect profile. Some opioids, notably codeine and
morphine, have a direct effect upon mast cells, leading to their degranulation and histamine release.
Such an effect may mimic an allergic reaction, causing erythema, pruritus and flushing.
138
Table 8.6 Terminology for opioid receptors.
Preferred terminology Alternative terminology Clinical effect of agonist binding
δ, OP1 • Respiratory depression
delta, DOP • Cough suppression
• Reduced gastric motility
• Spinal analgesia
κ, OP2 • Spinal analgesia
kappa, KOP • Dysphoria
• Hallucinations
μ, OP3 • Spinal and supraspinal analgesia
mu, MOP • Respiratory depression
• Reduced gastrointestinal motility
• Bradycardia
• Euphoria
• Nausea and vomiting
NOPa, OP4 • Anxiety
nociceptin receptor • Possible role in opioid tolerance and dependence
a
NOP receptors bind nociceptin (an antianalgesic) but not naloxone; it has little affinity to opioid drugs.

Constipation Arrhythmias Confusion

Vomiting Hypotension Drowsiness

Dry Mouth Histamine Release Respiratory Depression

Figure 8.7 Common opioid side-effects

Analgesics Chapter 8

Morphine
Morphine is often considered the standard and archetypal opiate and other drugs in this class are often
compared to it, in terms of their individual strengths or limitations. Clinically, morphine is a versatile
drug and can be administered by various routes. Most commonly, in prehospital practice it is adminis-
tered intravenously or intramuscularly, but the intranasal and intraosseous routes are also used.
Nebulised morphine is also being researched as an option for acute pain, although findings are mixed
at this time (Grissa et al., 2015; Mofidi et al., 2020). The metabolites of morphine are shown in Figure 8.8.

Codeine
Codeine is a weak agonist at the mu opioid receptor (MOP), but the majority of its analgesic effects
are produced by its active metabolite – morphine (Figure 8.9). There is significant genetic variation 139
in terms of gene expression of the hepatic enzymes responsible for the metabolism, meaning the
rate of metabolism and therefore clinical effect of codeine vary significantly between patients. Due
to this genetic difference, those of Asian or African descent may experience significantly less analge-
sic effect from codeine than someone whose genetic heritage is northern European. Some people
even appear to gain no analgesic benefit from codeine at all, and this variability of effect is a signifi-
cant drawback of codeine.

Diamorphine (heroin)
Diamorphine is a highly lipid-soluble opioid, which facilitates a rapid onset of action and also rapid
movement across the blood–brain barrier. Its analgesic actions, which result from its active metabo-
lites (Figure 8.10), are accompanied by a significant level of euphoria, making it a widely used drug
of abuse (Scarth and Smith, 2016).
Diamorphine is increasingly being utilised in prehospital care in the UK by both the intravascular
and intranasal routes of administration. It is available as a white powder in ampoules for reconstitu-
tion with water and a fairly large dose can be reconstituted into a small volume, making it ideal for
intranasal or subcutaneous administration. It is commonly used in children by the intranasal route.

Morphine-6-
glucuronide

Morphine-3-
Morphine
glucuronide

Normorphine

Figure 8.8 Morphine metabolism.

Codeine-6-
glucuronide

Codeine Norcodeine

Morphine

Figure 8.9 Codeine metabolism.

Chapter 8 Analgesics

Morphine

Diamorphine 3-monoacetylmorphine

6-monoacetylmorphine Morphine

140
Figure 8.10 Diamorphine metabolism.

Fentanyl
Fentanyl is a versatile synthetic opioid, suitable for use in trauma, with a more rapid onset of action
and greater analgesic potency than morphine. It also produces less cardiovascular depression than
morphine and lacks the unwanted histamine release seen with codeine and morphine, potentially
making it a better choice for use in the prehospital setting. It can be administered by multiple routes,
including intravenously, intranasally and orally as a lozenge. It has been widely adopted in civilian
and military prehospital practice as a first-line analgesic for acute severe pain (Committee on Tactical
Combat Casualty Care, 2020; Ellerton et al., 2013; Thies et al., 2018; Wedmore and Butler, 2017). Its
metabolites are shown in Figure 8.11.
Other fentanyl-related compounds include alfentanil, sufentanil and remifentanil, which are both
more potent and more lipophilic. They all respond to naloxone.
A comparison of the pharmacokinetic properties of the common opioids is shown in Table 8.7.

Norfentanyl

Fentanyl Hydroxyfentanyl Hydroxynorfentanyl

Despropionylfentanyl

Figure 8.11 Fentanyl metabolism.

Table 8.7 Pharmacokinetics of common opioids.

Pharmacologically Duration of
active metabolites Excretion action (h) Half-life
Morphine Yes 90% excreted in urine. 3–6 1.5–4.5 h
10% excreted as conjugated morphine in
faeces
Codeine Yes 17% unchanged in urine. 4–6 2.8 h
Other metabolites mostly excreted in urine
Diamorphine Yes 60% excreted in urine as metabolites. 4–5 3 minutesa
0.1% excreted unchanged in urine
Fentanyl No 5–20% excreted unchanged in urine. 0.5–1 2.3–14 h
9% in faeces
a
Rapidly converted to morphine.
Analgesics Chapter 8

Episode of care
Tenzing was riding his motorbike on an autumnal afternoon when he lost control on a sharp corner and
was thrown from the bike. He received injuries to the left side of his thorax and his left femur, with pain
in his neck and back. Prior to this incident he was a fit and well 28-year-old man.
He is initially attended to by a paramedic and an ambulance technician on a double-crewed ambu-
lance. They apply a traction splint to his broken leg, gain intravenous access and administer 10^mg of
morphine and an antiemetic. Tenzing is still in severe pain and they request further assistance. Entonox
is avoided due to the suspicion of a pneumothorax. While waiting, they prepare their immobilisation
equipment and attempt to keep him warm.
An advanced paramedic arrives to assist the crew, and administers a left-sided femoral nerve block
to provide complete analgesia for the fractured femur. They also administer an analgesic dose of keta- 141
mine and a gram of paracetamol intravenously. Being mindful that they want to accurately titrate
Tenzing’s analgesia but avoid unwanted side-effects, they opt for further aliquots of ketamine while en
route to the hospital rather than further morphine.
On arrival at hospital, Tenzing is found to have multiple fractured ribs and the anaesthetic team pro-
vide him with a thoracic epidural after his femoral fixation surgery in order to facilitate deep breathing
and reduce the risk of subsequent pneumonia. Ongoing multimodal analgesia is provided with mor-
phine, paracetamol and the epidural.

Find out more

Fentanyl has been used for many years by mountain rescue teams in the UK and such patients often
receive onward transfer from the ambulance service. To facilitate excellence in multiagency working
and high-quality patient care, it may be useful to review the analgesic agents used by other prehospital
care providers working in your area.
An overview of the usage of analgesic agents by mountain rescue team members is presented in
Ellerton’s 2013 paper.
Ellerton, J.A., Greene, M. and Paal, P. (2013). The use of analgesia in mountain rescue casualties with
moderate or severe pain. Emergency Medicine Journal 30(6): 501–505.

Skills in practice: intranasal diamorphine

administration
1. Consult a dosage table for the concentration required for patient by age or weight.
2. Add the specific volume of 0.9% saline to a 10 mg ampoule of diamorphine powder.
3. A volume of 0.2 mL of this solution is drawn up into a syringe (or more if accounting for device-
specific dead space).
4. Attach the nasal atomiser/aerosol device to the syringe via a Luer-Lock connector.
5. Tilt the patient’s head backwards and place the tip of the atomisation device just inside the nostril.
6. Aim slightly outwards towards the ipsilateral ear.
7. Compress the syringe plunger rapidly, delivering half of the medication into the nostril.
8. Move the device to the other nostril and repeat steps 5–7 to deliver the remaining medication.

Antagonists
There are two key antagonists of the opioid receptors: naloxone and naltrexone. Naloxone is com-
monly available in prehospital medicine to facilitate reversal of opioid overdose (e.g. heroin over-
dose or iatrogenic overdose) where this has caused unwanted decreased consciousness and
Chapter 8 Analgesics

Reflection
If you were assessing a patient with significant chronic pain, who was experiencing respiratory
depression as a result of an accidental morphine overdose (or drug accumulation from long-term
therapy or concurrent renal failure), how would you adjust your naloxone dosing?
What is the risk of administering a large bolus dose of naloxone to such a patient?

cardiorespiratory depression. Administration of naloxone is not risk free, however, as it can elicit
hyperalgesia, rapid opioid withdrawal, pulmonary oedema and significant dysrhythmias. Naltrexone
142 is used in alcohol and opioid dependence, but not in the acute setting. It has a very similar chemical
structure to naloxone. Naloxone should be available whenever opioids are being administered for
acute pain.
The duration of action of naloxone depends on both administration route and dose but it is often
a lot shorter than the effects of the opioid it is counteracting. This is one of the reasons why an intra-
muscular loading dose is sometimes advocated, and why significant opioid overdoses should be
observed for a number of hours (JRCALC, 2019).

Atypical analgesics
Ketamine
Ketamine is a dissociative anaesthetic (1–2 mg/kg) and, in smaller doses (0.2–0.75 mg/kg), an anal-
gesic agent. These effects are due to its actions as a glutamate N-methyl-D-aspartate (NMDA) recep-
tor antagonist with additional capabilities to reduce the presynaptic release of glutamate. Some of
its analgesic effects may be due to interaction with opioid receptors, adding to its analgesic proper-
ties, although its effects cannot be reversed with naloxone. Ketamine additionally has antagonistic
effects on various other neurotransmitters, probably explaining its anticholinergic symptoms. It is
also a bronchodilator and indirectly increases sympathetic tone, resulting in increased heart rate,
blood pressure and cardiac output. It also has a direct negative inotropic effect on the myocardium,
which is usually masked by the indirect positive effects, but the negative inotropic effect may
become clinically apparent in patients who are critically ill and catecholamine depleted.

As a result of ketamine’s positive inotropic and chronotropic effects, it is not a suitable agent for patients
with ischaemic cardiac chest pain. In such patients, increasing their myocardial oxygen demand may
worsen ischaemia and pain.

Ketamine is fast acting with an onset of action of around 30 seconds when given intravenously. It
is a safe and effective prehospital analgesic, particularly suited to situations where maintenance of
airway reflexes, respiratory rate and cardiovascular stability is vital, such as during technical rescue or
when providing Care Under Fire (Committee on Tactical Combat Casualty Care, 2020; Metcalfe, 2018;
Russell et al., 2014; Wedmore and Butler, 2017). It is especially important to carefully dose ketamine,
as while it is an effective analgesic at lower doses, with higher doses it acts as a general anaesthetic,
inducing loss of consciousness, and in overdose can easily prove fatal. This is particularly important
when more than one concentration of ketamine is available to the clinician, where a 10-fold overdose
could easily occur. At the lower analgesic doses, unwanted dissociation and agitation may occur,
requiring concurrent administration of a sedative agent.

Find out more

Providing analgesia in remote and hostile environments is challenging. The Wilderness Medicine
Society has provided a clinical practice guideline discussing this issue entitled ‘Wilderness Medical
Society practice guidelines for the treatment of acute pain in remote environments: 2014 update’
available from: https://wms.org/research/guidelines
Analgesics Chapter 8

Antidepressants and antiepileptics

A number of drugs originally developed as either psychiatric medications or antiepileptics are now
used to treat neuropathic pain. Drugs from the family of selective serotonin reuptake inhibitors
(SSRIs), traditionally used for anxiety and depression, are often used to treat neuropathic pain in the
primary care setting, but have limited to no value during the acute phase.
Amitriptyline is often considered the first-line treatment option for neuropathic pain. It is a tricyclic
antidepressant (TCA) medication, now used widely in primary and secondary care to treat pain.
Other TCAs such as nortriptyline and desipramine are also increasingly being used in pain medicine
and may provide a more favourable side-effect profile. While not yet common practice internation-
ally, there have been positive experiences in using amitriptyline for acute pain associated with cold
injuries, traumatic injuries and postoperatively (Joslin et al., 2014; Wong et al., 2014), and its use could 143
become more common in civilian urban and rural practice.
Anticonvulsants such as pregabalin and gabapentin are also used to treat pain (Reed and Schurr,
2020). They have been used successfully to treat neuropathic pain of various aetiologies. Unfortunately,
they have also both become drugs of abuse due to their perceived euphoric effects. There is some
evidence to support the use of pregabalin acutely for painful burns, but other than this their use is
usually limited to chronic and postoperative pain.

Nefopam
Nefopam is an analgesic agent often used in primary care for a wide variety of pathologies. It acts
centrally as a serotonin, norepinephrine and dopamine reuptake inhibitor. It also exerts an action on
sodium and calcium channels to inhibit glutamatergic transmission. Nefopam also has an anticho-
linergic effect and many of its side-effects are related to this mode of action. It can be administered
by the oral route, or by intravenous or intramuscular injection. It is unsuitable for use in patients with
a history of seizures, for those taking other serotonergic medications or for ischaemic cardiac pain.

Adjuncts to analgesia
Magnesium sulfate
Magnesium sulfate (MgSO4) has been discussed for some time as an adjunct to other analgesic
agents. This is probably due to its membrane-stabilising activity, but magnesium is also a cofactor in
ATP production and appears to antagonise calcium release, inhibit catecholamine release, antago-
nise NMDA receptors, and have an anti-inflammatory effect, reducing interleukin-6 and TNF-alpha
plasma levels, all of which may contribute to its analgesic properties. It has been shown to be effec-
tive in reducing pain in a postoperative setting (de Oliveira et al., 2013; Mussrat et al., 2019) and for
patients with acute pain (Hutchins and Rockett, 2019). However, a dosing regimen for its use specifi-
cally for analgesia is still unclear and its use in the treatment of pain in the prehospital setting is not
standard clinical practice.

Local anaesthetics
Lidocaine, which has been used for many years as an antidysrhythmic due to its sodium channel-
blocking actions, has also been used as an adjunct to analgesia. Significant work has been under-
taken to explore intravenous infusion of lidocaine as an analgesic, most commonly to enhance
intra- and postoperative analgesia, but also for chronic pain. It is also increasingly being used in the
management of acute pain (Hutchins and Rockett, 2019; Meaney et al., 2020); however, this is not
without risks and is not currently standard practice. Lidocaine is also used as a transdermal patch
(Figure 8.12), by local infiltration and also when used to deliver regional anaesthesia. Local anaes-
thetic toxicity is treated with lipid emulsion infusion, and this should be available to clinicians
undertaking regional anaesthesia with local anaesthetic agents.

While lidocaine can be carefully administered intravenously, other local anaesthetics, such as bupivacaine,
when given intravenously may cause catastrophic cardiovascular collapse, neurotoxicity and death.
Chapter 8 Analgesics

144

Figure 8.12 Lidocaine patch being applied.

Local anaesthetic agents can be effectively utilised in the prehospital setting when undertaking
regional anaesthesia techniques, such as fascia iliaca compartment block or ring blocks, which can
provide excellent analgesia and reduce the need for opioid administration and the attendant side-
effects (Simpson et al., 2012; Williams and Laws, 2019). For some techniques, longer acting local
anaesthetics such as levobupivacaine may be used to provide a longer duration of analgesia/anaes-
thesia for the patient.

Conclusion
The assessment of pain can be challenging, and a biopsychosocial approach may be required to
truly understand a patient’s lived experience. There are multiple effective analgesics available to the
paramedic and there is often benefit in utilising multiple agents acting synergistically (multimodal
analgesia), to achieve relief from pain and also to minimize dose-related side-effects from any one
class of drug. With paramedics increasingly working in diverse and advanced roles, a broad knowl-
edge of analgesics is essential to allow clinicians to select the best treatments and minimise pain
and distress for their patients.

Reflection choice of analgesia

Condition Your notes
Ischaemic cardiac chest pain (angina)
Inflammatory cardiac chest pain (pericarditis)
Polytrauma with cardiovascular instability
A brief painful procedure
Field amputation of a lower limb
Analgesics Chapter 8

Reflection: consider how the physical and pharmacological properties of these commonly used
prehospital analgesics compare with those of an ideal (imaginary) analgesic drug
Analgesic Pharmacological and physical properties
Ideal (imaginary) analgesic Pharmacological

Physical
Morphine sulfate Pharmacological
145

Physical
Paracetamol Pharmacological

Physical
Nitrous oxide/oxygen (Entonox) Pharmacological

Physical

Glossary
ATP Adenosine triphosphate
DOP Delta opioid receptor
ECG Electrocardiogram
Glutamate An excitatory neurotransmitter
Interleukin-6 A proinflammatory cytokine and anti-inflammatory myokine
JRCALC Joint Royal Colleges Ambulance Liaison Committee
KOP Kappa opioid receptor
TNF-alpha Tumour necrosis factor alpha, an endogenous pyrogen which regulates immune
cells
MOP Mu opioid receptor
Narcan® Trade name for naloxone
NOP Nociceptin opioid receptor
NSAID Non-steroidal anti-inflammatory
Opiate A substance derived from opium poppy
Opioid Any substance (natural or synthetic) which binds to opioid receptors
Penthrox Trade name for methoxyflurane administered via the Penthrox inhaler
TCA Tricyclic antidepressant
Chapter 8 Analgesics

References
Antman, E.M., Bennett, J.S., Daugherty, A., Furberg, C., Roberts, H. and Taubert, K.A. (2007). Use of nonsteroidal
antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association.
Circulation 115(12): 1634–1642.
Baker, C. and Wong, D. (1987). Q.U.E.S.T.: a process of pain assessment in children. Orthopaedic Nursing 6(1):
11–21.
Bannister, K. (2019). Descending pain modulation: influence and impact. Current Opinion in Physiology 11(1):
62–66.
Committee on Tactical Combat Casualty Care. (2020). Tactical Combat Casualty Care (TCCC) Guidelines for Medical
Personnel. Washington, DC: US Department of Defense: Defense Health Agency (DHA): Joint Trauma System.
146 de Oliveira, G.S., Castro-Alves, L.J., Khan, J.H. and McCarthy, R.J. (2013). Perioperative systemic magnesium to mini-
mize postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology 119(1): 178–190.
Ellerton, J.A., Greene, M. and Paal, P. (2013). The use of analgesia in mountain rescue casualties with moderate or
severe pain. Emergency Medicine Journal 30(6): 501–505.
Forrest, M., Porter, K. and van der Velde, J. (2019). Methoxyflurane (Penthrox®) – a case series of use in the prehos-
pital setting. Journal of Paramedic Practice 11(2): 54–60.
Gregory, P. and Mursell, I. (2015). Manual of Clinical Paramedic Procedures. Hoboken: John Wiley & Sons.
Grissa, M.H., Boubaker, H., Zorgati, A. et al. (2015). Efficacy and safety of nebulized morphine given at 2 different
doses compared to IV titrated morphine in trauma pain. American Journal of Emergency Medicine 33(11):
1557–1561.
Hutchins, D. and Rockett, M. (2019). The use of atypical analgesics by intravenous infusion for acute pain: evidence
base for lidocaine, ketamine and magnesium. Anaesthesia and Intensive Care Medicine 20(8): 415–418.
Jennings, P.A., Cameron, P. and Bernard, S. (2009). Measuring acute pain in the prehospital setting. Emergency
Medicine Journal 26(8): 552–555.
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). (2019). Clinical Practice Guidelines 2019. Bridgwater:
Class Professional Publishing.
Joslin, J., Worthing, R., Ladbrook, M. and Mularella, J. (2014). Amitriptyline use for acute pain in remote environ-
ments. Wilderness and Environmental Medicine 25(4): 488–489.
Meaney, E.D., Reid, L. and Srivastava, D. (2020). A survey on the use of intravenous lidocaine infusion for acute pain
in Scottish hospitals. British Journal of Pain 14(2): 98–103.
Merkel, S.I., Voepel-Lewis, T., Shayevitz, J.R. and Malviya, S. (1997). The FLACC: a behavioral scale for scoring post-
operative pain in young children. Pediatric Nursing 23(3): 293–297.
Metcalfe, M. (2018). Ketamine administration by HART paramedics: a clinical audit review. Journal of Paramedic
Practice 10(10): 430–437.
Mofidi, M., Dashti, A., Rezai, M., Ghodrati, N., Ameli, H. and Amiri, H. (2020). Comparing the efficacy of nebulized
morphine with intravenous morphine in traumatic musculoskeletal pain management. Journal of Research in
Clinical Medicine 8: 21.
Mussrat, R., Zahoor, A., Khan, M.A. and Ahmad, S. (2019). Comparison of perioperative magnesium sulphate infu-
sion with placebo for postoperative analgesia. Professional Medical Journal 26(11): 1937–1941.
Page, G.G. (2013). The immune-suppressive effects of pain. Madame Curie Bioscience Database. Austin: Landes
Bioscience.
Parkinson, M. (2015). Pain: understanding the biopsychosocial model and the paramedic’s role within the multi-
disciplinary team. Journal of Paramedic Practice 7(5): 250–255.
Przybyła, G.W., Szychowski, K.A. and Gmiński, J. (2021). Paracetamol – an old drug with new mechanisms of action.
Clinical and Experimental Pharmacology and Physiology 48(1): 3–19.
Reed, R.N. and Schurr, M.J. (2020). Acute pain in the trauma patient. Current Trauma Reports 6: 1–7.
Russell, K., Scaife, C., Weber, D. et al. (2014) Wilderness Medical Society Practice Guidelines for the Treatment of
Acute Pain in Remote Environments: 2014 Update. Wilderness and Environmental Medicine 25(4): S96–S104.
Scarth, E. and Smith, S. (2016). Drugs in Anaesthesia and Intensive Care, 5th edn. Oxford: Oxford University Press.
Simpson, P.M., McCabe, B., Bendall, J.C., Cone, D.C. and Middleton, P.M. (2012). Paramedic-performed digital nerve
block to facilitate field reduction of a dislocated finger. Prehospital Emergency Care 16(3): 415–417.
Swift, A. (2018). Understanding pain and the human body’s response to it. Nursing Times 114(3): 22–26.
Thies, K-C., Mountain, A. and Goode. P. (eds). (2018). European Trauma Course: The Team Approach, 4th edn. Market
Drayton: European Trauma Course Organisation.
Tsui, S.L., Law, S., Fok, M. et al. (1997). Postoperative analgesia reduces mortality and morbidity after esophagec-
tomy. American Journal of Surgery 173(6): 472–478.
Voepel-Lewis, T., Zanotti, J., Dammeyer, J.A. and Merkel, S. (2010). Reliability and validity of the face, legs, activity,
cry, consolability behavioral tool in assessing acute pain in critically ill patients. American Journal of Critical
Care 19(1): 55–61.
Analgesics Chapter 8

Wedmore, I.S. and Butler, F.K. (2017). Battlefield analgesia in tactical combat casualty care. Wilderness and
Environmental Medicine 28(2): S109–S116.
Williams, J. and Laws, S. (2019). Fascia iliaca compartment block versus IV morphine for femoral fracture pain.
Journal of Paramedic Practice 11(4): 156–164.
Wong, K., Phelan, R., Kalso, E. et al. (2014). Antidepressant drugs for prevention of acute and chronic postsurgical
pain: early evidence and recommended future directions. Anesthesiology 121(3): 591–608.

Further reading
AnaesthesiaUK. www.frca.co.uk/default.aspx
Online learning resource covering anatomy, physiology and pharmacology, as well as overviews of some of the
medical equipment used in clinical anaesthesia. 147
British Pain Society Publications. www.britishpainsociety.org/british-pain-society-publications/
A comprehensive suite of resource for both professionals and patients.
Dickman, A. (2012). Drugs in Palliative Care, 2nd edn. Oxford: Oxford University Press.
A useful pocket reference for the pharmacopoeia of palliative medicine.
Watson, M.,Ward, S., Vallath, N., Wells, J. and Campbell, R. (2019). Oxford Handbook of Palliative Care. Oxford: Oxford
University Press.
A comprehensive reference for the field of palliative care, and a valuable resource for both pharmacological and
non-pharmacological symptom management.

Multiple-choice questions
1. Ketamine is often used in military and austere environments. Why is this?
(a) Lower risk of hypotension compared to opioids
(b) It is easy to spell
(c) It has no restrictions in terms of import and export laws internationally
(d) You cannot be allergic to ketamine
2. Ketorolac belongs to which class of medication?
(a) Inhalational analgesic
(b) NMDA Antagonist
(c) Opioid
(d) NSAID
3. At which of the following receptors does morphine not have an effect?
(a) δ
(b) ψ
(c) μ
(d) κ
4. In terms of opioid mechanism of action, what does MOP stand for?
(a) Morphine-receptors occurring peripherally
(b) Morphine-related opiate
(c) Morphine phosphate
(d) Mu opiate receptor
5. Paracetamol in overdose causes which organ to fail?
(a) Heart
(b) Spleen
(c) Skin
(d) Liver
6. In comparison to morphine, fentanyl is:
(a) Slower acting
(b) 100 times less potent
(c) Approximately 20 times less likely to cause side effects
(d) More lipophilic
Chapter 8 Analgesics

7. Methoxyflurane is what type of chemical?

(a) A noble gas
(b) A fluorinated hydrocarbon
(c) An inert nitrous oxide donor
(d) A sympathomimetic
8. Which other medication is often prescribed alongside a course of ibuprofen?
(a) A Class I anti-dysrhythmic
(b) Amlodipine
(c) A beta-2 adrenoreceptor
(d) A proton pump inhibitor
148 9. Which of these statements is true regarding magnesium sulfate (MgSO4)?
(a) Should be administered as a rapid IV bolus
(b) Reduces pain in the postoperative period
(c) Is the British Army’s first-line analgesic
(d) Is usually administered intranasally
10. Aspirin is linked to what undesirable outcome in paediatric patients?
(a) Patau syndrome
(b) Reye syndrome
(c) Kawasaki disease
(d) Lennox-Gestaut syndrome
11. A common side-effect of morphine is:
(a) Leukonychia
(b) Respiratory depression
(c) Asterixis
(d) Inverted T-waves on ECG
12. Which of the following is incorrect in relation to diamorphine?
(a) It can be administered intranasally
(b) Morphine is a metabolite
(c) It is highly lipophilic
(d) It cannot be given to paediatric patients
13. Which of these statements is true about naloxone?
(a) Naloxone is a beta opioid antagonist
(b) Naloxone administration causes no side-effects
(c) The effects of fentanyl can be reversed by naloxone
(d) The effects of ketamine will be increased by naloxone
14. An overdose of aspirin may cause each of these, apart from:
(a) Blindness
(b) Tinnitus
(c) Metabolic acidosis
(d) Hyperpyrexia
15. COX inhibitors exert their analgesic effect by:
(a) Upregulating the noradrenaline and serotonin receptors
(b) Reducing GABA receptor activity
(c) Stimulating interleukin-3 release
(d) Reducing prostaglandin synthesis
Chapter 9
Antibacterials
Dean Whiting, Deborah Flynn and Dawn Ball

Aim
The aim of this chapter is to encourage the reader to develop an understanding and appreciation of
the differences in antibacterial use.

Learning outcomes
1. To understand how pathogens cause infections and the use of terminology associated with this
category of medication.
2. To understand the different antibacterial classes and be able to explain their actions and associated
side-effects.
3. To be able to explain the prehospital considerations for the use of each antibacterial class.
4. To understand the paramedic’s health-promoting role in antibacterial therapy and antimicrobial
stewardship.

Test your knowledge

1. What is the difference between bacteriostatic and bactericidal treatments?
2. Describe the professional responsibilities of registered healthcare professionals in relation to
antimicrobial stewardship.
3. What are the pharmacokinetics of aminoglycosides?
4. What considerations should be taken into account when administering benzylpenicillin?
5. What does the term ‘teratogenic’ mean?

Introduction
This chapter explores antibacterials. These are the miracle drugs of the last two centuries, as their use
reduced mortality rates in previously life-threatening conditions such as bacterial pneumonia, sepsis
and tuberculosis. This trend has started to reverse due to the development of resistance to currently
available antibacterials combined with a lack of research into the development of new antimicrobial
treatments (World Health Organization, 2020), which include antibiotics, antivirals and antifungals. A

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 9 Antibacterials

research briefing on trends in infectious disease produced by the United Kingdom Parliamentary
Office of Science and Technology (2017) suggests that infectious disease creates a significant burden
to the UK’s health and economic systems, causing 7% of all deaths and being responsible for a large
proportion of sick days.
Micro-organisms are ubiquitous in the world but can only be seen under microscopic examina-
tion. They include bacteria, viruses, fungi and protozoa. Micro-organisms live on and inside us, often
being more beneficial than harmful. The normal body flora, for example, consists of colonies of
mostly bacterial micro-organisms acquired through contact with the outside world. These micro-
organisms can be further classified as aerobic bacteria, which require the presence of oxygen for
survival, and anaerobic bacteria, which do not require oxygen for survival.
The presence of normal flora prevents colonisation by disease-causing micro-organisms, known as
pathogens. The capacity to cause disease depends on the micro-organism, its characteristics and
150 location. It is known that many strains of bacteria such as E.coli live harmlessly in the alimentary tract,
but can cause infection if they spread to other body compartments, such as the urinary tract. Some
strains of E. coli can also cause severe diarrhoea when they enter the intestines of a healthy human.
Normally harmless micro-organisms can also cause disease when the host is particularly vulnerable,
for example during suppression of the immune system.

Language and terminology

The terms antimicrobial, antibacterial and antibiotic are often used interchangeably, but each term
has its own specific meaning. An antimicrobial is active against bacteria and/or other micro-
organisms including viruses, fungi and protozoa. An antibacterial is active against bacteria. An anti-
biotic is a drug that is produced by one type of micro-organism to protect itself from another
micro-organism, and is therefore from natural sources. The more general terms antimicrobial and
antibacterial can refer to drugs that are both natural and synthetic in origin.
Selective toxicity is the ability of an antimicrobial to harm microbes without injuring human cells.
Antimicrobials do this by a range of different mechanisms, many of which exploit differences of
structure or function between microbial and human cells. However, when these differences are small,
antimicrobial actions can cross over to human cell function and cause cell damage.
The goal of antibacterial therapy is to either eliminate a bacterial infection or reduce the number
of bacteria to a level which the immune system can effectively deal with. Antibacterial drugs can
either be bactericidal, meaning they directly kill bacteria (e.g. penicillins and aminoglycosides), or
bacteriostatic, meaning they inhibit bacterial growth and rely on the immune system to kill the bac-
teria (e.g. tetracyclines). Some drugs are partly bactericidal and partly bacteriostatic, depending on
the dosage and plasma concentration of the drug, the number of bacteria, the time from the start of
treatment and the health of the person. Antibacterials with a relatively narrow therapeutic index,
such as aminoglycosides, require monitoring of the serum concentration to ensure it lies within ther-
apeutic range, to prevent underdosing or drug toxicity.
Based on the spectrum of their activity, antibacterials are categorised as broad spectrum or narrow
spectrum. Table 9.1 details the main differences.

Antibacterial mechanisms of action

There are four main antibacterial mechanisms of action.

Table 9.1 Broad- and narrow-spectrum antibiotics.

Broad-spectrum antibiotics Narrow-spectrum antibiotics
Effective against gram-positive and Effective against gram-positive bacteria only
gram-negative bacteria Used when causative organisms are known
Kills a variety of organisms Examples: macrolides, older penicillins (although others can be broad
Used when cause of infection is spectrum, e.g. amoxicillin, ampicillin), vancomycin
unknown.
Examples: erythromycin, ciprofloxacin,
doxycycline
Antibacterials Chapter 9

Disruption of bacterial cell wall synthesis: beta-lactams

Most bacterial cells have an outer, relatively rigid wall made up of a substance unique to bacteria,
called peptidoglycan. The cell wall supports the inner cell membrane and prevents it from rupturing
due to the high intracellular osmotic pressure. Penicillins, cephalosporins and carbapenems, known
collectively as beta-lactams because they all contain a beta-lactam ring in their chemical structures,
disrupt bacterial cell wall synthesis by binding with penicillin-binding proteins, the enzymes respon-
sible for bacterial cell wall synthesis, and preventing the formation and maintenance of the cell wall.
The weakened cell wall causes the bacteria to swell and burst due to the osmotic pressure.

Interference in folate metabolism: sulfonamides, trimethoprim

Bacteria, unlike human cells, must produce their own folic acid, which is necessary for synthesis of
DNA and RNA for growth and reproduction. The sulfonamides contain a chemical group which is 151
similar to para-aminobenzoic acid (PABA), a vital step in the production of folic acid. Sulfonamides
compete with PABA in this metabolic step, interrupting folic acid synthesis. Trimethoprim inhibits a
later step in folic acid production. Sulfonamides and trimethoprim are often used in combination, as
their actions may be synergistic.

Inhibition of bacterial DNA synthesis: quinolones

Bacterial cells have a single chromosome which consists of a supercoiled DNA molecule within the
bacterial cytoplasm. The quinolones inhibit the action of an enzyme, DNA gyrase, that is essential for
the replication of bacterial DNA and the survival of the bacterial cell.

Inhibition of bacterial protein synthesis: tetracyclines,

aminoglycosides, macrolides, chloramphenicol, lincosamides
Ribosomes are required for bacterial protein synthesis, as in human cells, but the ribosomal subunits
in bacteria are slightly different from those in human cells. Drugs such as aminoglycosides bind irre-
versibly to the bacterial ribosomal subunit 30S, disrupting the initiation of the synthetic process, the
reading of the genetic code or the completion of protein synthesis

Choosing the right treatment

‘The right drug for the right bug’ (Burchum and Rosenthal, 2019, p.1042).
Antimicrobials should only be prescribed and administered when infection has been recognised
or there is a high degree of suspicion of infection and when there is likely to be clear benefit to the
patient. The Joint Formulary Committee (NICE 2021) suggests that the key factor in choosing the
right treatment is establishing the causative micro-organism. Antimicrobial protocols are developed
through surveillance of common causative micro-organisms and trends in antimicrobial resistance.
In the prehospital environment, identification of the causative micro-organism is unlikely and there-
fore prompt empirical prescribing of the appropriate antibiotic to patients with signs and symptoms
suggestive of serious infection, such as sepsis or meningitis, is recommended. There may also be a
role for prehospital antimicrobial use in complex wound and open fracture management but further
research is required to inform and change future practice (Lack et al., 2019; Smit and Boyle, 2014).
Prior to prescribing or administering antibiotics, the paramedic must take note of the patient’s
allergies, medical and drug history, liver and kidney function, susceptibility to disease, route toler-
ance (for example, ability to swallow), severity of illness, age and whether pregnant, breast feeding
or taking oral contraceptives. Race may need to be considered, as genetics can influence the metabo-
lism of some antibacterials (Tsai et al., 2015).

Antimicrobial resistance
The World Health Organization (2020) defines antimicrobial resistance (AMR) as ‘the ability of micro-
organisms (like bacteria, viruses and some parasites) to stop an antimicrobial (such as antibiotics, anti-
virals and antimalarials) from working against it. As a result, standard treatments become ineffective,
infections persist and may spread to others’. Globally, addressing the problem of AMR is now considered
Chapter 9 Antibacterials

a public health priority, as resistance to antimicrobials is making infections harder and more costly to
treat. For example, the occurrence of bacteria resistant to penicillins, tetracyclines, cephalosporins, car-
bapenems, macrolides and quinolones is rising (World Health Organization, 2020).

Preventing antimicrobial resistance

The main method of preventing antimicrobial resistance is to preserve and prolong the effectiveness
of current antibacterials and prevent the occurrence and transmission of infections. The World Health
Organization (2020) sets out action points for individuals, healthcare professionals, health policy
makers and the healthcare industry.
The individual’s responsibility centres around managing expectations regarding the prescribing of
antibiotics and concordance with medication regimens, in addition to preventing the transmission
of infection.
152 The focus of the paramedic in preventing antimicrobial resistance is patient education. Patients
may need some explanation about the actions of antibacterials to clarify that these drugs cannot be
prescribed simply to provide symptom relief. The paramedic should explain to those who are pre-
scribed antibacterials the importance of completing the entire course, even if they feel better, as
incomplete treatment of a bacterial infection encourages resistance. Patients should similarly be
warned against keeping antibacterials for future use or sharing them with friends with similar symp-
toms. The importance of taking the medication as prescribed should also be reinforced, to maintain
an adequate plasma level of drug and prevent the development of resistant micro-organisms. The
paramedic also plays a vital role in promoting behaviour which prevents the spread of infection and
development of antibacterial resistance through measures such as hand washing, covering nose and
mouth when sneezing, vaccination, practising safe sex, maintaining awareness of current public
health campaigns, reducing unnecessary or inappropriate prescribing of antibacterials and support-
ing rapid diagnostics (World Health Organization, 2020).
The role of policymakers is to ensure there are robust systems for infection prevention and control
as well as surveillance of antimicrobial resistance.

Clinical consideration: Summary of the

paramedic’s role in the principles of good
assessment, combating microbial resistance
and prescribing practice considerations
• Establish if the person has a history of hepatic and/or renal impairment and allergies, is pregnant
or breast feeding and assess for any contraindications or cautions present in their history specific
to antibacterial groups.
• Prescribe and administer antibiotics in accordance with official guidelines and protocols.
• See best evidence, local guidelines or manufacturer’s guidance for specialist instructions regard-
ing dilution/reconstitution, route and rate of administration and concentration and scheduling of
administration.
• In treatment failure, the identity of the causative micro-organism should be established through a
microscopy, culture and sensitivity (MC&S) test.
• Assess the severity of the current illness.
• Determine previous antibacterial therapy.
• Ask about previous adverse/allergic reactions.
• Evaluate the therapeutic effect, for example improved wellbeing.
• Consider concurrent medications and be aware of interaction risk and monitor for potential effects.
• Encourage the person to adopt health-promoting behaviours towards the prevention of infection
spreading and maintain principles of antimicrobial stewardship.
Antibacterials Chapter 9

Antimicrobial stewardship (AMS)

According to the British Society for Antimicrobial Chemotherapy (2017), the definition of AMS is ‘the
right antibiotic, for the right indication (diagnosis), in the right patient, at the right time, with the right
dose and route, causing the least harm to the patient and future patients’. Furthermore, it argues that
there is a need to tackle the multifactorial drivers of antibiotic use through adoption of cautious pre-
scribing guidelines driven by AMS overarching goals. These goals include improving patient out-
comes, reducing collateral damage and impact costs. National Institute for Health and Care Excellence
(NICE) guidelines (2018) agree that this is about changing prescribing practice to slow development
of AMR and prolong the effectiveness of currently available antibacterials.

Antibacterials by clinical use 153

The conditions most frequently treated with antimicrobials in the primary care setting are respiratory
and urinary tract infections, with penicillin accounting for 50% of all prescriptions, followed by mac-
rolides (13%), tetracyclines (12%) and trimethoprim (11%) (Dolk et al., 2017).
The next section details the pharmacokinetics of each group of antibiotics, their actions, contrain-
dications and cautions, adverse effects, drug interactions and clinical considerations. However, some
antimicrobials mentioned will not be discussed in detail in this chapter, namely sulfonamides and
quinolones.

Beta-lactams
Penicillins
Examples of this group, used to treat mild to moderate infections, are benzylpenicillin, flucloxacillin,
ampicillin and piperacillin (with tazobactam). The spectrum of activity of the various penicillins
ranges from narrow to extended and they are bactericidal. The main differences between the pencil-
lins are their spectrum of activity, stability in stomach acid and duration of action.
Benzylpenicillin sodium (Pen G) and flucloxacillin are known narrow-spectrum penicillins, whereas
ampicillin and piperacillin (when combined with tazobactam) are broad spectrum. The pharmacoki-
netics of the penicillins differ. Benzylpenicillin sodium is the example used below. The variations of
Pen G are available in four salts which differ in route of administration and time course of action.
Table 9.2 describes the general pharmacokinetics of Pen G.

Contraindication, cautions and adverse effects

The penicillins are largely free from serious adverse effects. Hypersensitivity is the most common
adverse effect and can range from skin rash to anaphylaxis. Allergy to any penicillin may mean an
allergy to other pencillins and beta-lactam drugs, so a previous allergic reaction to any member of
the class is a contraindication to the use of any beta-lactam, as is a history of atopic allergy (asthma,
eczema and hay fever).
Diarrhoea is a common adverse effect, especially in oral treatment with broad-spectrum penicil-
lins, potentially leading to pseudomembranous enterocolitis (also known as antibiotic-associated
colitis). Superinfections (the opportunistic overgrowth of another microbe, such as yeast, after anti-
bacterial treatment) are commonly associated with the killing of the normal intestinal flora by broad-
spectrum agents.

Table 9.2 Pharmacokinetics of benzylpenicillin sodium.

Action
Absorption Poorly absorbed from the gastrointestinal tract. Best administered by intramuscular or intravenous
routes. Intrathecal injection of benzylpenicillin is not recommended
Distribution Distributes well to most tissues and fluids except cerebrospinal fluid (if no inflammation present),
joints and eyes
Metabolism Minimal metabolism
Excretion Renal – excreted largely unchanged
Chapter 9 Antibacterials

Drug interactions
This is not an exhaustive list, so further reading in NICE (2021) is recommended. This group has inter-
actions with anticoagulants (alters effect) and methotrexate (increases risk of toxicity). Risk of hepa-
totoxicity increases when flucloxacillin is combined with alcohol or paracetamol. Concurrent
administration of ampicillin and allopurinol increases the risk of a skin rash. Piperacilllin with tazo-
bactam increases the effect of suxamethonium and similar drugs if used in combination.

Considerations in the administration of penicillins

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Oral doses of penicillin should be taken with a full glass of water 1 hour before or 2 hours after
154 meals (antibiotic specific). Some food/drink (fruit juice, soft drinks, milk) may reduce the
absorption of some oral penicillins.
• Gastrointestinal discomfort is a common effect of penicillins. Patients should be advised how to
maintain adequate nutrition and hydration.
• Monitor renal function, by assessing fluid intake and output, to prevent injury, particularly in
older people, those with renal impairment, acutely ill or very young.
• Monitor patients following administration for signs of allergy.
• Advise patients with a known penicillin allergy to wear/carry appropriate identification.
• Advise patient to report any signs of an allergic reaction (skin rash, fever, itching, hives, wheezing
or swollen joints).
• If concomitant medications include anticoagulants, INR (how long it takes blood to form a clot)
should be monitored and dose adjusted as required.
• Consider concurrent medication and be aware of interaction risk.
• High-dose penicillins and aminoglycosides should not be administered in the same intravenous
solution, as aminoglycosides are inactivated.
• Monitor parenteral injection site as pain and inflammation can occur

Episode of care
You are dispatched to the home of Jaysal, a 24-year-old web designer, who has been unwell for about
2 days with coryzal symptoms. His partner is very concerned as Jaysal has deteriorated over the last 2
hours and seems to be confused with headache, stiff neck, aversion to bright lights, rapid breathing,
pale skin, and cold hands and feet. His partner informs you that Jaysal has no significant past medical
history, but she thinks that he had a mild reaction to penicillin as a child. He looks unwell and you sus-
pect that he may have meningitis. You consider administering benzylpenicillin 1.2 g IV and plan to
urgently transfer Jaysal to the hospital.

Cephalosporins
These have a broad antibacterial spectrum and are mostly bactericidal. There are five generations of
cephalosporins, and each successive generation has a broader spectrum of activity, greater resistance
to beta-lactamases and greater ability to penetrate the cerebrospinal fluid. The pharmacokinetics for
the generational group of cephalosporins are similar and are presented in Table 9.3.

Contraindications, cautions and adverse effects

Gastrointestinal disturbances are the most common adverse effects, with the risk of pseudomembra-
nous enterocolitis. Allergy and hypersensitivity risks are present with all beta-lactams. Cautious use is
recommended in people with renal impairment due to risk of toxicity. Common neurological effects
include, dizziness, headache, and lethargy.
Generally, this antibacterial group is well tolerated. Blood disorders can occur; for example, ceftriax-
one can cause bleeding tendencies by interfering with the metabolism of vitamin K. Thrombophlebitis
can occur at the IV injection site or an abscess at the site of an intramuscular injection.
Antibacterials Chapter 9

Table 9.3 Pharmacokinetics of cephalosporins.

Action
Absorption Only three (cefaclor, cephalexin and cefuroxime) are well absorbed after oral administration. The
rest are administered intramuscularly or intravenously
Distribution Widely distributed in tissues. Later generation agents (e.g. cefotaxime) cross the blood–brain barrier
more easily. They are known to cross the placental barrier and enter breast milk
Metabolism Primarily hepatic
Excretion Mainly renal but some (e.g. cefoperazone) in bile

155
Drug interactions
There is an increased risk of nephrotoxicity when cephalosporins are combined with some medica-
tions, including aminoglycosides Additionally, certain cephalosporins (ceftriaxone) can increase the
risk of bleeding if taken concurrently with drugs such as anticoagulants, thrombolytics, non-steroidal
anti-inflammatory drugs and other antiplatelet drugs
A disulfiram-like reaction (flushing, sweating, palpitations, dyspnoea, syncope, vertigo, blurred
vision, hypotension, throbbing headache, chest pain, nausea and vomiting, potentially leading to
convulsions, cardiovascular collapse and death), although rare, may occur if cephalosporins (particu-
larly cefazolin) are combined with alcohol, even after treatment has been completed.

Considerations in the administration of cephalosporins

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Advise the patient to take with food if gastric discomfort occurs.
• Advise the patient about the signs and symptoms of an allergic reaction – urticaria, rash, itching,
hypotension, dyspnoea and hives.
• If given intramuscularly or intravenously, monitor injection sites for signs of irritation (abscess or
phlebitis). Inform the person of potentially painful intramuscular injection.
• Advise the patient to refrain from alcohol for up to 72 hours after treatment to prevent a disulfiram-
like reaction.
• Monitor renal function if patient is taking cephalosporins and another drug with potential
nephrotoxicity.
• Monitor patients at risk of potential blood loss (bleeding gums, easy bruising) especially if taking
anticoagulant drugs (or similar). If prescribed ceftriaxone, observe for and instigate measures to
reduce haemorrhage risk. Prothrombin time and/or bleeding time should be monitored, and if
significant bleeding is present. administer parenteral vitamin K and transfer to hospital.
• If diarrhoea is experienced, advise the patient about replacing fluids and maintaining hydration.
• Inform the patient about treatment schedule and adverse effects and monitor them for signs of
superinfection.
• If CNS effects occur, refer to primary care practitioner or transfer to hospital.

Episode of care
Isini, a 36-year-old woman, is 12 weeks pregnant, and was seen by the nurse practitioner 2 days ago for
a lower urinary tract infection. Isini was prescribed cefalexin 500 mg BD for 3 days and was advised to
seek further assistance if the symptoms did not improve or if symptoms of upper urinary tract infection
developed. You arrive at her home and recognise that she looks quite unwell and is complaining of
vomiting, rigors, fever, lethargy and loin pain. Her past medical history is diabetes mellitus, and she has
had three urine infections over the last 6 months.
Chapter 9 Antibacterials

Table 9.4 Pharmacokinetics of imipenem.

Action
Absorption Is not absorbed by the GI tract therefore intravenous administration only
Distribution Distributes well to body fluids and tissues and penetrates the CSF. It is known to pass into the breast
milk but it is unclear if it passes the placental barrier
Metabolism Renal
Excretion Renal
CSF, cerebrospinal fluid; GI, gastrointestinal.

156 Carbapenems
Agents within this group include imipenem (with cilastatin), meropenem and ertapenem. They have
the widest spectrum of activity and are bactericidal in action. Carbapenems should be used spar-
ingly, which will delay development of resistance to them. Table 9.4 presents the pharmacokinetics
of imipenem.

Contraindications, cautions and adverse effects

Caution is advised in central nervous system disorders and epilepsy and in patients with renal
impairment.
Thrombophlebitis is a potential common side-effect. Commonly, GI tract effects can occur; how-
ever, rarely, pseudomembranous colitis, superinfections, seizures or hypersensitivity reactions ensue.

Drug interactions
These drugs increase the risk of seizures when given with the antivirals ganciclovir or valganciclovir.
They also decrease the concentration of the anticonvulsant valproate, increasing the risk of break-
through seizures

Considerations in the administration of carbapenems

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Assess for possible cautions or contraindications: known history of renal impairment or allergy to
carbapenem and/or other beta-lactam antibiotic or seizure disorder, pregnancy, lactational state
or inflammatory bowel disorders.
• If essential administration of imipenem is required alongside valproate, consider additional
anticonvulsant therapy to prevent the occurrence of breakthrough seizures.
• Regular urine function testing is advised, due to the metabolism and excretion route.
• Advise the patient to report any altered bowel patterns or superinfection symptoms.
• Advise on the need to take appropriate safety precautions, such as ensuring patient is
accompanied if CNS effects such as dizziness occur.
• Advise patient about signs of hypersensitivity.

Clinical consideration: medication

consideration during adulthood
Poor antimicrobial stewardship: management for antibiotic demand through patient education regarding
indications for use, completing the course, non-stockpiling for future use or sharing of antibiotics with
symptomatic people
Awareness of drug allergies and emergence of resistant strains
Consider use of contraceptive measures in women of reproductive age, if the prescribed antibiotic is
known to be teratogenic, and provide relevant patient education
Antibacterials Chapter 9

Cautions for use in pregnancy: dosage adjustment due to increased maternal hepatic metabolism
and glomerular infiltration rate; balance benefits of treatment against risk of foetal harm, due to drugs
crossing the placental barrier, for example sulfonamides
Caution in lactation as most drugs cross into the breast milk; for example, may cause tooth deformi-
ties and staining of teeth
Interference with hormone-based contraceptives
Awareness of renal or hepatic impairment in patient history or associated conditions

Table 9.5 Pharmacokinetics of tetracycline.

Action 157
Absorption Absorption from the gastrointestinal tract, as predominantly administered orally. Absorption is
reduced by the presence of food, drink or medications containing calcium, iron, aluminium or
magnesium in the stomach, as the drugs bind readily to these ions
Distribution Distributed to most body fluid and tissues but there is poor penetration to the cerebrospinal fluid. Is
known to cross the placental barrier and enter breast milk
Metabolism Concentrates in the liver
Excretion Urine

Tetracyclines
These include tetracycline, doxycycline, minocycline and demeclocycline. They have bacteriostatic
properties. Table 9.5 details the pharmacokinetics of tetracycline.

Contraindications, cautions and adverse effects

Contraindications include allergies, renal or hepatic impairment, pregnancy and lactation.
Tetracyclines are not recommended for administration to children under 12 years as they can cause
teeth discolouration in the younger child. If taken during pregnancy, the milk (deciduous) teeth of
the baby can be discoloured. These effects are due to the tendency of tetracyclines to bind to calcium
ions, resulting in their incorporation in teeth and bones.
Gastrointestinal adverse effects include direct irritation to the gastrointestinal tract causing
oesophageal irritation or ulceration, epigastric burning, nausea, vomiting, cramps and diarrhoea.
Fungal superinfection can result in vaginal or anal itching, sore mouth and black, furry tongue.
Dermatological effects include photosensitivity (increased skin sensitivity to ultraviolet light) as a
common adverse effect. Skin rashes and hypersensitivity reactions (urticaria to anaphylaxis) are less
common.
Intravenous high-dose tetracyclines can be hepatotoxic, especially in pregnant and postpartum
women who also have renal disease

Drug interactions
The most clinically significant interaction is between tetracyclines and antacids and mineral supple-
ments and is due to the tendency of tetracycline to bind to metal ions such as calcium, iron and
magnesium, reducing the absorption of the drug. Tetracyclines are also known to interact with
digoxin (monitor levels), anticoagulants (increases their action due to reduced gut flora producing
less vitamin K), retinoids (vitamin A drugs) (increased risk of benign intracranial hypertension) and
finally antacids and milk (interferes with absorption of tetracycline and may reduce effectiveness).
Hepatotoxicity is a further risk when tetracycline is taken with, for example, atorvastatin, valproate,
paracetamol or methotrexate. There is some evidence that tetracyclines may reduce the levels of
oral contraceptives, but whether this effect is clinically significant is not established. Additional
birth control precautions are, however, recommended for patients taking oral contraceptives with a
tetracycline.
Chapter 9 Antibacterials

Considerations in the administration of tetracyclines

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Take a whole tablet on an empty stomach 1 hour before or 2–3 hours after medication or meals.
• Do not take with dairy products, iron preparations, calcium supplements, magnesium- containing
laxatives or antacids. If required, there should be a minimum of 2 hours between ingestion of
tetracycline and these medications.
• Stand/sit upright and drink a full glass of water with each dose; this can prevent oesophageal
irritation/ulceration. Do not take immediately before going to bed.

Advise the patient:

158 • if the drugs produce GI disturbances on administration (epigastric burning, cramps, nausea),
tetracyclines should be taken with meals but this may affect the degree of absorption of the drug.
The meal should not include dairy products
• to seek medical advice for any hypersensitivity reaction
• to report any diarrhoea, due to superinfection risk
• to consult prescriber if any adverse effects occur, such as other infections, changes in faeces/urine
colour or pattern, severe abdominal cramps, difficulty in breathing, light sensitivity, rash/itching,
jaundice, headache or visual disturbances
• to avoid prolonged exposure to sunlight, wear protective clothing and use sunscreen (SPF 30 and
above) and avoid using sunbeds
• if drug was administered by injection, to report any signs of thrombophlebitis, such as swelling,
redness, tenderness and heat at the injection site.

Chloramphenicol
This is a broad-spectrum antibiotic with both bacteriostatic and bactericidal effects, dependent on
the sensitivity of individual bacteria. However, it should be reserved for life-threatening infections
when used systemically. See Table 9.6 for the pharmacokinetics of chloramphenicol.

Contraindications, cautions and adverse effects

A common side-effect of chloramphenicol is bone marrow failure, leading to blood cell abnormali-
ties. Because of this, chloramphenicol is only used to treat life-threatening infections. Acute por-
phyria is therefore a contraindication for its systemic use. Repeated or prolonged courses of oral or
intravenous treatment should be avoided, as this would increase the risk of blood disorders, and
even prolonged use of otic preparations of chloramphenicol should be avoided. Sore throat, fever
and unusual tiredness could indicate signs of blood abnormalities.
Intravenous and oral administration of chloramphenicol is best avoided in patients with severe
renal impairment but can be used (with caution) in patients with hepatic impairment, as there is an
increased risk of bone marrow depression. Intravenous and oral administration should be avoided in
pregnancy, as neonatal grey baby syndrome may occur, especially if used in the third trimester. This
syndrome presents with abdominal distension, diarrhoea, vasomotor collapse, hypothermia, flaccid-
ity, pallid cyanosis, abnormal respiratory rate and ashen skin colour. Chloramphenicol should also be
avoided for breast-feeding mothers, as it may cause bone marrow toxicity in the infant. Pregnant and

Table 9.6 Pharmacokinetics of chloramphenicol.

Action
Absorption It can be administered via oral, intravenous and topical routes. Rate of absorption varies with route
Distribution Distributes well through the body, including into cerebrospinal fluid, across the placenta and into
breast milk
Metabolism Hepatic
Excretion Renal
Antibacterials Chapter 9

lactating women should only receive chloramphenicol in optic preparations, if necessary, as it carries
a theoretical risk of bone marrow toxicity.
Other adverse effects, including eye and ear irritation, aplastic anaemia, headache and depression
after parenteral administration, ototoxicity, nausea and vomiting or circulatory collapse after oral
administration, are less common.

Drug interactions
Chloramphenicol is known to increase the levels of oral anticoagulants, antihyperglycaemics, immu-
nosuppressants (tacrolimus) and the anticonvulsant phenytoin. Phenobarbital or rifampicin may
reduce the effect of chloramphenicol.

Considerations in the administration of chloramphenicol 159

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Monitor plasma concentration after intravenous and oral administration in older persons or
patients under 4 years of age or with hepatic or renal impairment.
• Monitor blood cell counts for abnormalities prior to and during a course of treatment.
• Avoid using ear buds in the external ear canal during treatment.
• Potentially transient eye irritation occurs, so provide advice about avoiding driving and hazardous
work during initial stage of treatment. Periodic eye tests are advisable.
• When administered in combination with antihyperglycaemic drugs, monitor capillary blood
glucose.
• When administered in combination with anticoagulants, monitor INR.
When administered in combination with phenytoin, monitor
seizure pattern. Aminoglycosides
These include gentamicin, streptomycin, neomycin, tobramycin and amikacin. They have a broad
spectrum of activity and are bactericidal. The pharmacokinetics are similar for all aminoglycosides
(Table 9.7).

Contraindications, cautions and adverse effects

A known allergy to aminoglycosides is a contraindication for these drugs as well as myasthenia
gravis.
They should be used with caution in the older person, in dehydration, with renal impairment, hear-
ing or vestibular disorders, or in neuromuscular conditions such as Parkinson disease, as they can
cause muscle weakness and respiratory depression.
Aminoglyosides can produce ototoxicity (mostly irreversible), resulting in deafness and/or vestib-
ular (balance) disruption. These effects are dose dependent, and existing hearing impairment, tinni-
tus or vertigo may increase the risk of ototoxicity, as will use of aminoglycosides in combination with
other ototoxic drugs. Because the drugs are cleared entirely by the kidneys, their use in renally
impaired patients increases their toxicity, as they are likely to achieve higher plasma levels.

Table 9.7 Pharmacokinetics of aminoglycosides.

Action
Absorption Not absorbed from the gastrointestinal tract. Gentamicin is mainly administered parenterally but is
also available as eye and ear preparations. Other aminoglycosides are available in topical
preparations
Distribution Distribution tends to be limited to the extracellular fluid and does not reach sufficient concentration
in the cerebrospinal fluid unless given intrathecally
Metabolism Not metabolised
Excretion Renal
Chapter 9 Antibacterials

Nephrotoxic (usually reversible) effects can occur, and are more likely with existing renal impairment
or when combined with other nephrotoxic drugs.
These drugs should be used with caution in pregnancy as there is a risk of auditory or vestibular
damage in the foetus, especially if used in the second or third trimester – the benefits of the drug
must outweigh the risk to the foetus.

Drug interactions
Ototoxicity and nephrotoxicity generally occur when there is concurrent administration of other
agents with ototoxic or nephrotoxic effects.
Concurrent administration with neuromuscular blocking drugs, e.g. pancuronium, increases the
risk of respiratory arrest, as aminoglycosides intensify the neuromuscular blockade.
160 Aminoglycosides are synergistic when used with penicillins, increasing bactericidal efficiency.

Considerations in the administration of aminoglycosides

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Limit parenteral use of aminoglycosides to 7 days to reduce risk of toxicity.
• Initial dosing should be individualised due to variations in serum levels achieved with the same
dose. Factors affecting serum levels include weight, renal function, age, percentage body fat,
presence of fever, oedema and dehydration.
• Monitoring of both peak and trough plasma levels should be carried out to ensure both are within
therapeutic range.
• Correct dehydration before commencement of aminoglycosides.
• With intramuscular or intravenous gentamicin administration, doses for obese patients should be
calculated using ideal body weight to avoid excessive dosage.
• Serum concentration monitoring in parenteral administration of aminoglycosides must be
determined in older people, obese people, people with cystic fibrosis, those with renal impairment
(lengthen dose interval or reduce dose) and if high doses are being given. It should be monitored
in all persons receiving parenteral aminoglycosides. This is extended to when being used in
pregnancy.
• Encourage the patient to report signs and symptoms of ototoxicity (tinnitus, persistent headache,
high-frequency hearing loss, nausea, unsteadiness, dizziness, vertigo), and monitor for signs of
inner ear problems.
• Monitor for signs of nephrotoxicity (proteinuria, urinary casts, dilute urine production, increased
serum creatinine and blood urea nitrogen). If oliguria or anuria develops, report to medical team.
• Flush IV line if the patient has multiple antibiotic administrations.
• Observe patients with myasthenia gravis and those receiving muscle relaxants or general
anaesthetics with aminoglycosides due to the risk of respiratory depression resulting from
neuromuscular blockade.

Clinical consideration: medication

administration in the older adult
Signs and symptoms of infections can differ in this group
Culture and sensitivity are important to establish causative micro-organism
This group reacts more sensitively and with individual variability to the treatment regimens than
younger adults
Pharmacokinetic changes due to age-related decline of body systems require attention to sites of
metabolism (liver/kidney) and excretion (kidney) – may require dose adjustment
Rate of drug absorption is slower
More likely to have liver (prolongs drug effect) or renal (non-excretion of drug) impairment
Antibacterials Chapter 9

More likely to experience adverse drug reaction due to body system impairment, polypharmacy,
severe illness and pre- existing illness and drug regimens consisting of high-risk drug–drug
interactions
More susceptible to adverse effects of antimicrobials. Give consideration to hydration and nutritional
status alongside safety measures if CNS side-effects are noted
Consider dose adjustment and lengthen dose intervals in clients with liver or renal impairment,
those who depend on alcohol or take concomitant nephrotoxic or hepatoxic drugs
Unintentional non-concordance due to forgetfulness, inability to follow instructions, complicated
drug regimens, appearance of side-effects, inaccessibility to medication due to poor packaging or
health inequalities (distance to pharmacy or cost)
Intentional non-concordance due to complicated drug regimen, poor patient education, client feels
the drug is not necessary, increased side-effects, dosage is too high or poor client–practitioner 161
relationship.

Macrolides
Macrolides, which include erythromycin, azithromycin and clarithromycin, have a similar antibacte-
rial spectrum to penicillin. Erythromycin has both bacteriostatic and bactericidal properties. It is con-
sidered one of the safest antibiotics available. Table 9.8 describes the pharmacokinetics of
erythromycin.

Contraindications, cautions and adverse effects

Contraindications include known allergy to any member of the group, as cross-sensitivity occurs.
Cautious use in hepatic impairment as metabolism may be reduced and in renal impairment due to
effects on excretion.
The most common adverse effects are gastrointestinal, these being decreased appetite, anorexia,
nausea, vomiting and diarrhoea. Antibiotic-associated colitis and superinfections are rare effects.
There is a risk that the drugs may cause QT prolongation (with oral and intravenous administration)
and they may exacerbate myasthenia gravis. CNS effects such as hallucinations or seizures occur rarely.

Drug interactions
Erythromycin in combination with aminophylline increases the risk of hypokalaemia. Plasma levels of
carbamazepine, digoxin and some immunosuppressants can increase in the presence of macrolides,
increasing the risk of toxicity. Combination with warfarin leads to increased risk of bleeding. There is
a risk of increased adverse effects of ergotamine (antimigraine) and erythromycin. Concomitant use
of mizolastine (non-sedating antihistamine) and erythromycin increases the risk of adverse effects on
the heart, and concomitant use of erythromycin and statins increases the risk of muscle pains. The
potential for cardiotoxicity is increased when erythromycin is given with medications such as ami-
odarone which increase the QT interval.

Table 9.8 Pharmacokinetics of erythromycin.

Action
Absorption Absorption from GI tract is generally poor as erythromycin is destroyed by gastric acid. Acid-
resistant formulations are better absorbed. It can be administered IV but not IM as deemed too
painful
Distribution Distributes well to most tissues but penetration to CSF is poor. Crosses the placental barrier and
enters breast milk
Metabolism Hepatic
Excretion Bile (faeces) and urine (small amounts)
CSF, cerebrospinal fluid; GI, gastrointestinal; IM, intramuscular; IV, intravenous.
Chapter 9 Antibacterials

Erythromycin should not be used with chloramphenicol or clindamycin, as they antagonise

each other’s antibacterial actions. Verapamil (calcium channel blocker), azole antifungal drugs
(ketoconazole) and HIV protease inhibitors such as ritonavir inhibit the metabolism of
erythromycin.

Considerations in the administration of macrolides

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Limit oral course to a maximum of 14 days to limit the risk of liver damage.
• Advise patient to take the medication on an empty stomach, with a full glass of water, 1 hour
before meals or 2 hours afterwards.
162 • Advise that gastrointestinal adverse effects can be reduced by taking erythromycin (variant
dependent) with meals, if necessary.
• Monitor for signs of toxicity if patient is also taking aminophylline (monitor potassium levels),
carbamazepine or warfarin (monitor INR).
• Advise patient about reporting any adverse effects experienced, especially severe GI disturbances
due to potential for antibiotic-associated (pseudomembranous) colitis.
• Monitor hepatic and renal function.
• Monitor IV site for pain, swelling and redness.
Lincosamides
Although similar, lincosamides, which include clindamycin and lincomycin, are considered more
toxic than macrolides. Clindamycin is a bacteriostatic but it can assume bactericidal properties.
Table 9.9 presents the pharmacokinetics of clindamycin.

Contraindications, cautions and adverse effects

Contraindications include diarrhoeal illness, as diarrhoea associated with Clostridium difficile infec-
tion is a risk with these drugs. This can develop up to 6 weeks after completing a course of a lincosa-
mide. This is known to occur more frequently with clindamycin than other types of antibiotics. These
drugs should be used with caution in older people due to this risk.
Use should be avoided in patients with acute porphyria as it could induce an acute crisis. Caution
is advised in patients with renal or hepatic impairment.
Caution is advised in the first trimester of pregnancy and in breast-feeding women due to a risk of
infantile diarrhoea, as the drugs enter breast milk.
Clindamycin cream damages latex condoms and diaphragms, so additional birth control measures
are required.
Adverse effects include skin reactions, which are common, abdominal pain (with parenteral
and topical administration) and vulvovaginal infection (with parenteral, oral and vaginal
administration).
Electrocardiogram changes, hypotension or cardiac arrest may occur with rapid intravenous
administration.

Table 9.9 Pharmacokinetics of clindamycin.

Action
Absorption Absorbed from the gastrointestinal tract so can be administered orally. Intravenous, intramuscular
and topical administration also possible
Distribution Distributes well to most tissues and body fluids, including bone and synovial fluid, but does not
penetrate the cerebrospinal fluid or cross the blood–brain barrier
Metabolism Hepatic
Excretion Urine and bile
Antibacterials Chapter 9

Drug interactions
Clindamycin increases the effects of neuromuscular blockers (used in anaesthetic induction and
surgery) such as atracurium, cisatracurium and suxamethonium.

Considerations in the administration of lincosamides

• Promote principles of good patient assessment, prescribing practice and antimicrobial
stewardship through patient education.
• Advise patient to report any bouts of diarrhoea to their healthcare professional and discontinue
treatment immediately if prolonged, severe or bloody diarrhoea occurs.
• Oral capsules should be swallowed whole, with a glass of water.
• Advise using additional contraceptive measures if using vaginal preparations.
• If patient is breast feeding, advise monitoring the child for diarrhoea, bloody stools or candidiasis. 163
• In treatment (systemic) regimens of 10 days or more, monitor hepatic and renal function.
• Monitor hepatic and renal function in neonates and infants (by systemic use).
Conclusion
This chapter has provided the reader with an overview of the use of antibacterial medication. The
role of the paramedic is key in ensuring the principles of effective antimicrobial stewardship are
maintained to ensure their sustained usability to protect from emerging resistant pathogens. The
HCP’s role is paramount, primarily by offering advice and information to those who use health and
social care services regarding expectations of antimicrobial therapies.

The following is a list of conditions associated with the use of antibiotics. Take some time and write
notes about each of the conditions. Think about the medications that may be used in order to treat
these conditions and be specific about the pharmacokinetics and pharmacodynamics. Remember to
include aspects of patient care. If you are making notes about people you have offered care and sup-
port to, you must ensure that you have adhered to the rules of confidentiality.
The condition Your notes
Nausea and vomiting
Pseudomembranous colitis
Anaphylaxis

References
British Society for Antimicrobial Chemotherapy. (2017). Antimicrobial Stewardship. From Principles to Practice.
w w w.bsac.org.uk/antimicrobialstewardshipebook/BSAC- AntimicrobialStewardship - From
PrinciplestoPractice-eBook.pdf
Burchum, J.R.. and Rosenthal, L.D. (2019). Lehne’s Pharmacology for Nursing Care. St Louis: Elsevier.
Dolk, F.C., Pouwels, K., Smith, D. et al., (2018). Antibiotics in primary care in England: which antibiotics are pre-
scribed and for which conditions? Journal of Antimicrobial Chemotherapy 73(2): ii2–ii10.
Lack, W., Seymour, R., Bickers, A., Studnek, J. and Karunakar, M. (2019). Prehospital antibiotic prophylaxis for open
fractures: practicality and safety. Prehospital Emergency Care 23(3): 385–388.
National Institute for Health and Care Excellence. (2018). Antimicrobial stewardship. www.nice.org.uk/guidance/
ng15
National Institute for Health and Care Excellence. (2021). British National Formulary. https://bnf.nice.org.uk/
Parliamentary Office of Science and Technology. (2017). UK Trends in Infectious Disease. https://researchbriefings.
files.parliament.uk/documents/POST-PN-0545/POST-PN-0545.pdf
Smit, L and Boyle, M. (2014). Antibiotic prophylaxis in pre-hospital trauma care: a review of the literature.
Australasian Journal of Paramedicine 11(5).
Tsai, D., Jamal, J.A., Davis, J.S. et al. (2015). Interethnic differences in pharmacokinetics of antibacterials. Clinical
Pharmacokinetics 54(3): 243–260.
World Health Organization. (2020). Antibiotic resistance. www.who.int/en/news-room/fact-sheets/detail/antibiotic-
resistance
Chapter 9 Antibacterials

Further reading
Ashelford, S., Raynsford, J. and Taylor, V. (2016). Pathophysiology and Pharmacology for Nursing Students. London:
Sage Publications.
British Medical Association. (2018). New Guide to Medicines and Drugs, 10th edn. London: Dorling Kindersley.
Barber, P. and Robertson, D. (2020). Essential Pharmacology for Nurses, 4th edn. Buckingham: Open University
Press.
Cattini, P. Kiernam, M. (2020). Infection prevention and control. In: The Royal Marsden manual of Clinical Nursing
Procedures, 10th edn (eds S. Lister, J. Hofland and H. Grafton). Chichester: Wiley-Blackwell Publishing.
Coppoc, G.L. (1996). Chloramphenicol. www.cyto.purdue.edu/cdroms/cyto2/17/chmrx/cap.htm
Department of Health and Social Care. (2019). Antimicrobial resistance (AMR). www.gov.uk/government/
collections/antimicrobial-resistance-amr-information-and-resources
Ha, D., Forte, M., Olans, R. et al. (2019). A multidisciplinary approach to incorporate bedside nurses into antimicro-
164 bial stewardship and infection prevention. Joint Commission Journal on Quality and Patient Safety 45(5):
600–605.
Karch, A.M. (2017). Focusing on Nursing Pharmacology, 7th edn. Philadelphia: Wolters Kluwer Publishing.
Moffa, M. and Brook, I. (2015). Tetracyclines, glycylcyclines and chloramphenicol. In: Mandell, Douglas and
Bennett’s Principles and Practice of Infectious Diseases, 8th edn (eds J.E. Bennett, R. Dolin and M. Balser). St
Louis: Elsevier.
Olans, R.N., Olans, R.D. and DeMaria Jr, A. (2018). The critical role of the staff nurse in antimicrobial stewardship –
unrecognised, but already there. Clinical Infectious Diseases 62: 84–88.
Pearce, L. (2019). Antimicrobial resistance: how you can make a difference, Nursing Standard 34(5): 53–54.
Peate. I. (2015). Antimicrobial resistance: the nurse’s essential role. British Journal of Nursing 24(1): 5.
Wilson, A. (2019). Antimicrobial resistance: what can nurses do? British Journal of Nursing 28(1): 16–17.
World Health Organization. (2016). Global action plan on antimicrobial resistance. www.who.int/publications/i/
item/9789241509763
Xiu, P. and Datta, S. (2019). Pharmacology, 5th edn. London: Elsevier.

Multiple-choice questions
1. What does the term ‘bactericidal’ mean?
(a) Inhibits bacterial growth
(b) Destroys bacteria
(c) Aids bacterial growth
(d) Aids bacterial cell replication
2. Which group of antibacterials does imipenem belong to?
(a) Sulfonamides
(b) Quinolones
(c) Aminoglycosides
(d) Beta-lactams
3. Neonatal grey baby syndrome is associated with which antibiotic?
(a) Cefalexin
(b) Chloramphenicol
(c) Ciprofloxacin
(d) Co-trimoxazole
4. The action of clindamycin is:
(a) Folate interference
(b) Bacterial DNA inhibition
(c) Protein synthesis interference
(d) Disruption of the cell wall
5. Erythromycin is known to increase the levels of which drug?
(a) Warfarin
(b) Paracetamol
(c) Ferrous sulfate
(d) Gabapentin
Antibacterials Chapter 9

6. Tetracycline is contraindicated in:

(a) Pregnant women
(b) Breast-feeding mothers
(c) People with renal impairment
(d) All of the above
7. In which group of antibiotics is there a possibility of disulfiram-like reaction occurring
if alcohol is consumed alongside the treatment?
(a) Penicillin
(b) Aminoglycosides
(c) Sulfonamides
(d) Cephalosporins
8. Antibacterials can have _______ adverse effects. 165
(a) Hepatotoxic
(b) Nephrotoxic
(c) Ototoxic
(d) All of the above
9. Ototoxicity is a known adverse effect of which antibacterial group?
(a) Aminoglycosides
(b) Tetracyclines
(c) Cephalosporins
(d) Penicillins
10. Concomitant administration of erythromycin and which medication can induce
hypokalaemia?
(a) Theophylline
(b) Ferrous sulfate
(c) Warfarin
(d) Iburofen
11. Which antibiotic group disrupts the bacterial cell wall?
(a) Carbapenems
(b) Lincosamides
(c) Chloramphenicol
(d) Aminoglycosides
12. The term antibacterial is used interchangeably with which other term?
(a) Antihypertensive
(b) Antibiotic
(c) Antiemetic
(d) Anticoagulant
13. Which factors can affect the pharmacokinetics of antibiotics?
(a) Age
(b) Renal function
(c) Hepatic function
(d) All of the above
14. Photosensitivity is a potential adverse effect of which antibiotic group?
(a) Cephalosporins
(b) Penicllins
(c) Carbapenems
(d) Tetracyclines
15. A main priority of good antimicrobial stewardship is:
(a) Monitor for tendon damage
(b) Identify the causative organism
(c) Monitor hepatic function
(d) Monitor renal function
Chapter 9 Antibacterials

16. Breakthrough seizures are a possibility when imipenem is concurrently administered

with which drug?
(a) Paracetamol
(b) Levothyroxine
(c) Valproate
(d) Ferrous sulfate

166
Chapter 10
Medications used in the
cardiovascular system
Lisa Clegg and Fraser D. Russell

Aim
This chapter aims to provide the student paramedic with an understanding of the pharmacological
agents used to treat patients with cardiovascular disease.

Learning outcomes
After reading this chapter, the reader will be able to:
1. Define lifestyle choices that mitigate future development of cardiovascular disease
2. Understand the key role that the renin-angiotensin-aldosterone system (RAAS) plays in regulation
of blood volume and systemic vascular resistance and as a target for management of patients with
hypertension and heart failure
3. Compare pharmacological therapies for their potential to improve health outcomes (e.g. potential
to reduce hospitalisation for heart failure, reduce risk of stroke, reduce rate of mortality)
4. Recognise the pharmacological therapies that may be associated with unwanted effects, even at
therapeutic doses (e.g. hypotension, cough, hyperkalaemia).

Cardiovascular diseases
Paramedics have a critical role in the assessment and management of patients presenting with
cardiovascular disease (CVD). About 7.4 million people in the UK and 1.2 million people in Australia
live with CVD (Australian Bureau of Statistics, 2018; British Heart Foundation, 2021). With an esti-
mated 17.9 million deaths per year, CVD is the leading cause of death worldwide (World Health
Organization, 2021).
Coronary artery disease involves the impairment of blood flow through the coronary arteries,
commonly caused by atheromatous plaques and thrombosis formation. Risk factors for CVD
described as modifiable include hypertension, dyslipidaemias (hypercholesterolaemia) and physical
inactivity, while non-modifiable factors include family history and advanced age. Given the preva-
lence of CVDs in the community, patients with CVD presentations such as hypertension, heart fail-
ure and acute coronary syndrome are common in paramedic-led care.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 10 Medications used in the cardiovascular system

Hypertension and heart failure

Hypertension is a leading cause of cardiovascular morbidity and mortality. Hypertension is diag-
nosed when office or clinic systolic blood pressure (SBP) is ≥140 mmHg (≥135 mmHg for home
measurements) and/or diastolic blood pressure (DBP) is ≥90 mmHg (≥85 mmHg for home measure-
ments) (Unger et al., 2020).
Chronic hypertension leads to structural changes within the ventricles such as ventricular hyper-
trophy, resulting in ventricular dysfunction. High blood pressure increases afterload (the pressure
the ventricle works against to open the pulmonary or aortic valves to eject the blood). This eventu-
ally leads to heart failure as the ventricle loses its ability to pump adequately, resulting in increased
blood volume and pressure at the end of diastole (end-diastolic volume and end-diastolic pressure)
(Oh and Cho, 2020).
Hypertension is a modifiable risk factor not only for heart failure, but also for renal failure and
stroke and patients lower their risk through lifestyle changes and pharmacotherapies that include
168 the use of blood pressure-lowering medications.
Heart failure is defined as ‘a complex clinical syndrome with typical symptoms and signs that
generally occur on exertion but can also occur at rest. It is secondary to an abnormality of cardiac
structure or function that impairs the ability of the heart to fill with blood at normal pressure or eject
blood sufficient to fulfil the needs of the metabolising organs’ (Atherton et al., 2018).
This definition describes two processes that cause heart failure: the inability of the heart to ade-
quately fill (diastolic failure) and the inability of the heart to eject enough blood to meet metabolic
needs (systolic failure) (Figure 10.1).
The left ventricular ejection fraction (LVEF), the fraction of the left ventricular volume in systole
divided by the end-diastolic volume, expressed as a percentage, is commonly used in the classifica-
tion of heart failure. Normal LVEF is 50–70%; heart failure with reduced ejection fraction (HFrEF) is
<40%; heart failure with midrange ejection fraction (HFmEF) is 40–49% and heart failure with pre-
served ejection fraction (HFpEF) is ≥50% (Kemp and Conte, 2012).
Heart failure with reduced ejection fraction is commonly caused by ischaemic heart disease that
results in negative inotropy (decreased force of cardiac contraction). This leads to an increase in left
ventricular end-diastolic pressure (LVEDP) and left ventricular end-diastolic volume (LVEDV). Right
ventricular failure, primarily caused by an increase in afterload due to the high pressure in the pul-
monary system resulting from left ventricular failure (Arrigo et al., 2019), is reported to occur in at
least 60% of patients with HFrEF (Bosch et al., 2017).
Heart failure with preserved ejection fraction results from a failure of the left ventricle to ade-
quately relax and typically denotes a stiffer ventricular wall. The ‘stiffness’ and decreased compliance
of the ventricular wall cause an increase in ventricular end-diastolic pressure. Right ventricular fail-
ure occurs in 30–40% of patients with this form of heart failure (Bosch et al., 2017).

Management of hypertension and heart failure

Lifestyle modification is the cornerstone for reducing risk of hypertension and heart failure and is
achieved through smoking cessation, increased physical activity, weight loss, improved diet
(including increased consumption of fish, legumes, poultry, fruits, vegetables, whole grains and
low-fat dairy products), reduced sodium intake, enhanced dietary intake of potassium and mod-
eration in alcohol intake for individuals who drink alcohol (Arnett et al., 2019; Grundy et al., 2019;
Unger et al., 2020).
First-line pharmacological therapies for hypertension and heart failure include angiotensin-converting
enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor
(ARNI), beta-blockers and aldosterone receptor antagonists (Yancy et al., 2013, 2016, 2017; Unger
et al., 2020). For patients with hypertension without comorbid heart failure, blood pressure-lowering
medication can reduce the incidence of heart failure (Table 10.1). First-line treatment for a hypertensive
emergency requiring immediate reduction in blood pressure (e.g. hypertensive encephalopathy; acute
ischaemic stroke with SBP >220 mmHg or DBP >120 mmHg; acute haemorrhagic stroke and SBP
>180 mmHg) includes a beta-blocker such as labetalol and a dihydropyridine calcium channel blocker
such as nicardipine (Unger et al., 2020).
Medications used in the cardiovascular system Chapter 10

Heart failure: Diastolic heart failure (HFpEF)

Systolic heart failure (HFrEF)

Reduced Reduced renal

cardiac output perfusion pressure
Angiotensinogen
+

Decreased Renin release

baroreceptor +
firing – Angiotensin I
Angiotensin
converting enzyme
169
Increased Angiotensin II
sympathetic outflow AT1 receptor activation

+ive Inotropy Resistance vessel Vascular & cardiac Aldosterone Antidiuretic

+ive Chronotropy vasoconstriction remodelling secretion hormone
- Fibrosis (Adrenal cortex) secretion
- Hypertrophy (Posterior pituitary)
Increased blood pressure - Hyperplasia
Increased afterload Sodium and fluid
retention Fluid retention

Increased cardiac work and oxygen Increased blood pressure

consumption; worsening myocardial function Increased preload

Figure 10.1 Overview of pathways that lead to worsening myocardial function in heart failure patients.
Note the interplay between the sympathetic nervous system (blue arrow) and the renin-angiotensin-
aldosterone system (RAAS; orange arrow). HFpEF, heart failure with preserved ejection fraction (diastolic
heart failure); HFrEF, heart failure with reduced ejection fraction (systolic heart failure).

Beta-adrenoceptor antagonists (beta-blockers)

The administration of beta-blockers to patients with HFrEF is seemingly paradoxical given the sup-
pressive effect that these drugs have on myocardial contractility. While initial treatment may cause
a small reduction in ejection fraction, chronic administration of beta-blockers to patients with HFrEF
reduces mortality. The clue to success of this therapy resides in the underlying pathophysiology of
heart failure. During HFrEF, the reduced cardiac output is detected as a reduction in arterial pressure,
resulting in a compensatory increase in sympathetic outflow, to restore arterial pressure by increas-
ing cardiac rate and contractility (see Figure 10.1). Since arterial pressure is not the problem in these
patients, chronically elevated sympathetic drive is a cause of pathogenic myocardial remodelling
and increased risk for ventricular arrhythmias. Increased release of noradrenaline at JG beta-1
adrenoceptors also stimulates renin secretion. Chronic use of beta-blockers interrupts these effects,
improving haemodynamic performance of the heart. In patients with HFrEF who are treated with
beta-blocker therapy, rate of hospitalisation associated with cardiac causes decreases, as does risk of
sudden cardiac death and total mortality rate (Packer et al., 1996).
Chapter 10 Medications used in the cardiovascular system

• Beta-blockers can cause worsening of heart failure. The risk for this is curtailed by administration
of low doses that are slowly titrated upwards.
• Beta-blockers can compromise airflow by interfering with the binding of adrenaline to airway
beta-2 adrenoceptors and are therefore contraindicated in patients with asthma.

Table 10.1 Drug therapies for management of patients with hypertension or heart failure.

170 Aetiology Treatment References

Hypertension Black populations: thiazide-like diuretic with DHP-CCB, or DHP-CCB with an [1]
• Reduce the
incidence of HF
ARB. A diuretic and aldosterone receptor antagonist may be added
Non-black populations: ACE inhibitor or ARB with DHP-CCB. A thiazide or
thiazide-like diuretic and aldosterone receptor antagonist may be added
HFrEF ACE inhibitor, or ARBs, or ARNI with evidence-based beta-blockers and [2-4]
• Reduce morbidity
and mortality
aldosterone antagonists. For patients (NYHA Class II or III) who can tolerate
ACE inhibitors or ARBs, ARNI is the therapy of choice. ARNI is contraindicated
• Reduce HF
hospitalisations
in patients who have a history of angio-oedema and should not be used in
conjunction with ACE inhibitors or within 36 h of the last dose of ACE
(ivabradine) inhibitor. ARBs are used in preference to ACE inhibitors if ACE inhibitors
cause cough or angio-oedema. Ivabradine is used to lower heart rate
Atrial fibrillation Heart rate control: beta-blocker and/or digoxin (low dose – 0.125– [2,5,6]
(patient with HFrEF) 0.25 mg/day)
• Reduce
hospitalisations
for HF
• Reduce risk of
stroke (oral
anticoagulants)
HFmEF ACE inhibitors, ARBs, beta-blockers and aldosterone receptor antagonists. [7,8]
• Reduce
cardiovascular
Diuretics to manage volume overload

events
• Reduce
hospitalisations
for HF
Atrial fibrillation Heart rate control: beta-blockers, non-dihydropyridine calcium channel [6]
(patients with blockers (verapamil, diltiazem)
HFmEF)
HFpEF Diuretics to manage volume overload. Beta-blockers, ACE inhibitors, ARBs [2,4,8]
• Reduce
hospitalisations
to reduce SBP and DBP (coronary revascularisation for patients with
coronary artery disease)
for HF
Atrial fibrillation Heart rate control: beta-blockers, non-DHP-CCB (verapamil, diltiazem) [5,6,9,10]
(patients with
HFpEF)
ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; ARNI, angiotensin receptor-neprilysin
inhibitor; DBP, diastolic blood pressure; DHP-CCB, dihydropyridine calcium channel blocker; HFmEF, heart failure with
midrange ejection fraction (40–49%); HFpEF, heart failure with preserved ejection fraction (≥50%); HFrEF, heart failure
with reduced ejection fraction (<40%); SBP, systolic blood pressure.
[1]
Unger et al., 2020; [2] Yancy et al., 2013; [3] Yancy et al., 2016; [4] Yancy et al., 2017; [5] January et al., 2019; [6] Hindricks
et al., 2021; [7] Margonato et al., 2020; [8] Ponikowski et al., 2016; [9] Gard et al., 2020; [10] Mullens et al., 2019.
Medications used in the cardiovascular system Chapter 10

Angiotensinogen
–
Renin inhibitor Renin
ACE2
Angiotensin I Angiotensin-(1-9)
– Neprilysin
Degradation products ACE Inhibitor ACE ACE

– ACE2*
Neprilysin ARNI – Angiotensin II Angiotensin-(1-7)
(AT1R) (AT2R) (MasR)
Natriuretic peptides ARB
(NPRs) Aldosterone synthase

– Aldosterone
Mineralocorticoid (MR)
receptor antagonist
171
Figure 10.2 Classes of drug that target the renin-angiotensin-aldosterone-system (RAAS) and neprilysin
for the management of patients who have hypertension or heart failure. The diagram illustrates classic
(orange) and alternative RAAS pathways (purple), and the metabolism of natriuretic peptides by neprilysin
(blue). ACE, angiotensin-converting enzyme; ACE2, angiotensin-converting enzyme 2; ARB, angiotensin
receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; AT1R, angiotensin 1 receptor; AT2R, angi-
otensin 2 receptor; MasR, mitochondrial assembly receptor; MR, mineralocorticoid receptor; NPRs, natriu-
retic peptide receptors. *ACE2 is the main enzyme in the kidneys responsible for converting angiotensin II
to angiotensin-(1-7), while prolyloligopeptidase is important in the circulation and lungs.

Renin-angiotensin-aldosterone-system
The renin-angiotensin-aldosterone system (RAAS) has a critical role in the maintenance of physiologi-
cal blood volume and electrolyte balance. Angiotensin II, the primary effector of RAAS, mediates its
effects through activation of angiotensin II type 1 (AT1) and type 2 (AT2) receptors. Angiotensin II is
produced by sequential processing of the precursor molecules angiotensinogen and angiotensin I.
JG cells secrete renin into the blood in response to (i) low renal perfusion pressure, (ii) sympathetic
outflow that leads to JG cell beta-1 adrenoceptor activation, and (iii) low distal tubule sodium chlo-
ride concentration (Friis et al., 2013). Renin converts angiotensinogen to angiotensin I, which is in turn
converted to angiotensin II by ACE that is expressed in vascular endothelial cells and epithelial cells of
the lungs and kidneys (Figure 10.2).
While important for normal regulation of blood pressure and fluid and electrolyte balance, a dys-
regulated RAAS can contribute to detrimental pathophysiological remodelling of the cardiovascular
system. Angiotensin II mediates a plethora of effects that contribute to the development of hyper-
tension and heart failure, for example vasoconstriction, vascular smooth muscle cell and cardiomyo-
cyte hypertrophy and cardiac and renal fibrosis (AlQudah et al., 2020; Shafiq et al., 2008). The RAAS
represents an important target for drug treatment of patients with hypertension and/or heart failure
(see Figure 10.2).

Angiotensin-converting enzyme (ACE) inhibitors

Angiotensin-converting enzyme inhibitors (quinapril, enalapril, fosinopril, lisinopril, perindopril,
ramipril, captopril, trandolapril) are used to treat patients with heart failure and/or hypertension. In
patients with HFrEF, ACE inhibitors are reported to decrease all-cause mortality (risk ratio 0.72; p <
0.01 at 6 months) and cardiovascular mortality (risk ratio 0.83; p < 0.001 at 6–42 months) and lead to
fewer admissions to hospital for heart failure (risk ratio 0.71; p < 0.01) or for cardiovascular complica-
tions (risk ratio 0.94; p < 0.01) (Boeuf-Gibot et al., 2021).

Angiotensin receptor blockers (ARBs)

The ARBs (irbesartan, candesartan, valsartan, olmesartan, telmisartan, losartan, eprosartan) are AT1
receptor-selective antagonists. Angiotensin II mediates opposing cardiovascular effects through
activation of AT1 and AT2 receptors, and chronic activation of AT1 receptors can contribute to the
Chapter 10 Medications used in the cardiovascular system

pathogenesis of hypertension and heart failure through effects such as vasoconstriction, vascular
inflammation, cardiomyocyte hypertrophy, fibroblast hyperplasia and oxidative stress. A series of
large-scale clinical trials have shown a significant reduction in cardiovascular death and all-cause
mortality in HFrEF patients treated with candesartan (Pfeffer et al., 2003; Young et al., 2004). The
effects of angiotensin II at AT2 receptors may be cardioprotective. Activation of AT2 receptors leads
to vasodilation and suppression of myocardial fibrosis (Sumners et al., 2019; Wang et al., 2017).

Angiotensin receptor-neprilysin inhibitor (ARNI)

Natriuretic peptides modulate electrolyte–fluid balance by causing diuresis and have a critical role
in cardiovascular homeostasis since their actions tend to reduce fluid overload in the venous circula-
tion. The primary forms of natriuretic peptide are atrial natriuretic peptide, B-type natriuretic pep-
tide and C-type natriuretic peptide. The effects of the natriuretic peptides are terminated by the
activity of neprilysin, a membrane-bound endopeptidase (Bayes-Genis et al., 2016). ARNI, a combi-
172 nation of sacubitril (a neprilysin inhibitor) and valsartan (an ARB), prolongs the beneficial effects of
the natriuretic peptides by inhibiting their enzymatic breakdown and blocks the cardiovascular
effects of angiotensin II (see Figure 10.2). Sacubitril, in combination with the ARB valsartan, has been
found to be superior to the ACE inhibitor enalapril for reducing cardiovascular mortality and hospi-
talisations for heart failure (McMurray et al., 2014). Based on these findings, ARNI is now recom-
mended for patients who can tolerate ACE inhibitors or ARBs and who have HFrEF (see Table 10.1).

Mineralocorticoid receptor antagonists

The mineralocorticoid aldosterone causes the reabsorption of sodium ions from renal tubules back
into the blood, thereby maintaining plasma sodium and blood volume. In heart failure, this action
worsens fluid overload. Mineralocorticoid receptor antagonists reduce blood volume and provide
cardioprotective effects as a result.

• Troublesome cough is experienced in ~20% of patients who are treated with an ACE inhibitor and
this is attributed to reduced metabolism, and hence accumulation of bradykinin. For these
patients, ACE inhibitors can be replaced with an ARB.
• Combined use of ACE inhibitors and ARBs provides no survival benefit when compared to mono-
therapy with an ACE inhibitor or ARB and may cause a hypotensive response. For these reasons,
combined use of ACE inhibitors and ARBs is generally avoided.
• Angiotensin II is critical for normal renal development. Administration of ACE inhibitors and ARBs
is contraindicated in pregnancy because of the risk for fetopathy, including neonatal renal impair-
ment and pulmonary hypoplasia.
• Aldosterone contributes to potassium excretion. By blocking the effects of aldosterone, mineralo-
corticoid receptor antagonists can cause hyperkalaemia. Potassium levels >5.1 mmol/L have been
associated with increased mortality (Krogager et al., 2017).

Calcium channel blockers (CCBs)

Calcium channel blockers produce relaxation of vascular smooth muscle and negative chronotropic and
ionotropic effects in the heart. Dihydropyridine CCBs (DHP-CCBs) such as nifedipine and amlodipine have
greater selectivity for vascular smooth muscle over cardiac muscle compared to non-dihydropyridine
CCBs (NDHP-CCBs) such as diltiazem and verapamil and are therefore less likely to produce cardiac
effects. Both types of CCB are used to treat patients with hypertension and angina pectoris. NDHP-CCBs
are also used to manage patients with supraventricular tachyarrhythmias (they are known as Class IV
antiarrhythmic agents). NDHP-CCBs should be avoided in patients who are being treated with beta-
blockers and those who have HFrEF, because of the potential to cause excessive myocardial depression.
There is insufficient evidence of a benefit of CCBs to support their use in patients with HFpEF.
Medications used in the cardiovascular system Chapter 10

Diuretics
Diuretics are a first-line therapy for patients with uncomplicated hypertension (see Table 10.1).
Diuretics can also assist in alleviating the congestion in patients with congestive heart failure by
removing excess sodium and water and are therefore recommended for patients with HFrEF and
HFpEF (Ponikowski et al., 2016). Loop, thiazide and thiazide-like diuretics can cause potassium wast-
ing, a situation that is avoided by coadministration of a potassium-sparing diuretic. Readers are
referred to Chapter 11 for the pharmacology and clinical utility of diuretic agents in patients with
hypertension and heart failure.

Positive inotropes for patients with decompensated heart failure

A primary concern of low cardiac output is hypoxia caused by hypoperfusion of tissues that can lead
to end-organ dysfunction. Positive inotropes provide haemodynamic support in instances of low
cardiac output (e.g. in acute decompensated heart failure, cardiogenic shock, prior to heart trans- 173
plantation and following cardiac surgery). Most positive inotropes increase myocardial contraction
by increasing intracellular calcium concentration. Unfortunately, the use of positive inotropes in
patients with chronic heart failure has often failed to produce long-term clinical benefit and may
have increased the risk for death (see review by Ahmad et al., 2019).
Calcium sensitisers are agents that provide inotropic support without increasing cyclic AMP or
intracellular calcium concentration. Omecamtiv mecarbil increases myocyte contractility by increas-
ing sarcomere duration of contraction without causing appreciable effects on calcium transients.
The Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in
Heart Failure (GALACTIC-HF) clinical trial has been established to examine the safety and efficacy of
omecamtiv mecarbil in patient with HFrEF (Teerlink et al., 2020).

Acute coronary Syndrome (ACS)

Acute coronary syndrome includes unstable angina and myocardial infarction (MI). Patients with
ACS often experience pain or discomfort in the chest, commonly known as angina. The main cause
is an ulcerated atheromatous plaque with thrombus that occludes the coronary artery, resulting in
myocardial ischaemia which can lead to myocardial cell death if coronary artery blood flow is not
restored through coronary reperfusion.
Coronary reperfusion is required in patients diagnosed with ST-segment elevation myocardial
infarction (STEMI), with primary percutaneous coronary intervention (primary PCI) being the first-
line therapy. In PCI, a balloon catheter is inserted into the blocked coronary artery, opening the
artery to restore blood flow to the myocardium. A stent (mesh tube) may also be inserted to main-
tain coronary artery patency.
A fibrinolytic agent is used if the patient cannot receive PCI intervention within 2 hours of STEMI
diagnosis (Fazel et al., 2020; Ibanez et al., 2018). Major bleeding is a risk when fibrinolysis is coupled
with PCI (Fazel et al., 2020).

Management of acute coronary syndrome

Fibrinolytic therapy
Thrombin (coagulation factor IIa) catalyses the conversion of soluble fibrinogen to insoluble fibrin.
While fibrin is a critical factor in haemostasis to prevent blood loss following injury, it may also con-
tribute to thrombosis, resulting in reduced blood flow. The thrombus is dissolved by plasmin, a natu-
rally occurring fibrinolytic modulator derived from plasminogen. Plasminogen is converted to
plasmin by endothelial-derived tissue plasminogen activator (t-PA). Alteplase, produced using
recombinant technologies, is identical in structure to t-PA, with a half-life in plasma of less than
5 minutes. Reteplase and tenecteplase mimic the effects of t-PA, but with plasma half-lives of 15 and
20 minutes, respectively. Reteplase and tenecteplase have similar efficacy and safety profiles and are
used clinically in patients who have had a recent acute myocardial infarction (Zia-Behbahani
et al., 2019). Fibrinolytic agents are contraindicated in patients who have severe hypertension,
recent surgery or stroke, because of the risk of haemorrhage. The effect of fibrinolytic agents can be
reversed using tranexamic acid, a drug that inhibits plasminogen activation.
Chapter 10 Medications used in the cardiovascular system

Common clinical manifestations of ACS include the following:

• prolonged chest pain described as crushing, squeezing or stabbing

• anxiety or fear of death
• nausea and vomiting
• breathlessness.
Paramedics should also be aware that these clinical manifestations are not always present, and patients
may present pain free. Paramedics should not discount cardiac causes for atypical presentations.

174

Aspirin and dual antiplatelet therapy

Prior to PCI, patients are treated with dual antiplatelet therapy (DAPT) comprising a combination of
aspirin and an adenosine 5’-diphosphate (ADP) P2Y12 receptor inhibitor such as prasugrel or ticagre-
lor. Aspirin inhibits cyclo-oxygenase, which is responsible for the production of thromboxane A2 and
the prostaglandins, resulting in attenuated platelet aggregation. DAPT is indicated in patients with
acute coronary syndrome, particularly if undergoing PCI, and in patients who have had stent implan-
tation for coronary artery disease (Valgimigli et al., 2018). Benefits ascribed to DAPT include reduced
rate of myocardial infarction and stent thrombosis, aiding maintenance of arterial patency. Risk
scores are used to determine the duration of DAPT, with the aim of maximising cardiovascular ben-
efits and minimising bleeding risk.
P2Y12 receptor inhibitor monotherapy has been evaluated for efficacy and safety. Recent clinical
trials suggest that ticagrelor monotherapy produces similar cardiovascular risk reductions as DAPT,
but with a lower incidence of bleeding (Mehran et al., 2019).

Glyceryl trinitrate (nitroglycerin)

Glyceryl trinitrate (GTN) is used for rapid alleviation of angina pectoris and for treatment of patients
with acute heart failure and myocardial infarction. GTN causes dilation of venules (reducing preload)
and arterioles (reducing afterload). Where atherosclerotic plaques limit delivery of blood to tissues,
GTN dilates collateral blood vessels to facilitate improved tissue perfusion. It also dilates coronary
arteries to improve delivery of blood to the myocardium. The mechanism involves the liberation of
nitric oxide, which is a potent vasodilator.
Glyceryl trinitrate is administered sublingually as a spray or tablet, or intravenously, as the drug
undergoes extensive first-pass metabolism when ingested orally. Chronic exposure to GTN causes
tolerance (reduced responsiveness), via an as yet unidentified mechanism (Bilska-Wilkosz
et al., 2019). Intermittent use of the GTN patch (e.g. removal of the patch at night with reapplication
in the morning) helps to circumvent the loss of responsiveness to the drug. GTN is contraindicated
in patients who have a hypersensitivity to the drug, following use of phosphodiesterase type
5 inhibitors, such as sildenafil, and in patients with severe anaemia.

Lipid-lowering therapies
Lipid-lowering therapies provide significant survival benefits in patients who are at elevated risk of an
adverse cardiovascular event. Statins are the first-line therapy for reducing blood cholesterol levels.
Therapy is tailored to patient clinical profile, with high-, moderate- and low-intensity statin therapies
used to reduce serum LDL concentration by ≥50%, 30–49% and <30%, respectively (Grundy et al., 2019).
Other lipid-lowering drugs can be combined with statins if target LDL-C concentrations are not achieved.

HMG-CoA reductase inhibitors (statins)

Acetyl-coenzyme A is a precursor in a sequence of biochemical reactions that culminate in the for-
mation of cholesterol in liver cells. In an early step in this pathway, 3-hydroxy-3-methylglutaryl-
Medications used in the cardiovascular system Chapter 10

coenzyme A (HMG-CoA) is converted to mevalonic acid by the enzyme HMG-CoA reductase. By

inhibiting this enzyme, statins interfere with cholesterol synthesis. The response to this reduction in
cholesterol synthesis is an increase in LDL receptor number, which leads to increased clearance of
LDL from the blood. Statins approved for clinical use include atorvastatin, rosuvastatin, simvastatin,
pravastatin, lovastatin and fluvastatin.
Statin therapy has been reported to reduce the risk of a first major vascular event by 21%, the risk
of a major coronary event by 24%, and risk of vascular mortality by 12% when calculated as effect
per 1.0 mmol/L reduction in LDL-C (Cholesterol Treatment Trialists’ Collaboration, 2016). Increasing
age was associated with smaller risk reductions in major vascular events and vascular deaths. Statin
therapy is typically well tolerated and safe. Side-effects include myalgia, with rare cases of myopathy
and rhabdomyolysis (Grundy et al., 2019). A systematic review of side-effects of the statins has found
that muscle symptoms are often reported at a similar rate in patients taking a placebo as those tak-
ing the statin (Ganga et al., 2014).
175
Ezetimibe
This drug acts to reduce the uptake of cholesterol from the small intestine by inhibiting Niemann-
Pick C1-like 1 (NPC1L1), a transport protein that carries cholesterol from the intestinal lumen into
the intestinal cells, from where it is transported into the lymphatic vessels in the form of chylomi-
crons. This drug would usually only be considered as monotherapy if a patient could not tolerate
statins, as there is no evidence that it reduces cardiovascular risk when used on its own. It is also
used in combination with a statin if the statin alone does not produce a sufficient reduction in LDL.

PCSK9 inhibitors
Proprotein convertase subtilisin/kexin type-9 (PCSK9) targets LDL receptors in cells for destruction
rather than recycling, reducing their capacity to remove LDL from the circulation. By binding to
PCSK9, monoclonal antibodies such as evolocumab and alirocumab inhibit the enzyme, enabling
LDL recycling and continued sequestration of LDL from the blood.

Episode of care: chest pain

A paramedic crew has been called to attend Max Simons, a 76-year-old patient with chest pain and
breathing difficulties. The time of day is 0530 hours and it is a Friday morning in November.
On arrival the crew find the patient sitting on the couch, clutching at his chest. The patient is pale,
diaphoretic and grimacing.
Presenting medical history
Max tells the crew that he woke with severe chest discomfort which he described as central crushing
pain and a dull ache in the left arm (radiating pain).
Past medical history
Max states that he had a heart attack 5 years previously which resulted in stenting of two arteries.
Occasionally when exercising, he develops angina and he has also had high blood pressure (hyperten-
sion) for many years. Max also says that he has high cholesterol (hypercholesterolaemia).
Medications
Max is prescribed atorvastatin for high cholesterol, aspirin to prevent platelet aggregation, GTN for
episodes of angina and irbesartan for hypertension.
Assessments and clinical manifestations
After gaining patient consent, the crew undertake the following assessments with a 12-lead ECG as
a priority.

• Perfusion assessment:
∘ Skin: pale, cool, diaphoretic
∘ Oxygen saturations: 93%
∘ Pulse rate: 91
∘ BP: 155/95
Chapter 10 Medications used in the cardiovascular system

• Respiratory assessment:
∘ Respiratory rate: 24
∘ Speech: sentences
∘ Ventilatory effort: slight increase
∘ Breath sounds: clear
∘ Conscious state: orientated to time and place.
• Other findings:
∘ 12-lead ECG: sinus rhythm with ST elevation in V2, V3, V4 indicating an anterior wall myocardial
infarction (AWMI)
∘ Pain score: 7/10
∘ Temperature: 37.0
∘ Blood glucose level: 4.4 mmol
Management
176 Based on the patient’s history and clinical manifestations, a provisional diagnosis of AWMI is made.
Max is treated with the following.
• Positioning: upright to improve ventilatory function
• Oxygen: high flow to increase the fraction of inspired oxygen (FiO2)
• Glyceryl trinitrate (GTN): causes vasodilation of veins and arteries resulting in decreased preload
and afterload. This reduces the workload of the heart, thereby reducing myocardial oxygen
demand
• Aspirin to prevent the development of thrombosis and the extension of any current thrombi that
may have caused the coronary artery occlusion
• Analgesia such as fentanyl to help reduce pain
• Continual 12-lead ECG monitoring
• Transport to hospital
Risk factors and considerations
Max has a history of hypertension and hypercholesterolaemia which are risk factors for atherosclero-
sis, a common cause of cardiovascular disease which can cause myocardial infarction.

Reflection
Take some time to consider if time of day is an important factor in patients presenting with chest pain.
If so, why do you think this is?

Skills in practice: electrode placement for a

12-lead ECG
Explain the procedure and gain patient consent.
Always ensure the patient’s privacy is maintained.
Patient’s skin may need to be cleaned to ensure attachment of the ECG electrodes.
Chest hair may need to be removed.
Medications used in the cardiovascular system Chapter 10

Limb lead placement

• Right arm lead – inner wrist
• Left arm lead – inner wrist
• Right leg lead – inner ankle
• Left leg lead – inner ankle
Chest lead placement
• V1: fourth intercostal space, just right of the sternum
• V2: fourth intercostal space, just left of the sternum
• V3: in between V2 and V4
• V4: fifth intercostal space, midclavicular line
• V5: adjacent to V4, anterior axillar line
• V6: adjacent to V5, midaxillar line
In practice, it may not always be possible to access the patient’s limbs, for example a patient who has 177
been in a car crash where their legs are pinned under the dashboard. Modification can be made to the
limb leads using the patient’s torso.
• Right shoulder
• Left shoulder
• Right lower quadrant (lateral)
• Left lower quadrant (lateral)

Conclusion
Cardiovascular disease is the leading cause of death worldwide. Given this, calls to ambulance ser-
vices from patients presenting with cardiovascular disease are common and therefore it is essential
that paramedics have a sound understanding of cardiovascular disease pathophysiology, clinical
manifestations patients may present with and treatment regimes. It is important that paramedics
understand the pharmacology of drugs used in the clinical management of patients who have car-
diovascular disease.
The following is a list of conditions that are associated with the cardiovascular system. Take some
time and write notes about each of the conditions. Think about the medications that may be used in
order to treat these conditions and be specific about the pharmacokinetics and pharmacodynamics.
Remember to include aspects of patient care. If you are making notes about people you have offered
care and support to, you must ensure that you have adhered to the rules of confidentiality.

The condition Your notes

Hypertension
Heart failure
Hypercholesterolaemia
Arrhythmias
Myocardial infarction

Glossary
ACS Acute coronary syndrome
CVD Cardiovascular disease
HFmEF Heart failure with midrange ejection fraction
HFpEF Heart failure with preserved ejection fraction
Chapter 10 Medications used in the cardiovascular system

HFrEF Heart failure with reduced ejection fraction

LVEDP Left ventricular end-diastolic pressure
LVEF Left ventricular ejection fraction
MI Myocardial infarction
PPCI Primary percutaneous coronary intervention
STEMI ST-elevation myocardial infarction

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Further reading
Australian Paramedic Clinical Practice Guidelines. www.clinicalguidelines.gov.au/
Joint Royal Colleges Ambulance Liaison Committee (JRCALC). (2019). Clinical Practice Guidelines 2019. Bridgwater:
Class Professional Publishing.
Ward, J., Connolly, M. and Aaronson, P. (2020). The Cardiovascular System at a Glance, 5th edn. Oxford: Wiley
Blackwell.
Chapter 10 Medications used in the cardiovascular system

Multiple-choice questions
1. Drugs used to interfere with the renin-angiotensin system for control of blood
pressure include:
(a) Verapamil and digoxin
(b) Digoxin and endothelin-1
(c) Captopril and candesartan
(d) Salbutamol and salmeterol
2. Renin is released from juxtaglomerular cells in response to:
(a) An elevation in renal perfusion pressure
(b) Release of prostacylin (PGI2) from the macula densa
(c) An increase in Na+ concentration in the distal tubule
180 (d) Stimulation of receptors in the juxtaglomerular cell by angiotensin II
3. The enzyme chymase converts angiotensin I to angiotensin II. This type of processing
may also be achieved by the activity of:
(a) Angiotensin-converting enzyme (ACE)
(b) Bradykinin
(c) Endothelin-converting enzyme (ECE)
(d) Renin
4. A patient undergoes catheter-based radiofrequency ablation of the sympathetic
nerves that are located adjacent to the renal arteries to treat their hypertension. A
direct effect of renal denervation would be:
(a) Decreased release of adrenaline from the adrenal medulla
(b) Decreased renin secretion from the juxtaglomerular cells
(c) Decreased released prostacyclin from the macula densa
(d) Decreased reabsorption of chloride ions from the distal tubule
5. Why is the beta-1 adrenoceptor-selective antagonist, atenolol, contraindicated in
patients who have asthma?
(a) Beta-1 adrenoceptor-selective antagonists cause receptor supersensitivity
(b) At therapeutic doses, some airway beta-2 adrenoceptors will be blocked
(c) Beta-1 adrenoceptors are the predominant receptor subtype on bronchial smooth
muscle cells
(d) At therapeutic doses, renin release is inhibited
6. Dobutamine is a beta-1 adrenoceptor agonist and is used therapeutically in the:
(a) Management of patients who have asthma
(b) Chronic management of patients who have moderate heart failure
(c) Acute inotropic support of patients who have end-stage heart failure
(d) Treatment of patients who have ventricular arrhythmias
7. Treatment of a patient with myocardial infarction could include:
(a) The use of antiplatelet agents such as clopidogrel and aspirin
(b) A fibrinolytic drug such as tenecteplase
(c) Primary percutaneous coronary intervention
(d) Any of the above
8. The fibrinolytic agent tenecteplase:
(a) Combines with antithrombin III to inhibit factor Xa
(b) Stimulates conversion of plasminogen to plasmin
(c) Is inactivated by plasmin inhibitors such as PAI-1
(d) Inhibits the conversion of prothrombin to thrombin
9. Which of the following positive inotropes increases force of myocardial contraction
without increasing intracellular calcium concentration or sensitising troponin-C to
calcium?
Medications used in the cardiovascular system Chapter 10

(a) Digoxin
(b) Dobutamine
(c) Omecamtiv mecarbil
(d) Endothelin-1
10. The mechanism by which glyceryl trinitrate reduces cardiovascular preload is:
(a) Venodilation, resulting in reduced venous return
(b) Diuresis resulting in reduced intravascular volume
(c) Reduction in venous compliance
(d) Increase in ventricular compliance
11. Why is glyceryl trinitrate (GTN) used intermittently?
(a) To avoid tolerance that is associated with extended use of the drug
(b) To minimise toxicity that is associated with long-term use of GTN
(c) To minimise extensive metabolism of GTN by enzymes present in the 181
(d) To reduce the probability of development of a hypersensitivity reaction that is
12. Which of the following would be the primary indication for angiotensin receptor-
neprilysin inhibitor (ARNI), sacubitril/valsartan?
(a) A patient who has heart failure with reduced ejection fraction, and who can
tolerate ACE inhibitors or ARBs
(b) A patient who has low cardiac output and requires haemodynamic support
(c) A patient requiring treatment for familial hypercholesterolaemia
(d) A patient who has chest pain associated with coronary artery disease
13. Administration of ACE inhibitors and ARBs is contraindicated in someone who:
(a) Has diabetes
(b) Has elevated systolic blood pressure
(c) Is pregnant
(d) Has elevated diastolic blood pressure
14. Which of the following agents could be used to reduce the blood concentration of
low-density lipoprotein (LDL)?
(a) Alirocumab, a proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitor
(b) Atorvastatin, an HMG-CoA reductase inhibitor
(c) Both a) and b)
(d) None of the above
15. Which of the following is a potential cause of hypokalaemia?
(a) Lisinopril (angiotensin-converting enzyme inhibitor)
(b) Candesartan (angiotensin AT1 receptor blocker)
(c) Spironolactone (aldosterone receptor antagonist)
(d) Furosemide (loop diuretic)
Chapter 11
Medications used
in the renal system
Anthony Kitchener

Aim
The aim of this chapter is to orientate the reader to the renal system, explore some of the common
pathologies encountered by healthcare professionals and consider the pharmacological interven-
tions used in the management of these conditions.

Learning outcomes
After reading this chapter, the reader will:
1. Have gained an understanding of acute kidney injury and chronic kidney disease, including
pharmacology that can contribute to renal demise
2. Know how common renal-conditions can be treated or managed by pharmacological intervention
3. Be able to describe the different drug classifications used in renal medicine
4. Be able to differentiate and understand the side-effects of common renal pharmacotherapy and
how this knowledge can contribute to effective patient counselling for prescribed medications.

Test your knowledge

1. Identify the difference between acute kidney injury and chronic kidney disease.
2. Name four common renal conditions.
3. Discuss the potential risks associated with reduced renal function.
4. List the common types of drugs used to treat renal disorders.
5. Discuss the role and function of the National Institute of Health and Care Excellence (NICE) in the
management of renal disorders.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Medications used in the renal system Chapter 11

Introduction
The study of renal medicine is termed ‘nephrology’ and includes several conditions, both acute and
chronic, that can cause injury to the kidney. Acute kidney injury (AKI) is a sudden drop in renal func-
tion that can be caused by a reduction in blood flow to the kidney, produced by severe dehydration,
for example, or by certain groups of medicines that are toxic to the kidneys. Chronic kidney disease
(CKD) reflects a long-term disease process or stress on the kidney, which gradually reduces renal
function. Chronic, severe reduction in renal function is end-stage renal disease (ESRD), at which
point treatment options are limited to renal dialysis or renal transplant surgery.
Around 3 million people in the UK have CKD around 700 million globally and the largest contribu-
tors to this are uncontrolled diabetes and hypertension. Due to comorbid states and the finite
resources associated with dialysis and transplant, the options for treatment are sometimes limited or
include a lengthy wait. Haemodialysis and peritoneal dialysis are methods used to replace the work
of the kidneys until a renal transplant can be performed (if the patient is eligible). Patients in ESRD will
have disordered fluid and electrolyte balance, and are particularly at risk of cardiac arrhythmia due to
abnormally high extracellular potassium levels (hyperkalaemia) which can lead to sudden cardiac 183
death. There are approximately 30 000 people in the UK on dialysis at any one time, several million
worldwide. For every five people that need a renal transplant in the UK each year, there are only three
kidney donors. Eight of 10 patients on the donor organ waiting list are waiting for donor kidneys.
A discussion of the complex physiology of the renal system is outside the scope of this chapter,
but because of the multiple physiological roles played by the kidneys, the loss of renal function can
be expected to produce a range of disorders, as illustrated in Figure 11.1.
Renal diseases can be classified into pre-renal, intrarenal and postrenal, reflecting the causes of
the disease, which are reduced blood flow to the kidney (pre-renal), intrinsic damage to the kidneys
themselves (intrarenal) or damage due to obstructed outflow from the kidney (postrenal), as shown
in Table 11.1.

Acute kidney injury

Acute kidney injury can be caused by pre-renal, intrarenal and postrenal pathophysiology. The clini-
cal presentation may be oliguria (reduced urine output) or complete anuria (no urine output). There
is a resultant abnormally high level of nitrogenous products in the blood (azotaemia) due to failure
to excrete them and this may present clinically as being tired all the time (TATT), peripheral oedema,
muscle cramps, insomnia and itching. There may be a history of infection or other insult preceding
the clinical presentation or the diagnosis. Certain medications (see Box 11.1) are thought to be a

Kidney failure causes: Kidney failure causes: Failure → ↓red

↑ plasma urea → toxic effects of urea blood cell production → anaemia

Nitrogenous waste elimination Erythropoiesis

Kidney failure causes:

Kidney failure causes: ↓calcium absorption→↓
↓ clearance of drugs→
Activation of Vitamin D plasma calcium→
Drug elimination
↑ adverse & toxic effects ↑ parathyroid hormone→
↑ bone resorption

Acid-base balance
Electrolyte balance

Kidney failure causes: Kidney failure causes:

Hyperkalaemia Bicarbonate deficiency → Acidosis
Hyperphosphataemia Control of blood volume & pressure
Hypocalcaemia

Kidney failure causes: Fluid retention & Oedema

Figure 11.1 The major physiological functions of the kidneys (black boxes) and the sequelae of
renal failure (red boxes).
Chapter 11 Medications used in the renal system

Table 11.1 Pre-renal, intrarenal and postrenal disease characteristics.

Pre-renal disease Intrarenal disease Postrenal disease
Mechanism Reduced blood flow to Direct damage by drugs or Obstruction of renal pelvis,
kidney toxins. ureters, bladder or urethra
Aetiology • Prolonged • CKD progression • Obstruction from calculi
hypotension • Autoimmune disease • Retained clots
• Cardiac failure • Glomerulonephritis • Enlarged prostate
• Anaphylaxis • Localised infection • Bladder tumour
• Pulmonary embolism • Bacterial infections • Physical injury
• Sepsis (haemolytic uraemia) • Cervical cancer
• Renal artery stenosis • Acute tubular necrosis • Urethral stricture
• Blood loss • Meatal stenosis
• Hyperemesis • Meatal phimosis
• Vascular occlusion
184 • Medication
• Hepatorenal
syndrome (seen in
alcohol use disorders)
Plasma urea levels Increased Increased Increased
Plasma creatinine Increased Increased Increased
levels
Estimated glomerular Reduced Reduced Reduced
filtration rate (eGFR)
Urine output Reduced Reduced Reduced

CKD, chronic kidney disease.

Box 11.1 Drugs known to be nephrotoxic.

• Some antibiotics (e.g. aminoglycosides, cephalosporins, amphotericin B, bacitracin and
vancomycin)
• Diuretics
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Antihypertensives (e.g. angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor
blockers)
• Chemotherapy (e.g. cisplatin, carboplatin, methotrexate)
• Contrast media, such as used in medical imaging
• Recreational drugs (e.g. heroin and amphetamines)
• HIV medication, such as protease inhibitors
• Ulcer medication (cimetidine)

common cause. Where a patient presents with AKI, the patient care records should be immediately
reviewed for medication as a possible cause.
The term AKI is now more commonly used than acute kidney failure. It is also more accurate as it
reflects injury that can precede failure, including its reversibility if the cause can be identified early.
Given that several AKI presentations are due to pre-renal processes, conditions such as sepsis should
be the focus of active treatments by healthcare professionals, with focus on the ‘Sepsis 6’ bundle of
care to decrease the risk of AKI from this cause (McGregor, 2014). The degree of treatment will
depend on the stage of the AKI, defined in Table 11.2.
Medications used in the renal system Chapter 11

Table 11.2 Stages of acute kidney injury.

Stage Criteria
1 Creatinine rise of 26 μL or more within 48 hours OR
Creatinine rise of 50–99% from baseline within 7 daysa (1.50–1.99 × baseline) OR
Urine outputb < 0.5 mL/kg/h for more than 6 hours
2 100–199% creatinine rise from baseline within 7 daysa (2.00–2.99 × baseline) OR
Urine outputb <0.5 mL/kg/h for more than 12 hours
3 200% or more creatinine rise from baseline within 7 daysa (3.00 or more × baseline) OR
Creatinine rise to 354 μL or more with acute rise of 26 μL or more within 48 hours or 50% or more rise
within 7 days OR
Urine outputb <0.3 mL/kg/h for 24 hours or anuria for 12 hours
a
The rise is known (based on previous blood tests) or presumed (based on history) to have occurred within 7 days.
b
Measurement of urine output may not be practical in a primary care population but can be considered in a person
with a catheter.
185
Management of AKI can be undertaken in conjunction with the renal team at the local admitting
hospital and should be started as soon as possible and within 24 hours of detection of the AKI.
Where there is uncertainty around the cause, admission of the patient for further investigation and
identification of the cause is warranted. For Stage I AKI, urgent removal of the cause is a priority,
including deprescribing or reducing the dose of that medication. Appropriate hydration is required
to support the kidney and referral to the British National Formulary for guidance on prescribing in
renal impairment may be warranted. Close monitoring of renal function is required to ensure that
the AKI resolves adequately (NICE, 2013).

Chronic kidney disease

Chronic kidney disease is a progressive deterioration of kidney function over time, anaemia marked
by reduction of estimated glomerular filtration (eGFR) and a corresponding rise in the creatinine
levels in the blood. This deterioration is hastened by comorbid factors such as diabetes and hyper-
tension. Diagnosis of CKD is made when eGFR is less than 60 mL/min/1.73m2 , or there is proteinuria
(identified through a urinary albumin:creatinine ratio [UrACR] of more than 3 mg/mL), or persistent
haematuria (two out of three dispsticks show 1+ or more blood after local infection has been
excluded). Figure 11.2 shows an example of a blood test result indicating CKD which has the renal
failure pattern of reduced eGFR and a rise in serum creatinine. There is an absence of AKI staging and
if compared against previous test results would be expected to show a chronic deterioration or a
long-term (but possibly stable) CKD presentation.
Chronic kidney disease is often a silent disease that is picked up as part of testing for other dis-
eases, such as essential hypertension or diabetes, or during a normal medical check. The blood
panel urea and electrolytes (U&E) is a commonly requested and relatively low-cost investigation
used in a wide variety of clinical presentations that warrant investigation. The possibility of an acute-
on-chronic deterioration should be considered when there is a sudden deterioration, as per the
guidance related to AKI presentations. Dependent on the urine ACR and eGFR, CKD can be given a
grade of 1–5, as described in Table 11.3 (NICE, 2015). CKD warrants caution in prescribing and regu-
lar appraisal for signs of deterioration.

Management of CKD
The prescribing of iron is not routinely required for renal anaemias (‘anaemia of chronic disease’) but care
should be taken to exclude other types of anaemia, such as iron deficiency. If renal anaemia is suspected,
arrange referral to a nephrology specialist for further investigation and management.
As indicated in Figure 11.1, hypocalcaemia and increased parathyroid hormone secretion are seen
in renal disease, so checking these levels is recommended in CKD 1–3b stages (NICE, 2015). Calcium
abnormalities may present as an acute crisis and should be rapidly appraised and clinically corre-
lated. Prescribing vitamin D3 and calcium, available in a combined formulation for ease of adminis-
tration, should be considered in renal patients to try and correct these abnormalities.
Specimen: SERUM

Investigation Normal Result

Serum electrolytes

Serum sodium 133.0–146.0 mmol/L 141 mmol/L

Serum potassium 3.5–5.3 mmol/ 4.8 mmol/L

Serum creatinine 59.0–104.0 μmol/L 162 μmol/L

Serum chloride 95.0–108.0 mmol/L 104 mmol/L

Serum urea

Specimen: SERUM Collected: 25 Sep 2017 09:00

Investigation Normal Result

Serum urea 2.5–7.8 mmol/L 11.9 mmol/L

eGFR using creatinine (CKD-EPI) per 1.73 m2

Specimen: SERUM Collected: 25 Sep 2017 09:00

Investigation Normal Result

eGFR using creatinine (CKD- >60.0 mL/min 34 mL/min

EPI) per 1.73 m2
If Afro-Caribbean, multiply
result by 1.159

Figure 11.2 Blood tests that indicate chronic kidney disease.

Table 11.3 Categories of CKD.

Urinary ACR (mg/mmol)
2
eGFR (mL/min/1.73 m ) A1 (<3) A2 (3–30) Moderately A3 (>30) Severely
Normal to mildly increased increased
increased
G1 >90 <1 1 >1
Normal and high
G2 60–89 <1 1 >1
Mild reduction related to normal range
for a young adult
G3a 45–59 1 1 2
Mild to moderate reduction
G3b 30–44 <2 2 >2
Moderate to severe reduction
G4 15–29 2 2 3
Severe reduction
G5 <15 4 >4 >4
End-stage kidney failure
Medications used in the renal system Chapter 11

The aim of treatment of CKD is to slow the rate of decline of renal function and this will involve
managing comorbid conditions such as diabetes and hypertension. Medications such as angiotensin-
converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), perhaps paradoxi-
cally since they also have renotoxic potential, are known as renoprotective agents as, their
therapeutic action is to reduce blood pressure, and slow the rate of progression of CKD. If using
these medicines, a follow-up U&E blood test should be made 1–2 weeks after starting or changing
dosing, in order to screen for acute renal toxicity produced by these drugs (see Box 11.1). The drugs
may need to be stopped if there is significantly reduced eGFR. Failure to deprescribe can be a com-
mon pitfall of using these drugs.

Electrolyte abnormalities resulting

from poor renal function
Hyponatraemia (low serum sodium) 187
As the most abundant extracellular cation in the body, sodium exerts a large influence on the plasma
osmolality and therefore the extracellular fluid volume. The physiological control of serum sodium
concentration is achieved by adjusting water intake (through thirst) and water excretion (through
antidiuretic hormone). Hyponatraemia is defined as a serum sodium concentration of less than
135 mmol/L. Box 11.2 defines the various levels of severity of hyponatraemia. The rate of onset can
also be classified as acute (<48 h) or chronic (≥48 h).

Box 11.2 Levels of hyponatraemia

Mild 130–135 mmol/L
Moderate 125–129 mmol/L
Severe <125 mmol/L

Healthy kidneys are able to produce urine with a much higher osmolality than plasma, thereby
excreting solutes while conserving water, and adjusting the excretion of electrolytes and water to
control plasma osmolality.
Kidney disease may result in failure to maintain electrolyte balance, as the kidneys lose the ability
to produce urine of a different osmolality to the plasma. In this situation, if fluid intake is greater than
urine output, there will be water retention and a dilutional (volume overload) hyponatraemia.
Treatment of severe hyponatraemia will require hospital admission and infusion with hypertonic
saline (Ball et al., 2016).

Hypokalaemia (low serum potassium) and hyperkalaemia (high

serum potassium)
Potassium is the main intracellular cation and is integral to the maintenance of an electrochemical
gradient across cell membranes, and the normal functioning of electrically excitable tissues such as
nerve and muscle. Abnormalities in serum potassium levels can therefore cause serious, sometimes
fatal, cardiac dysrhythmias and should be considered life-threatening.

Urinary retention and incontinence

Clinical consideration
Urinary retention is often really uncomfortable, and the clue may be that the patient struggles to sit still
or is in a lot of pain. The intervention will be catheterisation, but you want to make sure the cause (maybe
a medicine) has been determined before removal of the catheter!
Chapter 11 Medications used in the renal system

Urinary incontinence can occur as a result of structural or other abnormalities or with no underlying
pathology. Medications that can contribute to incontinence include diuretics, muscle relaxants,
sedatives, narcotics and antihistamines. Assessment of prescribed medications and reduction in
dosing or deprescribing may be an option to address incontinence and is an important considera-
tion. Acute incontinence can also be caused by urinary tract infection and assessment for the infec-
tion and antimicrobial treatment may be an appropriate management option.
Initiation of urination is dependent upon the parasympathetic nervous system and relies upon
co-ordination of simultaneous detrusor muscle (in the body of the bladder) contraction and sphinc-
ter muscle (at the neck of the bladder) relaxation.
In the male, enlargement of the prostate can cause urethral compression, since the prostate
wraps around the urethra. Clinically this may present as changes in urinary habit, including strug-
gling to start urinating, weak urinary stream, multidirectional spray and postvoiding dribble.
In females, a clear clinical history will help differentiate between stress incontinence, urgency
urinary incontinence or a mixed presentation (Hsu and Pierre, 2019; NICE, 2019). Subtypes of incon-
tinence are also detailed in national guidelines, including those associated with overactive bladder
188 syndrome or OAB (Barkin et al., 2017).
Drugs which may exacerbate urinary incontinence include alpha-1 adrenoceptor antagonists,
beta-adrenoceptor antagonists, antipsychotics, anticholinergics, antiparkinsonism drugs, antide-
pressants, benzodiazepines, diuretics and hormone replacement therapy. Contributing conditions
may include spinal surgery, bladder prolapse, multiple sclerosis and Parkinson disease. Fluid volume
may be increased in heart failure and bladder irritation may be seen in diabetes mellitus where glu-
cosuria is present. Given the potential for bladder pathology to result in urine backflow to the
kidneys, assessment for AKI is sensible in acute presentations.
There are several non-pharmacological steps which can be taken to support the management of
urinary incontinence, including pelvic floor exercises, reduction of dietary caffeine and surgical
options in some cases.
As a second line and pharmacological treatment, duloxetine may be a consideration in people
over 18 years of age. Duloxetine inhibits the reuptake of serotonin and noradrenaline.
Urinary retention can cause an overflow incontinence as the bladder becomes distended and
starts to empty by passive overflow. The bladder distension can be very painful and patients often
present in great discomfort. Acute intervention will be with urinary catheterisation to relieve the
retention and pharmacological therapy may be used to support a trial without catheter process, for
example, modified-release alfuzosin (alpha-blocker) in men over 65 years of age.

Drug-induced renal damage

As previously highlighted, nephrotoxic drugs are a common but avoidable cause of acute kidney
injury that also potentially contribute to or accelerate the development of chronic kidney disease.
Figure 11.3 provides examples of medications which can cause or contribute to kidney damage.
Healthcare professionals and workers should be aware that administration of drugs can cause a rapid
deterioration in a patient’s condition, as detailed in the section on acute kidney injury. If kidney func-
tion is compromised by a drug, it is also likely that the concentration of the causative agent and other
drugs in the patient’s circulation may rise to toxic levels, resulting in other adverse effects. Prescribing
information which will allow for adaptive prescribing considerations is contained within electronic
prescribing systems or within the British National Formulary (BNF).

Drugs that act on the renal system

Diuretics
Diuretics increase the excretion of fluid and are used to treat a number of different pathologies,
most commonly hypertension and congestive heart failure (both acute and chronic). Diuretics act
by reducing the reabsorption of filtered salts and water from the nephrons back into the blood-
stream, consequently increasing the excretion of both in the urine. The result is increased quantity
of urine and increased frequency of micturition. This removal of extracellular fluid will lower blood
volume, and therefore pressure and reduce oedema.
Medications used in the renal system Chapter 11

Renal tubular acidosis

Acute tubular necrosis 1. Proximal
Acetazolamide
Aminoglycosides
Amphotericin 2. Distal
Cisplatin Amphotericin
NSAIDs Lithium
Radiocontrast media
Paracetamol (self-poisoning) Interstitial nephritis
Allopurinol
Fanconi’s syndrome Azathioprine
Tetracyclines (if out-of-date) Furosemide
NSAIDs
Penicillins
Glomerulonephropathies Sulfonamides
Thiazides
1. Membranous Vancomycin
Captopril
Gold salts
Heavy metals Nephrogenic diabetes insipidus
Penicillamine 189
Phenytoin Lithium
Troxidone
Demethylchlortetracycline
Crystalluria
2. Minimal charge
NSAIDs Methotrexate
Sulfonamides Renal papillary necrosis
3. Acute nephritis
Penicillins Aspirin + phenacetin
NSAIDs

Figure 11.3 Adverse effects of drugs on the kidney.

Table 11.4 Subclasses of diuretics and their clinical uses.

Subclass Common uses
Loop diuretics, e.g. furosemide, • Fluid retention/oedema due to chronic heart failure
bumetanide • Resistant hypertension (not as a first-line agent)
Thiazides and related diuretics, • Hypertension, not first-line agent, commonly used in diabetes patients
e.g. bendroflumethiazide, indapamide • Mild to moderate heart failure
Osmotic diuretics, e.g. mannitol • Cerebral oedema and raised intraocular pressure
Potassium-sparing and aldosterone Spironolactone
antagonists. • Oedema (as monotherapy)
e.g. amiloride, spironolactone • Potassium conservation when used as an adjunct to thiazide or loop
diuretics for hypertension, congestive heart failure or hepatic ascites
Amiloride
• Oedema
• Ascites in cirrhosis of the liver
• Nephrotic syndrome
• Moderate to severe heart failure (adjunct)
• Resistant hypertension (adjunct)
• Primary hyperaldosteronism in patients awaiting surgery
• Given with thiazide or loop diuretics to preserve serum potassium levels
Carbonic anhydrase inhibitors, • Reduction of intraocular pressure
e.g. acetazolamide • Glaucoma
• Epilepsy

There are several subclasses of diuretic, including loop diuretics, thiazide and related diuretics,
osmotic diuretics, potassium-sparing and aldosterone-antagonists and carbonic anhydrase inhibi-
tors (see Table 11.4).
Diuretics affect electrolyte and water balance within the nephrons by acting on cotransporter
pumps, antagonising the effects of aldosterone or inhibiting transport of bicarbonate. When sodium
Chapter 11 Medications used in the renal system

Osmotic diuretics
Mannitol
Loop agents Inhibit Thiazides
Na+
Distal tubule under bendroflumethiazide
furosemide Inhib
it + –
aldosterone control (bendrofluazide)
bumetanide K+ Na Cl metolazone

Carbonic Collecting duct

anhydrase Distal
K+ – tubule
inhibitors Proximal 2 Cl
Na +, K +
tubule Na + K+
acetazolamide Thick ascending
K+
minor action of Ca 2+ loop of Henle
thiazides and Mg 2+
loop agents Aldosterone

190 Antagonises
Potassium-sparing
diuretics
HCO3– Na+
Basolateral K + Na+
K+ Na+ spironolactone
membrane
+ 70 mV + + amiloride
Prevent H + 80 mV
– – triamterene
formation Carbonic
and HCO3– H 2O HCO3– Tubule cell anhydrase
+ +
+ + K Na (cytosol)
reabsorption NB cell membrane
CO2 H 2CO 3 H+ only
impermeable
H+ Block Na+ channels
to HCO3–
Na+ Luminal
–
membrane
Carbonic – 50 mV – 30 mV
anhydrase + +
Na+ K+ Na+ H+
Na+ reabsorption (stimulated by
LUMEN CO 2 H 2CO3 H ++ HCO3– LUMEN aldosterone) makes lumen more '–ve'
+ H 2O encouraging K+ and H+ secretion

Na +/K +-ATPase antiporters synporters channels

Figure 11.4 The site of action of various diuretics in the nephron.

excretion (natriuresis) is increased, water excretion (diuresis) will follow, leading to reduction of
body fluid volume. Manipulation of this mechanism is the key action of diuretics and this can occur
at various points in the nephron (the proximal tubule, the loop or the distal tubule) (Figure 11.4). The
pharmacological choices may include use of one or more diuretics, dependent on the desired phar-
macological effect, as they can act synergistically.

Clinical consideration
Diuretics will affect electrolyte levels, so careful consideration must be given to the use of these drugs
and high doses avoided if at all possible.

Loop diuretics
Loop diuretics act on the thick ascending limb of the loop of Henle to inhibit the sodium–potas-
sium–chloride (Na–K–Cl) cotransporter. This transporter normally returns a high sodium and chlo-
ride load from the nephron back to the blood, so inhibition of this pump has the potential to
reduce sodium and chloride reabsorption very significantly. This causes loss of both fluid (diuresis)
and sodium (natriuresis) in the urine. The additional sodium retained in the tubule travels to the
distal convoluted tubule, and stimulates the aldosterone-sensitive sodium transporter which
causes the reabsorption of sodium in exchange for potassium. The resulting increase in potassium
excretion can cause hypokalaemia, which is a serious complication and a consideration in the use
of loop diuretics.
Medications used in the renal system Chapter 11

In the UK, a loop diuretic such as furosemide is commonly prescribed for heart failure or hyperten-
sion. In acute heart failure, loop diuretics administered intravenously can be a life-saving interven-
tion where congestive heart failure has resulted in pulmonary oedema, hypoxia and associated
cerebral irritation.

Clinical consideration
Paramedics can use furosemide to treat acute heart failure presentations, although first-line treatment
should be with nitrates. If using furosemide, be careful to check the mg/mL, as different manufacturers
produce different concentrations. As furosemide is given IV, the nitrate spray or sublingual tablet will
be a quicker administration and may buy you time to site a cannula.

191
The pharmacology of the loop diuretics is shown in Table 11.5.

Thiazide diuretics
Thiazide diuretics such as bendroflumethiazide and hydrochlorothiazide exert their effect
on the proximal portion of the distal convoluted tubule (DCT), which normally reabsorbs
around 5% of the filtered sodium (this limits the impact of thiazide diuretics on sodium
excretion compared with the loop diuretics). The thiazides inhibit the sodium and chloride
cotransporter situated on the DCT cells. This reduces the reabsorption of sodium and chlo-
ride ions, increasing their delivery to the sodium/potassium exchangers further along the
distal tubule, causing increased secretion of potassium and hydrogen into the tubule, in
exchange for sodium reabsorption. This results in an increased excretion and therefore lower
serum levels of potassium and hydrogen, which can lead to hypokalaemia and a metabolic
alkalosis. The thiazides also cause increased calcium reabsorption by nephrons, which can
raise serum calcium levels.
Oral bendroflumethiazide is a thiazide commonly used in the treatment of hypertension. It is
advised not to take this medication late in the day, as it increases urine volume and may cause noc-
turia. Occasionally serum electrolyte and lipid levels may be altered when starting medicines in this
group and these should be monitored after starting treatment.
Table 11.6 details the pharmacology of bendroflumethiazide.

Osmotic diuretics
Osmotic diuretics, including mannitol and isosorbide, are reserved to treat life-threatening cerebral
oedema that can occur, for example, after traumatic brain injury. When swelling occurs in the brain,
reduction of blood flow and compression of brain tissue can occur without rapid treatment to free
up some room inside the rigid skull. Osmotic diuretics are freely filtered by the glomerulus, are mini-
mally reabsorbed by the renal tubules and have no other pharmacological effects. The presence of
these osmotically active particles in the filtrate generates an osmotic pressure, promoting the move-
ment of water into the renal tubule. Osmotic diuretics exert their effects in the proximal convoluted
tubule, the thin descending loop of Henle and the collecting ducts, as these are the segments that
are highly permeable to water. In the presence of an osmotic diuretic, water moves into the tubule,
producing a diuresis.
The osmotic action of mannitol is also used in the management of raised intracranial or intraocu-
lar pressure, as it remains within the circulation, raising plasma osmolarity, resulting in movement of
water from the target tissues (brain, eye) into the circulation. The diuretic effects are subsequently
exerted in the kidney. Other uses include prevention of renal injury during major cardiac and vascu-
lar surgery as well as promotion of diuresis following renal transplantation, poisoning, rhabdomy-
olysis or haemolysis.
Chapter 11 Medications used in the renal system

Table 11.5 Pharmacology of loop diuretics.

Drug name Furosemide Bumetanide
Mode of action Inhibition of the sodium–potassium–chloride (Na–K–Cl) cotransporter
Route of Oral, intramuscular, intravenous Oral
administration
Indications Adult
Oedema and resistant oedema Oedema and resistant oedema
Resistant hypertension
Child
Oedema in heart failure, renal disease and Oedema in heart failure, renal disease
hepatic disease and hepatic disease
Pulmonary oedema Pulmonary oedema (severe cases)
Oliguria
192
Contraindications Anuria
Comatose and precomatose states associated with liver cirrhosis
Renal failure due to nephrotoxic or hepatotoxic drugs
Severe hypokalaemia
Severe hyponatraemia
Previous anaphylactic reaction
Precautions Can exacerbate diabetes (but hyperglycaemia less likely than with thiazides)
Can exacerbate gout
Hypotension should be corrected before initiation of treatment
Hypovolaemia should be corrected before initiation of treatment
Urinary retention can occur in prostatic hyperplasia
Lower initial doses of diuretics should be used in the elderly because they are particularly
susceptible to the side-effects. Dose should then be adjusted according to renal function
Can cause acute urinary retention in children with obstruction of urinary outflow
If there is an enlarged prostate, urinary retention can occur, although this is less likely if
small doses and less potent diuretics are used initially; an adequate urinary output should
be established before initiating treatment
Hypokalaemia is dangerous in severe cardiovascular disease and in patients also being
treated with cardiac glycosides
In hepatic failure, hypokalaemia caused by diuretics can precipitate encephalopathy
Pregnancy and breast feeding
Furosemide crosses the placental barrier and should not be given during pregnancy unless
there are compelling medical reasons.
Furosemide is contraindicated in breast feeding as it passes into breast milk and may
inhibit lactation
Bumetanide should be avoided during the first trimester.
Bumetanide has no data on breast feeding and therefore should not be used in lactating
mothers unless essential
Side-effects Dizziness
(common and very Electrolyte imbalance
common ONLY) Fatigue
Headache
Metabolic alkalosis
Muscle spasms (secondary to electrolyte disorders)
Nausea

(Continued)
Medications used in the renal system Chapter 11

Table 11.5 (Continued)

Drug name Furosemide Bumetanide
Interactions The dosage of concurrently administered As for furosemide.
cardiac glycosides, diuretics, antihypertensive Should not be administered
agents or other drugs with hypotensive concurrently with lithium, as diuretics
potential may require adjustment as a more reduce the clearance rate of lithium,
pronounced fall in blood pressure must be leading to increased risk of toxic effects.
anticipated if given concomitantly with Should not be given concurrently with
furosemide. cephaloridine or amphotericin as
The toxic effects of nephrotoxic drugs may be increased risk of toxic effects
increased by concomitant administration of
potent diuretics such as furosemide.
Some electrolyte disturbances (e.g.
hypokalaemia, hypomagnesaemia) may
increase the toxicity of some other drugs (e.g.
digoxin and drugs inducing QT interval 193
prolongation syndrome)
Absorption Approximately 65% of the dose is absorbed Rapidly and almost completely
after oral administration absorbed from the gastrointestinal tract
(bioavailability 80–95%)
Distribution Furosemide is up to 99% bound to plasma 95% bound to plasma proteins
proteins Plasma elimination half-life 0.75–2.6 h
Metabolism Liver Liver
No active metabolites are known
Elimination Mainly excreted in the urine, largely ~50% excreted unchanged via the
unchanged. kidneys. Remainder via bile in faeces
Remainder via bile in faeces. This route
significantly increases in renal failure
Monitoring Patients receiving loop diuretics should undergo regular monitoring of their serum sodium
and potassium levels; this is particularly important in the following patient groups:
• the elderly population.
• patients with impaired renal function and creatinine clearance below 60 mL/min per
1.73m2 body surface area
• patients with a coexisting disease which may cause electrolyte deficiencies (e.g. liver
disease, anorexia nervosa)
• patients receiving chronic corticosteroid or digoxin therapy. Digoxin has a very narrow
therapeutic range and potassium deficiency can trigger or exacerbate digoxin toxicity
Ototoxicity Rapid intravenous administration of furosemide can cause tinnitus and permanent hearing
loss (ototoxicity). Intravenous administration rates should not usually exceed 4 mg/min,
but single doses of up to 80 mg may be administered more rapidly; a lower rate of infusion
may be necessary in renal impairment

Source: British National Formulary 2021.

Drugs used to treat urinary retention and urinary incontinence

The pharmacotherapy targets for these conditions are the receptors responsible for bladder
control – adrenergic and muscarinic receptors. Adrenergic alpha-1 receptors in the smooth sphinc-
ter muscle in the neck of the bladder cause contraction of the sphincter when activated, preventing
bladder emptying. Inhibition of this sphincter is necessary to allow bladder emptying.
Parasympathetic control of the body of the bladder results in contraction of the bladder when ace-
tylcholine acts on muscarinic receptors in the bladder muscle. Blockers (antagonists) of alpha-1
receptors such as tamsulosin and doxazosin are used in the treatment of acute and chronic urinary
retention, as they prevent the contraction of the bladder sphincter, helping to relieve urinary reten-
tion (Figure 11.5). Since normal bladder voiding involves parasympathetic contraction of the blad-
der while simultaneously relaxing the sphincter muscle by inhibiting the sympathetic influence on
Chapter 11 Medications used in the renal system

Table 11.6 Pharmacology of thiazide diuretics.

Drug name Bendroflumethiazide
Mode of action Inhibition of the sodium chloride cotransport protein with the proximal part of the distal
convoluted tubule (DCT)
Route PO
Indications Adult
Oedema
Hypertension
Child
Hypertension
Oedema in heart failure, renal disease and hepatic disease
Pulmonary oedema
Contraindications Addison disease
Hypercalcaemia
194 Hyponatraemia
Refractory hypokalaemia
Symptomatic hyperuricaemia
Cautions Diabetes
Gout
Hyperaldosteronism
Hypokalaemia – dangerous in severe cardiovascular disease and in patients also being
treated with cardiac glycosides
Lower initial doses of diuretics should be used in the elderly
Malnourishment
Nephrotic syndrome
Systemic lupus erythematosus
Pregnancy and breast feeding
• Crosses the placenta and its use may be associated with hypokalaemia, increased blood
viscosity and reduced placental perfusion, so should be avoided
• Small amounts pass into breast milk – should be avoided in breast-feeding mothers
• Suppresses lactation
Common Alkalosis due to hypochloraemia
side-effects Constipation
Diarrhoea
Dizziness
Electrolyte imbalance
Headache
Hyperuricaemia
Nausea
Postural hypotension
Urticaria
Interactions Antiarrhythmics
Antidepressants
Antidiabetics
Antiepileptics
Antifungals
Antihypertensives
Antipsychotics
Calcium salts
Corticosteroids
Cytotoxic agents
Hormone antagonists
Lithium
Vitamins

(Continued)
Medications used in the renal system Chapter 11

Table 11.6 (Continued)

Drug name Bendroflumethiazide
Absorption Completely absorbed from the gastrointestinal tract
Diuresis is initiated in about 2 h and lasts for 12–18 h or longer
Distribution >90% bound to plasma proteins
Metabolism Variable degree of hepatic metabolism
Elimination ~30% excreted unchanged in urine with the remainder excreted as metabolites

Source: British National Formulary 2021.

Ureters
Diuretics, alcohol 195
Peritoneum

Bladder
CCBs, opioids, muscle
Detrusor muscle
relaxants, antidepressants,
(M, β3, PDE1, PDE5)
antipsychotics, dopamine Trigone (α1)
agonists, anticholinergics,
Internal urethral
antihistamines
sphincter
Urine
Prostate gland
Alpha blockers (PDE5, α1, M3)

Bladder neck (α1)

Alpha blockers
Pelvic floor
(striated muscle)
Urethra (α1)
External urethral
sphincter (nicotinic)

α: alpha-adrenergic; β: beta-adrenergic; CCB: calcium channel blocker; M: muscarinic;

PDE: phosphodiesterase; UI: urinary incontinence.

Figure 11.5 Sites of drug action in the urinary tract.

it, combination treatment with both cholinergic agents and alpha-blockers can significantly improve
bladder emptying when compared to treatment with alpha-blocker therapy alone (Filson
et al., 2013). The pharmacology of these agents is shown in Table 11.7.

Conclusion
As an allied healthcare professional, you will undoubtedly be involved in the care of a number of
patients with one or multiple types of renal disorder. These disorders can be very complex and can
have detrimental effects on a patient’s activities of daily living. The causes of renal disorders can be
multifactorial and often are interlinked with other comorbidities, such as cardiovascular disease and
diabetes. The incidence of AKI continues to rise despite multiple public health campaigns and NHS
initiatives. As such, it is crucial that healthcare professionals involved in supporting this patient
group to manage their disease have a sound understanding of the pathophysiological and pharma-
cological evidence base that underpins the promotion of safe and effective care.
Chapter 11 Medications used in the renal system

Table 11.7 Pharmacology of two alpha-1 receptor antagonists used for urinary tract disorders.
Drug Doxazosin Tamsulosin
Mode of action Alpha-1 receptor antagonist Alpha-1 receptor antagonist
Route Oral PO
Indications Adult Adult
Benign prostatic hyperplasia (BPH) Benign prostatic hyperplasia
Hypertension Child
Dysfunctional voiding (administered on
expert advice)
Contraindications Previous anaphylactic response to drug Previous anaphylactic response to drug
History of micturition syncope (in patients History of micturition syncope (in patients
with BPH) with BPH)
History of postural hypotension History of postural hypotension
196 Cautions Care with initial dose (risk of postural Cataract surgery (risk of intraoperative
hypotension) floppy iris syndrome)
Cataract surgery (risk of intraoperative floppy Concomitant antihypertensives (reduced
iris syndrome) dosage and specialist supervision may be
Elderly required)
Heart failure Elderly
Pulmonary oedema due to aortic or mitral Pregnancy and breast feeding
stenosis Tamsulosin is not indicated for use in
Pregnancy and breast feeding women
No evidence of teratogenicity; use only when
potential benefit outweighs risk
Accumulates in milk in animal studies
Common Arrhythmias Dizziness
side-effects Chest pain Sexual dysfunction
Cough
Cystitis
Dizziness
Drowsiness
Dry mouth
Dyspnoea
Gastrointestinal discomfort
Headache
Hypotension
Muscle complaints
Nausea
Oedema
Palpitations
Vertigo
Interactions Phosphodiesterase inhibitors – additional Phosphodiesterase inhibitors (due to
vasodilation vasodilatory effects).
CYP 3A4 inhibitors such as clarithromycin, CYP 3A4 inhibitors such as clarithromycin,
indinavir, itraconazole, ketoconazole, indinavir, itraconazole, ketoconazole,
nefazodone, nelfinavir, ritonavir, saquinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
telithromycin or voriconazole. Results in slower telithromycin or voriconazole. Results in slower
metabolism and higher plasma level of drug metabolism and higher plasma level of drug
Absorption Absorbed from the intestine. Absorbed from the intestine.
Bioavailability 66% Bioavailability almost 100%
Distribution 98% bound to plasma proteins, so limited 99% bound to plasma proteins, so limited
distribution distribution
Metabolism Extensively metabolised in the liver Low hepatic first-pass effect, metabolised
slowly
Elimination In urine In urine

Source: British National Formulary 2021.

Medications used in the renal system Chapter 11

Skills in practice: identifying the need

for furosemide use
• Is this definitely acute heart failure (and not pneumonia?)
• Why are you using a diuretic instead of nitrates?
• Have you checked your JRCALC clinical guidelines for indications, cautions and contraindications?
• Have you checked the vial using the 5 Rs (right drug, right dose, right time, right route, right person)?
• If you haven’t done so, check your JRCALC clinical guidelines for the required dose level.
• Site a cannula and flush it for patency.
• Draw up the medicine and administer as a slow push.

Episode of care 197

You are dispatched to a 65-year-old male feeling short of breath. You and your crewmate attend a local
address in a ground floor flat. On entering the venue, you can hear a bubbly chest from down the
hallway and the male patient appears diaphoretic and tachypnoeic.
His observations show a marked tachycardia but no arrhythmia and signs of an old myocardial
infarction in the anterior leads. There are no other ischaemic or acute changes. His heart rate is 125
beats per minute, his blood pressure is 210/130 mmHg, his temperature is 37.0 °C and his oxygen satu-
rations are 65% on room air. You suspect acute heart failure.
Your management includes sitting the patient up, applying oxygen therapy and then a salbutamol
nebuliser to ease the respiratory distress. You now consider which treatments you are going to start first.
Do you start with sublingual glyceryl trinitrate or intravenous diuretics?

The red flags that may indicate the need for fluid offloading are:
• severe hypertension
• hypoxia
• audible pulmonary oedema.
The red flags which may indicate someone is in acute urinary retention include:
• not passing urine
• lower abdominal pain
• history of back pain (including cauda equina syndrome and pyelonephritis).

The following are a list of conditions associated with the renal tract. Take some time and write
notes about each of the conditions. Think about the medications that may be used to treat these
conditions and be specific about the pharmacokinetics and pharmacodynamics. Remember to
include aspects of patient care. If you are making notes about people you have offered care and
support to, you must ensure that you have adhered to the rules of confidentiality.

The condition Your notes

Acute kidney injury
Chronic kidney disease
Electrolyte imbalance
Oedema
Urinary retention
Chapter 11 Medications used in the renal system

Glossary
Acute A word meaning short-term and of rapid onset, usually requiring a rapid
response.
Albumin A type of protein that occurs in the blood.
Alphacalcidol A vitamin D supplement.
Anaemia A shortage of red blood cells in the body, causing tiredness, shortage of
breath and pale skin. One of the functions of the kidneys is to make EPO
(erythropoietin), which stimulates the bone marrow to make blood
cells. In kidney failure, EPO is not made and anaemia results.
Bicarbonate A substance that is normally present in the blood which is measured in
the biochemistry blood test. A low blood level of bicarbonate shows
there is too much acid in the blood.
Biochemistry blood test A test that measures the blood levels of various different substances.
198 Substances measured in people with kidney failure usually include
sodium, potassium, glucose, urea, creatinine, bicarbonate, calcium,
phosphate and albumin.
Bladder The organ in which urine is stored before being passed from the
body.
Blood level A measurement of the amount of a particular substance in the blood,
sometimes expressed in mmol/L (millimoles per litre) or μmol/L (micro-
moles per litre) of blood.
Blood pressure The pressure that the blood exerts against the walls of the arteries as it
flows through them. Blood pressure measurements consist of two num-
bers. The first is the systolic blood pressure, the second, the diastolic
blood pressure.
Blood vessels The tubes that carry blood around the body. The main blood vessels are
the arteries and veins.
BP Abbreviation for blood pressure.
CAPD Abbreviation for continuous ambulatory peritoneal dialysis. A continu-
ous form of peritoneal dialysis in which patients perform the exchanges
of dialysis fluid by hand. The fluid is usually exchanged four times dur-
ing the day, and is left inside the patient overnight.
Catheter A flexible plastic tube used to enter the interior of the body. A catheter
is one of the access options for patients on haemodialysis. For patients
on peritoneal dialysis, a catheter allows dialysis fluid to be put into and
removed from the peritoneal cavity. A catheter may also be used to
drain urine from the bladder.
Chronic A word meaning long-term and of slow onset, not usually requiring
immediate action.
CKD Abbreviation for chronic kidney disease. This is an abnormality in the
kidneys that is present for more than 3 months, and is graded stages 1,
2, 3a, 3b, 4 and 5 for minor to severe kidney disease.
Clearance The removal of substances from the body by the kidneys. In kidney fail-
ure, clearance is inadequate and toxins can build up in the blood.
Creatinine A waste substance produced by muscle metabolism. The clearance of
creatinine is also used as an indicator of kidney function.
Cystitis A type of infection that causes inflammation of the bladder.
Cytomegalovirus (CMV) A virus that normally causes only a mild ‘flu-like’ illness.
Dehydration A condition in which there is a lower than normal body water
content.
Diabetes mellitus A condition (also known as sugar diabetes or simply as diabetes) in
which the glucose level in the blood is poorly controlled, resulting in
chronically high blood glucose. This can lead to kidney failure over the
long term kidney failure.
Medications used in the renal system Chapter 11

Dialysis An artificial process by which the toxic waste products of food

and excess water are removed from the body. Dialysis therefore
takes over some of the work normally performed by healthy kid-
neys. The name dialysis comes from a Greek word meaning ‘to
separate’, i.e. to separate out the ‘bad things’ in the blood from
the ‘good things’.
Diuretic drugs The medical name for water tablets. These drugs increase the
amount of urine that is passed. Two commonly used diuretics
are furosemide and bumetanide.
eGFR Abbreviation of estimated glomerular filtration rate. Measurement
of how much blood is filtered by the kidneys, calculated from the
blood level of creatinine.
End-stage renal failure (ESRF) A term for advanced chronic kidney failure. People who develop
ESRF will die within a few weeks unless treated by dialysis or
transplantation. These treatments control ESRF but cannot cure
it.
199
End-stage renal disease (ESRD) An alternative name for end-stage renal failure.
Established renal failure (ERF) An alternative name for end-stage renal failure or end-stage
renal disease.
Fluid overload A condition in which the body contains too much water. It is
caused by drinking too much fluid, or not losing enough. Fluid
overload occurs in kidney failure because one of the main func-
tions of the kidneys is to remove excess water. Fluid overload
often occurs with high blood pressure. Excess fluid first gathers
around the ankles (ankle oedema) and may later settle in the
lungs (pulmonary oedema).
GFR Abbreviation of glomerular filtration rate. Measurement of how
much blood is filtered by the kidneys; if the GFR is low, there is
kidney disease.
Glomerulus One of the tiny filtering units inside the kidney.
Glomerulonephritis Inflammation of the glomeruli, which is one of the causes of
kidney failure.
Haemodialysis A form of dialysis in which the blood is cleaned outside the
body, in a machine called a dialysis machine or kidney machine.
The machine contains a filter called the dialyser or artificial
kidney. Each dialysis session lasts for 3–5 hours, and sessions are
usually needed three times a week.
Kidneys The two bean-shaped body organs where urine is made. They
are located at the back of the body, below the ribs. The two
main functions of the kidneys are to remove toxic wastes and to
remove excess water from the body. The kidneys also help to
control blood pressure, control the manufacture of red blood
cells and keep the bones strong and healthy.
Kidney failure A condition in which the kidneys are less able than normal to
perform their functions of removing toxic wastes, removing
excess water, helping to control blood pressure, control red
blood cell manufacture and to keep the bones strong and
healthy. Kidney failure can be acute or chronic. Advanced
chronic kidney failure is called end-stage renal failure (ESRF).
Liver function tests (LFTs) Blood tests that show how well the liver is working.
Marker A substance that is used as an indicator of physiological func-
tion. Both creatinine and urea are markers for kidney function.
Nephr- Prefix meaning relating to the kidneys.
Nephron Small filtering unit in the kidney, made up of blood vessels (glo-
meruli) and tubules.
Chapter 11 Medications used in the renal system

Nephritis A general term for inflammation of the kidneys. Also used as an

abbreviation for glomerulonephritis (GN). A kidney biopsy is needed
to diagnose nephritis.
Nephrology The study of the kidneys.
Oedema An abnormal build-up of fluid, mainly water, in the tissues. People
with kidney failure are prone to fluid overload leading to oedema. The
two most common places for water to collect in the body are around
the ankles (ankle oedema) and in the lungs (pulmonary oedema).
Potassium A mineral that is normally present in the blood, and which is measured
in the biochemistry blood test. Either too much or too little potassium
can be dangerous, causing the heart to stop. People with kidney fail-
ure may need to restrict the amount of potassium in their diet.
Pulmonary oedema A serious condition in which fluid builds up in the lungs, causing
breathlessness. People with kidney failure develop pulmonary
oedema if fluid overload is not treated promptly.
200 Pyelonephritis Inflammation of the drainage system of the kidneys, one of the causes
of kidney failure. It can be diagnosed by an ultrasound scan or by an
intravenous pyelogram (IVP).
Renal Adjective meaning relating to the kidneys.
Renal artery The blood vessel which carries blood from the heart to the kidneys.
Sodium A mineral that is normally present in the blood, and which is meas-
ured in the biochemistry blood test. Sodium levels are not usually a
problem for people with kidney failure and are quite easily controlled
by dialysis.
Uraemia An abnormally high level of nitrogenous wastes in the blood.
Symptoms may include nausea, weight loss, high blood pressure
and/or trouble sleeping.
Ureters The tubes that take urine from the kidneys to the bladder.
Urethra The tube that takes urine from the bladder to the outside of the body.
Urinary catheter A plastic tube inserted into the bladder for the removal of urine.
Urination The passing of urine out of the body.
Urine The liquid produced by the kidneys, consisting of nitrogenous waste
products, electrolytes and water.
Water tablets The common name for diuretic drugs.

References
Ball, S., Barth, J. and Levy, M. (2016).Emergency management of severe symptomatic hyponatraemia in adult
patients. Endocrine Connections 5(5): g4–g6.
Barkin, J., Habert, J. and Wong, A. (2017). The practical update for family physicians in the diagnosis and manage-
ment of overactive bladder and lower urinary tract symptoms. Canadian Journal of Urology 24(5S1): 1–11.
Filson, C.P., Hollingsworth, J.M., Clemens, J.Q. and Wei, J.T. (2013). The efficacy and safety of combined therapy
with alpha-blockers and anticholinergics for men with benign prostatic hyperplasia: a meta-analysis. Journal
of Urology 190(3): 2153–2160.
Hu, J.S. and Pierre, E.F. (2019). Urinary incontinence in women: evaluation and management. American Family
Physician 100(6): 339–348.
McGregor, C. (2014). Improving time to antibiotics and implementing the ‘Sepsis 6’. BMJ Open Quality 2: u202548.
National Institute for Health and Care Excellence (NICE). (2013). Clinical guideline 169: Acute kidney injury.
Prevention, detection and management up to the point of renal replacement therapy. London: National Institute
for Health and Care Excellence.
National Institute for Health and Care Excellence (NICE). (2015). Chronic kidney disease. Early identification and
management of chronic kidney disease in adults in primary and secondary care. London: National Institute for
Health and Care Excellence.
National Institute for Health and Care Excellence (NICE). (2019). Clinical guideline NG123. Urinary incontinence and
pelvic organ prolapse in women: management. London: National Institute for Health and Care Excellence.
Medications used in the renal system Chapter 11

Further reading
Renal and ureteric colic: https://cks.nice.org.uk/topics/renal-or-ureteric-colic-acute/
Incontinence in children: https://cks.nice.org.uk/topics/bedwetting-enuresis/
Chronic kidney disease: https://cks.nice.org.uk/topics/chronic-kidney-disease/
Hyponatraemia: https://cks.nice.org.uk/topics/hyponatraemia/
Lower urinary tract symptoms in men: https://cks.nice.org.uk/topics/luts-in-men/

Multiple-choice questions
1. What is the name of the loop within the kidney nephron?
(a) The loop of Destiny
(b) The loop of Henry
(c) The loop of Henle
(d) The loop of Bowman
201
2. Each of the tubes which connect the kidney to the urinary bladder is a:
(a) Ureter
(b) Urethra
(c) Uterus
(d) Uvula
3. Which of the following is an example of a pre-renal pathophysiology?
(a) Fibromuscular dysplasia
(b) Acute tubular necrosis
(c) Acute interstitial nephritis
(d) Benign prostatic hyperplasia
4. Which of the following is an example of an intrarenal pathophysiology?
(a) Fibromuscular dysplasia
(b) Low BP from a haemorrhage
(c) Cardiogenic shock from a myocardial infarction
(d) Acute glomerulonephritis
5. Which of the following is an example of a postrenal pathophysiology?
(a) Heart failure
(b) Anaphylaxis
(c) Renal calculus
(d) Acute tubular necrosis
6. Which of the following is an example of a pre-renal pathophysiology?
(a) Bladder tumour
(b) Extensive burns
(c) Renal calculi
(d) Benign prostatic hyperplasia
7. Which of the following is an example of a postrenal pathophysiology?
(a) Heart failure
(b) Anaphylaxis
(c) Sepsis
(d) Bladder tumour
8. Which of the following drugs have nephrotoxic potential?
(a) Propranolol
(b) Mannitol
(c) Aspirin
(d) Salbutamol
Chapter 11 Medications used in the renal system

9. Acute kidney injury is characterised by which change in blood measurement?

(a) A reduced estimated glomerular filtration rate (eGFR)
(b) A raised estimated glomerular filtration rate (eGFR)
(c) A raise in hepatic transaminases
(d) A decrease in hepatic transaminases
10. Plasma level of which nitrogenous chemical tends to rise in acute kidney injury?
(a) Uric acid
(b) Acetic acid
(c) Creatinine
(d) Basophils
11. What is the medical term for reduced urine output?
(a) Azotemia
(b) Polydipsia
202 (c) Polyuria
(d) Oliguria
12. What is the name of an increase in plasma level of nitrogenous waste products?
(a) Oliguria
(b) Azotemia
(c) Ketoacidosis
(d) Metabolic alkalosis
13. What is the blood vessel that encircles the nephron?
(a) Vasa recta
(b) Vas deferens
(c) Inferior vena cava
(d) Renal artery
14. How much urine does an average adult produce per hour?
(a) 0.5–1 mL/kg/h
(b) 50–100 mL/kg/h
(c) 500–1000 mL/kg/h
(d) 5000–10000 mL/kg/h
15. Which system, when activated, may worsen ischaemia caused by renal artery stenosis?
(a) Hepatorenal system
(b) Renin-angiotensin-aldosterone system
(c) Reno-diverse system
(d) Glomerular-tubular-interstitial system
Chapter 12
Medications and
diabetes mellitus
Hayley Croft and Olivia Thornton

Aim
This chapter aims to describe medicines used by patients with diabetes and their effects on blood
glucose, including medicines used to treat complications that could present to paramedics when
attending to a patient with diabetes.

Learning outcomes
After reading this chapter the reader will be able to:

1. Discuss the role of insulin and glucagon in maintaining blood glucose homeostasis
2. Recognise a range of antihyperglycaemic agents used in diabetes and describe their effect on
blood glucose levels and potential adverse effects
3. Recognise the signs and symptoms of common diabetic emergencies and their causes
4. Describe the management of common diabetic emergencies, including hyperglycaemia and
hypoglycaemia.

Test your knowledge

1. How are blood glucose levels regulated in the body?
2. What strategies could you use to determine if a patient was experiencing high or low blood
glucose?
3. What groups of patients are vulnerable to experiencing fluctuations in blood glucose levels?
4. What drugs are you aware of that may be used to increase or decrease blood glucose levels?

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 12 Medications and diabetes mellitus

Introduction
Insulin is necessary for normal carbohydrate, protein and fat metabolism. Diabetes mellitus (DM) is
defined as a group of chronic disorders characterised by high blood sugar (hyperglycaemia), arising
from insulin deficiency or insulin resistance, or both. DM is known for its association with long-term
damage and organ impairment. Although their names suggest two types of the same disease, the
pathophysiology of type 1 and type 2 diabetes mellitus is different.
People with type 1 diabetes mellitus (T1DM) do not produce enough insulin and rely on exoge-
nous insulin administration for survival. In type 2 diabetes mellitus (T2DM), the body’s cells cannot
respond to insulin as well as they should. In later stages of T2DM, the body may also not produce
enough insulin. People with T2DM are not completely dependent on insulin administration for sur-
vival. However, many of these individuals will experience decreased insulin production and may
therefore require supplemental insulin use, particularly during times of stress (Petersons, 2018).
Gestational diabetes mellitus (GDM) arises when the woman’s insulin reserves are insufficient to
meet the extra demands of pregnancy. Screening for hyperglycaemia during pregnancy is important
in detecting gestational diabetes as women may be asymptomatic. If left untreated, complications of
204 gestational diabetes such as fetal macrosomia (big baby syndrome) and neonatal hypoglycaemia
may not be recognised and managed appropriately. Many women with GDM develop T2DM later in
life (Sherwin and Svancarek, 2021).
People with diabetes can experience an acute decline in control of their condition if their blood
glucose levels and insulin are out of balance. Although many patients will be educated on strategies
to correct the problem, sometimes they will not be able to help themselves, and a rapid response to
a diabetic emergency may be necessary, to assess and attend to patients with life-threatening meta-
bolic disturbance.

Hormonal control of blood glucose

Glucose is the primary source of fuel for all cellular ATP energy. Glucose is obtained from dietary
sources of carbohydrate, from liver stores of glycogen (the main storage form of glucose in the body)
or synthesised from non-carbohydrate precursors (gluconeogenesis). Blood glucose concentration is
maintained within a relatively narrow range despite wide fluctuations in dietary intake, under the
control of the endocrine pancreas which produces two major hormones, insulin and glucagon, that
regulate its mobilisation and storage (Figure 12.1).
Under normal circumstances, nutrient intake stimulates secretion of insulin from pancreatic beta
cells in the islets of Langerhans. Insulin lowers blood glucose by facilitating movement of glucose across
cell membranes for use as an energy source. Insulin also regulates glucose levels by suppression of
hepatic glucose output, increased uptake of glucose in muscle and reduced fat breakdown. When there
is no nutrient intake, blood glucose level is maintained by glucagon, a peptide hormone produced by

Blood glucose
increases.

Pancreas
Pancreas releases releases insulin
glucagon (promotes glucose
(promotes glycogen uptake)
breakdown)

Blood glucose
drops.

Figure 12.1 Interplay between insulin and glucagon in control of blood glucose.
Medications and diabetes mellitus Chapter 12

Box 12.1 Major actions of insulin and gluca-

gon in the body.
Insulin has the following anabolic effects.
• Drives glucose into cells
• Decreases production glucose by liver
• Inhibits fat breakdown (lipolysis)
• Increases conversion of glucose to triglycerides (fats)
• Drives potassium into cells
Glucagon has the following catabolic effects.
• Increases hepatic glucose output
MIMS Australia, 2020a, 2020b.

205
Adipose cells Pancreatic beta cells
takeup glucose release insulin

Insulin

Increasing
blood sugar

Decreasing
Exercise blood sugar
Eating

Glucagon

Pancreatic alpha cells Liver breaks down

release glucagon glycogen to glucose

Figure 12.2 Major actions of insulin and glucagon in the body.

pancreatic alpha cells. Glucagon provides the major counter-regulatory mechanism for insulin in
maintaining glucose homeostasis. It raises blood glucose concentration by stimulating hepatic glucose
production. The major actions of insulin and glucagon in the body are outlined in Box 12.1.
While insulin and glucagon exert short-term glucose control, as shown in Figure 12.2, other hor-
mones exert long-term effects on blood glucose, including glucocorticoid hormones (e.g. cortisol),
growth hormone, thyroid hormones and catecholamines (adrenaline and noradrenaline).

Monitoring diabetes
Patients with diabetes will require ongoing monitoring of various aspects of disease. One of the main
aims of diabetes treatment is to keep the blood glucose levels within target range. Blood glucose
monitoring is used as an educational tool to aid understanding of glycaemic control by the patient,
family, carers and health personnel, including paramedics. For many, it is an important aspect of the
day-to-day care of a patient with diabetes which enables adjustment of medication, food and drink
intake and physical activity, and response to hypo- or hyperglycaemia.
While home monitoring of blood glucose levels shows the short-term fluctuations, a glycated haemo-
globin (HbA1c) check provides a longer-term measure of blood glucose over 10–12 weeks, as it indicates
the percentage of haemoglobin molecules that have reacted with excess blood glucose to become
glycated. For health professionals, information about blood glucose levels and HbA1c is used to opti-
mise diabetic control to eliminate symptoms of hyperglycaemia, with the longer-term aim of preventing
diabetic complications such as blindness, kidney damage, amputation, heart attack and stroke.
Chapter 12 Medications and diabetes mellitus

In the prehospital setting, however, blood glucose and blood ketone levels are the most useful
indicators, and blood glucose measurement should be considered in all patients with an altered level
of consciousness (Sherwin and Svancarek, 2021).

Measuring blood glucose

Blood glucose levels are measured in millimoles per litre of blood (mmol/L). Normal blood glucose
levels are between 4.0 and 7.8 mmol/L (Diabetes Australia, 2021). The usual target blood glucose
level range depends on the individual and factors such as the type of diabetes, their medications and
medical conditions, diet, activity level and age.
The measurement is made by applying a small amount of blood to a disposable test strip. An elec-
tronic meter is then used to read the strip and display the blood glucose level. Some newer devices
use a sensor applied to the upper arm which captures interstitial fluid glucose readings, and other
monitoring systems are embedded into insulin pump devices.

206
Skills in practice: Tips for measuring blood
glucose levels
• Always use gloves.
• Pretest topical alcohol swab is not routinely required but may be used when necessary to clean
test site.
• Check expiry date on individual test strips and ensure they have not been damaged.
• Use a lancing device to obtain a blood sample from the side of the fingertip. It may be appropriate
to massage the finger in the direction of the fingertip to make it easier to obtain a blood sample.
• Although alternative sites (e.g. palm, upper forearm, thigh, calf ) may be used to obtain a blood
sample, testing from these sites is less accurate when blood glucose levels are falling or rising
rapidly, and fingertip testing is appropriate for non-routine blood glucose testing.
• Apply blood sample to test strip.
• Ensure the lancet is disposed of in a sharps container.

Paramedics may find that a patient’s blood glucose reading is unexpectedly high or low, and it may be
difficult to identify the reason(s) for this. Changes in activity level, food intake or medication can cause
blood glucose readings to alter and illness, pain and stress are common causes of changes in blood glu-
cose patterns. However, it is also important to consider circumstances in which a blood glucose reading
may be inaccurate, such that the results shown do not reflect the true blood glucose level. This is particu-
larly important when the patient’s signs and symptoms do not match the blood glucose reading.

Clinical consideration: Factors that may

interfere with the accuracy of blood glucose
measurements
• Poor quality of test strips, e.g. test strips are expired/out of date, poor storage and handling, ageing
• Wrong strips or incorrect technique
• Not enough blood applied to test strip
• Residual substance on unwashed hands prior to testing
• Testing site still damp from pretest topical alcohol
• Altitude, temperature and humidity.
• Test site location: side of fingertip usually used; alternative sites may be used when blood glucose is
stable but not when it is changing rapidly (e.g. after eating or exercise, when hypoglycaemic or ill).
Medications and diabetes mellitus Chapter 12

Measuring ketones
Ketones are produced when the body metabolises fats, which can occur in patients with inadequate
insulin, since glucose is not transported into cells and metabolised under those conditions. Ketones
can be detected in blood or urine, and high ketones can indicate diabetic ketoacidosis (DKA), a
severe complication of lack of insulin. Not all patients will need to be tested for ketones, and although
DKA can occur in any patient with diabetes, it is rare in T2DM, so patients with T1DM and those with
DKA symptoms are most likely to be tested. Blood ketone testing may be performed using at-home
test kits or meter systems in a very similar way to blood glucose levels, by using specific test strips.

Drug use in diabetes

Treatment of diabetes involves lifestyle measures, including diet and physical activity, and self-blood
glucose monitoring (SBGM), as well as antihyperglycaemic medications (oral and/or injectable).
Paramedics should be familiar with therapeutic approaches to managing diabetes and the factors
that can lead to an emergency.
207
Insulin replacement therapy
When diet and other therapies provide insufficient control of hyperglycaemia, insulin replacement
therapy is required. In health, basal insulin secretion constitutes approximately 50% of total insulin
secreted, with the remainder secreted as a rapid bolus response to food. Endogenous insulin is
secreted into the hepatic portal vein and acts directly on the liver, which does not occur when insulin
is injected into peripheral sites. The aim of insulin replacement therapy is to mimic, as far as possible,
normal ‘basal bolus’ physiological insulin response by pancreatic beta cells.

Insulin is measured in international units, and while most formulations are 100 units per mL (U/mL),
some newer formulations contain 200 U/mL, 300 U/mL or 500 U/mL. Insulin is considered a high-risk
medicine and varying strength of formulations may be a source of medication error.

Insulin administration
As a protein, insulin is rapidly destroyed by proteases in the gastrointestinal (GI) tract, and there-
fore requires parenteral administration. Insulin is usually administered by injection into the subcu-
taneous tissue layer of the abdomen. This is generally the area that provides the fastest absorption.
It may also be injected subcutaneously in the upper arm or anterolateral aspects of the thigh or
buttocks. Although not recommended for routine use, insulin can be given intramuscularly under
certain circumstances, such as diabetic ketoacidosis. The injection site is rotated with every injec-
tion to avoid injection site reactions such as lipodystrophy (abnormal distribution of fatty tissue
under the skin). Rotations are usually within the one area (e.g. a systematic pattern within the
abdomen), aiming to ensure each injection site is at least one finger-width away from the previous
injection, and not used more than once every 4 weeks (American Diabetes Association, 2003).

Clinical consideration: insulin administration

Factors that may affect insulin absorption include the following.
Injection site: insulin may absorb at different rates depending on where it is injected. It is absorbed
fastest from the abdomen, followed by the upper arms, outer thigh and buttocks. Fatty areas under the
skin (lipohypertrophy) and/or scar tissue may cause slower or more erratic absorption.
Muscle: insulin injected into muscle rather than subcutaneous tissue will be absorbed faster.
Physical activity: exercise increases the rate of insulin absorption from the injection site.
Chapter 12 Medications and diabetes mellitus

Table 12.1 Properties of insulin preparations.

Examples Onset Peak Duration Other
Ultra-short OR Insulin aspart, 10–15 mins 1–2 hours 2–5 hours Preparations are colourless/
rapid-acting insulin glulisine, clear solutions
analogue insulin insulin lispro
Short-acting Neutral insulin 30 mins 2.5–5 5–8 hours Preparations are colourless/
human insulin hours clear solutions
Intermediate- Isophane/NPH 1–2 hours 4–12 12–18 Suspension of soluble insulin
long-acting hours hours complexed with protamine
biphasic insulin sulfate.
Preparations are cloudy in
appearance
Long-acting Insulin detemir, 2 hours ‘Peakless’ Up to 24 Preparations are colourless/
analogue insulin insulin glargine hours clear solutions
Ultra-long- Insulin degludec 2 hours ‘Peakless’ Up to 42 Only used in fixed-dose
208 acting hours combination with insulin aspart
Source: Adapted from AMH (2020a) and MIMS Australia (2020b).

Insulin preparations
There are several types of insulin preparations as shown in Table 12.1. Insulin dosages are titrated to
the glycaemic response of the individual, their food intake and level of physical activity.
Mixed/premixed insulins are a combination of ultra-short-acting and intermediate/long-acting insulins,
usually administered once or twice daily. Premixed insulins are useful for elderly people who may have dif-
ficulty mixing their own insulins, but the major disadvantage is inflexibility in dosing adjustment.

Some longer-acting insulins continue to exert blood glucose-lowering effects for up to 24 hours or
longer. These insulin preparations may contribute to hypoglycaemic emergencies for several hours
after their administration.

The appropriate insulin dosage is dependent on the glycaemic response of the individual and
requires adjustment in certain situations.

Clinical consideration: Dosing insulin in certain

situations
Intercurrent illness: there may be increased requirements for insulin during illness, increased
temperature and/or inflammation.
Exercise: lower doses of insulin may be required.
Surgery: additional insulin may be required during surgery and recovery.
Fasting: even during fasting, basal insulin is usually required, at an adjusted dose.

Adverse effects of insulin

Hypoglycaemia (blood glucose level below 4 mmol/L) is the most important adverse effect of insulin.
The onset of hypoglycaemia may be abrupt and dangerous, and if prolonged or repeated can lead to
neurological damage. It may be caused by administering too much insulin, inadequate food intake
or intense exercise. Excessive alcohol consumption may prolong or delay hypoglycaemia. Insulin, as
Medications and diabetes mellitus Chapter 12

an anabolic hormone, can also lead to weight gain, which may impact compliance with insulin
replacement therapy, as well as increasing the risk of cardiometabolic disease.

Metformin
Metformin acts by inhibiting the production of glucose (gluconeogenesis) by the liver and inhibiting
the breakdown of stored glycogen to glucose (glycogenolysis). The drug improves insulin sensitivity
and glucose uptake by peripheral tissues such as skeletal muscle and delays intestinal glucose
absorption. Metformin is a preferred first-line treatment option for patients with T2DM and may be
particularly useful for patients who are overweight as it tends to produce gradual weight loss.
Metformin may be used as monotherapy or in combination with other antihyperglycaemic agents
(AMH, 2020b; American Diabetes Association, 2019).
Metformin is administered orally, and steady-state concentrations are reached in 24–48 hours
at usual clinical doses. It is not bound to plasma proteins and does not undergo hepatic metab-
olism so its half-life is largely dependent on renal function. In patients with decreased renal
function, the plasma half-life of metformin is prolonged. Metformin is available in immediate-
release formulations usually given 2–3 times daily or extended-release preparations usually
given once daily in the evening.
209
Metformin is associated with GI adverse effects (flatulence, diarrhoea, nausea, vomiting, metallic
taste in the mouth, abdominal cramps). These effects are usually mild and transient and can be mini-
mised by starting at a low dose, gradual dose titration and taking after food. Hypoglycaemia is less
likely to occur when metformin is used as a single agent, but can occur when used in combination
with other antihyperglycaemic agents that cause hypoglycaemia. Vitamin B12 malabsorption lead-
ing to vitamin B12 deficiency with long-term metformin use can occur (AMH, 2020b).
Rarely, metformin may be associated with metabolic (lactic) acidosis and should not be given to
patients with other risk factors for this condition, including hypoxic conditions such as respiratory
and heart failure, kidney disease, procedures that require iodine contrast media, excessive alcohol
intake or poorly controlled diabetes (Misbin, 2004).

Lactic acidosis is a form of metabolic acidosis associated with a build-up of lactate in the body and low
blood pH. It is a rare but serious side-effect of metformin therapy. Lactic acidosis occurs rarely after met-
formin at normal therapeutic doses but is more of a risk in patients with conditions that can themselves
cause lactic acidosis, or where metformin accumulates, such as in patients with renal impairment.

Sulfonylureas
Sulfonylureas include glibenclamide, gliclazide, glimepiride and glipizide. They act by directly
stimulating pancreatic islet beta cells to increase insulin release. Consequently, they are only effec-
tive in patients with functioning pancreatic beta cells. The rise in plasma insulin concentration
results in decreased hepatic glucose production and increased peripheral utilisation of glucose.
These drugs may be used as monotherapy or in combination with other antihyperglycaemic
agents (Petersons, 2018).
Sulfonylureas are not alike and differ in their potency, duration of action, activity of metabolites
and route of elimination (AMH, 2020c). They are well absorbed after oral administration. After absorp-
tion, sulfonylureas bind almost completely to plasma proteins, especially albumin. Glibenclamide is
completely metabolised in the liver, and its metabolites, which continue to have some hypoglycae-
mic action, are excreted via a dual pathway in both bile and urine (MIMS Australia, 2020c). Other
sulfonylureas are extensively metabolised in the liver and their metabolites are predominantly
excreted in the urine (MIMS Australia, 2020c).
Sulfonylureas may cause weight gain (which may be particularly problematic in overweight
patients with T2DM) and hypoglycaemia. Hypoglycaemia is associated more with long-acting agents,
the highest risk being with glibenclamide, which can provoke long-lasting hypoglycaemic reactions.
Chapter 12 Medications and diabetes mellitus

The risk of hypoglycaemia is increased by taking sulfonylureas without food, alcohol consumption,
renal impairment and coadministration of other antihyperglycaemic agents (AMH, 2020c).

Incretin mimetics
Incretins are peptide hormones produced by cells of the intestinal mucosa in response to food. After
their release into the gastrointestinal tract (GIT), incretins, such as glucagon-like peptide-1 (GLP-1),
are responsible for a cascade of events culminating in secretion of insulin. This effect, known as the
incretin effect, depends on the nutrient composition of the food in the GIT and accounts for at least
50% of the total insulin secreted after oral glucose (Nauck et al., 1986).
Incretins have a short half-life due to rapid inactivation by dipeptidyl peptidase (DPP-4). The incre-
tin effect is blunted in some people with T2DM (Hinnen, 2017). There are two approaches to increas-
ing the activity of the incretin GLP-1 in the body. Oral DPP-4 inhibitors, known as gliptins, reduce the
degradation of endogenous GLP-1, and injectable GLP-1 receptor agonists produce the effect that
GLP-1 itself would produce at the receptors.

210 DPP-4 inhibitors

These include sitagliptin, vildagliptin and saxagliptin. DPP-4 is the enzyme responsible for the
breakdown of physiologically released incretin hormones. Inhibition of the enzyme leads to ele-
vated and prolonged GLP-1 levels. As a result, glucose- dependent insulin secretion is increased
and there is a reduction in glucagon production. The main effect is a reduction in postprandial
glucose levels.
DPP-4 inhibitors are available in stand-alone formulations or in fixed-dose combinations with met-
formin. They are not first line treatments.
These drugs have been linked with pancreatic agents but are used as add-on agents in dual or
triple therapy. Adverse effects should be avoided in patients with acute pancreatitis or history of
pancreatitis. They rarely cause hypoglycaemia except in combination with other antihyperglycaemic
agents (AMH, 2020d).

GLP1 receptor agonists

GLP-1 receptor agonists include exenatide, liraglutide and dulaglutide. These agonists share
sequence similarity with endogenous GLP-1 but exhibit increased resistance to degradation by DPP-
4. The shorter-acting agonists such as exenatide and liraglutide offer improved control of postpran-
dial hyperglycaemia, while longer-acting formulations such as exenatide extended-release,
dulaglutide and albiglutide further improve fasting plasma glucose and HbA1c. In addition to their
positive effects on glycaemic control, these drugs help with weight and blood pressure reduction.
They are usually used as add-on therapy for patients with T2DM who do not achieve adequate blood
glucose control with one first-line drug.
Administered GLP1-agonists achieve concentrations greater than endogenous GLP-1 levels and
delay gastric emptying, making nausea and vomiting the most common side-effects, especially if the
patient does not modify their usual food intake. This effect is usually transient and improves as treat-
ment continues. These effects can also be minimised by slow introduction of the GLP-1 agonist (AMH,
2020e; Rasalam et al., 2019).

SGLT-2 inhibitors
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors include empagliflozin, dapagliflozin and ertugli-
flozin. They act by inhibiting the transporter, located in the proximal convoluted tubule (PCT) of the
nephron, resulting in increased glucose excretion. SGLT-2 inhibitors may be used in combination
with other antihyperglycaemic agents in dual- or triple-therapy regimens for patients who do not
achieve the desired HBA1c with first-line agents.
These drugs are not effective for patients with impaired renal function and may be associated with
genitourinary infection due to the increased glucose in the urine. Patients should also be advised that
their urine will test positive for glucose and because of the osmotic diuresis produced, they should
consume more water to maintain hydration. SGLT-2 inhibitors do not cause hypoglycaemia except in
combination with other antihyperglycaemic agents. SGLT-2 inhibitors should be stopped 3 days prior
to surgery due to perioperative risks (dehydration, UTI, renal impairment). These agents may have addi-
tive effects with other diuretics, leading to dehydration (AMH, 2020f; Chesterman and Thynne, 2020).
Medications and diabetes mellitus Chapter 12

SGLT-2 inhibitors may cause ketoacidosis even if blood glucose level is normal. Patients who present
unwell should be monitored for signs of ketoacidosis, including severe vomiting and abdominal pain.
Monitoring for ketones should be performed.

Thiazolidinediones
Thiazolidinediones, also known as ‘glitizones’, are less frequently used by patients with diabetes
because of their adverse effects. Some drugs in this class have been withdrawn in some countries
due to their association with increased risk of fractures, heart failure and bladder cancer. Pioglitazone
is still included in management guidelines and acts to improve utilisation of glucose in peripheral
tissues. Weight gain and swollen feet are common adverse effects of pioglitazone and it is important
to assess the risk of fluid retention before increasing the dosage and stop treatment immediately if 211
heart failure is diagnosed (AMH, 2020g).

Alpha-glucosidase inhibitors
Acarbose works by inhibiting an enzyme, alpha-glucosidase, that breaks down carbohydrates (AMH,
2020h). It therefore delays the digestion of carbohydrates and the absorption of glucose into the blood-
stream. The tablets are taken just before a meal or chewed with the first few mouthfuls of food. Acarbose
has a limited role in management of diabetes due to its lower efficacy, but it may be a useful addition in
situations when control of blood glucose remains poor despite dietary modifications. The use of acar-
bose is limited by dose-dependent GI adverse effects such as diarrhoea, flatulence and abdominal pain.
When acarbose is used in combination with a sulfonylurea or insulin, hypoglycaemia may occur. If
it does, the patient must take glucose (e.g. glucose gel, glucose tablets) to restore normal blood glu-
cose concentration.

Acarbose does not affect the absorption of glucose or fructose. Therefore, if hypoglycaemia occurs, it
should be treated with glucose. Sucrose (e.g. fruit juice, milk) is ineffective to treat hypoglycaemia as its
absorption may be delayed.

Drug use in diabetic emergencies

Hypoglycaemic emergency
During hypoglycaemia, the brain is most vulnerable as it is unable to make or store glucose and
therefore requires an uninterrupted supply in the bloodstream to maintain normal function. People
with diabetes are at risk of a hypoglycaemic event because the medications used to manage diabe-
tes reduce blood glucose and because the normal physiological responses that counter low blood
glucose levels may be impaired (Box 12.2).
When blood glucose levels start to fall towards the lower end of the normal range, 4 mmol/L,
there is a hormonal response which causes insulin secretion to cease and glucagon secretion to
increase. Glucagon raises blood glucose levels by increasing hepatic glucose production. If blood
glucose is not restored and levels drop beow the normal range, a sympathetic autonomic response
is also triggered, which includes the release of adrenaline from the adrenal glands. Adrenaline pro-
duces many effects including suppression of insulin and stimulation of glucagon secretion and
increased lipolysis in fatty tissue as shown in Figure 12.1. Other indications of a sympathetic
response, such as raised heart rate and sweating, are often important signals to patients and health-
care professionals that they have become hypoglycaemic. If glucose levels drop still further, and
Chapter 12 Medications and diabetes mellitus

particularly if the hypoglycaemia is prolonged, growth hormone and cortisol secretion is stimulated
to further increase lipolysis in fatty tissue and promote ketogenesis and glucose production in the
liver (Briscoe and Davis, 2006; Tesfaye and Seaquist, 2010).

Box 12.2 Medications most likely to cause

iatrogenic hypoglycaemia.
These drugs elevate insulin levels independent of a patient’s blood glucose level.

• Sulfonylureas
• Gliclazide
• Glibenclamide
• Glipizide
• Glimepiride
212 • Insulins

A person with diabetes is most likely to experience iatrogenic hypoglycaemia, that is, hypogly-
caemia produced by the medications being used to control their hyperglycaemia. A hypoglycae-
mic episode can come about due to administration of more drug than is required under the
circumstances that existed at the time. There are many reasons for a medication dose to exceed
requirements on occasion, and only some medications are likely to produce this effect, as outlined
in Box 12.2. While many medications will not cause iatrogenic hypoglycaemia when used alone,
the risk of an episode of hypoglycaemia naturally increases when medications with glucose-
lowering actions are used in combination.

Clinical consideration: Important medication

interactions
• Alcohol decreases blood glucose levels and impairs the normal regulatory response, cognitive func-
tion and awareness of hypoglycaemia in the patient. The effect of alcohol on blood glucose levels
may be present 6–12 hours after alcohol consumption, increasing the risk of severe hypoglycaemia.
• Many oral antihyperglycaemic medications do not cause hypoglycaemia when used alone, but
may do so when used in combination with other diabetic medications.
• Beta-blockers, such as metoprolol and propranolol, may block important signs of acute hypogly-
caemia (e.g. palpitations, tremor) as a result of blockade of the adrenergic receptors mediating
these responses.

The risk of hypoglycaemia is highest where injected insulin is used to manage blood glucose levels
and education surrounding its use is vital to avoid hypoglycaemia. People with T1DM may use injected
insulin only, and those with T2DM may use insulin in conjunction with other injected or oral antihyper-
glycaemic medications. Where insulin is used, a person must know the amount of carbohydrate
required for their specific insulin dose (carbohydrate counting), and time their meals depending on
the type of insulin used (short-acting/regular/long-acting). Regular monitoring of blood glucose lev-
els will enable a person to assess their insulin requirements based on their diet, exercise and lifestyle
and will also allow early identification and self-treatment of hypoglycaemia at the first sign or symp-
tom. The maintenance of euglycemia in a person with diabetes relies on education in all aspects of
diabetes care, including hypoglycaemia risk factors, outlined in Box 12.3 (Briscoe & Davis, 2006).
The signs and symptoms of hypoglycaemia may be classified into two groups: neurogenic (auto-
nomic nervous system activation) and neuroglycopenic (brain glucose insufficiency), outlined in
Table 12.2. The neurogenic signs and symptoms, such as palpitations, trembling, dry mouth, sweat-
ing and nervousness, will often alert a person that blood glucose is low and are the consequence of
an autonomic nervous system response.
Medications and diabetes mellitus Chapter 12

Box 12.3 Hypoglycaemia risk factors

• Medication interactions, including alcohol
• Accidental or intentional overdose of antihyperglycaemic medication, especially insulin
• Unplanned reduction of food intake
• Missed or delayed meal
• Intensive exercise without increase in food intake
• Irregular or absent blood glucose monitoring
• Inability to identify or self-treat hypoglycaemia
Source: Modified from Briscoe and Davis (2006).

Table 12.2 Signs and symptoms of hypoglycaemia.

213
Brain glucose deficiency Autonomic activation

• Confusion • Hunger
• Tiredness • Shakiness
• Disorientation • Nervousness
• Seizures • Tachycardia
• Hypothermia • Hypertension
• Coma • Diaphoresis/sweating
Neuroglycopenic symptoms come about as a result of inadequate glucose to the brain and include
irritability, tiredness, difficulty thinking and confusion. Family members may recognise these signs of
developing hypoglycaemia in the patient. When blood glucose levels are not corrected, the condi-
tion will progress to cerebral agitation, seizures, coma and death.
Treatment of hypoglycaemia requires the administration of glucose either directly or indirectly.
The clinical context of a hypoglycaemia episode will determine the route of administration of
glucose.
Mild to moderate hypoglycaemia may be effectively self-treated by the consumption of approxi-
mately 15 g of oral glucose. Oral glucose may be available in many forms including gels, tablets and
jellybeans. Other foods that may be consumed are:

• ½ a can (150 mL) of regular soft drink (not diet) OR

• ½ a glass (125 mL) of fruit juice OR
• 3 teaspoons of sugar or honey.
It may take up to 15 minutes for blood glucose levels to rise to 4 mmol/L or above. If they are still
below this after 15 minutes, then administration of another 15 g of glucose is recommended. The
response to glucose is transient and if the next meal is not for more than 20 minutes, a small amount
of carbohydrate should also be consumed, to maintain blood glucose. This could be:

• a slice of bread OR
• 1 glass of milk OR
• 1 piece of fruit OR
• 1 small tub of yoghurt.
Oral administration of glucose is not possible in cases of severe hypoglycaemia resulting in
reduced consciousness, so these patients require an injectable form of glucagon or glucose
(NDSS, 2021).
Chapter 12 Medications and diabetes mellitus

Management of severe hypoglycaemia

Glucagon
Glucagon is a hormone produced by the alpha cells of the islets of Langerhans of the pancreas. It
stimulates the breakdown of liver glycogen to release glucose into the bloodstream. It can be given
via intramuscular (IM), subcutaneous (SC) or intravenous (IV) routes. Glucagon is available in a kit that
may be administered by a family member/carer or by ambulance personnel.
When the patient has recovered sufficiently to take oral foods, an immediate source of glucose and
complex carbohydrates will be required. Be aware that an adverse effect of glucagon is nausea and vomit-
ing which may make it difficult to ensure the patient consumes enough carbohydrate to prevent relapse.

Response to glucagon may be slow; most people will start to respond after 6 minutes. Where there are
insufficient stores of liver glucose, e.g. in chronic malnourishment, glucagon may not be sufficient and
214 intravenous glucose may also be required.

Skills in practice: preparation and administration

of glucagon
• Only administer glucagon if the person has an altered level of consciousness and is unable to take
glucose orally.
• Check expiry date.
• Do not mix the glucagon until you are ready to use it.
• Using universal precautions and aseptic technique, open the kit and mix the contents of the
syringe (sterile water) with glucagon powder in the vial and shake gently to dissolve the powder.
Do not use if a gel has formed or if you see particles in the solution. Using the same syringe, withdraw
all the mixed solution and dispense any air bubbles back into the vial.
• Withdraw syringe from the vial and deliver 1 mL (1 mg) of glucagon subcutaneously or intramus-
cularly into one of the main injection sites (upper arms, thighs or buttocks).
• Ensure the used syringe is disposed of in a sharps container.

(MIMS Australia, 2020b).

Intravenous glucose
Administration of IV glucose requires a securely positioned cannula, ideally into a larger vein, as
injection into the veins of the hand may cause superficial thrombophlebitis. Several different con-
centrations of glucose are available.

• Glucose 10% 150 mL or 20% 75 mL (15 g) by intravenous infusion over 15 minutes is the preferred
intravenous treatment.
• Glucose 50% may also be administered by slow intravenous injection, but extreme caution must
be used as extravasation can cause serious necrosis.
Response to IV glucose is rapid, but if blood glucose remains below 4 mmol/L 15 minutes after the
first administration, a second dose may be administered. When the person has recovered sufficiently
to take oral foods, a complex carbohydrate will be required (Diabetes, 2016).

Where a person uses a long-acting insulin, the action may last up to 24 hours (see Table 12.2). Due to
the prolonged action of insulin and higher risk of relapse, it would be advisable to transport these
people to hospital for close monitoring.
Medications and diabetes mellitus Chapter 12

When a person experiences hypoglycaemia (especially severe hypoglycaemia) or has a history of

hypoglycaemia, it is important to record details of the timing of the episode, medication dose and
events leading up to the episode so adjustments to the treatment regimen can be made to prevent
a recurrence. When this is not done, the risk of recurrent severe hypoglycaemia can be high.

Clinical consideration: hypoglycaemia

unawareness
The blood glucose threshold at which a person will recognise hypoglycaemia is not static and may
change depending on circumstances, a phenomenon known as ‘relative hypoglycaemia’.
Hypoglycaemia usually produces recognisable signs and symptoms when blood glucose levels
decrease below 4 mmol/L. However, people with persistently high blood glucose levels may experi-
ence hypoglycaemic signs and symptoms at higher blood glucose levels.
Of greater concern, though, is when people who have had a recent hypoglycaemic event may not
experience symptoms until their blood glucose levels are significantly lower than 4 mmol/L. Often the
characteristic autonomic symptoms that indicate low blood glucose are absent and the first sign of 215
hypoglycaemia is confusion or loss of consciousness. This is termed ‘hypoglycaemia unawareness’ and
can place people at risk of experiencing severe, life-threatening hypoglycaemia.
People over 60 years of age may have altered counter-regulatory responses as a result of ageing,
long-standing diabetes, multiple comorbidities and medications. Because of this, older people may
experience hypoglycaemia unawareness. Further, the initial signs and symptoms of brain glucose defi-
ciency may be misinterpreted as indications of cerebral vascular events, dementia or urinary tract infec-
tion. Thus, hypoglycaemia unawareness, especially in older adults, may delay treatment and increase
the risk of severe life-threatening hypoglycaemia (Martín-Timón and Javier del Cañizo-Gómez, 2015;
Tesfaye and Seaquist, 2010).

Episode of care: hypoglycaemia

Peter, a 65-year old male, has a 20-year history of type 2 diabetes and until recently his blood glucose
levels had been controlled by the oral diabetes medications metformin and empagliflozin. About
3 months ago, Peter commenced insulin therapy and his initial dose was 10 units of insulin glargine at
night.
About 1 month ago, Peter began experiencing chest pain and was diagnosed with unstable angina
which worried him as he hadn’t experienced any problems with his heart before. His cardiologist com-
menced Peter on metoprolol 50 mg twice daily to reduce his angina symptoms. Peter’s cardiologist also
explained to Peter the link between diabetes and the risk of a heart attack. Concerned about this, Peter
visited his general practitioner who agreed his long-term control of diabetes was not adequate. As a
result, his doctor increased his dose of insulin glargine to 15 units at night.
Peter is now taking the following medications.

• Metformin XR 2 g at night
• Empagliflozin 10 mg at night
• Aspirin 100 mg in the morning
• Metoprolol 50 mg morning and night
• Telmisartan 40 mg in the morning
• Atorvastatin 40 mg in the morning
• Insulin glargine 15 units night
Motivated by his recent diagnosis, Peter determined to start exercising and lose a bit of weight. He
began walking after work and stopped eating snacks before his evening meal. After about a week of his
new lifestyle regimen, he had lost about 1 kg of weight which made him feel great.
Chapter 12 Medications and diabetes mellitus

At about 4 am one morning about a week later, Peter’s wife Janet woke to the sounds of loud snoring.
When she tried to wake Peter, he pushed her away and started speaking incoherently. Janet called the
ambulance, and on arrival and paramedics measured his blood glucose level (BGL) as 2 mmol/L. They
administered 1 mL (1 mg) of glucagon and Peter slowly responded until after 20 minutes his BGL had
increased to 4 mmol/L. Peter then ate a jam sandwich and promptly booked an appointment with his
doctor.
At the appointment, Peter described the events and admitted that he wasn’t monitoring his BGL
regularly and couldn’t provide his nightly and morning BGL readings. He explained that he had
been feeling tired and light-headed when he went to bed that night, but thought his new heart
medication was responsible. The doctor reduced his insulin dose back to 10 units at night and
his metformin and empagliflozin were moved to a morning dose. Peter was also referred to a dia-
betes educator for information about blood glucose monitoring, hypoglycaemia symptoms and
self-treatment.

216
Hyperglycaemic emergency
Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is a medical emergency that is characterised by elevated blood glucose
and ketones accompanied by metabolic acidosis. DKA can occur in both type 1 and type 2 diabetes
(where insulin is used). The consequences of untreated DKA are renal failure, cerebral oedema, coma
and death.
Diabetic ketoacidosis occurs due to an absolute or relative insulin deficiency. Because of this defi-
ciency, glucose does not enter cells for use as a fuel and the body, effectively in a state of starvation,
is forced to switch to alternative fuel sources. This lack of glucose supply to the cells initiates a
counter-regulatory response and glucagon, adrenaline, noradrenaline, cortisol and growth hormone
are secreted. These hormones increase glucose production and lipolysis. The resulting hyperglycae-
mia produces an osmotic diuresis as the kidney is unable to reabsorb the excess filtered glucose, and
the additional water loss results in dehydration and loss of electrolytes such as sodium, potassium
and chloride. Free fatty acids are utilised during lipolysis as alternative fuel sources, but the keto acids
produced as by-products of this process accumulate rapidly, causing metabolic acidosis (Nyenwe
and Kitabchi, 2016). Important differential diagnoses for DKA include hyperosmolar hyperglycaemia
state (HHS) and euglycaemic ketoacidosis.

Clinical consideration: Hyperosmolar

hyperglycaemia
Hyperosmolar hyperglycaemia state (HHS) is a potentially life-threatening situation that occurs in peo-
ple with T2DM due to severe hyperglycaemia. It is rarer than DKA but has a higher mortality rate, partly
because type 2 diabetes sufferers tend to be older, with more comorbidities, and partly because HHS
produces venous blood clots.
Hyperosmolar hyperglycaemia state typically occurs in the presence of severe hyperglycaemia
(>30 mmol/L), which causes increased urinary output leading to severe dehydration, hypovolaemia
and plasma hyperosmolality (highly concentrated plasma) with high plasma sodium levels. The high
sodium levels cause an altered level of consciousness and, in severe cases, coma. The key difference
between HHS and DKA is that the former has little or no ketosis or metabolic acidosis. The absence of
ketosis is explained by the fact that people with T2DM can still produce insulin which, while not enough
to prevent hyperglycaemia, does suppress lipid metabolism and the production of ketones.
Hyperglycaemia and dehydration will produce signs and symptoms similar to DKA without those asso-
ciated with metabolic acidosis, such as abdominal pain, vomiting, fruity-smelling breath and Kussmaul
respirations.
Medications and diabetes mellitus Chapter 12

The causes and risk factors for developing HHS are the same as those that cause DKA: other medications,
infection and other physiological stressors (Table 12.3). Non-adherence to diabetes therapy, including oral
medicines, may precipitate HHS.
Treatment of HHS is also similar to DKA with the main aims of therapy being to correct dehydration
and plasma osmolarity, electrolyte abnormalities and reduce BGL using insulin (Kitabchi et al., 2009).

Table 12.3 Factors precipitating DKA.

Factor Causes
Insulin deficiency Insulin pump failure
Non-adherence to insulin therapy
Unrecognised symptoms of new-onset diabetes
Medications and illicit drugs Antipsychotics, e.g. olanzapine and quetiapine
Corticosteroids, e.g. dexamethasone and prednisolone
217
Sympathomimetic agents, e.g. pseudoephedrine and cocaine
Alcohol abuse
Infection Pneumonia, urinary tract infection,
Other physiological stressors Pregnancy, myocardial infarction, trauma, surgery

The primary determinant of DKA is the absolute or relative lack of insulin, with undiagnosed dia-
betes, unawareness of symptoms in newly diagnosed diabetes or non-adherence to insulin therapy
being the most common factors. Other factors include illicit drugs, alcohol abuse, infection and other
physiological stressors (see Table 12.3).

Signs and symptoms

When body cells are deprived of glucose, polyphagia (increased appetite) occurs, often in the pres-
ence of weight loss. The BGL threshold for hyperglycaemia is generally accepted to be 14 mmol/L.
Elevated serum ketones or the presence of ketones in the urine also may indicate DKA.
Hyperglycaemia causes polyuria (increased urination), resulting in polydipsia (increased thirst).
Dehydration and hypovolaemia also cause tachycardia, hypotension, dry mouth and poor skin
turgor.
Acidosis may cause Kussmaul breathing, which is a pattern of deep and forced breathing, an
attempt to compensate by increasing the excretion of carbon dioxide via the lungs. The exhaled
breath may smell fruity as it contains elevated levels of acetone, a type of ketone. Acidosis may also
cause abdominal pain and vomiting. A reduced level of consciousness is a sign of severe DKA and is
caused by both dehydration and acidosis. The signs and symptoms of DKA are outlined in Table 12.4
(Nyenwe and Kitabchi, 2016).

Table 12.4 Signs and symptoms of DKA.

Hyperglycaemia and dehydration Metabolic acidosis
• Polyphagia • Kussmaul breathing
• Weight loss • Abdominal pain
• Polyuria • Fruity breath
• Polydipsia • Nausea and vomiting
• Tachycardia • Altered level of consciousness
• Hypotension
• Dry mouth
• Poor skin turgor
• Altered level of consciousness
Source: Based on Nyenwe and Kitabchi (2016).
Chapter 12 Medications and diabetes mellitus

Clinical consideration: euglycaemic

ketoacidosis
Euglycaemic ketoacidosis is a medical emergency in which elevated ketones and metabolic acidosis
exist in the presence of either normal glucose levels or mild hyperglycaemia. This can occur in people
with type 1 or type 2 diabetes. It is important to be aware of this condition as it may not present with
the typical polyuria, polydipsia and marked dehydration. However, euglycaemic ketoacidosis may be
life threatening because of metabolic acidosis, and medical evaluation and treatment are necessary.
Euglycaemic ketoacidosis occurs when the factors that trigger DKA are present and the person still
continues with insulin treatment and/or glucose production is lowered and/or the excretion of glucose
is higher. Lower glucose production occurs in the presence of glycogen depletion and higher glucose
elimination may occur in the presence of SGLT-2 inhibitors.

Factors contributing to lower glucose production Factors contributing to higher excretion of glucose
(glycogen depletion)
218 Pregnancy (often third trimester) Sodium-glucose cotransporter 2 inhibitors,
Fasting states, e.g. nausea and vomiting, post e.g. empagliflozin and dapagliflozin
bariatric surgery
Liver dysfunction
(Barski et al., 2019)

Management of hyperglycaemia
Treatment of hyperglycaemic emergencies involves the correction of dehydration, electrolyte abnor-
malities and hyperglycaemia. All persons suspected to be experiencing DKA, HHS or euglycaemic
ketoacidosis should be transported to hospital. Careful treatment with close monitoring is necessary
to avert a life-threatening crisis and specialist advice may be required.

Fluid replacement
Intravenous fluids should be started. Initially most people will receive 0.9% normal saline at 15–20
mL/kg/h, or 1–1.5 L in the first hour. The initial rehydration will improve blood volume and tissue
perfusion. Administration of fluids 1 hour prior to administration of insulin is beneficial, as it prevents
deterioration due to hypotension, improves insulin action and allows serum potassium to be meas-
ured prior to insulin administration. Maintenance treatment for hydration will depend on the level of
hydration, electrolyte levels and urinary output. Half of the estimated fluid deficit should be replaced
over 12–24 hours. When blood glucose levels fall to 11 mmol/L, saline solution should be replaced
with 5% dextrose. Potassium, bicarbonate and phosphate levels should be monitored throughout
treatment and replacement should be initiated where required.

Electrolyte replacement
Initial hydration can reduce BGL and potassium levels by a dilution effect. When adequate blood
volume is achieved, further excretion of potassium occurs due to enhanced renal perfusion. When
insulin therapy is initiated, the correction of acidosis causes potassium to move back into cells. It is
therefore essential that electrolytes, particularly potassium, are monitored during treatment and
replacement initiated where indicated.

Insulin therapy
Regular intravenous insulin infusion is recommended to reduce blood glucose levels. Administration
usually starts 1–2 hours after fluids have been initiated and infusion rate should be titrated to
response. When BGLs reach approximately 11 mmol/L, 5% dextrose is added to the intravenous flu-
ids so a BGL of 8.3–11 mmol/L can be maintained (Diabetes, 2016).
Medications and diabetes mellitus Chapter 12

Episode of care: Hyperglycaemia

Mrs Lavinia Howard has been a type 1 diabetic for approximately 6 months. Her diabetes was
precipitated by a pancreatic cancer diagnosis and she has been managing it with a subcutaneous
insulin pump.
Over the past week, Lavinia has been complaining of abdominal pain and constipation which has
affected her appetite and caused her carbohydrate consumption to reduce significantly. Lavinia has
been very diligent about monitoring her blood glucose levels and has returned BGLs of 3.5 mmol/L and
3.8 mmol/L. Due to the episodes of hypoglycaemia, Lavinia decided to turn off the insulin pump as,
living alone, she was very worried about experiencing a serious hypoglycaemic episode. Lavinia visited
her general practitioner complaining of constipation Her doctor prescribed laxatives and enemas for
her constipation and measured her BGL, which returned a normal result.
Lavinia’s constipation resolved and her appetite improved, as did her carbohydrate consumption.
Lavinia, however, forgot to re-establish her insulin pump. The following day, she began to feel very
nauseous and experienced two episodes of vomiting. She also noticed that she was urinating a lot but
thought it was due to her increased appetite and fluid consumption. When Lavinia measured her BGL,
she was alarmed to see the reading was 24 mmol/L and she called the ambulance for advice. 219
The paramedics measured her BGL and confirmed a reading of 22 mmol/L. Her blood pressure was
95/50 mmHg, heart rate 120 beats/min and her blood plasma was positive for ketones. The possibility
of DKA was discussed and she was advised to go to hospital for treatment rather than simply re-
establishing her insulin pump.

Conclusion
For prehospital care providers, abnormal blood glucose level is a common cause of patients pre-
senting with altered mental status, with or without diabetes. One of the unintended complica-
tions of some medicines used for diabetes is iatrogenic hypoglycaemia, which must be managed
promptly. This may occur after usual therapeutic doses, or may be related to inadvertent admin-
istration of the wrong dose or type of insulin. Conversely, use of medicines may also be
implicated in poorly controlled or high blood sugar levels, for example when there are missed
doses, or concurrent illness which causes blood glucose levels to fluctuate more widely. This
chapter has described the medicines that could contribute to diabetic emergencies and medi-
cines used to manage complications that could present to paramedics when attending to a
patient with diabetes.
Find out more about these conditions.

Type 1 diabetes
Type 2 diabetes
Metabolic syndrome
Diabetes insipidus
Gestational diabetes mellitus (GDM)

Glossary
Analogue insulin Insulin proteins created in a laboratory using recombinant DNA
technology.
Adenosine triphosphate (ATP) Source of energy used by cells.
Blood glucose level (BGL) The concentration of glucose in the blood, measured in milli-
moles per litre (mmol/L).
Carbohydrate A group of compounds (including starches and sugars) that are a
major food source.
Catecholamines A collective term for adrenaline, noradrenaline and dopamine.
Chapter 12 Medications and diabetes mellitus

Diabetes mellitus An endocrine disorder affecting the regulation of blood glucose

levels.
Dipeptidyl peptidase-4 (DPP-4) A glycoprotein that breaks down a variety of substrates, includ-
ing incretin hormones.
Enzyme Protein that speeds up (catalyses) chemical reactions in the
body.
Euglycaemia Normal level of glucose in the blood.
Exogenous Originating from outside the body.
Fatty acids Dietary fats that have broken down into elements that can be
absorbed into the blood.
Gastrointestinal (GI) tract Organs of the digestive system that make up the continuous
passage from mouth to anus.
Glucose-like peptide 1 (GLP-1) An incretin hormone produced in the gut in response to food.
Gestational diabetes
mellitus (GDM) Diabetes mellitus first recognised during pregnancy.
Gluconeogenesis Creation of glucose from non-carbohydrate substrates.
220 Glycogen A carbohydrate (complex sugar) made from glucose.
Glycogenesis Conversion of glucose to glycogen.
Glycogenolysis Breakdown of glycogen in liver and muscle to glucose.
Hypoglycaemia Lower than normal blood levels of glucose.
Hyperglycaemia Higher than normal blood levels of glucose.
Iatrogenic Caused by medical treatment.
Insulin resistance When tissues (e.g. fat, liver, muscle) do not respond well to insulin
and therefore do not effectively take up glucose from the blood.
Interstitial fluid Body fluid found in the tissue spaces that surrounds the cells.
Ketones Organic compounds that are by-products of fat metabolism, a
process known as ketogenesis.
Lipolysis Breakdown of stored lipids to release fatty acids into the
bloodstream.
Parenteral Medicines administered by a route that does not involve the gas-
trointestinal tract.
Plasma proteins Protein molecules present in blood plasma which serve a variety
of functions.
Postprandial After a meal.
Steady-state drug concentration Concentration at which the amount of drug being absorbed is
the same as the amount cleared from the body when given
continuously.
Thrombophlebitis Inflammatory condition of a vein due to a blood clot.
Triglyceride A form of fatty acid having three fatty acid components.

References
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American Diabetes Association. (2019). Pharmacologic approaches to glycemic treatment: standards of medical
care in diabetes – 2019. Diabetes Care 42(Suppl. 1): s90–s102.
Australian Medicines Handbook (AMH). (2020a). Insulins. https://amhonline-amh-net-au.ezproxy.newcastle.edu.
au/chapters/endocrine-drugs/drugs-diabetes/other-drugs-diabetes/insulins
Australian Medicines Handbook (AMH). (2020b). Metformin. https://amhonline-amh-net-au.ezproxy.newcastle.
edu.au/chapters/endocrine-drugs/drugs-diabetes/other-drugs-diabetes/metformin
Australian Medicines Handbook (AMH). (2020c). Sulfonylureas. https://amhonline-amh-net-au.ezproxy.newcastle.
edu.au/chapters/endocrine-drugs/drugs-diabetes/sulfonylureas?menu=vertical
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ezproxy.newcastle.edu.au/chapters/endocrine- drugs/drugs- diabetes/dipeptidyl-peptidase-4-inhibitors?
menu=vertical
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ezproxy.newcastle.edu.au/chapters/endocrine-drugs/drugs-diabetes/glucagon-like-peptide-1-analogues?
menu=vertical
Medications and diabetes mellitus Chapter 12

Australian Medicines Handbook (AMH). (2020f). Sodium-glucose co-transporter 2 inhibitors. https://amhonline-

amh- net- au.ezproxy.newcastle.edu.au/chapters/endocrine- drugs/drugs- diabetes/glucagon- like-
peptide-1-analogues?menu=vertical
Australian Medicines Handbook (AMH). (2020g). Pioglitazone. https://amhonline-amh-net-au.ezproxy.
newcastle.edu.au/chapters/endocrine- drugs/drugs- diabetes/other- drugs- diabetes/pioglitazone?
menu=vertical
Australian Medicines Handbook (AMH). (2020h). Acarbose. https://amhonline-amh-net-au.ezproxy.newcastle.
edu.au/chapters/endocrine-drugs/drugs-diabetes/other-drugs-diabetes/acarbose?menu=vertical
Barski, L., Eshkoli, T., Brandstatter, E. and Jotkowitz, A. (2019). Euglycemic diabetic ketoacidosis. European Journal
of Internal Medicine 63: 9–14.
Briscoe, V.J. and Davis, S.N. (2006). Hypoglycemia in type 1 and type 2 diabetes: physiology, pathophysiology and
management. Clinical Diabetes 24(3): 115–121.
Chesterman, T. and Thynne, T. (2020). Harms and benefits of sodium-glucose co-transporter 2 inhibitors. Australian
Prescriber 43: 168–171.
Diabetes (2016) Melbourne: Therapeutic Guidelines Limited. www-tg-org-au.ezproxy.newcastle.edu.au
Diabetes Australia. (2021). Blood Glucose Monitoring. www.diabetesaustralia.com.au/living-with-diabetes/
managing-your-diabetes/blood-glucose-monitoring/
Hinnen, D. (2017). Glucagon-like peptide 1 receptor agonists for type 2 diabetes. Diabetes Spectrum 30(3):
202–210.
221
Kitabchi, A.E., Umpierrez, G.E., Miles, J.M. and Fisher, J.N. (2009). Hyperglycemic crises in adult patients with diabe-
tes. Diabetes Care 32(7): 1335–1343.
Martín-Timón, I. and Javier del Cañizo-Gómez, F. (2015). Mechanisms of hypoglycemia unawareness and implica-
tions in diabetic patients. World Journal of Diabetes 6(7): 912–926.
MIMS Australia. (2020a). Glucagon. www.mimsonline.com.au
MIMS Australia. (2020b). Insulin. www.mimsonline.com.au
MIMS Australia. (2020c). Glibenclamide. www.mimsonline.com.au
Misbin, R.I. (2004). The phantom of lactic acidosis due to metformin in patients with diabetes. Diabetes Care 27(7):
1791–1793.
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managing-diabetes/hypoglycaemia/
Nauck, M.A., Homberger, E., Siegel, E. et al. (1986). Incretin effects of increasing glucose loads in man calcu-
lated from venous insulin and C-peptide responses. Journal of Clinical Endocrinology and Metabolism
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esis and management. Metabolism 65(4): 507–521.
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and their role in primary care: an Australian perspective. Diabetes Therapy 10: 1205–1217.
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of Sciences 1212: 12–28.

Multiple-choice questions
1. Which of the following adverse reactions is not a concern when taking metformin
alone?
(a) Hypoglycaemia
(b) Metabolic acidosis
(c) Vitamin B12 malabsorption
(d) Gastrointestinal adverse effects including metallic taste in the mouth
2. Which of the following statements is incorrect with regard to insulin administration?
(a) Administered via injection into subcutaneous tissue
(b) Usual site of administration is the abdomen
(c) Physical activity may increase the rate of insulin absorption from the site of
administration
(d) Insulin injected into muscle, rather than subcutaneous tissue, will absorb significantly
slower
Chapter 12 Medications and diabetes mellitus

3. SGLT-2 inhibitors may be associated with which of the following adverse effects?
(a) Ketoacidosis, even when BGLs appear within the normal range
(b) Lactic acidosis, especially in patients with kidney damage
(c) Hyperglycaemia
(d) Weight gain
4. Which of the following statements is incorrect in relation to a paramedic attending to a
patient with suspected hypoglycaemia?
(a) DPP-4 inhibitors rarely cause hypoglycaemia except in combination with other
antihyperglycaemic agents that cause hypoglycaemia
(b) Sugars such as sucrose (e.g. fruit juice, milk) may be used to treat hypoglycaemia
in patients using acarbose
(c) Insulin glargine may contribute to hypoglycaemic emergencies for several hours
after it has been administered
(d) Sulfonylureas such as gliclazide commonly contribute to hypoglycaemia and
weight gain
222 5. Which of the following would not be likely to interfere with the accuracy of blood
glucose measurements?
(a) Temperature and humidity
(b) Residual substance on hands prior to testing
(c) Use of metformin on the same day as testing
(d) Incorrect use of test strips
6. Identify from the following medications which would most likely contribute to
hypoglycaemia.
(a) Oral metformin
(b) Oral gliclazide
(c) Oral sitagliptin
(d) Subcutaneous exenatide
7. Identify which sign or symptoms of hypoglycaemia would most probbly be masked by
the administration of beta-blockers.
(a) Confusion
(b) Tiredness
(c) Tachycardia
(d) Hunger
8. Which one of the following is not classified as a neuroglycopenic sign/symptom?
(a) Sweating
(b) Disorientation
(c) Fatigue
(d) Seizure
9. As a paramedic in the prehospital environment, identify which of the following
scenarios is most correct.
(a) BGL of 2.3 mmol/L, unconscious and unrousable treated with a slow infusion of
intravenous glucose 10% 150 mL
(b) BGL of 3.2 mmol/L, confused but able to swallow treated with 1 mL (1 mg)
subcutaneous injection of glucagon
(c) BGL of 3 mmol/L, irritable and confused, refusing to eat, treated with glucose gel
inserted onto mucosa for absorption
(d) BGL of 2.8 mmol/L, unconscious, history of fasting treated with 1 mL (1 mg)
subcutaneous injection of glucagon
Medications and diabetes mellitus Chapter 12

10. Which of the following are not contributing factors to hyperglycaemia and diabetic
ketoacidosis (DKA)?
(a) Pneumonia, prednisolone therapy, pseudoephedrine therapy
(b) Metoprolol therapy, heart disease, non-adherence to metformin
(c) Surgery, insulin pump failure, quetiapine therapy
(d) Pregnancy, non-awareness of diabetes symptoms, refusal to use insulin
11. Which of the following are symptoms of hyperglycaemia and metabolic acidosis?
(a) Dry skin, cool extremities, abdominal pain, vomiting and lethargy
(b) Headache, breathing difficulties, chest wheezes and high body temperature
(c) Sweating, tachycardia, hunger, confusion and tremors
(d) Slurred speech, facial droop, incontinence and altered level of consciousness

223
Chapter 13
Medications used in the
respiratory system
Jason McKenna

Aim
The aim of this chapter is to familiarise the reader with key pathophysiological processes in respiratory
emergencies and the pharmacological management often utilised in prehospital care.

Learning outcomes
After reading this chapter the reader will:

1. Have gained an understanding of the key pathophysiological and clinical characteristics of common
respiratory emergencies
2. Be able to describe the principal characteristics and mechanisms of action of the key pharmacological
agents used in each of these problems
3. Be able to effectively manage various respiratory emergencies utilising the pharmacological agents
described in this chapter
4. Be able to describe the various side-effects associated with the medication classes and how to
safely consider these when applying pharmacology management to any respiratory conditions.

Test your knowledge

1. Describe the main components of the respiratory system and their functions.
2. Describe how the autonomic nervous system innervates the respiratory system and its two
opposing branches of control.
3. List the similarities and differences between asthma and COPD.
4. List the medication classes utilised to manage respiratory emergencies.
5. Describe the mechanism of action of the pharmacological agents used to manage respiratory
emergencies.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Medications used in the respiratory system Chapter 13

Introduction
Respiratory disease is the third most common cause of death (after cardiovascular disease and can-
cer) and affects around one in five people. Hospital admissions for lung disease are three times higher
than other admissions, with chronic obstructive pulmonary disease (COPD), pneumonia and lung
cancer the leading causes of death. The incidence and mortality due to respiratory diseases are
higher within socially deprived areas and among disadvantaged groups where there are higher rates
of occupational hazards, smoking, increased air pollution and poor housing conditions (NHS
England, 2020).
Dyspnoea can be the initial life-threatening symptom of respiratory failure and its importance is
highlighted by the Airway, Breathing, Circulation (ABC) approach in emergency medicine (Lindskou
et al., 2019). Patients in respiratory distress are at increased risk of morbidity and mortality, often seek
emergency care from prehospital services, and are subsequently transported to emergency depart-
ments via ambulance. Prehospital personnel play a prominent role in the triage, treatment and trans-
port of patients with respiratory distress, and evidence shows that prehospital interventions decrease
mortality among these patients (Prekker et al., 2014).

225
Anatomy and physiology
The respiratory system’s primary roles are to deliver oxygen (O2), essential for glycolysis (energy pro-
duction), and removal of carbon dioxide (CO2), the waste product of respiration (Figure 13.1). There are
two processes involved in this: (1) air is moved into and out of the lungs through a process called

Branching of bronchial tree

• Trachea
• Primary bronchi
• Secondary bronchi
• Tertiary bronchi
• Bronchioles
• Terminal bronchioles
Larynx

Trachea

Right lung Left lung

Visceral pleura

Parietal pleura
Carina
Pleural cavity
Left primary
Right primary bronchus
bronchus
Left secondary
Right secondary bronchus
bronchus
Left tertiary
Right tertiary bronchus
Cardiac
bronchus
notch
Right Left bronchiole
bronchiole
Diaphragm
Left terminal
Right terminal
bronchiole
bronchiole
Anterior view

Figure 13.1 The respiratory system. Source: Nair, M. and Peate, I. (2015). Pathophysiology for Nurses at a
Glance. Chichester: John Wiley & Sons, Ltd.
Chapter 13 Medications used in the respiratory system

mechanical ventilation, and (2) gas exchange across the alveolar–capillary membrane in a process
called diffusion. The respiratory system has an important role in protection against pathogens, acid–
base balance and phonation.
The respiratory system can be divided into the upper respiratory tract and the lower respiratory
tract. The upper respiratory tract encompasses the nose, nasal cavity, mouth, pharynx, epiglottis and
larynx. Inhaled air is warmed and moistened as it swirls within the nasal cavity due to scroll-shaped
bones known as the nasal conchae. Mucous membranes lining the respiratory tract clean the inhaled
air by trapping foreign particles and pollutants. During swallowing, the epiglottis closes like a trap
door, routing food down the oesophagus away from the trachea. Failure of this process will lead to
aspiration of food contents into the lungs.
Below the glottis are the structures of the lower airway and lungs. These include the trachea, bron-
chial tree (primary bronchi, secondary bronchi and bronchioles), alveoli and lungs. The right lung has
three lobes and the left lung has two lobes and the heart lies within the cardiac notch adjacent to the
left lung. The conducting airways include the trachea which bifurcates at the carina into the two
main bronchi which divide into smaller secondary bronchi, ultimately leading to the terminal bron-
chioles. The bronchi are made up of complete rings of cartilage combined with smooth muscle and
lined with pseudostratified ciliated epithelium. Further down the bronchial tree, lesscartilage exists
226 and additional smooth muscle is found. Terminal bronchioles lead to respiratory bronchioles, which
represent the transition zone between the conducting airways and the gas exchange part of the
respiratory system.The respiratory bronchioles lead to alveolar ducts and finally to the alveolar sacs
which are entirely composed of alveoli.
There are around 300 million alveoli in the two lungs; they are the functional components of the
respiratory system and are the chief component of lung tissue. The wall of an alveolus comprises a
single layer of epithelial cells and elastic fibres. These fibres allow the alveolus to stretch and contract
during breathing. The exchange of oxygen and carbon dioxide in the lungs takes place in the alveoli
in a process known as diffusion (Paramothayan, 2019).
Each alveolus is encircled by a fine network of capillaries which are arranged so that air in the alveo-
lus is separated by a thin respiratory membrane from the blood in the alveolar capillaries. Oxygen
crosses from the alveoli and enters the blood via diffusion because the PO2 (partial pressure of oxygen)
of alveolar air is greater than the PO2 within the blood. This is known as a pressure gradient and oxygen
molecules diffuse across the membrane to equalise the gradient. Simultaneously, carbon dioxide mol-
ecules leave the blood by diffusing across the membrane into the alveoli in the same manner due to
the partial pressure of carbon dioxide (PCO2) in venous blood being higher than the PCO2 within the
alveoli (Peate, 2015).
The diffusion of gases at the capillary-alveolar level can be affected in a number of ways. Some
respiratory diseases destroy and collapse the alveolar walls, resulting in the formation of fewer
but larger alveoli. The degenerative process reduces the total area available for diffusion. In
some diseases the alveolar- capillary membrane becomes thick or less permeable which forces
gas molecules to travel farther, reducing the rate of diffusion. An example of such a disease is
pulmonary oedema. In this condition, fluid collects in the alveoli and pulmonary interstitial
space. This forces gases to diffuse through a thicker than normal layer of fluid and tissue
(Paramothayan, 2019).

Nervous system control

The autonomic nervous system can be subdivided into the sympathetic nervous system (SNS) and
parasympathetic nervous systems (PNS). One division carries impulses which inhibit certain func-
tions whereas the other division usually carries impulses which enhance a function. As a rule, the SNS
prepares the body for ‘action’ and is commonly referred to as the ‘flight or fight’ response. In contrast,
the PNS reduces muscular activity, conserves energy and produces selective localised responses
such as increased gastrointestinal activity and is commonly referred to as the ‘rest and digest’
response. The two systems operate at the same time, but at any given time one is normally more
dominant (Sanders et al., 2019).
Figure 13.2 shows the two branches of the autonomic nervous system and their systemic
effects. Within the respiratory system, the postganglionic SNS nerves secrete the neurotransmit-
ter norepinephrine which acts on beta-2 receptors within airway smooth muscle, causing relaxa-
tion and bronchodilation of the airways. In contrast, the PNS secretes the neurotransmitter
Medications used in the respiratory system Chapter 13

SYMPATHETIC SYSTEM PARASYMPATHETIC SYSTEM

Release Release
Postganglionic
nerves (– – –) Acetylcholine
Norepinephrine

Effects Action Action Effects

α dilatation of pupil radial muscle (+) lacrimal gland tear secretion

of pupil (+) III
α secretion of thick Midbrain (+) circular muscle constriction of
saliva salivary glands (+) VII
of iris pupil
α vasoconstriction
blood vessels (+) Pons/
β2 vasodilatation (–) medulla (+) ciliary muscle accommodation
IX for near vision
β1 rate and force heart (+)
increased X (+) salivary glands much secretion
of watery saliva
β2 bronchodilatation lung airways (–) (–) heart rate and force
reduced
α/β2 decrease in gut wall (–)

muscarinicre receptors
α motility and tone gut sphincters (+) (+) lung airways bronchoconstriction
β2 glycogenolysis bronchosecretion
Spinal
α/β2 gluconeogenesis liver (+) (+) gut wall
cord
(glucose release (–) gut sphincters increase in
into blood) motility and tone
(+) gut secretions
α capsule contracts* spleen (+) 227
EPINEPHRINE adrenal (+) (+) pancreas increase in
medulla Preganglionic exocrine and
nerves endocrine
β2 relaxation bladder secretion
α contraction detrusor (–) ( )
α contraction or sphincter (+) (+) bladder
β2 relaxation uterus (+) detrusor micturition
(depends on (–) (–) sphincter
hormonal state)
vas deferens (+)
(+) rectum defaecation
α ejaculation seminal
vesicles (+) erection
muscarinic (+) penis
sweating sweat glands (+) (co-release of
α piloerection (hairs pilomotor nitric oxide)
stand on end) muscles (+)

Predominant
Note: (+) = excitation In the sympathetic system (+) and (–)
adrenoceptor (* not in humans)
(–) = inhibition generally correspond to α- and β-receptors, respectively

Figure 13.2 The autonomic nervous system. Source: Neal (2015).

acetylcholine which acts on muscarinic receptors in lung tissue, causing bronchoconstriction

and increased bronchosecretions (Neal, 2015).

Reflection
Medications used to treat respiratory conditions will often take advantage of the body’s natural physi-
ology. Consider how some of the medications in this chapter inhibit or enhance autonomic nervous
system control to elicit a response.

Common respiratory emergencies

Asthma
Asthma is a disease that affects the airways which carry air in and out of the lungs. In asthma, the
airways become oversensitive and they react to things that would not typically cause an issue, such
as dust particles or cold air. These are also known as triggers.
When the airways react to triggers, the smooth muscles of the airway walls constrict, making the air-
way narrow and leaving little room for air to flow in and out of the lungs. The lining of the airway pas-
sages then becomes swollen and a sticky mucus is produced which clogs up the breathing passages.
Chapter 13 Medications used in the respiratory system

Wall inflamed
and thickened

Normal Asthma

Figure 13.3 Normal airway vs asthmatic airway. Source: Nair, M. and Peate, I. (2015). Pathophysiology for
Nurses at a Glance. Chichester: John Wiley & Sons, Ltd.

With narrowing of the airways, it becomes hard for air to move in and out of the lungs and the
chest muscles have to work much harder to breathe. Constriction of the muscles around the air-
ways can occur rapidly (Figure 13.3) and this is the most common cause of asthma symptoms.
228 Asthma cannot be cured, but with appropriate treatment it can be well managed so there is no
reason why individuals with asthma should be unable to live a full and active life, free from symp-
toms. Anybody can develop asthma but it often commences in childhood. In 2016 the World Health
Organization (WHO) estimated that globally, over 339 million people had asthma, with over 400 000
deaths in the same year attributed to the disease (WHO, 2020). It is especially common in Ireland,
where more than 380 000 adults and children have asthma, which equates to approximately 7.75%
of the population (Asthma.ie, 2020).
In the initial acute phase, smooth muscle spasm is accompanied by excessive secretion of mucus
that may clog the bronchi and bronchioles and exacerbate the attack. The late chronic phase is
characterized by inflammation, oedema, fibrosis and necrosis of bronchial epithelial cells. A host of
mediator chemicals, including histamine, prostaglandins, leukotrienes, platelet-activating factor
and thromboxane, take part (Figure 13.4) (Tortora and Derrickson, 2014).
Status asthmaticus is a severe, protracted asthmatic attack which cannot be stopped with con-
ventional management and is a life-threatening emergency. Just as an individual with COPD (see
Table 13.2) usually does not call for an ambulance unless their condition has changed noticeably, a

A person with asthma does not ring for an ambulance unless the event is considerably worse than their
typical attack. Assume status asthmaticus until proven otherwise.

Thickening by
inflammation
Disrupted with oedema
epithelium and cellular
infiltration
Fibrosis under
basement Mucus plugs
membrane
Hypertrophied
Hypertrophied
smooth muscle
mucus glands

Figure 13.4 Inflammatory changes in the airway. Source: Rees, J., Kanabar, D. and Pattani, S. (2010). ABC of
Asthma, 6th edn. Chichester: Wiley-Blackwell.
Medications used in the respiratory system Chapter 13

Figure 13.5 Peak flow meter. Source: Paramothayan (2019).

person with asthma does not ring for an emergency ambulance unless the event is considerably
worse than their typical attack. It is practical to assume that an asthmatic who feels sick enough to 229
call for an emergency ambulance is in status asthmaticus until proven otherwise (Pollak et al., 2018).
Signs and symptoms include anxiety, dyspnoea, wheezing, chest tightness, coughing, fatigue,
tachycardia, diaphoresis and, in a severe life-threatening presentation, hypotension and a silent
chest. Initial assessment should include a peak expiratory flow reading to help guide treatment
(Figure 13.5). A mild/moderate acute asthma attack is managed by initiating oxygen therapy fol-
lowed by administering an inhaled B2-agonist to help relax smooth muscle in the bronchioles and
open the airways. This can be supplemented with a short-acting muscarinic antagonist, such as ipra-
tropium bromide, if there is no improvement following initial therapy or if the patient has acute
severe asthma (Table 13.1). One of the main contributors to severe asthma is inflammation, so early
administration of intravenous hydrocortisone is indicated to reverse this process. For those who pro-
gress to life-threatening asthma, continue nebulised B2-agonist therapy in conjunction with intra-
muscular epinephrine (adrenaline) and/or a magnesium sulfate infusion (BTS/SIGN, 2019; JRCALC,
2019; PHECC, 2018).

Table 13.1 Signs and symptoms of acute asthma exacerbations.

Moderate acute asthma Life-threatening asthma

• Increasing symptoms In a patient with severe asthma any one of:

• PEF >50–75% best or predicted • PEF <33% best or predicted

• No features of acute severe asthma • SpO <92%

• Poor 2
respiratory effort
Acute severe asthma • Silent chest
• Altered conscious level
Any one of:
• Exhaustion
• PEF 33–50% best or predicted • Arrhythmia
• Respiratory rate ≥25/min • Hypotension
• Heart rate ≥110/min • Cyanosis
• Biphasic wheeze
• Inability to complete sentences in one breath
Near fatal asthma

• Raised PaCO and/or requiring mechanical ventilation with raised inflation pressures
2

Source: BTS/SIGN (2019).

PEF, peak expiratory flow.
Chapter 13 Medications used in the respiratory system

Skills in practice: obtaining a peak flow reading

(DeVrieze et al., 2020)
Ensure patient is sitting or standing upright

1. Ensure peak flow marker is at the start point marked zero on the scale.
2. Attach the disposable mouthpiece to the peak flow meter.
3. Instruct the patient to take in a full, deep breath.
4. Place the mouthpiece between the patient’s lips and hold level.
5. Instruct the patient to exhale in a single, fast, forceful expiration.
6. The marker should slide down the numbered scale.
7. Note the peak expiratory flow rate number obtained.
8. Obtain a total of three readings.
9. Record the best reading from the three attempts.

230
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease includes at least two different clinical pathologies: chronic
bronchitis and emphysema. Chronic bronchitis is defined as a sputum-producing cough for at least
3 months a year over a period of two consecutive years (Fayyaz, 2020).
The characteristic of the disease is excessive mucus production in the bronchial tree, which is
almost constantly accompanied by a chronic or recurrent productive cough. A typical patient with
chronic bronchitis is virtually always a heavy cigarette smoker, is typically overweight, and congested
(Figure 13.6).
Blood gas levels have a tendency to be abnormal, with elevated PaCO2 which is indicative of hyper-
capnia and decreased PaO2 levels which indicates hypoxemia. Inhaled irritants cause chronic inflam-
mation and growth in the size and number of goblet cells and mucous glands within the airway
epithelium. The excessive, thick mucus that is produced narrows the airways and weakens ciliary
function, causing inhaled pathogens to become embedded in airway secretions and reproduce
quickly. In addition to a productive cough, signs and symptoms of chronic bronchitis are dyspnoea,
wheezing, cyanosis and pulmonary hypertension.
Management of chronic bronchitis is similar to that for emphysema and frequently the patient will
have related heart disease, including right-sided heart failure, known a Cor pulmonale.
Emphysema is a condition characterized by destruction of the walls of the alveoli, producing unchar-
acteristically large air sacs that remain full of air throughout exhalation. Emphysema damages or destroys
the delicate structures of the terminal bronchioles. Clusters of alveoli combine into large blebs, or bullae,
which are not as efficient as regular lung tissue due to having less surface area for gas exchange. This part
of the tracheobronchial tree becomes so weak that its branches collapse during exhalation, trapping air
in the alveoli. With less surface area for gas exchange, O2 diffusion across the damaged respiratory mem-
brane is impaired. Blood oxygen levels are slightly lowered and any minor exertion that increases the

Swelling and
inflammation

Mucus
production

Restricted
airflow

Normal Bronchitis

Figure 13.6 Inflammation and mucus production associated with bronchitis. Source: Nair, M. and Peate, I.
(2015). Pathophysiology for Nurses at a Glance. Chichester: John Wiley & Sons, Ltd.
Medications used in the respiratory system Chapter 13

oxygen requirements of the cells leaves the patient dyspnoeic. As growing numbers of alveolar walls are
damaged, lung elastic recoil declines due to the loss of elastic fibres, and an increasing amount of air
becomes trapped in the lungs at the end ofe xhalation. Over several years, further effort during inhala-
tion is required and it increases the size of the chest cage, resulting in a ‘barrel chest’.
Emphysema is usually caused by a long-term irritation such as cigarette smoke, occupational
exposure to dust and gases and air pollution. Some destruction of alveolar sacs may be caused by an
enzyme imbalance. In most cases, COPD is avoidable because its greatest common cause is cigarette
smoking or breathing second-hand smoke. Other causes include genetic factors and pulmonary
infection (Pollak et al., 2018; Tortora and Derrickson, 2014).
Some COPD exacerbations are mild and self-limiting whereas others are severe, potentially life-
threatening and require intervention. Prehospital management of a COPD exacerbation involves the
use of oxygen therapy, nebulised bronchodilators (short-acting B2-agonists [SABA], short-acting
muscarinic antagonists [SAMA] and intravenous corticosteroids) (JRCALC, 2019; PHECC, 2018).
Caution should be exercised when administering oxygen therapy in patients with COPD as it may
cause respiratory depression (NICE, 2018).

231
COPD patients are at risk of respiratory depression if overoxygenated. Maintain SpO2 ≤92%.

Croup
Croup (laryngotracheobronchitis) is usually caused by a respiratory virus that is spread by person-to-
person interaction, contact with contaminated nasopharyngeal secretions or by expelled large drop-
lets. It mainly affects children between 6 months and 6 years old and it is the most frequent cause of
upper airway distress in children. Croup affects the upper respiratory tract, leading to swelling and
inflammation of the mucosal and submucosal tissues at the level of the cricoid ring, which is the nar-
rowest part of the paediatric airway.
The diagnosis of croup is typically based on the physical examination and pertinent history. The
child classically has a history of a runny nose, sore throat and a cough for a few days prior to the onset
of croup symptoms which are frequently worse at night and when the child is agitated. These symp-
toms may be accompanied by a low-grade fever. Narrowing of the upper airway due to laryngeal
swelling and inflammation leads to accompanying stridor, hoarseness and a ‘seal-like’ barking cough
that may last up to10 days. The initial emergency management of croup is determined by the sever-
ity of the child’s presenting symptoms.

• Mild croup is distinguished by an occasional cough, minimal respiratory distress and the absence
of stridor when at rest.
• With moderate croup, the child’s mental status and behaviour are normal, but inspiratory stridor
and retractions are evident when the child is at rest and the level of respiratory distress has elevated.

Table 13.2 Clinical features differentiating COPD and asthma.

COPD Asthma
Smoker or ex-smoker Nearly all Possibly
Symptoms under age 35 Rare Often
Chronic productive cough Common Uncommon
Breathlessness Persistent and progressive Variable
Night-time waking with breathlessness and/or wheeze Uncommon Common
Significant diurnal or day-to-day variability of symptoms Uncommon Common
Source: Adapted from Overview | Chronic obstructive pulmonary disease in over 16s: diagnosis and management |
Guidance (2018).
Chapter 13 Medications used in the respiratory system

• In severe croup there are mental status changes in conjunction with substantial respiratory
distress and declining air entry, signifying looming respiratory failure. Intercostal and suprasternal
accessory muscle retractions along with inspiratory and expiratory stridor are frequently present
(Aehlert, 2017).

The treatment of croup depends on its severity. Maintain the child in a position of comfort sat
upright and on a parent’s lap if appropriate. A calm approach is recommended as any distress can
lead to deterioration and complete airway occlusion. Patients with reduced oxygen saturations
should receive supplemental oxygen therapy via flow-by method or humidified oxygen with a
nebuliser mask (Sizar and Carr, 2020). Steroids are the mainstay of croup treatment and children
may benefit from early steroid administration (JRCALC, 2019). In moderate and severe presentations
where hypoxia and/or signs of severe obstruction are present, the administration of nebulised
epinephrine is appropriate (PHECC, 2018) to decrease upper airway oedema with its faster onset of
action over steroids. Children with the most severe croup symptoms benefit from medications with
a rapid onset which may reduce the need for invasive interventions such as intubation (Bjornson
et al., 2011).

232 Pneumonia
Pneumonia is not a single disease but a group of specific infections that cause acute inflammation of
the respiratory bronchioles and alveoli. Pneumonia can be a result of bacterial, fungal or viral infec-
tion and related risk factors include cigarette smoking, extremes of age, exposure to cold and alco-
holism. These diseases can be spread through interaction with infected individuals by respiratory
droplets. Pneumonia can be classed as aspiration, bacterial, mycoplasmal or viral and usually mani-
fests with classic signs and symptoms (Sanders et al., 2012). Pathophysiology, swelling of respiratory
tissues, the production of pus and increased mucus secretion occur. The swelling can be dramatic
and lead to airflow resistance due to narrowing of the airways. In conjunction, the alveoli lose the
ability to function when they fill with fluid or pus (consolidation) which occurs in pneumonia. People
with chronic illnesses, the elderly and those who smoke are at increased risk of developing pneumo-
nia. Individuals who produce excessive mucus or do not ventilate effectively, such as asthmatics,
COPD patients, the immunocompromised and those who are bedridden or sedentary, are at an
increased risk of developing pneumonia (Pollak et al., 2018).
The classic signs and symptoms of pneumonia include pleuritic chest pain, a productive cough and
fever that produces rigor which is typically related to a bacterial infection. It also may cause non-
specific complaints, particularly in older and weakened patients. These non-specific complaints can
include headache, sore throat, fatigue and a non-productivecough (Sanders et al., 2012). Auscultation
may reveal crackles typically at the lung base unilaterally, but in advanced cases breath sounds may be
diminished or absent. Due to dehydration, sputum may be thick and discoloured (Pollak et al., 2018).
Management of pneumonia in the prehospital field is primarily supportive, ensuring adequate
oxygenation and assessing for sepsis. Patients who present with sepsis may also require intravenous
fluids, antibiotics and antipyretics (JRCALC, 2019; PHECC, 2018).

Pneumothorax
A pneumothorax is defined as a collection of air trapped inside the pleural cavity outside the lung
and happens when air gathers between the visceral and parietal pleurae within the thorax. As the air
gathers within the pleural space, it applies pressure to the lung, causing it to collapse, and the grade
of collapse will determine the patient’s clinical presentation. Air can enter the pleural space by two
possible mechanisms: due to trauma which causes air to enter the thorax via an open wound in the
chest wall, or via a rupture of the visceral pleura causing air to escape from the lung.
A traumatic pneumothorax is a result of penetrating or blunt trauma and can be further classified
as a simple, tension or open pneumothorax. A simple pneumothorax occurs when the air trapped
with the pleural space does not apply pressure to the mediastinal structures such as the heart, great
blood vessels, trachea and oesophagus. A tension pneumothorax is present when the volume of air
trapped within the pleural space increases to the point where the contents of the mediastinum are
Medications used in the respiratory system Chapter 13

compressed. This is a time-sensitive emergency which should be corrected immediately when

identified. In an open pneumothorax, air enters the thorax via an open wound in the chest wall
(McKnight and Burns, 2020).
Non-traumatic pneumothorax can be characterised as primary or secondary. A primary spontane-
ous pneumothorax (PSP) happens suddenly without any known precipitating event, whereas a sec-
ondary spontaneous pneumothorax (SSP) occurs due to pre-existing lung disease such as COPD or a
congenital disease. Individuals with severe asthma along with tall, thin smokers are prone to blebs
which are weak spots that can rupture when under stress. These blebs can rupture simply by cough-
ing or by aggressive bag-valve-mask ventilation.
The majority of patients with a pneumothorax will not require an immediate intervention, such as
a needle chest decompression. Patients with an open pneumothorax should have the wound cov-
ered with a three-sided occlusive dressing. Oxygen therapy may be required and the patient should
be reassessed regularly for signs of a tension pneumothorax developing which should be decom-
pressed when identified (Pollak et al., 2018).

Pulmonary oedema
Pulmonary oedema is characterised as an abnormal build-up of extravascular fluid within the
lungs. This leads to reduced gas exchange within the alveoli, causing dyspnoea and hypoxia 233
which can potentially progress to respiratory failure. Pulmonary oedema can be classified as
cardiogenic or non- cardiogenic based on the underlying process leading to fluid accumulation
in the lungs. In cardiogenic pulmonary oedema, the heart is not sufficiently moving blood
through the pulmonary circulation due to injury or disease (see Chapter 10). This leads to
increased pulmonary venous pressure and increased hydrostatic pressure resulting in a fluid
shift (Malek and Soufi, 2020). In non- cardiogenic pulmonary oedema, there is an increase in pul-
monary vascular permeability leading to fluid moving from the intravascular space to the inter-
stitial and alveolar spaces. The main causes of non- cardiogenic pulmonary oedema are acute
respiratory distress syndrome (ARDS), allergic reaction, acute kidney injury (AKI), aspiration,
drowning, inhalation injury, fluid overload and intracranial haemorrhage (neurogenic pulmo-
nary oedema) (Sureka et al., 2015).
Acute pulmonary oedema is an emergency in which immediate intervention is required. It is char-
acterised by dyspnoea, hypoxia and crackles on auscultation as a result of increasing fluid accumula-
tion within the lungs, which is impairing lung compliance and gas exchange.
Management of patients with pulmonary oedema focuses on improving symptoms and treat-
ment of the underlying condition (Malek and Soufi, 2020), but the management differs depend-
ing on the underlying pathology (Manne et al., 2012). Pharmacological therapy for acute
cardiogenic pulmonary oedema includes oxygenation, nitrates and the administration of diuret-
ics. To supplement the pharmacological treatment, the use of continuous positive airway pres-
sure (CPAP) in the management of acute pulmonary oedema has been shown to decrease
mortality and the need for intubation (Williams et al., 2013). Oxygen therapy should be adminis-
tered to any patient with acute pulmonary oedema and guided by a target oxygen saturation
level of 94–98%. Sublingual glyceryl trinitrate (GTN) can be administered to reduce preload
and afterload, therefore improving cardiac output and reducing pulmonary congestion (Kim
et al., 2020).
Diuretics remain the backbone of acute pulmonary oedema management (Malek and Soufi, 2020);
however, with the introduction of prehospital CPAP, the administration of intravenous diuretics has
been moved further down the treatment algorithms. Diuretics are recommended in acute cardio-
genic pulmonary oedema patients who are in severe respiratory distress with signs of systemic fluid
retention (JRCALC, 2019; PHECC, 2018). Loop diuretics, such as furosemide, are normally the diuretics
of choice and have been used in prehospital care for many years (Purvey and Allen, 2017). For patients
in respiratory distress, initiate non-invasive ventilation in conjunction with medical management by
nitrates and diuretics based on systolic blood pressure and the degree of pulmonary congestion
(Mebazaa et al., 2015). Management of non-cardiogenic pulmonary oedema focuses on addressing
the underlying cause, providing supportive care including oxygen therapy and CPAP if required
(Clark and Soos, 2020).
Chapter 13 Medications used in the respiratory system

Reflection
Treatment of cardiogenic and non-cardiogenic pulmonary oedema differs. Why would the pharmaco-
logical agents used to manage cardiogenic pulmonary oedema not have the same effect on patients
with non-cardiogenic pulmonary oedema?

Classes of medications
In this section the various classes of medications used to manage respiratory emergencies in the
prehospital field are discussed.

Bronchodilators
Bronchoconstriction is common in individuals with respiratory diseases such as asthma, COPD and
cystic fibrosis, which may require bronchodilators. Bronchodilators are fundamental in the manage-
ment of obstructive airway diseases, and their mechanism of action either enhances (agonist) or
234 inhibits (antagonist) the actions of the autonomic nervous system to elicit a response which reverses
asthma symptoms or improves lung function in COPD patients (Almadhoun and Sharma, 2020).
Airway smooth muscle tone is largely controlled by the parasympathetic nervous system via cho-
linergic and non-cholinergic innervation. Parasympathetic fibres release acetylcholine, causing con-
striction of the smooth muscle layer surrounding the airways. Increased vagus nerve activity has a
significant role in provoking airway obstruction in asthma and COPD patients and is a reversible
element of airway obstruction (Cotes, 2006; Matera et al., 2020). Bronchodilator therapy often reduces
the symptoms of airflow obstruction by relaxing smooth muscle in the bronchi and bronchioles,
decreasing dyspnoea and improving quality of life (Williams and Rubin, 2018).
The types of bronchodilators utilised in prehospital care are:

• beta-2 adrenergic receptor agonists (B2-agonists)

• muscarinic receptor antagonists (anticholinergics)
• sympathomimetics
• electrolytes and minerals.
Beta-2 adrenergic receptor agonists (B2-agonists)
Beta-2 agonists are the fundamental therapy for respiratory diseases such as asthma and COPD. Beta-
agonists bind to beta-receptors on cardiac and smooth muscle tissues, especially bronchial smooth
muscle where they cause relaxation of the muscle. Drugs defined as agonists work by binding to a
receptor and stimulating it to produce the anticipated therapeutic effect. The patient subsequently
experiences improved airflow for a time.
Beta-adrenoceptors usually bind to circulating epinephrine and to norepinephrine released by
sympathetic adrenergic nerves. Therefore, beta-agonists mimic the actions of sympathetic adrener-
gic stimulation (sympathomimetic) acting through beta-adrenoceptors (Klabunde, 2012). B2-
agonists work by binding to B2-receptors in airway smooth muscle where they set in progress a chain
of events similar to that produced by the action of the natural neurotransmitters. In other words, they
mimic norepinephrine and normal sympathetic nervous system response.
The onset of action and duration of B2-agonists determine their classification. The classifications
are shortacting beta-agonists (SABA) and long-acting beta-agonists (LABA). SABAs have a short
half-life and are primarily used for rapid relief of symptoms. LABAs, in contrast, have a longer half-life
and deliver continuous symptomatic relief, however, they are not routinely used in prehospital care.
The most familiar SABAs are:

• salbutamol (Ventolin®);
• terbutaline (Bricanyl®).
Medications used in the respiratory system Chapter 13

Short-acting beta-agonists start to work within a few minutes of being inhaled and last from 4–6 hours.
They are used for rapid symptom relief and are given in high doses in cases of acute exacerbations of
airway obstructive disease. The use of high-dose inhaled B2-agonists as first-line agents in patients with
acute asthma is recommended and should be administered as early as possible via an oxygen-driven
nebuliser (BTS/SIGN, 2019). Patients with COPD also benefit from symptom relief with SABA therapy
during an exacerbation; however, caution should be applied when using an oxygen-driven nebuliser to
maintain an oxygen saturation level of 92% (GOLD, 2020). Side effects of SABA’s are associated with
their sympathomimetic action. These include tachycardia, tachyarrythmias, and tremors.

Muscarinic receptor antagonists (anticholinergics)

Muscarinic receptor antagonists produce bronchodilation by inhibiting muscarinic acetylcholine
receptors in bronchial smooth muscle. Acetylcholine is a neurotransmitter secreted from terminal
parasympathetic fibres which bonds with M3 muscarinic receptors within bronchial smooth muscle,
producing bronchoconstriction. Muscarinic receptor antagonist drugs block the bronchoconstric-
tion effects of acetylcholine (anticholinergic) on M3 muscarinic receptors within bronchial smooth
muscle (GOLD, 2020) and are often combined with a B2-agonist for the management of serious bron-
chial airway narrowing (Long et al., 2020). M3 receptors are also located within bronchial glands
which secrete mucus when stimulated. Antimuscarinics compete with acetylcholine and antagonise
235
the normal parasympathetic effect reducing bronchial mucus secretion.
There are two types of muscarinic receptor antagonists: short-acting muscarinic antagonists (SAMA)
and long-acting muscarinic antagonists (LAMA). LAMAs are not routinely used in prehospital care.

Short-acting muscarinic antagonists

Short-acting muscarinic antagonists, similar to SABAs, are utilised in both acute and chronic manage-
ment of asthma and COPD. Ipratropium bromide is the most commonly used and blocks all mus-
carinic receptors. Its onset of action is within minutes, with peak activity taking place at 1–2 hours
and a duration of action of approximately 4 hours in the majority of patients (Ejiofor and Turner, 2013).
Common side-effects of SAMAs include gastrointestinal motility disorder, headache, dizziness, nau-
sea, cardiac arrhythmias and throat complaints such as dry mouth and coughing (Joint Formulary
Committee, 2019a).

Skills in practice: preparing and administering

nebulised medications
1. Select appropriately sized nebuliser device for the patient.
2. Using aseptic technique, mix medication into nebuliser chamber.
3. Attach nebuliser chamber to mask and ensure tight seal.
4. Connect oxygen tubing to port on the oxygen flowmeter.
5. Adjust oxygen flowmeter to 4–8 L/min and ensure visible mist is obtained.
6. Place mask over patient’s mouth and nose, ensuring tight seal.
7. Instruct patient to take deep steady breaths to disperse medications throughout the bronchial tree.

Clinical consideration: inhalation therapy

There are a number of devices available for administering medications via inhalation. These include the
nebuliser mask, hand-held nebuliser, metred dose inhaler and spacer devices. Some prehospital ser-
vices carry multiple devices which can be utilised to deliver medications to the patient. Consider the
devices available to you and which patients are better suited to each one.
Chapter 13 Medications used in the respiratory system

Sympathomimetics: epinephrine (adrenaline)

Epinephrine is a synthetic preparation of the naturally occurring catecholamine produced by the
adrenal glands which has bronchodilation and vasoconstricting properties. It is a potent alpha- and
beta-adrenergic stimulant although its effect on beta-receptors is more profound. Stimulation of
alpha-receptors within blood vessels causes vasoconstriction, increasing vascular resistance and
blood pressure. Through its beta-receptor stimulation, epinephrine increases the rate (chronotropic)
and force (inotropic) of myocardial contraction and causes bronchodilation by relaxing bronchial
smooth muscle. In children with severe croup, nebulised epinephrine causes localised vasoconstric-
tion which reduces the upper airway oedema and stridor. In addition to the above conditions, epi-
nephrine is the main drug administered during cardiac arrest management due to its chronotropic
and inotropic effects (Paramothayan, 2019; PubChem, 2021).
Side-effects of epinephrine are related to its sympathomimetic action and include tachycardia,
tachyarrhythmias, anxiety, hypertension, palpitations, tremors and angina-like symptoms (Joint
Formulary Committee, 2019b).

236
Epinephrine comes in multiple presentations and concentrations. Double check the dose and route
prior to administration.

Electrolytes and minerals: magnesium sulfate

Magnesium sulfate (MgSO4) is an electrolyte important for many biochemical reactions which occur in
the body. It is also an adjunct medication for the management of severe life-threatening asthma exac-
erbations and has a role as a cardiovascular drug, an antiarrhythmic and an anticonvulsant. MgSO4
causes bronchodilation by inhibiting acetylcholine release from cholinergic nerve endings, histamine
release from mast cells and calcium influx to the cytosol. Through this inhibitory action, MgSO4 induces
bronchial smooth muscle relaxation (Song and Chang, 2012). In a systematic review of randomised
control trials, asthmatic patients treated with MgSO4 had a reduction in hospital admission and
improved lung function (Paramothayan, 2019). When administered intravenously, it has an immediate
onset of action with a duration of action of around 30 minutes. If the intramuscular route is used, the
onset of action is around 60 minutes with a duration of action of 3–4 hours (HPRA, 2019).
Side-effects of MgSO4 are hypotension, confusion, drowsiness, decreased deep tendon reflexes,
muscle weakness, slurred speech, nausea, vomiting, thirst, flushing, respiratory depression, arryth-
mias, coma and cardiac arrest. Bradycardia can happen during administration which can be reduced
by slowing the rate of infusion (Joint Formulary Committee, 2019c).

Diuretics
Loop diuretics, such as furosemide, are the most powerful diuretics and are widely utilised for the
management of pulmonary and systemic oedema. They bind to chloride receptors in the ascending
loop of Henle within the kidneys, inhibiting reabsorption of chloride and sodium. This leads to a
hypertonic state where water is retained within the loop of Henle and eliminated by the bladder
(Sniecinski et al., 2007). Loop diuretics are administered in cases of cardiogenic pulmonary oedema
with intravenous administration relieving dyspnoea and reducing preload in acute presentations.
Side-effects of loop diuretics are electrolyte imbalances, dizziness, headache, hypotension, fatigue,
muscle spasms, nausea, vomiting and metabolic alkalosis (Joint Formulary Committee, 2019d).

Nitrates
Nitrates, such as glycerol trinitrate, cause smooth muscle relaxation by releasing nitric oxide, result-
ing in dilation of systemic veins and reduction of preload. These actions reduce intravascular pres-
sure within the lungs, allowing fluid within interstitial lung tissue to cross into pulmonary capillaries,
thus reducing pulmonary oedema. Higher doses of nitrates lead to arterial dilation, resulting in
reduced afterload and blood pressure. Dilation of the coronary arteries results in increased coronary
blood flow. These actions collectively improve oxygenation and reduce cardiac workload.
Medications used in the respiratory system Chapter 13

Nitrates can cause hypotension due to the methods of action mentioned above, so blood pressure
monitoring is essential prior to administration: nitrates should be withheld if systolic blood pressure is
<90 mmHg.
There are a number of formulations of nitrates but in prehospital care the most commonly used is
the sublingual route via dissolvable tablet or aerosol pump spray. Nitrates are usually well tolerated
with the most common side-effects being headache, flushing, dizziness and transient hypotension
(Purvey and Allen, 2017).

Steroids
Corticosteroids are synthetic equivalents of the natural steroid hormones produced in the adrenal
gland, which include glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Glucocorticoids
have anti-inflammatory, immunosuppressive and vasoconstrictive properties, whereas mineralocor-
ticoids regulate electrolytes and water balance via an effect on ion transport within the renal tubules.
Corticosteroids are utilised in the management of conditions in almost all areas of medicine and
have both endocrine and non-endocrine indications. Their non-endocrine role takes advantage of
the potent anti-inflammatory and immunosuppressive properties of the medication to manage
patients with a wide range of inflammatory and immunological conditions (Hodgens and
Sharman, 2020). Two examples of corticosteroids used in prehospital care are dexamethasone and 237
hydrocortisone. In respiratory conditions, steroids are indicated for the management of acute inflam-
mation in asthma exacerbations, COPD exacerbations, anaphylaxis and croup (JRCALC, 2019;
PHECC, 2018). Side-effects of corticosteroids are hypertension, vertigo, abdominal distension, head-
ache, hiccups, nausea and hyperglycaemia (HPRA, 2020).

Clinical consideration: corticosteroids

Prolonged therapy with corticosteroids can cause serious life-threatening side-effects. Adrenal atrophy
can develop due to supplemental steroid use and can persist for years after ceasing the medication.
Patients who stop taking their corticosteroids abruptly can present with an adrenal crisis resulting in
hypoglycaemia, hypotension and death (Joint Formulary Committee, 2019e).

Episode of care: COPD exacerbation

You are dispatched to a 67-year-old female patient with shortness of breath. On arrival, you enter the
living room of the house and observe the patient sitting in an armchair at the other side of the room.
She is sitting upright with both hands on her knees and she has a home nebuliser mask on. You notice
that she has a very slight build and a flushed complexion, and from your position you can easily see that
she is breathing fast while utilising accessory muscles. As you glance around the room, you notice signs
of recent smoking and several empty nebuliser pods sitting on the table along with other medication
boxes. When you introduce yourself, the patient replies with one word and a head nod to acknowledge
your greeting.
On examination, the patient is tachypnoeic with bibasal absent breath sounds, a nearly inaudible
expiratory wheeze in all other fields and significant accessory muscle use. Her pulse oximetry is read-
ing 86%, her pulse is fast and regular, she has dry skin and hypertension, her temperature is 36.8 °C,
and her blood glucose is 8.6 mmol/L. You obtain a 12-lead ECG which shows sinus tachycardia with
right ventricular hypertrophy.
The patient’s daughter tells you that her mum’s breathing has been getting worse for the last 4 days
and that she went to the GP 3 days ago. The GP started prophylactic antibiotics and a course of oral
prednisolone. Along with this, the patient is prescribed salbutamol, Atrovent®, Spiriva® and ramipril for
daily management of COPD and hypertension.
What do you think is the cause of the COPD exacerbation?
What is the significance of the respiratory examination findings?
Why did the GP prescribe prophylactic antibiotics and oral prednisolone?
Chapter 13 Medications used in the respiratory system

Smoking is a major cause of COPD and a common trigger of exacerbations. COPD patients are also
prone to chest infections due to excessive mucus accumulation within the airways which can trigger severe
symptoms. When assessing any respiratory patient, the absence of breath sounds should raise a red flag. In
asthmatic and COPD patients, this can be due to significant bronchospasm and mucus plugging resulting in
minimal air movement. These patients should be handled with caution as they can deteriorate very quickly.

• Patients with COPD exacerbations should be managed with a step-wise approach beginning with
a B2-agonist such as salbutamol. B2-agonists start to work quickly, causing bronchial smooth mus-
cle relaxation and aiding airflow through the lungs.
• In moderate exacerbations B2-agonists can be supplemented with a short-acting muscarinic
antagonist such as ipratropium bromide. These medications also aid bronchial smooth muscle
relaxation and reduce bronchial secretions which clog the airways.
• Inflammation plays a major role in exacerbations and COPD patients will often be prescribed cor-
ticosteroids to alleviate this. Parenteral corticosteroids have a slow onset of action, so in severe
exacerbations early administration is recommended.

238
Medical gases
Oxygen (O2) is an odourless, colourless, tasteless gas which is necessary for life and is an important
part of patient care. It is essential in the management of hypoxic patients as it raises their O2 levels by
increasing the inspired percentage of O2, the concentration within the alveoli, the arterial O2 levels,
and increases the volume of O2 delivered to systemic tissues and cells. O2 should be administered to
hypoxic patients only, as per Table 13.3, and to maintain their O2 saturation level within the normal
range (Weekley and Bland, 2020). The normal target O2 saturation for adults is 94–98%, for patients
with COPD the normal target O2 saturation is 88–92%, and for paediatric patients aim for an O2 satu-
ration greater than 96% (JRCALC, 2019; PHECC, 2018). O2 administration is commonly based upon
pulse oximetry readings, but pulse oximetry can provide false readings in cases of carbon monoxide
poisoning, anaemia and shock (Weekley and Bland, 2020). Hyperoxia should be avoided.

Oxygen devices
There are numerous oxygen delivery devices available which can be divided into ‘low-flow’ devices and
‘high-flow devices’. Table 13.4 lists some of the various types and the O2 flow rates associated with them.

Table 13.3 Indications for oxygen administration.

Chronic Acute
Chronic obstructive pulmonary disease Shock
Cystic fibrosis Sepsis
Pulmonary fibrosis Major trauma
Sarcoidosis Cardiac arrest
Asthma exacerbation Anaphylaxis
Lung cancer Carbon monoxide poisoning
Sickle cell disease Myocardial ischaemiaa
Acute pulmonary oedema
SpO2 < 94% for all acutely unwell or injured patients.
SpO2 < 92% for patients with an acute exacerbation of COPD.
SpO2 < 96% for all paediatric patients.
a
Studies have shown that routine oxygen therapy in myocardial infarction patients with a normal range SpO2 is not
associated with any clinical benefit (Sepehrvand et al., 2018).
Medications used in the respiratory system Chapter 13

Table 13.4 Oxygen delivery devices.

Low-flow devices
Devices O2 rate High-flow devices O2 rate
Nasal cannula 2–6 L/min Non-rebreather mask 10–15 L/min
Venturi mask 2–15 L/min Bag-valve-mask ventilator 15 L/min
Simple face mask 5–8 L/min High-flow nasal cannula Up to 60 L/min
Continuous positive airway pressure (CPAP) Up to 25 L/min
Source: Weekley and Bland (2020).

Devices frequently used to administer O2 in prehospital care are the nasal cannula, non-rebreather
mask, bag-valve-mask ventilator and, less frequently, the Venturi mask and CPAP device. The O2 delivery
device used should be appropriate to the patient’s needs and tolerances. Those with mild hypoxia may be
managed with a low-flow O2 device, such as the nasal cannula which can deliver O2 concentrations of
24–4%. The simple face mask is appropriate for patients who are suffering from moderate hypoxia as it can
deliver O2 concentrations of 40–60%. The disadvantage of the face mask is that it requires a tight seal
which can be confining for the patient and muffle their speech. The non-rebreather mask can deliver 239
80–100% concentration of O2. When the patient inhales, the O2 within the reservoir bag is drawn into the
mask and subsequently the patient’s lungs. As the patient exhales, the rubber flaps at the side of the mask
open to allow air to escape. This means the non-rebreather mask is a closed system and if the O2 flow rate
cannot inflate the reservoir bag, the patient could potentially suffocate (Bledsoe and Claden, 2012).

Conclusion
Respiratory distress is a common reason for people to request emergency ambulance assistance. With
ever improving methods of care, people with respiratory diseases are living longer than ever before. This
has a knock-on effect for prehospital services when these patients have an exacerbation of their illness.
Evidence supports that prehospital management of respiratory diseases improves outcomes and reduces
mortality. Therefore, prehospital practitioners should have a good understanding of the pathophysiologi-
cal and pharmacological processes that underpin respiratory emergencies and their management.

Find out more

The following is a list of respiratory conditions or conditions that affect the respiratory system which are
also encountered in the prehospital field. Take some time to review these conditions, paying close attention
not only to the pharmacological management but also the medications (if any) which the patient may be
prescribed by their doctor to manage their symptoms.

Condition Notes
Cystic fibrosis
Lung cancer
Motor neuron disease
Acute respiratory distress syndrome
Bronchiectasis

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for croup in children. Cochrane Database of Systematic Reviews 10: CD06619.
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management-of-asthma
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bronchitis-defined
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uploads/2020/03/GOLD-2020-POCKET-GUIDE-ver1.0_FINAL-WMV.pdf
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Professional Publishing.
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Klabunde, R. (2012). Beta-Adrenoceptor Agonists (Β-Agonists). www.cvpharmacology.com/cardiostimulatory/
beta-agonist
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gency medical service patients. PLoS One 14(2): e0213145.
Long, B., Lentz, S., Koyfman, A. and Gottlieb, M. (2020). Evaluation and management of the critically ill adult asth-
matic in the emergency department setting. American Journal of Emergency Medicine 44: 441–451.
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ing electroconvulsive therapy: short review of the pathophysiology and diagnostic approach. Clinical
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chodilators revisited. Pharmacological Reviews 72(1): 218–252.
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Further reading 241

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(COPD) – differences and similarities. Materia Socio-Medica 24(2): 100.

Multiple-choice questions
1. Ventilation is:
(a) The movement of gases between cells
(b) Movement of air into and out of the lungs
(c) The total volume of air in forced expiration
(d) The process of administering inhaled medication.
2. Diffusion of gases across a membrane occurs due to:
(a) Differences in gas pressure gradients
(b) Total lung volume capacity
(c) Pulmonary blood flow rate
(d) Respiratory rate and heart rate.
3. COPD patients with dyspnoea should have oxygen therapy administered to achieve an
O2 saturation of:
(a) 94–98%
(b) ≤92%
(c) >96%
(d) 94%.
4. Wheezes most commonly suggest:
(a) Secretions in large airways
(b) Abnormal lung tissue
(c) Airless lung areas
(d) Narrowed airways.
5. Which of the following would not be found in a patient with chronic bronchitis?
(a) Weight loss
(b) Pulmonary hypertension
(c) Cyanosis
(d) Right-sided heart failure
6. Which of these drugs are M3-receptor antagonists?
(a) Bronchodilators
(b) Antimuscarinics
Chapter 13 Medications used in the respiratory system

(c) Antihistamines
(d) Sympathomimetics
7. Which of these drugs dilate constricted airways by relaxing smooth muscle?
(a) Beta-2 adrenergic receptor agonists
(b) Glyceryl trinitrate
(c) H1-receptor antagonists
(d) Hydrocortisone
8. In the emergency management of COPD, which of the following is the initial medication
of choice?
(a) Ipratropium bromide
(b) Salbutamol
(c) Hydrocortisone
(d) Chlorphenamine
9. Muscarinic receptors antagonists cause:
(a) Bronchodilation and increased mucus secretion
(b) Bronchoconstriction and increased mucus secretion
242 (c) Bronchodilation and reduced mucus secretion
(d) Bronchoconstriction and reduced mucus secretion.
10. Which of the following is a synthetic form of an endocrine hormone?
(a) Magnesium sulfate
(b) Oxygen
(c) Chlorphenamine
(d) Hydrocortisone
11. Which of the following should be administered to an asthmatic patient who shows no
improvement following a B2-agonist nebuliser?
(a) A H1-receptor antagonist
(b) An anticholinergic
(c) A nitrate
(d) An electrolyte
12. Which of the following is a sign of life-threatening asthma?
(a) Peak expiratory flow = 50%
(b) Respiratory rate of 25 bpm
(c) Heart rate of 120 bpm
(d) Hypotension
13. Which of the following is indicated for severe upper airway stridor?
(a) Salbutamol
(b) Epinephrine
(c) Chlorphenamine
(d) Ipratropium bromide
14. Which of the following oxygen delivery devices are ‘high-flow’ devices?
(a) Nasal cannula
(b) Simple face mask
(c) Non-rebreather mask
(d) Venturi mask
15. Which of the following patients requires oxygen therapy?
(a) A 72-year-old with mild COPD exacerbation with an SpO2 of 90%
(b) A 24-year-old allergic reaction patient with isolated urticaria
(c) A 56-year-old with carbon monoxide poisoning and an SpO2 of 99%
(d) A 2-year-old with upper airway stridor, mild distress and SpO2 of 96%
Chapter 14
Medications used in the
gastrointestinal system
George Bell-Starr and Ashley Ingram

Aim
The aim of this chapter is to provide the reader with an introduction to common pharmacological
interventions and the gastrointestinal conditions that they may encounter.

Learning outcomes
After reading this chapter the reader will be able to:

1. Understand the pharmacological interventions commonly available to paramedics, their indications

and contraindications
2. understand the pharmacological interventions available in a wider healthcare setting for various
common gastrointestinal disorders
3. Develop a fundamental understanding of common gastrointestinal presentations, and their causes
4. Relate the signs and symptoms of common gastrointestinal conditions to their underlying
pathophysiology.

Test your knowledge

1. Describe the components and main functions of the gastrointestinal tract.
2. Write down the common gastrointestinal disorders that you have encountered in clinical practice.
3. What are the common routes for the administration of gastrointestinal medications?
4. Identify common causes for constipation and potential interventions for this condition.
5. Consider some of the most common gastrointestinal medications you see prescribed to the patients
you encounter.

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 14 Medications used in the gastrointestinal system

Introduction
Homeostasis is dependent on the consumption, absorption and metabolism of food and water.
Paramedics will often come across disorders found within the gastrointestinal system, such as
nausea and vomiting, peptic ulcers, constipation, diarrhoea, inflammatory bowel disease and gastro-
oesophageal reflux disorder. Frequently those patients presenting to paramedics or the ambulance
service may exhibit more severe conditions than those presenting to primary care. It is important to
consider that patients may also present to this service as a result of not having resolved their condition
with primary care providers or a failure to access primary care services. Approximately 40% of the UK
population have at least one gastrointestinal symptom at any one time (NHS, 2019). This is comparable
to other high-income countries. Medications such as omeprazole and lansoprazole (proton pump
inhibitors) are often used in the treatment of gastrointestinal (GI) disorders and are the most commonly
prescribed medication in the UK.
The chapter will be broken down into sections covering the disorders separately; these will feature an
overview of the gastrointestinal disorder and the most likely medications utilised in its treatment and
management. Furthermore, administrative considerations associated with pharmacological interventions
commonly available to paramedics will be discussed. Additionally, specific cases pertinent to paramedic
practice will be covered.

244
Anatomy and physiology of the
gastrointestinal system
The GI tract begins at the mouth and ends at the anus. Its purpose is to mechanically and enzy-
matically digest food, absorb nutrients and water, protect the body from microbial invasion and
expel faeces. Food enters the mouth where mechanical and enzymatic digestion begins and then
is propelled down the oesophagus and into the stomach where digestion continues. As the food
bolus passes through the small intestine, further digestion and absorption take place with the
help of enzymes secreted by the stomach, small intestine, liver and pancreas. Most of the water
absorption and formation of faeces occur in the large intestine, until it is temporarily stored in the
rectum and defecated through the anus (Bruneau, 2017). See Figure 14.1 for an overview of the
gastrointestinal tract.

Nausea and vomiting

Nausea and vomiting (emesis) are very common and have broad aetiology. Common causes include
migraines, motion (car sickness), pregnancy and medications (such as opioids and cytotoxic agents).
Due to this broad aetiology, it is very common for paramedics to assess and manage patients with
nausea and/or vomiting secondary to their presenting condition.
A wide range of medications are used to treat nausea and vomiting, but not all are commonly
available to paramedics. A cautionary approach should be taken in administering antiemetics
prior to diagnosis as identification of the underlying cause might be delayed, particularly with
children (NICE, 2020a). If an antiemetic is indicated, then the drug should be chosen according to
the aetiology.

Clinical consideration: management of vomiting

in the patient receiving palliative care
Nausea and vomiting are common symptoms in patients receiving palliative care. The paramedic
should carefully consider the underlying pathology and whether this is reversible. Careful considera-
tion should also be given to the side-effects of the chosen antiemetic. One of the most common
reversible causes of vomiting is constipation (Albert, 2017). Paramedics may carry Ondansetron to use
in the treatment of opiate-induced vomiting. This should be avoided for a constipated patient as the
Medications used in the gastrointestinal system Chapter 14

medication itself is constipating and may worsen a patient’s condition. To serve as further examples,
cyclizine would not be used in patients with heart failure as this could exacerbate the condition.
Levomepromazine would be the choice if the cause of the vomiting and nausea was not obvious.
Ondansetron may be useful if symptoms are likely to be caused by renal failure, chemotherapy or
gastric cancers. The paramedic should seek GP support from either the patient’s registered GP or out
of hours so the most appropriate drug can be offered. Or the use of ‘just in case’ medication may be
appropriate as this would have likely been considered (Blackmore, 2020).

The two key sites in the central nervous system involved with the vomiting reflex are the vomiting
centre and the chemoreceptor trigger zone. The five neurotransmitters that provide feedback to
these areas are:

• H1 receptors
• dopamine (D2)
• serotonin (5-HT3)
• acetylcholine (muscarinic)
• neurokinin (substance P). 245
Antiemetics are antagonists for these receptors, thus they block or dampen the biological response
by binding to or blocking a receptor. Often they are simply called blockers, e.g. beta-blockers.

Mouth (oral cavity)

contains teeth
and tongue
Parotid gland
(salivary gland) Sublingual gland
(salivary gland)
Submandibular gland Pharynx
(salivary gland)
Oesophagus

Liver Stomach
Duodenum
Pancreas
Gallbladder
Transverse
Jejunum colon
Ileum Descending
colon
Ascending colon
Sigmoid colon
Caecum
Rectum
Appendix
Anus

Figure 14.1 The gastrointestinal tract.

Chapter 14 Medications used in the gastrointestinal system

H1 receptor antagonists (antihistamines)

The most common type of antiemetic, these agents are primarily used to combat motion sickness
and vertigo. However, they can also be used to treat opioid-induced sickness and morning sickness
secondary to pregnancy (hyperemesis gravidarum).
Examples of H1 receptor antagonists include:

• promethazine
• doxylamine
• meclizine
• cyclizine.
All antihistamines cause anticholinergic effects which can include vasodilation, hallucinations and
urinary retention. Cardiac toxicity effects induce tachycardia and prolonged QT may be seen on an
electrocardiogram (ECG) (Brady et al., 2020).

Dopamine (D2) receptor antagonists

Dopamine receptors are located in the chemoreceptor trigger zone (CTZ) and respond to dopamine
released from nerve endings. The most common cause of CTZ stimulation is from the GI tract, with
246 the neurotransmitters dopamine and serotonin being released by GI irritation.
Dopamine receptor antagonists are most commonly used to treat the nausea and vomiting associ-
ated with chemotherapy or opioid administration. They are unlikely to be effective in reducing the
nausea and vomiting caused by motion sickness.
Examples of D2 receptor antagonists include:

• prochlorperazine, commonly used to treat hyperemesis gravidarum

• metoclopramide
• domperidone.
Side-effects of these drugs can include diarrhoea, drowsiness and lower seizure thresholds.
Metoclopramide should not be given to patients under the age of 18 years due to an increased risk
of neurological events. Full monitoring including a 12-lead ECG should be considered post adminis-
tration due to a risk of arrhythmia, QT prolongation, AV blocks and cardiac arrest (Brady et al., 2020).

Metoclopramide
JRCALC contraindicates the use of metoclopramide in patients younger than 18 years of age. The rea-
sons behind this are as follows.
The European Medicines Agency’s Committee on Medicinal Products for Human Use has reviewed
the benefits and risks of metoclopramide. The review was done at the request of the French medicines
regulatory agency, following concerns over side-effects and efficacy. The review confirmed the well-
known risks of neurological effects such as short-term extrapyramidal disorders and tardive dyskinesia.
The conclusion of the review was that these risks outweigh the benefits in long-term or high-dose
treatment.
The EU review has recommended changes that include a restriction to the dose and duration of use
to help minimise the risk of potentially serious neurological adverse effects. The risk of acute neurologi-
cal effects is higher in children than in adults (Medicines and Healthcare products Regulatory
Agency, 2014).

Serotonin (5-HT3) receptor antagonists

Serotonin receptor antagonists act upon receptors found within the vagus nerve, certain areas of the
brain and the GI tract. These antagonists are the gold standard in controlling nausea and vomiting pro-
duced by chemotherapy; they can stop symptoms in up to 70% of people and reduce symptoms in the
Medications used in the gastrointestinal system Chapter 14

remaining 30% (NICE, 2016). Like D2 receptor antagonists, 5-HT3 receptor antagonists are ineffective in
controlling motion sickness (Muth and Elkins, 2007).

Peptic ulcers
The phrase ‘peptic ulcer’ is used to describe any ulcer that develops in the stomach, duodenum or
oseophagus (NHS, 2018). Ulcers form when there is an imbalance between the mucus layer (which
protects the mucosa) and acid secretion (aids with digestion of proteins); where excessive acid is
produced in combination with a reduction in mucus, erosion of the mucosa can occur and peptic
ulcers can form (Neal, 2015). See Figure 14.2 for the common sites of peptic ulcer.
Factors that can cause this imbalance include:

• Helicobacter pylori infections

• long-term use of non-steroidal anti-inflammatory drugs
• in rare circumstances, tumours (both cancerous and non-cancerous) of the stomach or duodenum
(National Institute of Diabetes and Digestive and Kidney Diseases, 2014).

Helicobacter pylori infections 247

Helicobacter pylori is a gram-negative rod found deep within the mucosal layer where a pH level of
7.0 is optimal for its growth. The bacteria can invade the cells of the mucosa, causing damage and
reducing the production of the protective mucus layer. H. pylori can persist for years without treat-
ment, and is associated with an increase in gastrin and thus stomach acid which further causes an
imbalance between the damaging processes and the protective factors. Over half of the world’s
population is colonised with H. pylori and unless treated, it is likely to persist for life (Kusters
et al., 2006).
If a patient tests positive for H. pylori then a trio of medications will be prescribed to eliminate the
ulcer and the bacteria. These include a proton pump inhibitor (PPI) (e.g. lansoprazole or omeprazole)
that will be used to try to reduce the amount of acid produced. Additionally, the antibiotic amoxicil-
lin, alongside a further antibiotic such as metronidazole or clarithromycin, will be administered to
further assist with healing of the damaged mucosa (BNF, 2020). Studies have suggested that due to
antibiotic resistance, the efficacy of triple therapy is decreasing and new therapies are required
(Fiorini et al., 2012).
The third medication that will probably be prescribed is an H2-receptor antagonist such as ran-
itidine. Similarly to the PPI, this is used to reduce the amount of acid the stomach produces. As well
as this trio of medications, a further antacid such as aluminium hydroxide gel, calcium carbonate

Oesophagus
Lesser
curvature
Fundus

Greater
curvature

Pyloric sphincter
Commom sites for peptic ulcer

Figure 14.2 Common sites for peptic ulcer.

Chapter 14 Medications used in the gastrointestinal system

or magnesium hydroxide may be useful in the management of symptoms such as pain that may
present with diarrhoea, stomach cramping and/or flatulence (NHS, 2018).

Non-steroidal anti-inflammatory drugs

There are several ways in which NSAIDs can damage the gastroduodenal mucosa. They can
reduce the positive barrier properties of the mucus, suppress gastric prostaglandin synthesis
(gastric prostaglandins help protect the mucosa) and interfere with the natural repair of mucosal
injury.
Treatment for peptic ulcers not linked to H. pylori does not need an antibiotic. A H2-receptor antag-
onist such as ranitidine/cimetidine/famotidine is usually sufficient in promoting ulcer healing.
Therefore, H2-receptor antagonists are often given prophylactically to prevent gastrointestinal
complications.
Antacids are not commonly prescribed or encouraged as they only manage symptoms and do not
eradicate the ulcer, although they can be given for symptom management.

Symptoms of peptic ulcer

Patients are most likely to present to a paramedic with a dull ache or burning sensation in their stom-
ach, but this pain can be located anywhere between the umbilicus and sternum. This fact alone may
248 mean that many patients are presented as having cardiac chest pain.
Common factors associated with the presentation of peptic ulcers include:

• the pain presenting frequently when the stomach is empty

• worsening over weeks or months
• discomfort fades temporarily after ingesting antacids.
In more serious cases a patient might present to the paramedic with a GI bleed. Approximately
50% of all GI bleeds are caused by gastric ulcers (Pirastehfar et al., 2010); it is likely that they will pre-
sent with either coffee-ground vomiting or haematemesis.

Clinical consideration: Presentation of

haematemesis
Ultan is a 26-year-old male. He is normally fit and well and takes no regular medication. He has felt
nauseated for the last few days and has today vomited a small amount of what looked like coffee-
ground vomit. His partner phoned 111 and an ambulance was dispatched to him.
Upon arrival you find a well-looking man. His observations are all within normal range. His abdom-
inal exam is otherwise normal. He has some tenderness over his epigastria. He reports his bowels
have been normal and daily. He has no other symptoms. He reports that he is prescribed no
medication.
What further history or exam would be appropriate?
When questioned further, Ultan states that he has been training far harder than he normally
does at the gym in anticipation for a triathlon he is due to compete in. He has found it increasingly
hard to concentrate at work due to aches and pains post workout. He has been taking ibuprofen
to combat this which has worked very well. He has been taking his full daily dose for around
3 weeks now.
What do you think is the likely cause of his haematemesis and abdominal pain? He is probably suf-
fering with a peptic ulcer as a side-effect of his use of NSAIDs.
What would your next steps be for this patient?
Explain to the patient the risks with taking NSAIDs long term and advise that he stops.
If he is well, he can be followed up by his GP.
Medications used in the gastrointestinal system Chapter 14

Constipation
Constipation is defined as bowel movements that are less frequent (less than every other day) or
those that are hard, dry or lumpy to pass. Symptoms may include pain, bloating or the feeling of
incomplete evacuation, nausea and abdominal discomfort (National Institute of Diabetes and
Digestive and Kidney Diseases, 2018).
Constipation is ubiquitous; one study found up to 90% prevalence in patients on regular opioid
medication (Canadian Agency for Drugs and Technologies in Health, 2014) whilst in the UK around
20% of adults complain of constipation. In the US, constipation accounts for 5.3 million prescrip-
tions annually (National Institute of Diabetes and Digestive and Kidney Disease, 2014). Bowel
habits can vary considerably in frequency without doing harm. Some people erroneously consider
themselves constipated if they do not have a bowel movement each day, but this is not the case
(NICE, 2020b).
Whilst most episodes of constipation will generally resolve with self-help, medication or a combi-
nation of both, constipation can be indicative of or the result of other health conditions.

Laxatives
Laxatives come as four predominantly different types of drugs. Bulk-forming laxatives work by
increasing the ‘bulk’ or weight of faeces, which in turn stimulates the bowel; these include Fybogel 249
(ispaghula husk) and methylcellulose. Osmotic laxatives draw water from the rest of the body into the
bowel to soften faeces, making them easier to pass; the most common is lactulose. Stimulant laxa-
tives stimulate the muscles that line the gut, helping them to move faeces along to the rectum; these
include drugs such as bisacodyl and senna. Finally, softener laxatives work by letting water into faeces
to soften it, making it easier to pass (NHS, 2019).
It is important for paramedics to consider abuse of these medications. A high index of suspicion
should be considered with patients suffering from bulimia nervosa or anorexia. Medical complica-
tions of laxative abuse are often a result of chronic diarrhoea and the associated severe electrolyte
disturbances. Potassium is the primary electrolyte in stool water. Patients may develop hypokalae-
mia, they may present with generalized muscle weakness, lassitude, skeletal muscle paralysis or
rhabdomyolysis with renal impairment, and nerve palsies. More severe hypokalaemia can result in
cardiac arrhythmias with an increased risk of sudden death (Roerig et al., 2010).

Bulk-forming laxatives
These work by increasing the ‘bulk’ or weight of faeces, which in turn stimulates the bowel. They are
of particular value in adults with small hard stools if fibre cannot be increased in the diet. Symptoms
of flatulence, bloating and cramping may be exacerbated. Adequate fluid intake must be maintained
to avoid intestinal obstruction. Examples of these are Fybogel (ispaghula husk) and methylcellulose
(BNF, 2020).

Osmotic laxatives
These agents increase the amount of water in the large bowel, either by drawing fluid from the body
into the bowel or by retaining the fluid they were administered with. Lactulose is a semisynthetic
disaccharide which is not absorbed from the GI tract. It produces an osmotic diarrhoea of low faecal
pH and discourages the proliferation of ammonia-producing organisms. It is therefore useful in the
treatment of hepatic encephalopathy. Macrogols (such as macrogol 3350 with potassium chloride,
sodium bicarbonate and sodium chloride) are inert polymers of ethylene glycol which sequester
fluid in the bowel; giving fluid with macrogols may reduce the dehydrating effect sometimes seen
with osmotic laxatives (BNF, 2020).

Stimulant laxatives
These increase intestinal motility and often cause abdominal cramp; manufacturer advice is that they
should be avoided in intestinal obstruction. The use of co-danthramer and co-danthrusate is limited
Chapter 14 Medications used in the gastrointestinal system

to constipation in terminally ill patients because of potential carcinogenicity (based on animal stud-
ies) and evidence of genotoxicity.
Docusate sodium is believed to act as both a stimulant laxative and a faecal softener. Glycerol sup-
positories act as a lubricant and a rectal stimulant by virtue of the mildly
irritant action of glycerol, stimulating the muscles that line the gut, helping to move faeces for-
ward to the rectum.
Stimulant laxatives include bisacodyl, sodium picosulfate and members of the anthraquinone
group (senna, co-danthramer and co-danthrusate) (NICE, 2017).

Softener laxatives
These act by decreasing surface tension and increasing penetration of intestinal fluid into the faecal
mass. Docusate sodium and glycerol suppositories have softening properties. Enemas containing
arachis oil (groundnut oil, peanut oil) lubricate and soften impacted faeces and promote a bowel
movement. Liquid paraffin has also been used as a lubricant for the passage of stools but manufac-
turer advice is that it should be used with caution because of its adverse effects, which include anal
seepage and the risks of granulomatous disease of the GI tract or of lipoid pneumonia on aspiration
(NICE, 2020a).
Again, it is important for paramedics to consider the abuse of these medications. A high index
250 of suspicion should be considered with patients with bulimia nervosa or anorexia. Medical com-
plications of laxative abuse are often a result of chronic diarrhoea and the associated severe
electrolyte disturbances. Potassium is the primary electrolyte in stool water. Patients may
develop hypokalaemia; they may present with generalised muscle weakness, lassitude, skeletal
muscle paralysis, or rhabdomyolysis with renal impairment, and nerve palsies. More severe
hypokalaemia can result in cardiac arrhythmias with an increased risk of sudden death (Roerig
et al., 2010).

Episode of care: constipation

Derek, a 72-year-old male, lives alone since his wife died a year ago. She was the cook in the house and
while he states he gets by, he feels now there is little point in cooking meals for just one person. His
daughter who lives close by prepares him a home-cooked meal once a week. In between these times,
Derek finds himself eating fast and convenience food. Derek fell 2 months ago and while he was not
injured, he admits this has affected his confidence. He now finds he sits and watches television more
than tending to the garden like he used to. He has developed gradually increasing, generalised abdom-
inal pain and feels bloated more frequently. Due to being increasingly worried about this and unable to
acquire a GP appointment, he called 111 which has dispatched an ambulance with the provisional
diagnosis of dissecting aorta.
On arrival of the crew, Derek answers the door and looks well. The crew discuss his presentation and
find out the information above. The paramedic discovers that his weekly bowel movements have
reduced from 5–7 to three episodes and he often finds it difficult to pass motions.
During physical examination, the paramedic finds nothing of concern. The indicated observations
are within normal ranges. Derek’s current pain score is 3/10.
The paramedic notes this is probably chronic constipation as it has been ongoing for a few months
now and that it may be exacerbated by poor diet and a more sedentary lifestyle. Derek has little medi-
cal history, he takes an antihypertensive and he had a dose of antibiotics for a urinary tract infection
(UTI) around the time he was bereaved. He is fully independent at home but is showing signs of slowing
since his fall.
There is no familial history of bowel cancer. Nevertheless, it is noted by the paramedic that this is a
change in bowel habit for a patient over the age of 60 years and therefore he is indicated for NHS bowel
screening. This is discussed with the patient who can self-refer to this service; however, Derek is not the
best on computers so it is suggested that his daughter assist him with this.
It is discussed with Derek that there are many things he can do to help with his constipation.
Medications used in the gastrointestinal system Chapter 14

Initially, secondary causes should be considered, particularly organic issues in a patient of this age,
including but not limited to diabetes mellitus, strictures, haemorrhoids and hypothyroidism. These
would need to be considered by the GP so referral to them is important. Derek has not started any new
medication since this presentation so that can be excluded.
Lifestyle measures are then discussed with Derek as this may be the biggest cause of his consti-
pation. He is advised to gradually increase his fibre intake and eat fruits high in sorbitol and to aim
to drink 1500 mL of water daily which will have the added benefit of preventing UTIs. Upon discuss-
ing this, it is again highlighted that Derek used to enjoy his garden and that he would grow many of
his own vegetables. The paramedic feels it would be a good idea to arrange for a falls prevention
team to visit the property to see if they can offer some aids to facilitate safer movement and allow
Derek to enjoy his garden again. The paramedic also discussed this with Derek’s daughter who
states she may start to cook more frequently for him or assist him with his shopping to enable a
better diet.
The paramedic discusses worsening advice with Derek and states that if his conditions get worse or
do not resolve within a certain time frame after making these changes, he should report back to his GP.
His GP is also notified regarding the bowel habit change.

251
Episode of care: suspected bowel perforation
Tamwar is a 55-year-old man. He saw his GP 10 days ago due to difficulty passing bowel motions. He
was started on laxatives. Since then, he has still not passed a significant bowel motion. This afternoon
he developed a sudden onset of abdominal pain. His wife called 999.
Upon arrival, the paramedic notes Tamwar is shouting out in pain. He is very pale, tachycardic,
tachypnoeic, hypotensive and has a temperature of 39.0 °C. He is GCS 15 but the pain inhibits him from
discussing his situation in detail to allow full assessment.
Abdominal assessment is difficult as the patient will not allow the paramedic to touch his abdomen.
His abdomen is hard, the pain is predominantly in the left lower quadrant and there are no bowel
sounds.
Typically bowel perforation results from insult or injury to the mucosa of the bowel wall resulting
from rupture of the closed system. This then exposes the peritoneal cavity to gastrointestinal contents.
Bowel perforation can be most commonly attributed to obstruction, trauma, invasive surgery or infec-
tion as well as many other less frequent causes.
Red flags are difficult to determine as presentations can differ. Nevertheless, patients who pre-
sent with abdominal pain and distension, especially with a pertinent history, should be assessed
thoroughly as delayed diagnosis carries a high mortality rate. Even when appropriately managed,
mortality is up to 70% when secondary complications such as peritonitis are present (Jones
et al., 2020).

Gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GORD) is a common condition, where acid from the stomach
leaks up into the oesophagus. It usually occurs as a result of the ring of muscle at the bottom of the
oesophagus becoming weakened. GORD causes symptoms such as heartburn and an unpleasant
taste in the back of the mouth. It may just be an occasional nuisance for some people, but for others
it can be a severe, lifelong problem. GORD can often be controlled with self-help measures but on
occasion, medication may need to be prescribed. In very rare cases patients may require surgery
(NHS Inform, 2020).
Current NICE guidance is to first request patients to change behaviours that may exacerbate the
condition. For example, changing eating patterns/times, smoking cessation and raising the head of
the bed when sleeping may help reduce or cure symptoms.
Chapter 14 Medications used in the gastrointestinal system

There are a number of drugs that can be a cause or a contributing factor to GORD, namely
alpha-blockers, anticholinergics, benzodiazepines, beta-blockers, bisphosphonates, calcium
channel blockers, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), nitrates, theo-
phyllines and tricyclic antidepressants (NICE, 2019).

Drug interventions (patients with confirmed

endoscope diagnosis)
Proton pump inhibitor
Proton pump inhibitors work by irreversibly inhibiting gastric H+K+ ATPase (the proton pump) in
the stomach. They inhibit both basal and stimulated acid secretion (Therapeutics Initiative, 2016).
In recent years there has been significant media coverage regarding the side-effects of PPIs and
they have been linked to stomach cancer and an increased risk of hip fracture. It may be important
for paramedics to consider if patients are indeed compliant with their prescribed PPI medication
(NHS, 2017).
Examples of PPIs include omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole and
dexlansoprazole.

252
Prokinetic/promotility/gastrointestinal stimulants (GIS)
These are drugs that increase motility of the gastrointestinal smooth muscle, without acting as a
purgative. These drugs have different mechanisms of action but they all work to move the con-
tents of the GI tract faster. They also decrease the reflux of stomach acid by strengthening the
muscle of the lower oesophageal sphincter (International Foundation of Gastrointenstinal
Disorders, 2018).
Examples of GIS medications include metoclopramide and domperidone (both are also commonly
prescribed as antiemetics).
Sometimes an H2 antagonist (H2Ras) may be prescribed to GORD patients who are not respond-
ing to an initial dose of PPI. However, this is rare and this medication is discussed later under peptic
ulcers.

Paramedic practice
While paramedics will encounter patients presenting with GORD, they are generally attending
because the patient is experiencing chest pain. While differentiating between GORD and cardiac
chest pain is beyond the scope of this chapter, it is best to be cautious. Chest pain should not be
assumed to be gastric related.

Clinical consideration: chest pain mimics

There are many conditions which can cause chest pain. A presentation of GORD may be suggestive if it
starts after eating, bringing up food or bitter-tasting fluids, feeling full and bloated.
A sprain or strain may be indicative if the pain starts after chest injury or chest exercise, and feels
better when resting.
An anxiety- or hyperventilation-related pain may be indicated if the pain is triggered by worries or a
stressful situation, heartbeat gets faster and sweating and dizziness occur.
The pain may be of respiratory origin if it gets worse when the patient breathes in and out, is cough-
ing up yellow or green mucus, and has a high temperature.
The cause of the pain may be shingles if there is a tingling feeling on the skin, or a skin rash appears
that turns into blisters.
Despite this, other risk factors should also be considered such as smoking status, obesity, hyperten-
sion, hypercholesterolaemia, age over 60 years and/or a history of myocardial infarction or failure, as
well as familial history (NHS, 2020).
See Table 14.1 for a comparison of cardiac-related chest pain and gastric-related chest discomfort.
Medications used in the gastrointestinal system Chapter 14

Table 14.1 Comparison of cardiac-related chest pain and gastric-related chest discomfort. Source:
Adapted from Harvard Health Publishing (2018).
Common symptoms of gastric-related chest
Common symptoms of cardiac-related chest pain discomfort
Tightness, pressure, squeezing, stabbing or dull pain, Burning chest pain that begins at the sternum
most often in the centre of the chest
Pain that spreads to the shoulders, neck or arms Pain that moves up toward the throat but doesn’t
typically radiate to shoulders, neck or arms
Irregular or rapid heartbeat Sensation that food is coming back into the mouth
Cold, sweaty or clammy skin Bitter or acidic taste at the back of the throat
Light-headedness, weakness or dizziness Pain that worsens when the person lies down or
bends over
Shortness of breath The appearance of symptoms after a large or spicy meal
Nausea, indigestion and sometimes vomiting
The appearance of symptoms with physical exertion or
extreme stress 253

Reflection
Over 16% of all ambulance conveyances to the emergency department (ED) are directly related to
chest pain (Pedersen et al., 2019). Take some time and write some notes about a patient you have trans-
ported to the ED who might have been experiencing chest pain mimic. Are there any other questions
you would have asked that patient?
Could you have changed your treatment plan?
Remember to adhere to all the rules of confidentiality when writing anything that includes patient
information.

Clinical consideration: assessing diarrhoea

Diarrhoea is the passage of three or more loose or liquid stools per day (or more frequently than is
normal for the individual).

• Acute diarrhoea is defined as lasting less than 14 days.

• Persistent diarrhoea is defined as lasting more than 14 days.
• Chronic diarrhoea is defined as lasting for more than 4 weeks.
Acute diarrhoea is usually caused by a bacterial or viral infection. Other causes include drugs, anxi-
ety, food allergy and acute appendicitis.

Dehydration increases the risk of life-threatening illness and death, particularly in young infants
and children, and older people. For this reason, care should be taken when assessing these patients,
particularly in the presence of abdominal pain. Thorough assessment including hydration status
should be considered. Red flags for dehydration include weakness, confusion, tachycardia, profound
hypotension and oliguria/anuria.
Arrange emergency admission to hospital if:

• the person is vomiting and unable to retain oral fluids, or

• they have features of severe dehydration or shock (for more information, see clinical features of
dehydration).
Chapter 14 Medications used in the gastrointestinal system

Other factors that influence the threshold for admission include (use clinical judgement):

• older age (people 60 years of age or older are more at risk of complications)
• home circumstances and level of support
• fever
• bloody diarrhoea
• abdominal pain and tenderness
• increased risk of poor outcome, for example:
• coexisting medical conditions – immunodeficiency, lack of stomach acid, inflammatory bowel
disease, valvular heart disease, diabetes mellitus, renal impairment, rheumatoid disease, systemic
lupus erythematosus
• drugs – immunosuppressants or systemic steroids, proton pump inhibitors, angiotensin-converting
enzyme inhibitors, diuretics.
Adapted from NICE (2018).

Antidiarrhoeals
Antimotility agents are the class of drugs used for the management of diarrhoea. These agents act by
modulating intestinal contractions and reducing frequency of bowel movements. The most effective
254 antimotility agents are synthetic opiates, diphenoxylate with atropine (Lomotil®) and loperamide
(Imodium®). Historically, opiates such as paregoric, tincture of opium and codeine were noted to be
effective in the short-term treatment of diarrhoea, but their effects on the central nervous system
and potential for drug dependency limited their use (Keystone, 2008).
Loperamide is the most commonly prescribed antimotility agent worldwide. In 2013, loperamide
was added to the list of essential medications by the World Health Organization (WHO, 2014).
Loperamide may be prescribed to patients who have a colostomy, Crohn’s disease, ulcerative colitis
and other common conditions such as irritable bowel syndrome (NHS, 2008).
Paramedics should consider that loperamide is an opioid medication and patients can develop
dependency (Zarghami and Rezapour, 2017). It also has serious adverse effects and patients abusing
the drug or those having overdosed can present with severe cardiotoxicity. Profound electrocardio-
gram (ECG) abnormalities (sinus bradycardia, wide QRS, prolonged PR interval, markedly prolonged
QTc, Brugada-like ECG pattern), malignant ventricular arrhythmias and ventricular dysfunction have
all been reported (Kohli et al., 2019).

Skills in practice: assessing bowel sounds

Auscultation of the bowel sounds is performed to detect altered bowel sound, vascular bruits or rubs.
Peristalsis (the involuntary constriction and relaxation of the intestinal muscles) creates bowel sounds
that might be altered or completely absent in the presence of disease or obstruction. This should be
done before palpation as this may compromise assessment due to the palpation causing bowel sounds.
The patient should be positioned in a comfortable supine position lying at around 45°. Using a
warmed stethoscope, the examiner should listen to multiple areas across the abdominal wall for sev-
eral minutes. The stethoscope should be applied with a firm pressure, ensuring minimal discomfort is
caused.
When bowel sounds are not clearly heard, the examiner should listen for a full 3 minutes to
ensure that they are in fact, absent. Remember that the thickness of the abdominal wall may affect
auscultation, and so the bowel sounds of an obese patient or a patient with ascites may be more
difficult to hear.
Common causes of absent bowel sounds include:

• partial or complete blockage of the bowels

• strangulation of the bowel
• peritonitis.
Medications used in the gastrointestinal system Chapter 14

Inflammatory bowel disease (IBD)

The cause of inflammatory bowel disease (IBD) remains unknown, but increasing evidence suggests
that these conditions, like many chronic inflammatory disorders, involve immune-mediated tissue
damage due to a variable interaction amongst genetic factors and environmental triggers. IBD is the
collective term for the conditions that include Crohn’s disease and ulcerative colitis (Rampton, 2008).

Crohn’s disease
Crohn’s disease is a chronic disease of the gastrointestinal tract with symptoms evolving in a relaps-
ing and remitting manner. It is also a progressive disease that leads to bowel damage and disability.
All segments of the GI tract can be affected, the most common being the terminal ileum and colon.
Inflammation is typically segmental, asymmetrical and transmural. Most patients present with an
inflammatory phenotype at diagnosis, but over time complications (strictures, fistulas, abscesses)
will develop in half of patients, often resulting in surgery (Torres et al., 2017).

Ulcerative colitis
Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend
continuously to proximal segments of the colon. It usually presents with bloody diarrhoea and is
diagnosed by colonoscopy and histological findings. The management is to induce and then main- 255
tain remission, defined as resolution of symptoms and endoscopic healing. Some patients can
require colectomy for medically refractory disease or to treat colonic neoplasia (Ungaro et al., 2017).

Drug treatment for inflammatory bowel disease

There is currently no cure for IBD. Around 1 in 5 patients with ulcerative colitis will require surgery
and as many as 3 in 4 patients with Crohn’s disease may require surgery. Nevertheless, there are drugs
that can help manage symptoms. These come under four main categories (NHS, 2020).

Aminosalicylates (5-ASAS)
These include sulfasalazine, mesalazine, Pentasa®, Mezavant® and olsalazine. These drugs contain
5-aminosalicylic acid, which is called 5-ASA for short. 5-ASA can help to reduce inflammation in the
digestive tract by working directly on the lining of the bowel. 5-ASA drugs are chemically related to
aspirin and work by reducing inflammation, allowing damaged tissue to heal. These are mainly used
in the treatment of ulcerative colitis (Crohn’s and Colitis UK, 2018).

Immunosuppressants
Immunosuppressants include adalimumab, azathioprine, golimumab, infliximab, methotrexate, ster-
oids, tofacitinib and Entocort®.
Immunosuppressive drugs suppress actions of the immune system and its inflammatory response.
These drugs are useful for very active IBD that does not respond to standard therapy and help main-
tain remission. An immunosuppressant is often combined with a steroid to speed up response dur-
ing active disease (Gionchetti et al., 2017).

Corticosteroids
Corticosteroids such as prednisolone can be used with or instead of 5-ASAs to treat a flare-up if
5-ASAs alone are not effective. Like 5-ASAs, steroids can be administered orally or via a suppository
or enema. Corticosteroids are not used as a long-term treatment to maintain remission because they
can cause potentially serious side-effects such as osteoporosis and cataracts (NHS, 2020).

Biologic medicines (infliximab, adalimumab, golimumab and vedolizumab)

These drugs reduce inflammation of the intestine by targeting proteins the immune system uses to
stimulate inflammation. These medicines block these receptors and reduce inflammation. They may
be used to treat adults with moderate to severe ulcerative colitis if other options are not suitable or
Chapter 14 Medications used in the gastrointestinal system

not working (NHS, 2020). It is useful for paramedics to have a generalised understanding of the above
conditions. At times, patients with IBD may need hospitalisation and it would be sensible to discuss
such patients with a general practitioner or other healthcare professional who may be more versed
in these specific conditions. As a general rule, patients with IBD who have not responded to oral
corticosteroid-based therapy as outpatients usually have to be admitted to hospital for inpatient
supervised care (Baidoo, 2017).

Skills in practice: how to assess dehydration

Dehydration is common, specifically in the older person. There is a strong correlation between dehydration
and increased mortality. The make-up of babies is 70% water. By the time patients are over the age of
65, years this has reduced to 50%. With age comes a decreasing sense of thirst and a reduced ability for the
body to concentrate urine; this, coupled with a reduction in mobility, can mean that dehydration is a very
real problem and one that paramedics should be investigating in the prehospital setting.
In hospital, a blood sample and measuring serum osmolality can show dehydration. However, this is
not possible prehospital so a non-invasive alternative must be used.
First, it is important to consider risk factors for dehydration.

• Increasing age (Stookey, 2005; Warren et al., 1994)

256 • Gender – women are more at risk than men (Stookey, 2005; Stookey et al, 2005; Warren et al., 1994)
• Ethnicity – Afro-Caribbean Americans are at greater risk than white Americans (Stookey, 2005;
Lancaster et al., 2003; Warren et al., 1994).

Second, it is important to consider that specific long-term conditions may cause certain patients to be
at increased risk of dehydration

• Diabetes (Stookey et al., 2005)

• Hypertension (Stookey et al., 2005)
• Obesity (Stookey et al., 2005)
• Oral problems (Dyck, 2004)
• Functional limitations (Stookey et al., 2005)
• Dementia (Albert et al., 1989).
Non-invasive tests that may be done prehospital have little evidence to prove them as effective, therefore
it would appear sensible for this advice to be seen as a guide only.
Simple observations such as orthostatic hypotension, increased heart rate and increased temperature
may all be signs of patients at risk of dehydration.
paramedics should ask questions such as: do you have a headache; do your muscles feel weak; do
you feel dizzy and or sick; does your mouth feel dry; do you feel thirsty?
Further to this, physical signs can also indicate dehydration, including increased skin turgor tested at
various sites (often the back of the hand), although this may be non-specific due to the ageing process
of skin, increased capillary refill time, a fissured and/or dry tongue and oral mucosa as well as a dry
underarm. Also, dark urine colour and reduced urine output may also be signs of dehydration.
Whilst no single sign may completely rule out dehydration, a holistic approach should be considered
to determine the likelihood of dehydration.

The following is a list of common conditions associated with patients who have GI disorders. Patients
suffering with these disorders might present frequently to the ambulance service and having a deeper
understanding of the condition and treatment pathways will allow you to offer optimal care to your patient.
Take some time to research and reflect on these conditions, possibly by thinking of patients you have
treated who might have been suffering from them. Be detailed, look at the pharmacokinetics and phar-
macodynamics and remember to look at all aspects of patient care.
Medications used in the gastrointestinal system Chapter 14

Remember, though, if reflecting on specific patients, you must adhere to the rules of confidentiality.
Condition Your notes
Barrett oesophagus
Crohn’s disease
Gastro-oesophageal reflux disease
Diverticulitis

Conclusion
This chapter has provided an overview of common disorders within the gastrointestinal system and
the medications used to treat them. Evidence has been provided for the use of each drug along with
an understanding of the pharmacokinetics and pharmacodynamics, as well as considerations for
administration and common adverse effects. Wider issues have been covered including patient man-
agement, non-pharmacological interventions relevant to paramedic practice and self-care.
257

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illnesses-and-conditions/stomach-liver-and-gastrointestinal-tract/gastro-oesophageal-reflux-disease-gord
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niddk.nih.gov/health-information/digestive-diseases/peptic-ulcers-stomach-ulcers/definition-facts.
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59–63.

Multiple-choice questions
1. An example of a proton pump inhibitor (PPI) is:
(a) Omeprezole
(b) Ranitidine
Medications used in the gastrointestinal system Chapter 14

(c) Simvastatin
(d) Gliclazide
2. Peptic ulcer is a term to describe an ulcer found in which areas of the body?
(a) Stomach, oral cavity, oseophagus
(b) Oesophagus, stomach, duodenum
(c) Small intestine, stomach, duodenum
(d) Anus, large intestine, oral cavity
3. Loperamide is an opioid medication, Paramedics should be aware that in extreme
doses it can have severe adverse effects, including:
(a) Sinus bradycardia
(b) Prolonged PR
(c) Wide QRS
(d) All of the above
4. The most common type of antiemetic used to combat motion sickness is:
(a) H1 receptor antagonists
(b) Dopamine D2 antagonists
(c) Serotonin (5-HT3) antagonists
(d) H2 receptor antagonists 259
5. Below what age does metoclopramide become contraindicated in the JRCALC
guidelines?
(a) 18 months
(b) 21 years
(c) 18 years
(d) 12 years
6. Which antacid would you use to treat loose stools?
(a) Aluminum hydroxide
(b) Magnesium hydroxide
(c) Both
(d) Neither
7. An example of a H1 receptor antagonist antiemetic is:
(a) Chlorpromazine
(b) Ondanestron
(c) Metaclopramide
(d) Cyclizine
8. Which of these is not a common cause of constipation?
(a) Becoming less active
(b) Stress, anxiety, depression
(c) A new prescription of codeine
(d) Eating oily foods
9. Chest pain that worsens when the patient lies down or bends over is generally
associated with:
(a) Gastric-related pain
(b) Cardiac-related pain
(c) Premenopause
(d) All of the above
10. Which groups are at increased risk of dehydration secondary to diarrhoea?
(a) Elderly patients
(b) Young children
(c) Certain ethnic minorities
(d) All of the above
Chapter 14 Medications used in the gastrointestinal system

11. Which of these is not a common cause of absent bowel sounds?

(a) Complete blockage of the bowels
(b) Strangulation of the bowel
(c) Peritonitis
(d) Ulcerative colitis
12. Red flags for dehydration include:
(a) Pyrexia and hypertension
(b) Profound hypotension, oliguria/anuria
(c) Weakness, confusion, tachycardia, profound hypotension, oliguria/anuria
(d) None of the above
13. Risk factors for peptic ulcer include:
(a) Long-term use of non-steroidal anti-inflammatory drugs
(b) Helicobacter pylori infections
(c) In rare circumstances, tumours
(d) All of the above
14. Loperamide is likely to be prescribed to a patient who is complaining of:
(a) Constipation
260 (b) Nausea
(c) GORD
(d) None of the above
15. A peptic ulcer is:
(a) Any ulcer in the stomach, duodenum or esophagus
(b) Any ulcer in the stomach only
(c) Any ulcer in the duodenum only
(d) Any ulcer in the oesophagus only
Chapter 15
Medication and the nervous
system
Geoffrey Bench, Alastair Dolan, Lena Solanki,
Paul Doherty, Charlotte White, Ricky Lawrence
and Emma Beadle

Aim
The aim of the chapter is to provide the reader with an introduction to pharmacology relating to
common neurological disorders in the prehospital setting.

Learning outcomes
After reading this chapter the reader will be able to:

1. Explain the most common medications used in the management of Parkinson disease, epilepsy,
dementia and strokes
2. Describe the mechanism and side-effects of the drugs used to treat common neurological
conditions
3. Discuss the red flags you would consider in relation to medications used in neurological conditions
4. Discuss the treatment and management of patients with common neurological conditions,
highlighting any red flags.

Introduction
This chapter will address conditions that affect the nervous system and the medication commonly
prescribed for those conditions, and outline the drugs paramedics can administer. It is essential that
the student paramedics and paramedics practise within the parameters of local policy and proce-
dure, adhering at all times to their Code of Conduct.
Due to the number of conditions that affect the nervous system, the focus will be on the most
common conditions that paramedics encounter in the prehospital setting. Some of the mental

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 15 Medication and the nervous system

health conditions that affect the nervous system will be explored in Chapter 16. By the end of this
chapter readers will have greater understanding of neurological conditions, how they are managed
and the treatments available in everyday paramedic practice to ensure safe and effective care. The
conditions included within this chapter are Parkinson disease, dementia, epilepsy and stroke.

The nervous system

The nervous system (NS) is a complex and sophisticated system. It acts as the master controller and
communication system of the body (Marieb, 2004). It consists of both the central nervous system
(CNS) and the peripheral nervous system (PNS). The CNS contains the brain and spinal cord whereas
the PNS is made up of nerves and ganglia. Changes that occur inside and outside the body are
detected by the NS and acted upon to control and co-ordinate vital aspects of bodily functions to
maintain homeostasis. The NS helps us breathe, regulates blood pressure and heart rate, aids with
digestion, allows us to eat, drink, gather new thoughts and skills, etc. The main functions of the NS
overlap each other. By using millions of sensory receptors, it gathers information (sensory input),
monitors changes that occur both inside and outside the body which in turn elicit a response (motor)
by activating effector organs. This occurs by voluntary (involvement of thought) and involuntary
control without conscious control (autonomic).

262 Parkinson disease and parkinsonism

Parkinson disease (PD) occurs in all ethnic groups and can be described as idiopathic or having no
specific cause. PD has no definite cause but is thought to ‘result from a genetically determined
vulnerability to particular environmental factors’ such as toxins, recreational drug abuse, head
trauma and genetic influences (Jones, 2011).
Parkinson disease most commonly affects the elderly and is defined as a progressive neurological
disorder of the basal ganglia. Parkinsonian patients show a substantially reduced concentration of
dopamine in their basal ganglia; this is due to a continuing degeneration of the dopaminergic neu-
rons of the substantia nigra located in the basal ganglia of the brain (Donizak and McCabe, 2017). The
basal ganglia in patients without PD have an effect on voluntary motor control, procedural learning
relating to routine behaviours such as eye movement, as well as emotional and cognitive functions.
The number of people diagnosed with PD worldwide is around 10 million; in the UK it is about
145 000 (www.parkinsons.org).
Figure 15.1 shows an image of the brain and the substantia nigra in Parkinson disease.
Although there are numerous causes of parkinsonism, for example cerebral ischaemia, stroke, viral
encephalitis or other pathological damage, the most common cause is PD. PD can be characterised
by slow initiation of movements, known as bradykinesia, muscle rigidity and tremors. Collectively,
these symptoms are known as the ‘parkinsonian triad’.
Patients start to show direct symptoms of parkinsonians when more than 80% of the dopaminer-
gic neurons of the substantia nigra have degenerated (Dawson et al., 2002). The terms ‘On’ and ‘Off’
are often used by practitioners to describe the different stages of motor variants: the ‘On’ period
where the patient’s PD symptoms are under control and the ‘Off’ period when the symptoms are
worsening due to medication ineffectiveness. ‘PD is progressive with continued loss of dopaminergic
neurons, which in turn leads to worsening of the clinical symptoms. Untreated PD eventually results
in dementia and subsequent death’ (Dawson et al., 2002).
People with PD may present with characteristic signs which include:

• speech impairments
• inability to perform skilled tasks
• a shuffling gait
• a blank ‘mask-like facial expression (Dawson et al., 2002).
The neurotransmitter acetylcholine opposes the dopamine neurotransmitter involved in the co-
ordination of motor responses. This is important as many of the therapies against the progression of PD
and the loss of motor function are directed at addressing the imbalance between these neurotransmit-
ters. Research suggests that a decline in dopamine levels would increase acetylcholine production and
Medication and the nervous system Chapter 15

Substantia nigra

Cut section
of the midbrain
where a portion
of the substantia
nigra is visible

Diminished substantia
nigra as seen in
Parkinson disease

263

Figure 15.1 Parkinson disease and the substantia nigra.

these high levels of acetylcholine are the cause of uncontrolled, involuntary movements known as
dyskinesia (Parkinson’s News Today, 2019). Drugs taken for treatment of PD increase the amount of dopa-
mine in the brain; they may act as a ‘dopamine substitute by stimulating the parts of the brain where
dopamine works or block the action of other factors that break down dopamine’ (Parkinson’s UK, 2019).
Parkinson drugs that paramedics may encounter in the prehospital setting are detailed in
Table 15.1.
The potential harms and benefits of PD agents are shown in Table 15.2.

Table 15.1 Drugs used for Parkinson disease.

Drugs Actions
Levodopa Converts to dopamine in the brain
(co-beneldopa and co-careldopa)
MAO-B inhibitors (rasagiline, Enzymes that chemically break down the dopamine within the brain
selegiline, safinamide)
Dopamine agonists Initiate actions of dopamine when levels are low
(pramipexole, ropinirole)
COMT inhibitors Enzymes that metabolise or degrade neurotransmitters (dopamine)
(entacepone, opicapone)
Amantadine Increases dopamine release and blocks dopamine reuptake
Anticholinergics Block the action of the neurotransmitter acetylcholine inhibiting nerve
(procyclidine, trihexphenidyl) impulses responsible for involuntary muscle movements and bodily
functions
Apomorphine Dopamine agonist
Rotigotine skin patch Dopamine agonist administered through the skin
(Neupro®)
Source: Based on Inacio P. (2019). Imbalance in dopamine and acetylcholine levels may drive disease progression.
https://parkinsonsnewstoday.com/
Chapter 15 Medication and the nervous system

Table 15.2 Potential benefits and harms of dopamine agonists, levodopa and MAO-B inhibitors.
Monoamine oxidase B
Levodopa Dopamine agonists (MAO-B) inhibitors
Motor symptoms More improvement in Less improvement in Less improvement in motor
motor symptoms motor symptoms symptoms
Activities of daily living More improvement in Less improvement in Less improvement in
activities of daily living activities of daily living activities of daily living
Motor complications More motor complications Fewer motor Fewer motor complications
complications
Adverse events Fewer specified adverse More specified adverse Fewer specified adverse
(excessive sleepiness, events events events
hallucinations and impulse
control disorders)
Source: Based on Patricia Inacio PhD. 2019., Imbalance in Dopamine and Acetylcholine levels may drive disease
progression, Parkinson’s news today.

Episode of care
264 You are called to attend a 53-year-old male who has suddenly became lethargic and will not respond
or does not want to respond to his normal daily living activities. His wife on scene states that he seems
extremely fatigued and that this is unusual for him. She states that her husband was diagnosed with
Parkinson disease about 2 years ago and that he takes levodopa (co-beneldopa) 100 mg four times a
day. On further questioning, the patient’s wife states that she had noticed a pungent smell of urine over
the last day, when helping her husband dress. The patient has no other significant medical history.
Baseline observations

Pulse Respiration rate SpO2 Temperature Blood glucose Blood pressure GCS
O
85 18 98% on air 38.1 C 5.1mmol/L 105/70 14/15

What are your thoughts?

Underlying causes of lethargy in Parkinson patients can be due to the motor symptoms making the
muscles tired but it is important to identify and treat illnesses that are not related to PD. It is important
to interpret the baseline observations and take into account any new medications prescribed. Gaining
a comprehensive history from a relative or carer, has this happened before? What was the treatment
plan? What was the outcome?
What is your plan?
A comprehensive history will allow the clinician to make the correct decision for either transporta-
tion to the emergency department or referral to another healthcare practitioner.

Infections
Parkinson patients are prone to bladder infections due to the reduction of muscle control related to
their illness and they have a difficult time passing urine. Ineffective emptying of the bladder acts as a
breeding ground for bacteria. If the urinary tract infection is not treated, this could lead to a more
systemic infection, i.e. sepsis. The patient needs referral to their GP for further investigations and
antibiotics if indicated.

Dementia
The word ‘dementia’ describes over 200 different types of progressive neurological disorders that
affect the brain.
Medication and the nervous system Chapter 15

As we go through life, the effects of ageing slowly start to affect our lives. We all suffer from memory
problems to some degree as we get older. For some people, these early memory problems can indi-
cate a medical condition such as dementia. It is a progressive disease that is irreversible with a decline
of cognitive function, behavioural abilities, independent and social living.
Dementia patients can become tired and stressed, making them more anxious, which can lead to
depression as well as physical illnesses.
There are a number of factors that can lead to the development of dementia.

• Genetics: a person’s genetic history is known to have a role in the development of the disease
though the effects may differ considerablely.
• Medical history: people who experience conditions such as multiple sclerosis, Down syndrome,
HIV, diabetes and metabolic syndrome are at higher risk of developing dementia.
• General lifestyle: sedentary lifestyles and excessive use of drugs or alcohol consumption can
increase the risk of developing dementia.
• Age: getting older will increase the risk of developing dementia in combination with other
conditions such as high blood pressure or those at risk from other diseases such as acute coronary
syndrome and cerebrovascular accidents.

Due to an increase of the ageing population, those with dementia worldwide is estimated to be
around 50 million, with nearly 10 million new cases each year.
Understanding of dementia and its cause is not clear but is improving, with research into 265
the involvement of a nuclear protein called TDP-43 causing proteinopathy, where certain proteins
become structurally abnormal, disrupting cell function. This is associated with hippocampal
sclerosis and dementia, known as limbic-predominant age-related TDP-43 encephalopathy or
LATE, predominantly found in those 80 and older. TDP-43 protein is also associated with the disease
pathology of Alzheimer disease, found in up to 57% of Alzheimer disease patients (Boer et al.,
2020).

Drugs used in dementia

There are many different types of drugs that may be used to treat the specific symptoms of
dementia, such as antipsychotics, antianxiolytics and antidepressants (Table 15.3). The goal of
treatment is to maintain current health. The most popular medications are cholinesterase inhibi-
tors and memantine.
Cholinesterase inhibitors work by increasing acetylcholine, a chemical in the brain that aids in
memory and judgement. It is believed that this may delay dementia-related symptoms and may
even prevent it from worsening.

Table 15.3 Dementia drugs that paramedics may encounter in the prehospital setting.
Drugs Actions
Donepzil Inhibits the enzyme function of acetylcholinesterase which breaks down acetylcholine. This
allows for higher concentrations of acetylcholine to facilitate communication between the
synapses of nerve cells in the brain
Galantamine Weak acetylcholinesterase inhibitor; binds to the choline binding site, thereby blocking the action
of acetylcholinesterase and increasing availability of choline
Rivastigmine Binds to acetylcholinesterase, making it inactive. This stops acetylcholinesterase from destroying
choline, which helps towards increasing levels
Memantine Not a cholinesterase inhibiter. Blocks the effects of glutamate, which is known to cause excessive
stimulation in Alzheimer disease
Source: Based on Drugbank.com. www.alzheimers.org.uk/about-dementia/treatments/drugs/
how-do-drugs-alzheimers-disease-work
Chapter 15 Medication and the nervous system

Cautions
Cholinesterase inhibitors are known to have significant interactions with a number of comorbidities,
as shown in Table 15.4, and also side-effects, shown in Table 15.5.

Table 15.4 Interactions of cholinesterase inhibitors.

Cardiac Respiratory Gastrointestinal Lymphatic Neurological Environmental
Coronary Asthma Peptic ulcers Hepatic dysfunction Seizures Alcoholic
artery disease cirrhosis
Bradycardia Obstructive Thyroid Epilepsy
pulmonary disease
Effects
Constriction of the Increase gastric Cholinesterase is Can cause Can cause
bronchi secretions and metabolised by the convulsions convulsions and
contractions liver and can lead to and tremors tremors
hyperthyroidism
Source: Based on Drugs.com. (2020). Donepezil Side Effects. www.drugs.com/sfx/donepezil-side-effects.html

266
Table 15.5 Side-effects of cholinesterase inhibitors: minor, severe and rare.
Donepezil Galatamine Rivastigmine Memantine
Respiratory Cough Dyspnoea Dyspnoea
Dry mouth SOB
SOB Tachypnoea
Tachypnoea
Wheezing
Cardiovascular Arrhythmia Arrhythmia AV block Arrhythmia Dizziness Drowsiness
BP Chest pain Dizziness Drowsiness Embolism
Chest pain Dizziness HTN Heart failure
Dizziness Syncope Syncope HTN
Drowsiness Tachycardia
Tachycardia
Abdominal Appetite loss Decreased urination Abdominal pain Constipation Vomiting
Genitourinary Constipation Diarrhoea Dehydration Diarrhoea
Diarrhoea Dry mouth Gastric ulcer
Melaena Dyspepsia Hepatitis
Nausea Incontinence
Polyuria Nausea
Vomiting Pancreatitis
UTI
Vomiting
Integumentary Bleeding Reddening Skin reactions Fungal infections
Bruising Sunken eyes
Hives Sweating
Itching
Sweating
Musculoskeletal Joint pain Anorexia Abnormal gait Fatigue Fatigue
Muscle cramps Fatigue Weight loss Impaired balance
Stiffness Tremors
Swelling Weight loss
Tiredness
Tremors
Weakness
Weight loss

(Continued)
Medication and the nervous system Chapter 15

Table 15.5 (Continued)

Donepezil Galatamine Rivastigmine Memantine

Neurological Aggression Blurred vision Anxiety Confusion
Agitation Confusion Confusion Depression Hallucinations
Blurred vision Hallucinations Seizures
Burning Headache
sensations Insomnia
Delusion Nightmares
Depression Parkinsonism
Headache Seizure
Mood changes Tremor
Nightmares
Restlessness
AV, atrioventricular; BP, blood pressure; HTN, hypertension; SOB, shortness of breath; UTI, urinary tract infection.

Epilepsy
Epilepsy is a neurological condition which is characterised by at least one of the following.
267
• Two or more unprovoked seizures occurring more than 24 hours apart.
• One unprovoked seizure and a probability of further seizures after two unprovoked seizures,
occurring over the next 10 years.
• Diagnosis of an epilepsy syndrome (NICE, 2019).

Epilepsy and status epilepticus are connected to excessive activation of excitatory neurons or a
reduction of inhibitory neurotransmission (Jones-Davis and MacDonald, 2003). Epilepsy is not an illness
or disease, it is a controllable neurological condition managed with antiepileptic drugs (AEDs). Alternative
management can be surgery, when optimal management cannot be achieved.
There are over 40 different presentations of seizures which include focal, focal aware, tonic,
absence, myoclonic and tonic clonic. Seizures occur due to sudden, spontaneous uncontrolled depo-
larisation of neurons, as a result of excessive excitation or loss of normal inhibitory mechanisms. This
depolarisation causes abnormal sensory or motor activity and possible unconsciousness.
In essence, the origin of seizures is a malfunction of the ion (sodium, potassium, calcium) chan-
nels. Neurotransmitters travel across synapses between neurons. They cross the synaptic cleft between
neurons and attach to receptors on the adjoining neuron. Some neurotransmitters function to excite
the joining neuron (e.g. glutamate) to send a subsequent electrical signal. The function of other neuro-
transmitters is to inhibit the joining neuron (e.g. GABA) and inhibit electrical impulses conducted down
that neuron. These chemical and electrical pathways enable the neurons to function normally.
A fundamental principle of the pathophysiology of epilepsy is that seizures result from an imbalance
in the normal excitatory and inhibitory mechanisms. The two main classes of neurons responsible for
such properties are glutamatergic and GABAergic neurons.
The incidence of epilepsy is approximately 50 million worldwide (www.epilepsysociety.org).
Epilepsy is a significant cause of mortality. People with epilepsy have a reduced life expectancy of 8
years compared to the rest of the population.
There are many underlying conditions which can lead to epilepsy, including brain damage during
prenatal or perinatal care, head injuries, stroke, brain tumours, infections of the brain and certain
genetic conditions. One in three people diagnosed with epilepsy may have a family member with
the condition (NHS, 2020). In 50% of cases the cause of epilepsy is not identified (World Health
Organization, 2018).
Seizures may be caused by a trigger such as stress, flashing lights (photosensitivity epilepsy),
alcohol and lack of sleep. Many patients will describe an abnormal experience moments before the
seizure presents, describing feelings of hallucinations/flashing lights, unusual smell or taste, numb-
ness or tingling in limbs, déjà vu or feelings of sadness/joy. An epilepsy aura is a focal aware seizure
and the patient will remain conscious and alert, remembering the experience (Epilepsy Society, n.d.).
This is a pre-emptive warning that a greater seizure is likely to occur.
Chapter 15 Medication and the nervous system

Table 15.6 Common AEDs seen in the prehospital setting.

Sodium valproate Carbamazepine (Tegretol®) Lamotrigine Levetiracetam
(Epilim®, Episenta®, Epival®) (Lamictal®) (Keppra®, Desitrend®)

Antiepileptic medication
Currently two-thirds of epilepsy patients are actively managing their condition with AEDs (Table 15.6).
Healthcare professionals aim to manage the patient’s seizures through optimal therapy, thus enhancing
the health outcomes to maintain social, educational and employment activity which can be adversely
affected through this chronic condition. Monotherapy is the optimal management for epilepsy
patients, with sodium valproate described as an ideal therapy for generalised and unclassifiable
epilepsy. The SANAD (Standard and New Antiepileptic Drugs) trial identified lamotrigine and/or
carbamazepine as the optimum therapy for focal seizures (Marson et al., 2007).
Healthcare professionals managing epilepsy patients should tailor their treatment with an indi-
vidualised plan, considering the prevalence of the seizures, manifestations, comedication and
comorbidity. The lifestyle and preferences of the individual, family and carers should be discussed
before prescribing an optimal AED management plan. This is due to the potential side-effects of the
drugs; for example, sodium valproate must be avoided in females of child-bearing age and those
who are pregnant in order to avoid birth defects in the baby (MHRA, 2018).
268 Depending on the presentation of the AED, they can be administered as tablet, capsules, liquid
and syrups daily. Poor compliance with drug therapy can result in an increased likelihood of seizures,
potentially leading to status epilepticus.

Psychogenic non-epileptic seizures (PNES) versus bilateral tonic

clonic seizures (BTCS)
Convulsions in adults and children in the prehospital setting can be challenging to distinguish, lead-
ing to incorrect diagnosis of epilepsy (Table 15.7). Psychogenic non-epileptic seizures are a common
cause of prolonged seizures and are often mistaken for status epilepticus, resulting in incorrect
management and treatment. Administering emergency drug treatment such as diazepam can cause
adverse side0effects such as respiratory depression, aspiration and death. Therefore, paramedics on
scene should gain an accurate history from individuals, seeking an emergency care plan to aid deci-
sion making for the patient.
Thorough recording of the characteristics of the patient’s seizure will aid in the diagnosis of a PNES.
Doctors/specialists encourage the use of video recording of the seizure to aid in making a formal
diagnosis retrospectively.

Emergency medication in the prehospital setting

Paramedics typically carry diazepam in their drug packs, either an ampule of 10 mg in an oil-in-water
emulsion making up to 2 mL or a rectal tube containing 2.5 mg, 5 mg or 10 mg diazepam.
Current guidelines states diazepam should be administered to patients who have prolonged
seizures (lasting 5 minutes or more) or a repeated convulsion (three or more in 60 minutes). The
patient is currently convulsing which is not secondary to uncorrected hypoxia or hypoglycaemic
episode (JRCLAC, 2021).
Diazepam will depress the actions of the CNS, causing a sedative effect. Caution should be exercised
for patients who have consumed alcohol, are prescribed antidepressants and other CNS depressants
due to an increased likelihood of side-effects. Diazepam in the emergency setting is typically a safe
drug to administer but must be avoided if there is known hypersensitivity.
Administration of diazepam can cause respiratory depression, so be prepared to ventilate the
patient using a bag-valve-mask and have this prepared before administration of the drug.
Hypotension has also been noted in patients who have been rapidly removed from their location.
Allow a 10-minute recovery period before extrication; if this is unachievable, keep the patient flat.
Buccal midazolam is a medication similar to diazepam and known epileptic patients, children will
usually have an emergency tube of prefilled midazolam. If this medication is available, clinicians should
prioritise administering it over intravenous diazepam due to the complexity of cannulation in children,
Medication and the nervous system Chapter 15

Table 15.7 Differentiating psychogenic non-epileptic seizures (PNES) from bilateral tonic clonic
seizures (BTCS).
Signs that favour PNES Signs that favour BTCS
During seizure During seizure
Fluctuating intensity/location Consistent, repeated, rhythmic myoclonic jerking
Brief pauses, tremor or slow flexion/extension ‘Shock-like’ movement
movements
Arms and legs often not synchronised Arms and legs mostly synchronised
Convulsion may move from one body area to Convulsions may spread from focal to generalised and clonic
another merging to clonic
May respond (e.g. speech, NPA insertion, etc.) Unresponsive GCS 3 or 4 (grunting)
Tongue biting rare Lateral tongue biting common
Eyes mostly shut Eyes often open
Mouth often shut Mouth often open
Pupils reacting Pupils not reacting
May carry out purposeful movement No purposeful movement
269
Normal SpO2, no cyanosis Low SpO2 or cyanosis
May be prolonged (>3 min) Typically short(<90 sec)
Pelvic thrusting common Pelvic thrusting rare
Postictal Postictal
Rapid end to convulsion Gradual slowing down of seizure
Rapid recovery Gradual recovery
Normal breathing Noisy laboured breathing
History History
Onset over 15 years Onset under 10 years
Recurrent ‘status epilepticus’ (misdiagnosis) Alcohol misuse
PTSD or psychological distress Provoked seizures (e.g. brain injury)
GSC, Glasgow Coma Scale: NPA, nasopharyngeal airway; PTSD, post-traumatic stress disorder.
Source: Modified from JRCALC (2021).

administering en route to hospital. Buccal midazolam should only be administered if the clinician is
confident in this skill; most caregivers on scene will have already administered a first dose of buccal mida-
zolam. Clinicians can subsequently administer a second dose 10 minutes after the first dose.

Administering buccal midazolam

Patients who have been prescribed buccal midazolam will usually have an individualised treat-
ment plan for an emergency situation (Figure 15.2). Clinicians should follow the epilepsy pass-
port plan, utilising the prefilled syringe of midazolam, checking the dosage, date and quality. Prefilled
syringes are 2.5 mg, 5 mg, 7.5 mg or 10 mg. Medication should be administered into the oral mucosa,
aiming for the gums and providing gentle stimulation to ensure the medication is absorbed and not
trickling into the airway.

Administering rectal diazepam

It may be appropriate for patients to receive rectal diazepam instead of intravenous (IV) diazepam
due to inability to gain IV access. This will mostly be seen in paediatric and elderly patients. As previ-
ously noted, the rectal tubes will be in various dosages and it is imperative to check the clinical
Chapter 15 Medication and the nervous system

Figure 15.2 Emergency buccal midazolam presentation. Source: © Epilepsy Awareness Ltd.

Table 15.8 Adverse reactions associated with common antiepileptic drugs.

Drug Adverse reactions
Carbamazepine Rash, headache, ataxia, tremor, diplopia, hyponatraemia, hepatic failure
Gabapentin Peripheral oedema, behaviour changes, acute pancreatitis, hepatitis, acute renal failure,
270 Stevens–Johnson syndrome
Lamotrigine Rash, headache, dizziness, ataxia, blurred vision, hepatic failure
Levetiracetam Behavioural changes, headache, dizziness
Pregabalin Dizziness, ataxia, confusion, renal failure, heart failure
Sodium valproate Nausea, vomiting, hepatic and pancreatic failure
Source: Based on Brown, C. (2016). Pharmacological management of epilepsy. Progress in Neurology and Psychiatry
20(2): 27–34c.

guidelines for drug dosage before administering the medication. Due to the route of medication,
inform individuals on scene and maintain dignity where possible. The nozzle on the tube will have
a marker indicating where to stop; general guidance is 2.5 cm for children and 4–5 cm for adults
(JRCALC, 2021). When inserting the medication, keep a firm hold on the tube while removing, otherwise
the medication will retract back into the nozzle.
Adverse reactions associated with common antiepileptic drugs are detailed in Table 15.8.

Strokes (including transient ischaemic

attacks)
Over 13 million people suffer a stroke worldwide each year, of which 5.5 million die from the stroke
(World Stroke Organization, 2020). The incidence of stroke and TIA increases with age; in one study
more than 75% of events happened in people over the age of 65 (Rothwell et al., 2005). However,
though strokes and TIAs are mostly associated with the elderly, anyone at any age can have a stroke;
it is thought that around two out of 100 000 children worldwide are affected each year (betterhealth.
vic.gov.au).
About 15% of strokes are haemorrhagic; 85% of haemorrhagic strokes are from intracranial aneu-
rysms, 10% from a non-aneurysmal perimesencephalic haemorrhage and vascular abnormalities,
including arteriovenous malformation, account for the other 5% (CKS, 2020; JRCALC, 2019). Haemorrhagic
strokes are generally more severe and associated with higher fatality, with 1 in 10 patients dying before
reaching hospital, and a higher fatality rate compared to ischaemic strokes within the first 3 months and
beyond, intracranial haemorrhage being the more disabling and devastating (JRCALC, 2019). Though
subarachnoid haemorrhage (SAH) is an intracranial bleed, the clinical presentation differs from other
strokes and typically presents with a sudden onset of severe headache, with vomiting and no focal
neurology signs (ISWP, 2016; JRCALC, 2019).
Medication and the nervous system Chapter 15

Definition of a stroke and a transient ischaemic attack

The World Health Organization (2002) defines a stroke as ‘rapidly developing clinical signs of focal (or
global) disturbance of cerebral function, lasting more than 24 hours’. This definition and the term
‘stroke’ cover a number of different pathologies causing lost neurological function and cerebral
damage (Sacco et al., 2013).
The JRCALC (2019) identifies two types of stroke: those caused by ischaemia resulting in cerebral
infarction and those caused by intracerebral haemorrhage. Ischaemic strokes account for 85% of
strokes; they are caused by a thrombus (a complication from atherosclerosis), an embolus from a clot
in the heart or larger artery (caused by atrial fibrillation or atherosclerosis) or fatty embolism from
ruptured atherosclerotic plaque (CKS, 2020). This results in ischaemia of the distal tissue beyond the
blockage; if blood flow is not restored then that tissue dies (Caroline, 2014).
Transient ischaemic attacks (TIA) have no formal WHO definition, though the generally used one is
‘an acute loss of focal cerebral or ocular function with symptoms lasting less than 24 hours’. Tthere is
also a recently suggested definition of ‘an event lasting less than 1 hour without cerebral infarction
on magnetic resonance imaging scan’ (ISWP, 2016). The causes of TIAs are thought to be similar to
those that cause ischaemic strokes, with reduced blood flow and perfusion of the cerebral and ocular
tissue (JRCALC, 2019). The IWSP (2016) states that ‘all suspected cerebrovascular events need to be
investigated and treated urgently’, as the risk from stroke in the first month after a TIA is very high and
for up to a year after.
There are a number of risk factors associated with the development of strokes and TIAs (Table 15.9);
some of these are modifiable, others are not (CKS, 2020).
271

Assessment of a stroke
The ISWP (2016) highlights the importance of public awareness in recognising the signs and
symptoms of a stroke and of stroke prevention, using campaigns such as the FAST campaign in
the UK. The ISWP (2016) notes that research suggests that one- off campaigns have little effect
and repeated and continuous campaigns are better. However, there is a weak link between aware-
ness and recommended behaviours, prompting the importance of the healthcare professional
(HCP) as a source of healthcare education, as these campaigns have a higher impact on HCPs
(ISWP, 2016).
There are a number of tools used in healthcare for the recognition of a stroke. The two recom-
mended by NICE are FAST for prehospital and lay public use and the Recognition of Stroke in the
Emergency room (ROSIER) for within the emergency department (ISWP, 2016; JRCALC, 2019; NICE,
2019; Rudd et al., 2016). ROSIER is a superior tool in the recognition of strokes within the emergency
department, although a study by the London Ambulance Service found that it was not better than
the FAST tool for prehospital recognition (JRCALC, 2019). The ISWP (2016) and JRCALC (2019) both
recognised that the person may still be having a stroke and be FAST negative. The recommendation
is that if there is any suspicion of stroke in the FAST-negative patient, the patient should still be
treated for a stroke. JRCALC (2019) and NICE (2019) emphasize that a blood glucose level needs to be

Table 15.9 Risk factors associated with the development of strokes and TIAs.
Lifestyle Established cardiovascular disease Other
Poor diet Hypertension Age
Smoking Atrial fibrillation Gendera
Alcohol Infective endocarditis Hyperlipidaemia
Substance misuse Valvular disease Diabetes
Lack of exercise Carotid artery disease Sickle cell disease
Congestive heart failure Antiphospholipid disease
Congenital or structural heart disease Other hypercoagulation disorders
Chronic kidney disease
Obstructive sleep apnoea
a
Although men are more likely to have a stroke at a younger age than women, women’s risk is increased with
current use of the contraceptive pill, migraines with aura, pre-eclampsia and in the immediate postpartum period.
Source: CKS (2020).
Chapter 15 Medication and the nervous system

assessed in any patient with a sudden onset of neurological symptoms as hypoglycaemia can mimic
the signs and symptoms of a stroke.
It is recommended that all patients with suspected stroke be transferred to a specialist acute stroke
unit after initial assessment (NICE, 2019). As TIAs and strokes initially present with the same signs and
symptoms and for the prehospital clinician it is difficult to determine one from the other, conveying
to a specialist acute stroke unit is recommended. However, there are different criteria depending on
commissioning arrangements for transport to a hyperacute stroke unit (HASU) (JRCALC, 2019).

Treatment
Pharmacological treatment prehospital is limited in the treatment of a stroke and the emphasis is on
recognition, management of life-threatening conditions and rapid transfer to an appropriate hospital
(JRCALC, 2019).
The use of oxygen is only recommended if the patient is hypoxic, to achieve an oxygen saturation
of >94% as per the JRCALC guidelines (JRCALC, 2019).
NICE (2019) states that hypoglycaemia needs to be excluded as a cause of neurological symp-
toms before a stroke or TIA can be confirmed. For the prehospital clinician, this means that any
hypoglycaemia needs to be corrected before managing a suspected stroke (JRCALC, 2019). The
current definition of hypoglycaemia for ambulance services is a blood glucose level of <4 mmol/L
in the known diabetic patient and <3 mmol/L in the non-diabetic patient (JRCALC, 2019). Treatment
272 for hypoglycaemia would depend on the level of consciousness and the patient’s ability to swal-
low; the options available to the prehospital clinician include glucose 40% oral gel, glucagon or
glucose 10% (JRCALC, 2019).
One of the most influential factors in the management of stroke and TIA patients is time, in par-
ticular the time from the onset of symptoms to hospital and then to brain scan (JRCALC, 2019; NICE,
2019).
Thrombolysis is indicated for those patients identified as having an ischaemic stroke within 4.5
hours from onset of symptoms (NICE, 2012, 2019). Thrombectomy with thrombolysis is indicated for
those patients with an onset of symptoms within 6 hours and based on computed tomographic
angiography (CTA) or magnetic resonance imaging (MRA) (NICE, 2019). Thrombectomy with or with-
out thrombolysis is also considered for patients with an acute ischaemic stroke who were well up to
24 hours before, again depending on CTA and MRA imaging (NICE, 2019). The ISWP (2016) suggests
imaging within 1 hour of arrival to hospital for those patients with a suspected stroke.
It is agreed that referral or transport to a specialist acute stroke unit for any patient suspected of a
stroke or TIA, even when the onset of symptoms is outside the time scales mentioned above, is of
great benefit. The single location of a multidisciplinary team for acute assessment and management,
secondary preventive measures and rehabilitation for stroke patients, and preventive measures for
those who have had a TIA, has been shown to improve patient outcomes for up to 1 year after the
event (ISWP, 2016; JRCALC, 2019; NICE, 2019).
The recommendation within stroke units, once haemorrhagic stroke has been excluded and if
presenting within the 4.5 hour window, is for thrombolysis using alteplase (for patients aged between
18 and 79 years old) (BNF, 2021; NICE, 2019). Alteplase comes under a group of drugs called fibrino-
lytic drugs used for thrombolytic therapy; paramedics may be familiar with tenecteplase which is
used for the treatment of myocardial infarctions within some UK ambulance services (Galbraith et al.,
2015; JRCALC, 2019). Alteplase is a plasminogen activator; plasminogen is a proenzyme in the blood
which can be converted to the enzyme plasmin which breaks down fibrin in blood clots and other
clotting factors present (Galbraith et al., 2015; NICE, 2012). Alteplase is used to accelerate this process
in cases of acute ischaemic strokes, the aim being to restore blood flow and perfusion of the distal
tissue (NICE, 2012).
The advantages of alteplase over other thrombolytics such as streptokinase is that it is clot specific,
meaning it only activates the plasminogen within the clot; this results in fewer haemorrhagic epi-
sodes due to generalised plasminogen activation and the action of streptokinase (Galbraith et al.,
2015). Alteplase does not stimulate the production of antibodies, like streptokinase, and can be used
repeatedly with little fear of anaphylactic reaction (Galbraith et al., 2015). The main adverse effect is
haemorrhagic events; other common side-effects of all fibrinolytics include nausea and vomiting,
pulmonary oedema, fever, chills, hypotension, ecchymosis, pericarditis, angina, cardiogenic shock
Medication and the nervous system Chapter 15

and cardiac arrest (BNF, 2021). Though anaphylactic reaction is among the common side-effects the
BNF indicates that this is due to hypersensitivity to gentamicin residue from the manufacturing
process (BNF, 2021).
The initial dose of alteplase is 900 μg/kg (maximum dose 90 mg), 10% given as an intravenous
injection bolus, the remainder as an intravenous infusion over 60 minutes.
Patients presenting with an acute ischaemic stroke should be started on an antiplatelet agent as
soon as possible and certainly within 24 hours (NICE, 2019). NICE recommends starting people
with suspected TIA on a daily dose of 300 mg aspirin (if not contraindicated). In the community,
patients should be referred to a specialist unit for further assessment and preventive treatment.
A protein pump inhibitor should also be offered, especially for those patients with a history of
dyspepsia (NICE, 2019).
Aspirin has a number of actions and is part of a group of drugs known as salicylates, which have
analgesic, antipyretic and anti-inflammatory actions; aspirin is the only drug in this group that has
significant antiplatelet action (Galbraith et al., 2015). Aspirin inhibits the enzyme cyclo-oxygenaese
which is needed in the synthesis of thromboxane. Thromboxane is released when platelets bind to
collagen fibres to form a platelet plug as part of the clotting mechanism. Thromboxane inhibits
adenylate cyclase, an enzyme which is used to make cyclic adenosine monophosphate (cAMP),
which inhibits the adhesiveness of the platelets; any change in the concentration of cAMP has an
effect on the adhesiveness and aggregation of platelets (Galbriath et al., 2015).
Dosage for acute ischaemic stroke is 300 mg aspirin (if not contraindicated) either orally or per
rectum as soon as possible and within 24 hours of symptoms for 2 weeks or until long-term antico- 273
agulant treatment is started (NICE, 2019).
Once acute treatment has started, emphasis shifts to the long-term and secondary preventive
treatment, which should be started as soon as possible (ISWP, 2016). Long-term management starts
with advising the patient about modifying risk factors around lifestyle, encouraging healthier eating
habits, exercise, stop smoking advice and reducing alcohol intake (CKS, 2020). NICE (2019) and ISWP
(2016) recommend that alongside lifestyle changes, a review of medication and the start of second-
ary preventive medication should take place to prevent further vascular events.

Episode of care
You receive a call to attend in the centre of town to a 30-year-old female patient. On arrival at the scene,
you see a female patient in an agitated state being helped by friends and the police. The friends say that
she started acting strangely about 2 hours ago. They say that they have been drinking for the last 4 hours
and just thought that their friend was drunk but noticed about 30 minutes ago that her face looks
dropped and that she seems unable to smile properly.
On examination, you notice that the patient appears frustrated and scared. She is unable to use
appropriate words but appears to understand what you are saying and fully co-operates with your
examination. You also notice that the left side of her face is dropped and she is only able to move the
right side of her face.
Baseline observations

Resp rate Pulse rate Oxygen Blood Blood glucose Temperature GCS
stats pressure level
18 rpm 90 bpm 98% 127/90 2 mmol/L 36.7 °C 13
Eyes Voice Motor
4 3 6

F.A.S.T. positive = Face dropped on left side, use of inappropriate words.

What are your thoughts?
It is important to establish a timeline of events so that the patient gets treatment quickly as the time
window for thrombolysis is 4.5 hours. You should also be aware of any further deterioration and
Chapter 15 Medication and the nervous system

possible airway compromise and inadequate breathing. The patient is frustrated, possibly due to
being unable to communicate. Establishing a method of communication will help with calming and
reassuring the patient.
What is your plan?
A good history of events and timeline is important. Consider if there have been any previous epi-
sodes that may have led up to this event. Also a good past medical history, social and family history
might highlight any risk factors. Drug history also highlights any risks; remember to ask about over-the-
counter medications, contraception pills or devices, alternative therapies and any illicit drugs.
The key to the management of this patient is rapid recognition of symptoms and their cause. The
correction of hypoglycaemia is an important step in excluding this as a cause of the symptoms; once
corrected, then a stroke or TIA can be suspected. Rapid transport to an appropriate hospital is vital,
preferably one with a hyperacute stroke unit to start initial treatment and further rehabilitation and
support for ongoing care and treatment.

Considerations
The above symptoms could be due to the patient being drunk as she has been drinking for the last
4 hours. Be careful with this assumption as alcohol can hide symptoms of more serious pathology, so
274 question further. Be aware of the confirmation bias present here as the patient has been drinking, is
of a young age and female, and is having a hypoglycaemic event; each of these could lead to incor-
rect treatment of this patient. Careful observation of the patient’s actions and behaviour is needed
alongside a thorough history of events.
The patient also has hypoglycaemia and that can mimic the sign and symptoms of a stroke or TIA.
Alcohol consumption can also cause hypoglycaemia. However, the patient is F.A.S.T. positive and
understands what you are saying and is cooperating with your requests.

Conclusion
This chapter has covered four neurological conditions that paramedics encounter in the prehospital
setting. It has addressed the common medications associated with those conditions, the pharmaco-
dynamics, administration and side-effects. The nervous system is an extremely complex system and
new conditions/disease are being discovered regularly so it is important for clinicians to maintain
high standards of patient care.

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Further reading/resources
Diagnoses in the UK. www.dementiastatistics.org/statistics/diagnoses-in-the-uk/
• Understanding Dementia.www.dementiauk.org/understanding-dementia/what-is-dementia/?msclkid=709a
c90120a41997c67aa9113d22e17e&utm_source=bing&utm_medium=cpc&utm_campaign=Dementia%20
Information%20%5BTier%203%5D&utm_term=define%20dementia&utm_content=Information%20-%20
Dementia%20Definition
• Drugbank.com. Galantamine. https://go.drugbank.com/drugs/DB00674
• Drugbank.com. Donepzil. https://go.drugbank.com/drugs/DB00674
• Drugbank.com. Rivastigmine. https://go.drugbank.com/drugs/DB00674
• Drugbank.com. Memantine. https://go.drugbank.com/drugs/DB00674
• www.alzheimers.org.uk/about-dementia/treatments/drugs/how-do-drugs-alzheimers-disease-work
• https://bnf.nice.org.uk/drug/galantamine.html
• https://bestpractice.bmj.com/topics/en- gb/319#:~:text=The%20aetiology%20is%20also%20often%20
multifactorial%2C%20with%20several,embolisation%2C%20thrombosis%2C%20lacunar%20
infarction%2C%20hypoxia%2C%20hypoglycaemia%2C%20or%20ischaemia.
• Gazettereview.com. Brain Atrophy in Advanced Alzheimer’s Disease. https://gazettereview.com/wp-content/
uploads/2015/04/Alzheimers-Disease.jpg
• www.bing.com/images/search?view=detailV2&ccid=YyizLzhb&id=B33635825776BD77863584B8E38073620
DCAEB79&thid=OIP.YyizLzhbyQa8P6nKKToGBwHaEp&mediaurl=https%3A%2F%2Fwww.americanscientist.
org%2Fsites%2Famericanscientist.org%2Ffiles%2F2018-106-3-152-perspective-2-figcap.jpg&exph=726&ex
pw=1156&q=pictures+of+the+the+hippocampal&simid=608020700793274944&ck=B5F931BD5E2C41DF4
E9B2B9FF23B907C&selectedindex=124&form=IRPRST&ajaxhist=0&vt=0&sim=11
• www.drugs.com/mcd/dementia
• www.epilepsysociety.org
• www.health.harvard.edu/a_to_z/parkinsons-disease-a-to-z
• www.healthline.com/health/dementia-drugs-and-medication#effectiveness
• www.nationalmssociety.org
• www.Parkinsons.org.uk
• www.progressnp.com/article/pharmacological-management-epilepsy/
• www.mytutor.co.uk/answers/23361/A-Level/Biology/How-can-donepezil-improve-communication-between-
nerve-cells/
• www.who.int>health topics>stroke-cerebrovascular accident
Chapter 15 Medication and the nervous system

• www.epilepsy.org.uk/press/facts
• www.who.int/news- room/fact-sheets/detail/epilepsy
• https://cks.nice.org.uk/topics/epilepsy/
• www.rch.org.au/neurology/patient_information/antiepileptic_medications/
• www.gov.uk/guidance/valproate-use-by-women-and-girls
• www.sciencedirect.com/topics/neuroscience/hippocampal-sclerosis

Multiple-choice questions
1. Parkinson’s disease is defined as:
(a) A progressive neurological disorder of the basal ganglia
(b) An organ-specific immune-mediated inflammatory condition that affects the
central nervous system
(c) A neurological condition characterised by two or more unprovoked seizures
occurring more than 24 hours apart
(d) Rapidly developing clinical signs of focal (or global) disturbance of cerebral function,
lasting more than 24 hours.
2. Parkinsonian patients show reduced levels of:
276 (a) Acetylcholine
(b) Dopamine
(c) Glutamate
(d) Adrenaline
3. Drugs taken for treatment of Parkinson disease:
(a) Increase the amount of dopamine in the brain
(b) Decrease the amount of glutamate in the brain
(c) Decrease the amount of dopamine in the brain
(d) Increase the amount of adrenaline in the brain.
4. Cholinesterase inhibitors:
(a) Help increase the amount of the neurotransmitter acetylcholine in the brain
(b) Help decrease the amount of the neurotransmitter acetylcholine in the brain
(c) There is little evidence that the neurotransmitter acetylcholine has any notifiable
effect to the brain
(d) Acetylcholine blocks the function of neurons.
5. The action of donepezil will allow for a higher concentration of:
(a) Acetylcholinesterase
(b) Acetylcholine
(c) Cholinesterase
(d) Glutamate.
6. Memantine:
(a) Is a potentially disease modifying treatment because it is considered‘neuroprotective’
(b) Is an ‘N-methyl-D-aspartate (NMDA) receptor agonist
(c) Can only help with Lewy body dementia
(d) Is likely to be prescribed for patients with mild cognitive impairment.
7. One of the characteristics for diagnosing epilepsy is:
(a) At least two unprovoked seizures occurring more than 24 h apart
(b) Three unprovoked seizures occurring more than 48 h apart
(c) Unknown pyrexia in an infant (2–5) years of age
(d) An unexplained rash with pyrexia and seizure.
8. Which is an uncommon trigger of a seizure?
(a) Flashing lights (photosensitivity)
(b) Alcohol
Medication and the nervous system Chapter 15

(c) Stress
(d) Exercise
9. Sodium valproate is also known as:
(a) Epilim
(b) Episenta
(c) Tegretol
(d) Epival.
10. The WHO definition of stroke is:
(a) ‘Rapidly developing clinical signs of facial (or global) disturbance of cerebral
function lasting more than 24 hours’
(b) ‘An acute loss of focal or ocular function with symptoms lasting less than 24 hours’
(c) ‘An event lasting more than 1 hour without cerebral infarction on magnetic
resonance imaging scan’
(d) All of the above.
11. Which is not an advantage of alteplase?
(a) It is clot specific.
(b) Fewer haemorrhagic episodes.
(c) Can be used repeatedly.
(d) No anaphylactic reaction. 277
12. The emphasis of prehospital treatment of an acute stroke is:
(a) 300 mg of aspirin and high-flow oxygen to prevent further infarction of the brain
tissue
(b) High-flow oxygen to prevent further infarction of the brain tissue
(c) Ensuring a good ROSIER assessment is done to confirm that this is a stroke
(d) Recognition and management of life-threatening conditions and rapid transfer to
an appropriate hospital.
13. Drugs used to control the symptoms of dementia can have adverse effects on which of
the following?
(a) Cardiac system
(b) Respiratory system
(c) Abdominal system
(d) All of the above
14. Drugs used to control the symptoms of dementia are known as:
(a) ACE inhibitors
(b) Cholinesterase inhibitors
(c) Proton pump inhibitors
(d) Monoamine oxidase inhibitor.
15. Which is not a presentation of a prefilled syringe of midazolam in the prehospital
setting?
(a) 15 mg
(b) 5 mg
(c) 7.5 mg
(d) 10 mg
Chapter 16
Medications used in
mental health
Liam Rooney

Aim
This chapter provides the reader with an introduction to some of the common psychotropic medications
used to treat mental health disorders (MHD).

Learning outcomes
After completing this chapter, the reader should be able to:

1. Expand knowledge and understanding on MHD you will encounter as a paramedic

2. Develop an understanding of the pharmacology related to the drugs used in MHD
3. Develop an understanding of the risks associated with medications used to treat MHD
4. Explore the role of the paramedic, to aid those in an emergency as a result of medication use.

Test your knowledge

1. Name some mental health disorders you may come across in the course of your duty
2. What are neurotransmitters?
3. How many classes of antidepressant drugs are there and can you name any?
4. What drug is recommended for use in the emergency treatment of ingested toxins/overdose?
5. Some drugs used to treat MHD were initially intended for unrelated conditions. Can you name any?

Introduction
There are many different MHDs, with different presentations. These include depression, anxiety dis-
orders, bipolar disorder, schizophrenia and other psychoses, dementia, substance use disorders and
developmental disorders such as autism. They are generally categorised by a combination of abnormal

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Medications used in mental health Chapter 16

thoughts, perceptions, emotions, behaviour and relationships with others (World Health Organization
(WHO), 2019b). COVID-19 has had a strong psychological impact on the global population, with
some studies suggesting that levels of stress, depression, anxiety and the risk of post-traumatic stress
disorder (PTSD) have increased due to fear of the disease, its consequences and lockdown measures
(Passavanti et al., 2021).
There are effective treatments for MHD, many of which involve the use of psychotropic medica-
tions. Most of these medications act through neurotransmitters, having a direct effect on the brain
and consequently behaviour. It is common practice for medications classified for a particular use or
condition to be prescribed for treatment of a different condition; for example, valproate, an anticon-
vulsant, is prescribed for manic episodes associated with bipolar disorder. As discussed in Chapter 5,
understanding the pharmacokinetics (what the body does with the medications) and pharmacody-
namics (what the medication does to the body) of common psychotropic medications is key to iden-
tifying any issues a paramedic may encounter in the prehospital environment.

Neurotransmitters
The primary functions of the central nervous system (CNS) are to control and co-ordinate other body
systems. Nerve pathways within the CNS connect areas of the brain that serve similar functions.
Neurons in these pathways are linked together by synapses. These neurons release neurotransmit-
ters, regulating transmission across these synapses, so nerve impulses are conducted along the
nerve pathways to different areas of the brain, influencing the level of activity. While there are a sig-
nificant number of neurotransmitters identified in the brain, key neurotransmitters that are relevant 279
to this chapter are listed in Table 16.1.
Some MHDs are associated with abnormal changes in the amount of, or activity of, a specific neu-
rotransmitter. Most medications used for MHDs act on the brain by affecting neurotransmitter con-
centrations and activity. When a neuron releases a neurotransmitter across a synapse, it binds to a
receptor site on the dendrites of the adjoining neuron. Figure 16.1 illustrates this synapse process.
Neurotransmitters can be either excitatory or inhibitory. Excitatory neurotransmitters attach to the
receptor of the adjoining neuron, generating action potentials along the nerve axon, stimulating
that neuron to release more neurotransmitters, and so on, generating nerve impulses which transmit
information along the nerve pathway. Inhibitory neurotransmitters impede the generation of these
action potentials on the adjoining neuron due to the response of their inhibitory receptor action,

Table 16.1 Key neurotransmitters.

Neurotransmitter Function
Acetylcholine Powerful regulator of neuronal activity throughout the peripheral nervous system
and CNS. Important in maintaining cognitive function. Damage to cholinergic
neurons of the CNS associated with Alzheimer and Parkinson disease
Glutamate The primary excitatory neurotransmitter in CNS with powerful excitatory effects
Gamma-aminobutyric acid A derivate of glutamate, primary inhibitory neurotransmitter, found only in the CNS.
(GABA) It controls many processes, including the brain’s overall level of excitation
Dopamine A monoamine neurotransmitter with several pathways (D1–D5). Involved in multiple
functions, including motor control, reward and reinforcement, and motivation
Noradrenaline A monoamine neurotransmitter, the primary neurotransmitter in the sympathetic
nervous system, controls blood pressure, heart rate, liver function, among many
other functions
Serotonin (5HT) Another monoamine with numerous receptors, involved in functions such as sleep,
memory, appetite, mood and other functions. Also produced in the GI tract in
response to food
Histamine Last of the major monoamines, plays a role in metabolism, temperature control,
regulating various hormones, and controlling the sleep–wake cycle, among other
functions
CNS, central nervous system; GI, gastrointestinal.
Chapter 16 Medications used in mental health

Synaptic Reuptake
cleft Vesicles pump

Neurotransmitter

Receptor

280

Figure 16.1 The synapse. Source: Queensland Brain Institute (2017).

reducing neural activity. Released neurotransmitters are inactivated and reabsorbed (reuptake) into
their respective nerve endings. Whether a neurotransmitter is excitatory or inhibitory depends on
the receptor to which it attaches (Hitner and Nagle, 2012).

Reflection
As a paramedic, you will attend a patient who has had a cerebrovascular accident, a stroke. Oxygen
deprivation of the brain due to ischaemia causes a build-up of the neurotransmitter glutamate in the
interstitial fluid of the CNS. Lack of oxygen causes the glutamate transporters to fail so glutamate accu-
mulates in the interstitial space between the neurons and glia, overstimulating the neurons leading to
cell death. This destruction of neurons through prolonged activation of excitatory synaptic transmis-
sion is called excitotoxicity (Tortora and Derrickson, 2011).

Antidepressants
Depression is a broad and diverse diagnosis. Severity of the disorder is determined by the number
and severity of symptoms, as well as the degree of functional impairment (National Institute for
Health and Care Excellence (NICE), 2009). It can substantially impair people’s ability to function nor-
mally at work and school, and cope with daily life. At its most severe, depression can lead to suicide
(WHO, 2019a). Drug treatments, such as antidepressants, are not recommended for use in people
diagnosed with mild depression or with subthreshold depressive symptoms, but should be consid-
ered for those with moderate or severe depression, or those with persistent mild or subthreshold
Medications used in mental health Chapter 16

Table 16.2 The stepped care model.

Focus of the intervention Nature of the intervention
STEP 1: All known and suspected presentations of Assessment, support, psychoeducation, active
depression monitoring and referral for further assessment and
interventions
STEP 2: Persistent subthreshold depressive symptoms; Low-intensity psychosocial interventions,
mild to moderate depression psychological interventions, medication and referral
for further assessment and interventions
STEP 3: Persistent subthreshold depressive symptoms or Medication, high-intensity psychological interventions,
mild to moderate depression with inadequate response combined treatments, collaborative care and referral
to initial interventions; moderate and severe depression for further assessment and interventions
STEP 4: Severe and complex depression; risk to life; Medication, high-intensity psychological interventions,
severe self-neglect electroconvulsive therapy, crisis service, combined
treatments, multiprofessional and inpatient care
Source: Adapted from Depression in adults: recognition and management. Retrieved from: https://www.nice.org.uk/
guidance/cg90 (2009).

symptoms who have not responded to psychosocial interventions such as psychotherapy or cogni-
tive behaviour therapy (CBT) (NICE, 2009). Table 16.2 shows the stepped care approach.
Complex depression includes depression that shows an inadequate response to multiple treat-
281
ments, is complicated by psychotic symptoms and/or is associated with significant psychiatric
comorbidity or psychosocial factors. The class of drug prescribed will be based on the individual
patient’s requirements, taking into consideration the presence of concomitant disease, existing ther-
apy, previous response to antidepressant therapy and suicide risk, as there is little difference in their
efficacy (Joint Formulary Committee, 2021a).

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed medication for the treatment
of depression, first-line pharmacotherapy for depression and other MHDs due to their safety, efficacy
and tolerability. Overdoses of SSRIs usually do not have serious consequences due to this increased
safety profile and tolerability compared to other antidepressants (Chu and Wadhwa, 2020). Examples
of SSRIs include citalopram, escitalopram, fluoxetine, paroxetine and sertraline. It is thought that
depressive illnesses are attributed to a deficiency in the neurotransmitter serotonin (5HT). SSRIs
decrease this deficiency by inhibiting reuptake of synaptic serotonin by the presynaptic neuron. This
enables the serotonin to remain in the synapse for longer, which enables the neurotransmitter (sero-
tonin) to repeatedly stimulate its postsynaptic receptors, thereby increasing serotonin activity.
There are more than 15 serotonin receptor subtypes and an SSRI may have more affinity or less
affinity with a particular receptor subtype. They have little effect on other neurotransmitters, and
have less impact on muscarinic, adrenergic, cholinergic and histaminergic receptors than other
antidepressants, consequently leading to fewer side-effects. Common side-effects include insom-
nia, agitation, nausea, gastrointestinal (GI) upset and sexual dysfunction. Monitoring by the
patient’s doctor is imperative when beginning treatment with antidepressants, ensuring treat-
ment response is adequate. SSRIs may take up to 6 weeks to achieve this adequate response
(Hantsoo and Mathews, 2019).
Withdrawal or discontinuation syndrome may occur if SSRIs are abruptly stopped, doses are
missed or reduced. These symptoms are usually mild and self-limiting but may be severe, particularly
if the medication is stopped abruptly. Table 16.3 describes in detail the reported symptoms of with-
drawal syndrome from SSRI discontinuation. Pharmacokinetics such as the half-life and metabolites
produced by a particular SSRI may explain the potential for withdrawal syndrome if doses are missed.
For example, all the SSRIs mentioned have a half-life of 24–36 hours, except for fluoxetine, whose
half-life ranges from 4 to 16 days. SSRIs are metabolised by microsomal liver enzymes and excreted
in the urine (McDermott, 2021).
Chapter 16 Medications used in mental health

Table 16.3 Symptoms of withdrawal syndrome

System involved Symptoms
General Flu-like symptoms, fatigue, weakness, tiredness, headache, tachycardia, dyspnoea
Balance Gait instability, ataxia, dizziness, lightheadedness, vertigo
Sensory Paraesthesias, electric shock sensations, myalgias, neuralgias, tinnitus, altered taste, pruritus
Visual Visual changes, blurred vision
Neuromotor Tremor, myoclonus, ataxia, muscle rigidity, jerkiness, muscle aches, facial numbness
Vasomotor Sweating, flushing, chills
Sleep Insomnia, vivid dreams, nightmares, hypersomnia, lethargy
Gastrointestinal Nausea, vomiting, diarrhoea, anorexia, abdominal pain
Affective Anxiety, agitation, tension, panic, depression, intensification of suicidal ideation, irritability,
impulsiveness, aggression, anger, bouts of crying, mood swings, derealisation and
depersonalisation
Psychotic Visual and auditory hallucinations
Cognitive Confusion, decreased concentration, amnesia
Sexual Genital hypersensitivity, premature ejaculation
Source: Fava et al. (2015).
282

Tricyclic antidepressants (TCAs)

Tricyclic antidepressant medication predominantly blocks the reuptake of both serotonin and
noradrenaline, although to different extents, also acting to antagonise alpha-cholinergic (alpha-1
and alpha-2), muscarinic and histamine receptors. Some are more selective for their serotonergic
properties, such as clomipramine, or noradrenergic properties, such as imipramine. They can also be
divided by their sedative properties. Amitriptyline, clomipramine, dosulepin and trimipramine are
examples of sedative TCAs, while imipramine, lofepramine and nortriptyline are less sedative.
Because of their varying degrees of antimuscarinic and anticholinergic side-effects, and a lower
threshold for overdose, they are not typically used as first-line treatment for depression as they are
usually less well tolerated in comparison to SSRIs (Joint Formulary Committee, 2021a).
The most common side-effects are dry mouth, constipation and dizziness. Blurred vision, urinary
retention, confusion and tachycardia could be due to the blockade of cholinergic receptors. Blockade
of adrenergic receptors may cause dizziness and orthostatic hypotension. Histamine blockade may
lead to sedation, increased appetite, weight gain and confusion. TCAs should be used with caution in
patients with pre-existing ischaemic heart disease as there is a possibility of cardiovascular complica-
tions (Moraczewski and Aedma, 2020). Some TCAs are now commonly used for the treatment of
other conditions, such as neuropathic pain in adults and enuresis in children.
Due to the narrow therapeutic index of TCAs, intentional or unintentional overdose is possible.
Prehospital activated charcoal may be used to absorb any ingested medication not absorbed by the
gastrointestinal tract. TCA overdose may induce cardiotoxicity symptoms such as wide QRS com-
plexes or even cardiac arrest. A medication paramedics may have access to, depending on their juris-
diction, to alleviate cardiotoxicity symptoms of TCA overdose is sodium bicarbonate, which can
increase the pH of blood plasma, decreasing the concentration of active free TCA medication
(Moraczewski and Aedma, 2020; PHECC, 2018).

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are used less frequently than other antidepressants due to
the dangers of dietary and drug interactions, side-effects and safety concerns. They are generally
used when other treatment options have been unsuccessful.
Monoamine oxidase inhibitor medication blocks the monoamine oxidase enzyme. This enzyme
breaks down different amine neurotransmitters in the brain, among them serotonin, dopamine,
noradrenaline and tyramine. By inhibiting the breakdown of these neurotransmitters, their levels are
Medications used in mental health Chapter 16

increased, allowing them to continue their effect. Tyramine, one of the neurotransmitters inhibited
by MAOIs, has a role in regulating blood pressure. Because of the accumulation of these amine
neurotransmitters, the metabolism of some amine medications is also inhibited, potentially causing
a hypertensive crisis. Common cough and decongestant medications are examples of these amine
medications, as these contain pseudoephedrine, a sympathomimetic (Joint Formulary Committee,
2021a).
Some foods contain high levels of tyramine, such as:

• mature cheese
• salami
• pickled herring
• meat
• yeast extracts like Bovril , Oxo and Marmite
® ® ®

• some beers, lagers and wine.

As food ages, levels of tyramine can increase, so over-ripe fruits and stale foods should also be
avoided. Patients should be aware of these issues and are advised to eat fresh foods only. This danger
of interaction persists for up to 2 weeks on discontinuation with MAOIs due to the washout period of
these medications (Stavert, 2021).
Monoamine oxidase inhibitors have either a reversible or irreversible effect on neurotransmitters.
Moclobemide is a reversible MAOI, phenelzine, tranylcypromine and isocarboxazid are irreversible.
They should not be taken with any other antidepressants, especially SSRIs, due to the potential for 283
serotonin syndrome, discussed below. Concomitant use of some analgesics, such as tramadol, may
increase the risks of this potentially fatal syndrome. Common side-effects include dry mouth, consti-
pation, nausea, dizziness, drowsiness, insomnia, blurred vision, tremor,and postural hypotension
(Laban and Saadabadi, 2020).

Serotonin and noradrenaline reuptake inhibitors

Serotonin and noradrenaline reuptake inhibitors (SNRIs) inhibit the reuptake of serotonin
and noradrenaline with varying levels of potency and affinity.Venlafaxine and duloxetine are
examples of SNRIs, while reboxetine inhibits only noradrenaline with minimal effects on other
neurotransmitters.
Venlafaxine is a relatively weak serotonin inhibitor and weaker noradrenaline inhibitor. It has a 30:1
serotonin:noradrenaline affinity ratio; as dose increases, noradrenaline binding increases. This gives
this medication clear dose progression which can be beneficial in an individual’s treatment. Therefore,
at low doses, the side-effect profile is similar to SSRIs as it predominantly affects serotonin levels,
insomnia, agitation, nausea, GI upset and sexual dysfunction. At higher doses it may cause hyperten-
sion, diaphoresis, tachycardia, tremors,and anxiety due to its noradrenergic effects (Sansone and
Sansone, 2014).
Duloxetine also has a dominant serotonergic effect compared to its noradrenergic effect, but to a
lesser degree than venlafaxine. It has a 10:1 affinity ratio, making it a more potent SNRI. It also dem-
onstrates a weak dopamine reuptake. Common side-effects include dry mouth, nausea, headache,
dizziness, constipation, insomnia and hypertension. It is also licensed for use in the treatment of
diabetic neuropathy and urinary incontinence (Joint Formulary Committee, 2020a; Shelton, 2018).
Reboxetine is a potent noradrenaline reuptake inhibitor with a weak serotonergic effect and
no effect on dopamine. Evidence suggest it is not an effective treatment for depressive disorders
and it is linked to an increased incidence of adverse effects (Eyding et al., 2010). Side- effects
include sexual dysfunction, insomnia, decreased appetite, anxiety, palpitations, paraesthesia,
hypo/hypertension, skin reactions, nausea/vomiting and urinary disorders (Joint Formulary
Committee, 2020c).

Serotonin syndrome
Serotonin syndrome is a relatively uncommon but potentially life-threatening consequence of too
much serotonin in the synapses of the brain. It can occur due to overdose of SSRIs or more com-
Chapter 16 Medications used in mental health

Table 16.4 Symptoms of serotonin syndrome.

Altered mental Neuromuscular Serious
status Autonomic dysfunction abnormalities complications
Agitation Tachycardia Tremor Rhabdomyolysis
Confusion Hypertension Clonus Metabolic acidosis
Anxiety Diaphoresis Hyper-reflexia Renal failure
Delirium Diarrhoea Muscle rigidity Respiratory failure
Mania Hyperthermia Akathisia Seizures
Coma Mydriasis (dilated pupils) Death
Shivering
Source: Modified from Zick et al. (2019).

monly, combining multiple medications that increase serotonin levels, such as MAOIs and SSRIs or
SNRIs. Herbal remedies, for example St John’s wort, and illicit drugs can contribute and must not be
overlooked. Symptoms can range from mild to life-threatening, often categorised by changes in
mental status, autonomic dysfunction and neuromuscular abnormalities. Onset can be rapid, devel-
oping after beginning treatment, increasing dosage or overdose. These symptoms are outlined in
284 Table 16.4. Mild symptoms such as nervousness, nausea, diarrhoea, tremor and dilated pupils can
progress to moderate symptoms such as increased reflexes, sweating, agitation, rhythmic muscle
spasms and ocular clonus. Severe symptoms such as hyperthermia, delirium, rhabdomyolysis and
sustained clonus or rigidity, usually bilaterally in the legs rather than arms, require emergency
intervention in hospital (Chu and Wadhwa, 2020; Foong et al., 2018).

Other atypical antidepressants

Some drugs have unique pharmacological properties and do not easily fall into a particular class.
Agomelatine is unique among antidepressants, in that it can regulate circadian rhythms due to mela-
tonin receptor agonist properties. Mirtazapine is generally only used when other pharmacological
interventions have been unsuccessful, and has sedative, antiemetic, antianxiolytic and appetite
stimulant effects (Jilani et al., 2021). Vortioxetine has a unique mechanism of action with a distinct
clinical profile, which has proven effective as an alternative therapy for patients with documented
failure of other antidepressants (Chen et al., 2017).

Clinical consideration: activated charcoal

The administration of activated charcoal is recommended for the emergency prehospital treatment
of acute oral poisoning and oral drug overdose with antidepressant medication (Joint Formulary
Committee, 2021d; JRCALC, 2019). The toxic effect will depend primarily on the individual sub-
stance used. Activated charcoal has well- documented adsorptive properties and is effective in
reducing the absorption of a wide range of toxicants, including drugs taken in overdose. When
orally administered, it does not get absorbed within the GI lumen so any ingested toxins that have
not been absorbed by the GI lumen will bind to the activated charcoal, reducing the systemic
absorption of the toxic agent. It can also enhance the elimination of some compounds after they
have been absorbed. Elimination is through faecal excretion (Silberman et al., 2020). Usual dose for
>12 years is 50 g within 1 hour of ingestion, 25 g for <12 years. Presentation is usually granules or
suspension in water, 50 g/250 mL. If vomiting occurs after dosing, it should be treated with an
antiemetic drug (e.g. cyclizine or ondansetron), as vomiting may reduce the efficacy of charcoal
treatment.
Medications used in mental health Chapter 16

Reflection
Patients who have features of poisoning or who have taken poisons with delayed action should be
transported to hospital, even if they appear well. Treatment depends on the substance or toxin taken.
It is advisable to look for further information about the degree of risk or management required. Many
countries have their own poisons information service to help practitioners with regard to management,
and this should be the first port of call when dealing with poisoning/overdose.

Anxiolytics
Anxiety disorders affect more than 280 million worldwide, making them the most prevalent form of
MHD. Anxiety disorders include generalised anxiety disorder (GAD), post-traumatic stress disorder
(PTSD), obsessive compulsive disorder (OCD) and phobic, social and panic disorders (Ritchie and
Roser, 2018). While symptoms and diagnostic criteria differ for each, collectively, the WHO notes that
anxiety is characterised by apprehension or fear, sometimes accompanied by physical symptoms
such as headaches, trembling, fidgeting, restlessness, diaphoresis, tachycardia, dyspnoea and epigas-
tric discomfort (WHO, 2019a). The use of antipsychotic or anxiolytic medication initially is not advised
as it may mask the true diagnosis. Supplementing antidepressants with anxiolytics may be necessary
in patients with some psychotic symptoms (Joint Formulary Committee, 2021a).

Pregabalin 285
An anticonvulsant, this medication is also used for neuropathic pain and GAD. The mechanism of
action of pregabalin is thought to be different from all other anxiolytics. Although similar in structure
to the inhibitory neurotransmitter GABA, it has no significant effects at GABA receptors. It is not a
glutamate antagonist nor does it inhibit the reuptake of serotonin. Instead, it binds to voltage-gated
calcium channels, reducing the release of excitatory neurotransmitters such as glutamate. This
reduction in postsynaptic neuron stimulation is thought to be responsible for its anxiolytic, anticon-
vulsant and analgesic effects (Baldwin and Ajel, 2007). Side-effects are numerous and include dizzi-
ness, drowsiness, confusion, impaired concentration, abnormal appetite leading to weight gain, GI
upset and headache. Pregabalin is rapidly absorbed with a bioavailability of >90%, its half-life is 6.3
hours and it is eliminated primarily by renal excretion as unchanged drug (EMC, 2021b).

Pregabalin is a Class C controlled substance in some countries. There are concerns about potentially fatal
risks when interacting with alcohol or other medications that may cause CNS depression, particularly
opioids. A recent European review of pregabalin safety data has identified reports of severe respiratory
depression in some patients, without concomitant opioid use, prompting an advisory issued by the
Medicines and Healthcare products Regulatory Agency (MHRA) and Commission on Human Medicines
(CHM), to consider adjustments in dosing for patients at higher risk of respiratory depression, including
those with compromised respiratory function, those taking other CNS depressants and those over
65 years of age (Joint Formulary Committee, 2021e; MHRA, 2021).

Benzodiazepines
Benzodiazepines are indicted for short-term use only in severe anxiety. They are the most used
anxiolytics and hypnotics, acting at benzodiazepine receptors which are associated with GABA
receptors. As discussed earlier, GABA is the primary inhibitory neurotransmitter in the CNS, reduc-
ing the excitability of neurons; it produces a calming effect on the brain. Benzodiazepines increase
the activity of GABA receptors, enhancing this calming effect (Griffin et al., 2013). Anxiolytic benzo-
diazepine treatment should be limited to the lowest possible dose for the shortest period.
Dependence may become an issue, especially in patients with a history of alcohol or drug abuse
and those with personality disorders.
Chapter 16 Medications used in mental health

Examples of drugs you are likely to encounter are diazepam, lorazepam and alprazolam (Joint
Formulary Committee, 2021c). They are usually well absorbed in the GI tract; elimination depends on
whether they are short or long acting. Short-acting benzodiazepines (alprazolam, lorazepam) have a
median elimination half-life of 1–12 hours, long-acting benzodiazepines between 40 and 250 hours. For
diazepam, a long-acting benzodiazepine, the elimination half-life increases by 1 hour for each year of
age; for example, the elimination half-life in a 75-year-old would be 75 hours. Common side-effects for
all benzodiazepines include drowsiness, lethargy and fatigue. Dizziness, inco-ordination, slurred speech,
vision disturbances, mood swings and euphoria may be experienced at higher doses, as well as aggres-
sion and hostile behaviour (Griffin et al., 2013).
Benzodiazepine withdrawal syndrome can develop at any time up to 3 weeks after stopping a
long-acting benzodiazepine, due to accumulation of the drug in the fatty tissues, but may occur
within a day of stopping a short-acting one. Therefore, withdrawal should be gradual, as abrupt ces-
sation may induce symptoms such as confusion, convulsion, toxic psychosis or a condition resem-
bling delirium tremens (Joint Formulary Committee, 2021c).

Buspirone
Buspirone displays anxiolytic activity but lacks sedative, anticonvulsant and muscle relaxant activity.
It is thought to act as an agonist of presynaptic and partial antagonist of postsynaptic 5HT1A recep-
tors. This initiates changes in 5HT neurotransmission, which is thought to benefit the treatment of
anxiety. Relative to other anxiolytics, buspirone has low toxicity and potential for abuse and there is
no associated risk of dependence or withdrawal due to lack of effects on the GABA receptors (Wilson
286 and Tripp, 2021). It has little efficacy as an acute anxiolytic as response to treatment may take up to
2 weeks. Common side-effects include abdominal pain, chest pain, confusion, fatigue, paraesthae-
sias, nausea and vomiting (Joint Formulary Committee, 2021b). It is rapidly absorbed in the GI tract,
with peak plasma levels noted at 60–90 minutes after oral administration, with equilibrium of plasma
levels reached 2 days after repeated dosing (EMC, 2020).

Beta-blockers
Beta-blockers (e.g. propranolol) are sometimes used in the management of anxiety. Although they
do not affect psychological symptoms of anxiety, worry, tension and fear, they do reduce autonomic
symptoms, palpitations and tremors. Therefore, patients with predominantly somatic symptoms may
be prescribed these to alleviate the onset of worry and fear (Joint Formulary Committee, 2021c). You
can read more about beta-blockers in Chapter 10.

Hypnotics
Sleep disorders are common, and sometimes serious enough to interfere with normal physical,
mental, social and emotional functioning. While non-pharmacological measures are deemed the
appropriate first step in tackling insomnia, medication may or may not be used in conjunction with
these measures. Long-term use of benzodiazepines and non-benzodiazepines, known as Z-drugs,
have associated risks including falls, accidents, dependence and withdrawal symptoms, cognitive
impairment and an increased risk of developing dementia and therefore should be avoided in the
elderly. Recent studies have also raised similar safety concerns with melatonin, used in persons
aged 55 years and older for the short-term treatment of insomnia (NICE, 2019).

Benzodiazepines
Although benzodiazepines are effective in the short term for improving sleep, adverse effects are
common, including dizziness and drowsiness, sometimes lasting into the following day, potentially
causing psychomotor impairment and affecting normal mental function. Nitrazepam and fluraze-
pam are examples which have a prolonged action and may give rise to these effects. Temazepam,
loprazolam and lormetazepam act for a shorter time and have little or no ‘hangover effect’. If a patient
is symptomatic for both daytime anxiety and insomnia, diazepam prescribed as a single night-time
dose may be effective for both conditions (Barry, 2018; Joint Formulary Committee, 2021c).
Medications used in mental health Chapter 16

Z-drugs
Zolpidem and zopiclone are non-benzodiazepine hypnotics, acting as benzodiazepine receptor
agonists, enhancing GABA neuronal inhibition. Initially developed with the intention of overcoming
some disadvantages of benzodiazepines, such as next-day sedation, dependence and withdrawal
issues, no clear evidence of differences in effects between Z-drugs and short-acting benzodiaz-
epines has been found (Barry, 2018). Zolpidem has a rapid absorption and onset of action; peak
plasma levels can be achieved in as little as 30 minutes, with a short half-life of 2.4 hours (EMC,
2019b). Zopiclone is also absorbed rapidly, with a slightly longer onset of action, up to 2 hours
before peak concentrations are reached, with a half-life of approximately 5 hours (EMC, 2016).
Common side-effects include dry mouth, bitter taste, dizziness, fatigue, headache, nausea, vomiting
and diarrhoea.

Pharmaceutical drugs used for non-medical

purposes
Analgesics, anxiolytics and hypnotics are used by some people for non-medical purposes. These may
be illegally sought or some, such as codeine, may be obtained without prescription.

287
Mood-stabilising medications
Bipolar disorder may consist of both manic and depressive periods separated by periods of nor-
mal mood, although those who only experience manic but not depressive periods are still classi-
fied as having this disorder (WHO, 2019b). Some studies have suggested that suicide rates among
people with bipolar disorder may be up to 30 times higher than the general population. Indeed,
an estimated 71% of those diagnosed have coexisting psychological and psychiatric conditions,
such as anxiety, substance use disorders, personality disorders and attention deficit-hyperactivity
disorder (ADHD).
Recommendations from NICE suggest an antipsychotic be offered when a person first develops
manic episodes, such as haloperidol, olanzapine, quetiapine or risperidone. If these antipsychotics
prove insufficient at their maximum licensed dosage, lithium may be considered. The anticonvulsant
valproate may also be considered if lithium is not tolerated or unsuitable (NICE, 2020).

Lithium
Lithium has multiple pharmacodynamic effects and it has proved difficult to establish which ones
are responsible for its mood-stabilising properties (Alda, 2015). Careful monitoring of patients tak-
ing lithium must take place due to its narrow therapeutic window. The difference between sub-
therapeutic, therapeutic and toxic dosage is small. Signs of lithium toxicity may include vomiting
and diarrhoea, ataxia, muscle weakness, twitching, tremors and confusion. Convulsions, coma,
hypotension, dehydration leading to electrolyte imbalance and possible renal failure may result
from severe toxicity. Increasing fluid intake to increase urine output may be all that is required to
eliminate excess drug from the system, otherwise gastric lavage may be considered if performed
within 1 hour of ingestion (Joint Formulary Committee, 2021f ). Non-steroidal anti-inflammatories
(NSAIDs), such as ibuprofen, should be avoided, as these can increase the plasma concentrations
of lithium (NICE, 2020).

Valproate
Sodium valproate is traditionally used as an antiepileptic drug but is also used in the long-term
treatment of bipolar disorder. It is thought to increase GABA activity, but its exact effect on mood
stabilisation is not well understood. It is contraindicated in women or girls of child-bearing age
unless other treatments have proved ineffective or are not tolerated and a rigorous pregnancy
Chapter 16 Medications used in mental health

prevention programme is followed by both prescriber and patient (EMA, 2018; NICE, 2020).
Common side- effects include abnormal behaviour, weight gain, drowsiness, confusion, diarrhoea
and urinary disorders. Overdose may present with CNS depression, coma, hypotension and circu-
latory collapse (EMC, 2021a).

Antipsychotics
A psychotic episode causes the person to lose some contact with reality. This may involve seeing,
hearing or in some cases feeling, smelling or tasting things that do not exist outside their mind
but feel very real to the person. A quite common hallucination is hearing voices. Hallucinations
and delusions are recognised as positive psychotic symptoms. Negative psychotic symptoms
include emotional apathy, social withdrawal and self-neglect. Psychotic disorders include schizo-
phrenia, schizoaffective disorder and delusional disorder (Joint Formulary Committee, 2021f;
NHS, 2019).
Antipsychotic medications are effective for treating positive psychotic symptoms but may be less
effective for treating negative psychotic symptoms. Many patients will require life-long treatment as
discontinuation has a high relapse rate (Stavert, 2021).
There are two distinct types of antipsychotic medications available: first- and second-generation
drugs. First-generation antipsychotics (also known as ‘typical’) predominantly block only dopamine
D2 receptors, which may cause a range of undesirable side-effects, particularly acute extrapyramidal
symptoms (EPS) and elevated prolactin hormone. Second-generation antipsychotics (also known as
288 ‘atypical’) are more diverse and act on a range of receptors, dopamine, serotonin and others, so have
more distinct clinical profiles. This leads to a lower risk of EPS, although the extent varies between
drugs; however, they are associated with metabolic adverse effects, primarily weight gain and glu-
cose intolerance (Joint Formulary Committee, 2021f ). Examples of typical antipsychotics are chlor-
promazine, flupentixol, haloperidol and trifluoperazine, atypical examples include amisulpride,
olanzapine, quetiapine and risperidone. The plasma half-life of most antipsychotics is 15–30 hours,
hepatic transformation accounting for their entire clearance. As well as oral preparations, medication
can be administered as a depot injection, a formulation which releases gradually, permitting less
frequent administration.The drug acts for 2–4 weeks but may produce acute side-effects.These
treatments are reserved for those at risk of relapse who have difficulty adhering to oral medication
regimens (Jones and Jones, 2016).

Antipsychotic-related side-effects
Extrapyramidal symptoms
One of the main disadvantages of antipsychotic medications, EPS include the conditions acute dys-
tonia, akathisia, pseudo-parkinsonism and tardive dyskinesia, as a result of direct or indirect D2 recep-
tor blockade. Acute dystonias are involuntary movements, restlessness, muscle spasms, protruding
tongue often accompanied by symptoms of Parkinson disease such as tremor, abnormal shuffling
gait, dysarthric speech and dysphagia. Akathisia is defined as the inability to remain still.

Cardiovascular side-effects
The antagonism of alpha-1 adrenergic and alpha-1 adrenaline receptors leads to cardiovascular side-
effects such as postural hypotension, tachycardia and arrhythmias. Postural hypotension can lead to
syncope and fall-related injuries, especially in the elderly. Overall risk tends to be dose related but QT
prolongation is of concern in patients who take doses exceeding the recommended maximum
(Harris et al., 2009).

Endocrine side-effects
As dopamine inhibits prolactin release, blockade of dopamine pathways leads to a rise in prolactin
levels causing hyperprolactinaemia. This condition may lead to symptoms such as sexual dysfunc-
tion, reduced bone density, menstrual disruption, breast enlargement and lactation; weight gain is a
common side-effect.
Medications used in mental health Chapter 16

Neuroleptic malignant syndrome

The rarest but most important adverse reaction, this syndrome is life-threatening if not recognised and
treated. It may occur within 24 hours of initiating treatment, with 65% occurring within the first 7 days.
Progression of symptoms is quite fast and reaches peak intensity within 72 hours. Neuroleptic malig-
nant syndrome does not usually develop from overdose and happens even if medication is within
therapeutic range. Symptoms include hyperthermia (>38 oC) with profuse diaphoresis, altered level of
consciousness, including delirium, stupor and coma, muscle rigidity with tremors, autonomic dysfunction
with tachycardia, blood pressure changes, drooling and incontinence. Treatment requires immediate
cessation of the antipsychotic, with most symptoms being self-limiting. In severe cases, supportive care
is required, including fluid replacement, fever reduction and support of cardiac, respiratory and renal
function, with mortality approximately 5% (Doran, 2013; Joint Formulary Committee, 2021f).

Other side-effects
Typical antipsychotics generally block D2 receptors while atypical antipsychotics block a variety of
receptors, particularly acetylcholine (muscarinic), histamine, noradrenaline and serotonin, which
gives rise to a wide range of side-effects. Decreased libido and decreased arousal lead to sexual
dysfunction through blockade of dopamine, muscarinic and alpha-1 receptors. Drowsiness and
sedation are common but lessen through continued use; they are caused by the antihistamine activity
of some antipsychotics. Blockade of muscarinic receptors may cause blurred vision, dry mouth and
eyes, constipation and urinary retention (Ritter et al., 2018).

289
Clinical consideration: acute behavioural
disturbance
Most acutely disturbed patients or those with a mental health emergency can be treated using reassur-
ance and de-escalation techniques. It is a clinical emergency as the patient may suffer collapse or car-
diac arrest with little or no warning. Physical restraint may be warranted. Sometimes sedation or rapid
tranquillisation is required. Appropriately qualified clinicians may use medicines parenterally to calm
the patient sufficiently for clinical care or transport to be initiated.
There are currently three medications used for prehospital rapid tranquillisation: benzodiazepines
(lorazepam and midazolam), antipsychotics or a dissociative agent (ketamine). It is contraindicated in cases
where the patient has decreased vital signs, alcohol-related altered level of consciousness or respiratory
depression, or is hypoperfused. Oral lorazepam 2 mg is the recommended dose, with a repeated dose if
necessary. More commonly, midazolam is required, which is given by either intramuscular (IM) injection or
intranasal (IN) administration (see Skills in Practice feature) through an atomiser device, at a dose of 5 mg,
with up to two repeated doses allowed to achieve effect. In paediatric patients, the dose is 0.1 mg/kg IN
(repeat twice as required). Midazolam has an intense sedative and sleep-inducing effect. It also exerts an
anxiolytic, anticonvulsant and a muscle relaxant effect. It has a short duration because of rapid metabolic
transformation (EMC, 2019a). The aim of this procedure is to calm the patient without reducing their level
of consciousness, but if the patient is already physiologically compromised, this may occur inadvertently. It
is vital that resuscitative equipment is available and ready prior to administration.

Skills in practice: intranasal medication

administration
The intranasal route of medication administration is a useful and reliable form of drug delivery. The nasal
mucosa is well supplied by blood vessels, ensuring a rapid absorption, avoiding first-pass metabolism
and enhancing drug bioavailability. It is achieved using a mucosal atomiser device (MAD), which attaches
directly to a Luer-Lock syringe and atomises medication to a fine mist. Delivery of intranasal medication
is painless, inexpensive and easy (Our Lady’s Hospital for Sick Children, 2016). For volumes between
0.5 mL and 2.0 mL, drug absorption is optimised if both nostrils are used, half of the dose in each nostril.
If volumes >2.0 mL are required, an alternative route of administration should be sought.
Chapter 16 Medications used in mental health

Equipment required:

• Luer-Lock syringe
• filter needle for drawing medication
• mucosal atomiser device (single-patient use)
• medication.
Figure 16.2 illustrates the procedure for using a MAD.

1. Wash/decontaminate hands.
2. Withdraw required dose of medication into syringe. An extra 0.1 mL should be drawn up to account
for dead space in unprimed devices.
3. Connect the MAD to the Luer-Lock connector on the syringe.
4. Place the tip of the MAD snugly against the nostril, aiming slightly upward and outward.
5. Briskly compress the syringe plunger to deliver the medication.
6. Dispose of used equipment using local policy and procedure.
7. Wash/decontaminate hands.
8. Document actions.

290

Figure 16.2 MAD nasal device procedure.

Episode of care TCA overdose

A 58-year-old female was attended by an emergency ambulance following a call by the patient’s daughter
who reported her Mum had taken an overdose. An advanced paramedic solo responder was also
dispatched to assist ambulance crew. On arrival, the patient had an altered level of consciousness and was
very distressed. It was quickly established that the patient had taken an overdose of amitriptyline
40 minutes earlier, prescribed to her husband for a chronic pain condition.
Treatment was initiated by paramedics; activated charcoal was indicated (it was less than 1 hour since
ingestion), and the patient was alert enough to swallow the preparation.
Medications used in mental health Chapter 16

Baseline vital signs were as follows.

• Pulse: 126 beats per minute

• Respiratory rate: 12 breaths per minute
• Oxygen saturation: 98% on room air
• Temperature: 37.6 C o

• Pupils: Dilated size 6, reactive

• Blood pressure: 110/66 mmHg
• GCS: 13
These findings are consistent with typical anticholinergic symptoms. Abnormal ECG findings were wide
QRS complexes with prolonged PR and QT intervals. As the paramedics were preparing the patient for
transport, she began seizing. Midazolam 5 mg was administered IN, while IV access was obtained.
Respiratory support was initiated. Sodium bicarbonate 8.4% was indicated due to the anticholinergic
poisoning and wide QRS arrhythmia. Dose required is 1 mEq (milliequivalent)/kg, maximum 50 mEq IV
(50 mL) bolus, as per prehospital clinical guidelines. Seizure activity ceased, the patient was transferred
to the ambulance and vital signs were repeated.

• Pulse: 54 beats per minute

• Respiratory rate: assisted ventilations with BVM and 100% oxygen
• Oxygen saturation: 99% on 100% oxygen
• Blood pressure: 86/54 mmHg
• GCS: 3 291
• Blood glucose: 4.8 mmol/L
Sodium chloride (NaCl) (0.9%) 250 mL infusion to address hypotension was started. Repeated ECG noted
narrowing of QRS complex with reduced PR and QT interval. On arrival at the emergency department,
the patient’s level of consciousness had increased and she was maintaining her own airway with
adequate respiratory effort (Clark et al., 2015).

Dementia
Dementia is characterised by progressive cognitive impairment. There may be memory loss, communi-
cation difficulties, changes in personality and spatial awareness issues. Alzheimer’s is the most common
type, accounting for 60–70% of total cases. Vascular, mixed dementia (Alzheimer and vascular), demen-
tia with Lewy bodies, Huntington’s disease and Creutzfeldt–Jakob disease are other less common types.
Medication used for treatment of dementia aims to decelerate the progression of the disease as there
is no cure at present. As discovered earlier, with Alzheimer’s, damage to cholinergic neurons in the brain
leads to a reduction of acetylcholine in the brain. For mild to moderate disease, medications that block
the enzyme which breaks down the acetylcholine are used to prevent further loss of acetylcholine.
These medications are called acetylcholinesterase (AChE) inhibitors. For moderate to severe disease,
the glutamate inhibitor memantine is recommended (NICE, 2018).

Acetylcholinesterase inhibitors
The three AChE inhibitors recommended for the treatment of Alzheimer’s are donepezil, galantamine
and rivastigmine. The three drugs, although achieving the same therapeutic goal, are different from each
other. Donepezil is a long-acting, selective, reversible AChE inhibitor. It has 100% oral bioavailability and
a half-life of 70 hours, so once-daily dosage is sufficient. Higher dosage showed mild improvement in
cognitive function but caused an increase in cholinergic side-effects. Galantamine is a selective,
competitive, rapidly reversible AChE inhibitor. It is also a nicotinic agonist and enhances the nicotinic
receptors in the presence of AChE. Twice-daily dosage is recommended as the plasma half-life is 7 hours.
Rivastigmine is a powerful, slow, non-competitive, reversible AChE inhibitor. It has good absorption and
an oral bioavailability of 40%, and twice-daily treatment is recommended; it is excreted through urine
and has relatively few drug-to-drug interactions. It is also available in a transdermal patch.
Common side-effects of AChE inhibitors are GI upset, including nausea and vomiting, and diar-
rhoea. Headaches, dizziness, insomnia and psychiatric disturbances may also occur (Colović et al.,
2013; Harris et al., 2009; Joint Formulary Committee, 2018).
Chapter 16 Medications used in mental health

Memantine
Memantine is a treatment option for those who have moderate Alzheimer disease and are not
tolerant of AChE therapy, or those with severe disease. It may also be used as an adjunct to AChE
inhibitors in moderate to severe disease on the recommendation of a specialist clinician. As dis-
cussed, overexposure to the excitatory neurotransmitter glutamate leads to neuronal death, excito-
toxicity, due to ischaemia. A receptor involved in this process is the glutamate N-methyl-D-aspartate
(NMDA) receptor. Memantine is a voltage-dependent, moderate-affinity, uncompetitive NMDA
antagonist, blocking the effects of elevated levels of glutamate that may lead to neuronal dysfunc-
tion. This delays progression of symptoms (NICE, 2018). Side-effects include constipation, head-
aches, drowsiness and dizziness. Less common are confusion, hallucinations and fatigue.It has a
100% bioavailability, a half-life of 3–8 hours and is renally excreted.

Attention deficit-hyperactivity disorder

Paramedics attend patients of all ages so it is appropriate to include the most prevalent paediatric
neurodevelopmental disorder, attention deficit-hyperactivity disorder (ADHD), and the medications
used for it. It is a behavioural disorder characterised by hyperactivity, impulsiveness and inattention,
which may lead to psychological, social, educational or occupational difficulties because of the
functional impairment. While some may experience all symptoms, some patients are predominantly
hyperactive and impulsive, while others are primarily inattentive. The two main categories of medica-
tion used in the treatment of ADHD are stimulants and non-stimulants.
292
Stimulants
Methylphenidate or lisdexamfetamine are recommended as first-line treatment for ADHD.
Dexamfetamine is also a consideration if the patient has a beneficial response to lisdexamfetamine
but cannot tolerate its longer duration of effect. Lisdexamfetamine and dexamfetamine are ampheta-
mines; these are slow-release formulations, delivering more stable concentrations of drug, below that
required to produce euphoria, and therefore with a reduced potential for abuse (Ritter et al., 2018).
The primary pharmacological effects of stimulants are related to increased central dopamine and
noradrenaline activity in certain regions of the brain. Common side-effects of stimulants include
aggression, alopecia, arrhythmias, abdominal pain, dry mouth, cough, movement disorders, muscle
cramps, nausea, palpitations and vomiting. Overdose of amphetamines causes wakefulness, exces-
sive activity, paranoia, hallucinations and hypertension, followed by exhaustion, convulsions, hyper-
thermia and coma.The early stages of overdose are managed by benzodiazepines, temperature
control and anticonvulsants, and respiratory support may be required (Joint Formulary Committee,
2021d).

Non-stimulants
Non-stimulant medication such as atomoxetine or guanfacine may be prescribed by a specialist if
stimulant medication has not achieved the desired benefit, is not suitable, not tolerated or ineffective,
or there is a coexisting condition which precludes stimulant therapy.
Atomoxetine is a selective noradrenaline reuptake inhibitor, achieving its therapeutic effects by
increasing the concentrations of synaptic noradrenaline in the CNS, without directly affecting the sero-
tonin or dopamine transporters (EMC, 2021c). Common side-effects include headache, abdominal
pain, decreased appetite, nausea, vomiting and somnolence. Severe adverse effects are uncommon,
with mostly mild or moderate effects reported (Garnock-Jones and Keating, 2009).
Guanfacine is a selective alpha-2 adrenergic receptor agonist, enhancing noradrenaline neuro-
transmission, producing a beneficial effect on cognitive function and improvement in attention and
working memory (Huss et al., 2015). Common side-effects include anxiety, decreased appetite,
arrhythmias, drowsiness, dizziness, GI upset and skin reactions. Somnolence and sedation may occur
during initial treatment or on dose increase. Discontinuation or dose reduction is recommended if
symptoms are clinically significant or persistent. Overdose symptoms may include initial hyperten-
sion, bradycardia, lethargy, respiratory depression and hypotension (Joint Formulary Committee,
2020b).
As discussed, paramedics should contact their local poison information centre for further advice in
all cases of overdose with medications.
Medications used in mental health Chapter 16

Conclusion
There are many different MHDs with many different presentations, many different medications used
to treat them, and many different side-effects and adverse events that are possible. This chapter has
provided the reader with insight into these disorders and the classes of medications encountered in
a practice setting. Understanding how these medications work will give you an insight into how they
may be affecting the patient or how they may interact with other medication.

Find out more about these conditions

The following are a list of conditions associated with mental health disorders. Take some time and write
notes about each of the conditions. Think about the medications that may be used in order to treat these
conditions and be specific about the pharmacokinetics and pharmacodynamics. Remember to include
aspects of patient care. If you are making notes about people you have offered care and support to, you
must ensure that you have adhered to the rules of confidentiality.

The condition Your notes

Depression
Bipolar disorder
Schizophrenia and other psychoses
Anxiety disorders
293
Dementia and Alzheimer disease

Glossary
Akathisia A movement disorder that makes it hard for a person to stay still;
causes an urge to move that the person cannot control.
Anticonvulsant A category of drugs treating seizures.
Antiemetic Category of drugs preventing nausea.
Autonomic Part of the peripheral nervous system responsible for involuntary bod-
ily functions.
Cardiotoxicity Injury to the heart muscle.
Circadian rhythm Wake–sleep cycle.
Clonus Involuntary muscular contractions and relaxations.
Cognitive behavioural A talking therapy that can help manage problems by changing the
therapy way the person thinks and behaves.
Concomitant Occurring or existing at the same time.
Delirium tremens Condition characterised by rapid onset of confusion, shaking, shiver-
ing, irregular heart rate and sweating.
Diaphoresis Sweating.
Dyspnoea Difficulty breathing.
Dystonia Uncontrollable and sometimes painful muscle spasms.
Efficacy The ability to produce the desired or effective result.
Electroconvulsive therapy Small electric currents passed through the brain, intentionally triggering
a brief seizure.
Enuresis Bedwetting.
Excitotoxicity Injury to neurons caused by release of excitatory neurotransmitter.
Gastric lavage Gastric suction or stomach washout.
Melatonin Naturally occurring hormone produced by the pineal gland in the brain.
Neuropathic Nerve origin.
Neurotransmitters Chemical messengers transmitting a signal from a neuron across the
synapse to a target cell.
Paraesthesia A sensation, such as tingling or numbness.
Primary insomnia Difficulty in initiating or maintaining sleep, early waking or non-restorative,
poor-quality sleep.
Chapter 16 Medications used in mental health

Psychiatric comorbidity The coexistence of two or more psychiatric disorders.

Psychosocial The effect of social factors on thoughts and behaviours.
Psychotherapy Treatment to change behaviours and overcome psychological issues.
Psychotropic Medications that have effects on psychological function.
Rhabdomyolysis Death of muscle tissue and release of toxins into the bloodstream.
Somnolence Drowsiness, sleepiness.
St John’s wort A flowering plant, believed to have some benefits in depression treatment.
Sympathomimetic Physiological effects characteristic of the sympathetic nervous system
by promoting the stimulation of sympathetic nerves.
Therapeutic index A ratio comparing the blood concentration at which a drug causes
a therapeutic effect to the amount that causes toxicity.
Washout Time taken for concentrations of drugs to be eliminated.

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Harris, N., Baker, J. and Gray, R. (2009). Medication Management in Mental Health. Oxford: Wiley-Blackwell.
Hitner, H. and Nagle, B. (2012). Pharmacology, 6th edn. New York: McGraw-Hill.
Huss, M., Chen, W. and Ludolph, A. (2015). Guanfacine extended release: a new pharmacological treatment option
in Europe. Clinical Drug Investigation 36(1): 1–25.
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Joint Formulary Committee. (2020a). British National Formulary (BNF): Duloxetine. London: British Medical Journal
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Joint Formulary Committee. (2020b). British National Formulary (BNF): Guanfacine. London: British Medical Journal
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Joint Formulary Committee. (2020c). British National Formulary (BNF): Reboxetine. London: British Medical Journal
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Joint Formulary Committee. (2021a). British National Formulary (BNF): Antidepressant Drugs. London: British
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Joint Formulary Committee. (2021b). British National Formulary (BNF): Buspirone Hydrochloride. London: British
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Medical Journal (BMJ) and Pharmaceutical Press.
Joint Formulary Committee. (2021d). British National Formulary (BNF): Poisoning, Emergency Treatment. London:
British Medical Journal (BMJ) and Pharmaceutical Press. 295
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296
Further reading
Guidance on appropriate prescribing of benzodiazepines and z-drugs (BZRA) in the treatment of anxiety and insomnia.
www.hse.ie/eng/about/who/cspd/ncps/medicines- management/bzra- for- anxiety- insomnia/
bzraguidancemmpfeb18.pdf
Harris, N., Baker, J. and Gray, R. (2009). Medications Management in Mental Health. Chichester: Wiley-Blackwell.
McKnight, S.E. (2020). De-Escalating Violence in Healthcare. Indianapolis: Sigma Theta Tau International Honor
Society of Nursing.
Spencer, S., Johnson, P. and Smith, I. (2018). De-escalation techniques for managing non-psychosis induced aggression
in adults. https://doi.org/10.1002/14651858.CD012034.pub2

Resources
• A–Z glossary of street drug names: www.taltofeank.com
• Mind, a UK-based charity dedicated to information and support for all mental health-related
issues: www.mind.org.uk

Multiple-choice questions
1. What is the name of the group of medicines used to treat mental health disorders?
(a) Analgesics
(b) Antiemetics
(c) Psychotropics
(d) Anticholinergics
2. Which of these is not classified as a mental health disorder?
(a) Depression
(b) Bipolar disorder
(c) Autism
(d) Epilepsy
3. Neurotransmitters can be described as being either:
(a) Positive or negative
(b) Excitatory or inhibitory
Medications used in mental health Chapter 16

(c) Acting or non-acting

(d) Agonist or antagonist.
4. Which neurotransmitter is important for maintaining cognitive function?
(a) Acetylcholine
(b) GABA
(c) Noradrenaline
(d) Serotonin (5HT)
5. The destruction of neurons through prolonged activation of excitatory synaptic
transmission is called:
(a) Cardiotoxicity
(b) Neurotoxicity
(c) Hepatotoxicity
(d) Excitotoxicity.
6. Current evidence suggests the first-line pharmacotherapy for depression and other
MHD due to their safety, efficacy, tolerability is:
(a) Selective serotonin reuptake inhibitors (SSRIs)
(b) Tricyclic antidepressants (TCAs)
(c) Serotonin and noradrenaline reuptake inhibitors (SNRIs)
(d) Antipsychotics.
7. What is another common use for tricyclic antidepressants? 297
(a) Anticonvulsant for seizures
(b) Insomnia and other sleep disorders
(c) Anxiety
(d) Neuropathic pain in adults
8. Suicidal behaviour is associated with MHD; which disorder is more strongly linked to
suicidal behaviours than others?
(a) Alzheimer disease
(b) Generalised anxiety disorder
(c) Bipolar disorder
(d) Attention deficit-hyperactivity disorder
9. With more than 280 million affected worldwide, the most prevalent form of MHD is:
(a) Substance abuse disorders
(b) Anxiety disorders
(c) Psychotic disorders
(d) Dementia.
10. The most used drugs in the anxiolytic and hypnotic class of drugs are:
(a) Selective serotonin reuptake inhibitors (SSRIs)
(b) Pregabalin
(c) Benzodiazepines
(d) Beta-blockers.
11. Melatonin can be described as:
(a) A non-benzodiazepine hypnotic
(b) A naturally occurring hormone
(c) A naturally occurring element
(d) A histamine receptor antagonist.
12. The conditions acute dystonia, akathisia, pseudo-parkinsonism and tardive dyskinesia
are collectively known as what?
(a) Extrapyramidal symptoms
(b) Serotonin syndrome
(c) Neuroleptic malignant syndrome
(d) Delirium tremens
Chapter 16 Medications used in mental health

13. First-generation ‘typical’ antipsychotics generally block which receptors?

(a) α1 adrenergic receptors
(b) 5HT1A receptors
(c) D2 receptors
(d) H1 receptors
14. Acetylcholinesterase inhibitors are used for which condition?
(a) Creutzfeldt–Jakob disease
(b) Schizophrenia
(c) Hyponatraemia
(d) Alzheimer disease
15. The primary pharmacological effects of which stimulants used to treat ADHD are
related to increased activity in certain regions of the brain?
(a) Dopamine and adrenaline
(b) Dopamine and noradrenaline
(c) Dopamine and serotonin
(d) Dopamine and GABA

298
Chapter 17
Immunisations
Michael Fanner

Aim
The aim of this chapter is to develop essential public health knowledge of infectious diseases and
immunisations for paramedic practice, including fundamental epidemiological, pharmacological,
social and clinical considerations of immunisations in paramedic consultations.

Learning outcomes
After completing this chapter, the reader will be able to:
1. Understand the fundamental epidemiological concepts and theories in preventing infectious
diseases
2. Be familiar with vaccine design to underpin clinical practice knowledge
3. Appreciate public concerns in the acceptability and uptake of immunisations
4. Identify the role of the paramedic in health promotion and immunisation administration.

Test your knowledge

1. What are the key epidemiological concepts to consider in the prevention of infectious diseases?
2. What makes immunisations different from other medicines?
3. What routine immunisations are given in childhood?
4. Why is it important to appreciate public concerns surrounding immunisations?
5. What health promotion information and advice would you give to a patient prior to consenting
for immunisation?

Introduction
Immunisations are one of the greatest global developments of modern medicine and after the pro-
vision of clean water and sanitation, with 26 separate diseases prevented by vaccination, the British
Society for Immunology (2020) estimates that 2–3 million lives are saved each year. The universal
offer of a diverse range of immunisations can provide significant protection from infectious diseases,
with some immunisations offering up to 97% protection, for example after two doses of the mea-
sles, mumps and rubella (MMR) immunisation (Centers for Disease Control and Prevention, 2021).
So, the simple construction one may form from this evidence is that if immunisations are clinically

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Chapter 17 Immunisations

effective and economically sound at saving lives, why do individuals, communities and populations
still become majorly affected by infectious diseases? This chapter will explore some of the reasons
behind this.
At the time of writing this chapter, the first UK anniversary of the novel coronavirus and SARS-CoV-19
pandemic had arrived, so the timeliness of this chapter reinforces the importance of stressing public
health messages and interventions surrounding infectious diseases in all clinical practice. Before
Covid-19 in the UK, public perceptions of infectious diseases were perhaps less obvious than in devel-
oping nations with more visible detriment of infectious diseases. With first-hand witnessing of Covid-19,
this perception has changed with unprecedented, emergency reprioritisation of health services, the
social significance of government pandemic rules and the national rollout of new vaccines (Fanner and
Maxwell 2021).
The public health knowledge of infectious diseases including immunisations requires a greater
understanding than viewing health via an episodic care lens; a traditional, defining feature of para-
medic care, historically a distinguishing characteristic from other professions. With the increasing
numbers of paramedics now working in non-ambulance settings such as primary and urgent care, a
more central role in preventing infectious diseases arises and the likelihood for directly administer-
ing immunisations with the associated health promotion is inevitable. This should not, however,
detract from the importance of paramedics working in emergency settings embracing essential
public health knowledge, whereby health promotion opportunities for immunisations may arise,
such as Health Education England’s Making Every Contact Count behaviour change approach.
As a general observation, all paramedics are likely to meet patients who have a varied interaction
and experience with the NHS, so each paramedic–patient clinical interaction is vital to include
exploration of immunisation history with associated health promotion, including if presenting med-
300 ical complaints are related to vaccinatable infectious diseases. Paramedics may also be called to
emergency situations due to suspected anaphylaxis in vaccination settings.
This chapter will explore the epidemiological concepts and theories in relation to infectious
diseases, the pharmacology of immunisations, the public concerns about immunisations and the
emerging role of the paramedic in immunisations.

Being mindful of clinical terminology

The terms ‘immunisations, inoculations and vaccinations’ are often used interchangeably or synony-
mously yet each is defined differently.

• Inoculation: the process of ‘introducing’ a pathogen into a human to stimulate an antibody production.
• Vaccination: the process of receiving a vaccine.
• Immunisation: the process that results in an acquired immune response to receiving a vaccine.
Stern and Markel (2005) advise that the preferred term is immunisation, as this is inclusive of an
immunological agent (vaccination or inoculation) resulting in the development of an adequate
immune response and immunity. Avoid terms such as ‘shot’, ‘dose’, ‘bout’, ‘hit’, ‘jab’ or ‘injection’ to solely
define an immunisation.

Understanding the fundamental

epidemiological concepts and theories
in preventing infectious diseases
Infectious diseases and their resultant immunopathogenic mechanisms are some of the main
aetiologies behind mass mortality throughout human history. The immunopathogenic mechanisms,
or immunopathogenesis, can be defined as the development of disease with involvement of the
Immunisations Chapter 17

immune system response. Infectious pathogens can exist as bacteria, fungi, parasites or viruses
and are responsible for deadly diseases such as Mycobacterium tuberculosis (3300 years ago),
coronaviruses including severe acute respiratory syndrome (SARS) 1 and 2 (2003 and 2019 respectively)
and Middle East respiratory syndrome (MERS) (2013).

Essential ways of examining infectious diseases

Infectious diseases are communicable diseases and, unlike non-communicable diseases such as dia-
betes mellitus or asthma, can spread through communities and populations, regionally, nationally
and internationally, as endemics, epidemics and pandemics. The spread of infectious disease can
occur via different modes of transmission, including human-to-human contact and animal-to-
human contact. Infectious disease spread can occur through ingestion, inhalation, skin penetration
and mucosal membrane penetration and be transmitted horizontally or vertically (Balakrishnan and
Bhanu Rekha, 2018). Horizontal transmission refers to spread across individuals within the same
generation and vertical transmission refers to spread from individuals from one generation to the
next. Sutherst (2004) points out that, through holistic assessment of ever-moving societal vulnera-
bilities to infectious diseases in the world, the infectivity status and transmission opportunities also
change. Societal vulnerabilities can include urbanisation with poverty or wealth, climate variability,
climate change, changes to land use, changes in human migration and changes in cultural practices
(Sutherst 2004), thus illuminating the importance of the social determinants of health.
Sutherst (2004) identifies that adopting conceptual frameworks such as the disease triangle to
consider the ecology and epidemiology of infectious diseases is important to evaluate the risks and
opportunities for transmission. In order to conceptualise this, the disease triangle, or epidemiologi-
cal triad (Celentano and Szklo, 2019), provides a visualised way of examining the varying factors of 301
infectious disease status and transmissibility in any given situation.
The three main components of the disease triangle represent the complexity that can occur during
infectious disease spread (including viral shed): a host (a human or animal, usually), a pathogen and
the environment (such as living conditions or public transport). Each component has an interac-
tional relationship with the other two components that is mediated by the degree of exposure and
sensitivity which determines the likelihood of transmission through what is known as a vector (such
as overcrowding, poor hand washing practices, poor ventilation or poor cleaning practices)
(Figure 17.1). This framework enables a variety of ways for examining aetiological factors and

Hosts
(Human / Animal)
ity

Ex
iv

po
sit

su
en

re
/S

/
Se
re
su

ns
po

itiv

Vector
Ex

ity

ic) al /
ec Bio nt
om ic
(H

cio l / me
on log
um
Pa n / Z

So sica iron

Exposure / Sensitivity
a
tho oo

hy Env
ge nos
ns es

(P
)

Figure 17.1 The host–pathogen–environment framework. Source: Modified from Sutherst (2004).
Chapter 17 Immunisations

ecological drivers that facilitate the increase or decrease of infectious disease spread. With the
presence and optimal uptake of a vaccine, the host can be near guaranteed protection from serious
pathogenesis even if a vector allows for increased sensitivity and exposure to pathogens in physical,
biological or socioeconomic environments. With optimal uptake, immunisation strategy has eradi-
cated infectious diseases such as smallpox (Fenner et al., 1988). However, during pandemics of novel
or non-vaccinatable infectious diseases, immunisation strategy or vaccines in development alone
should not be relied upon to prevent spread, for example, human immunodeficiency virus 1
(Pitisuttithum and Marovich, 2020) and malaria (Frimpong et al., 2019).
The aforementioned discussion draws attention to immunisations, which should be appreciated
from both epidemiological and social determinant perspectives in order to achieve optimal uptake
and effect on individuals, communities and populations, such as herd immunity.
Herd immunity is an important immunisation goal, which is not as easily achieved when solely
considered as a pandemic strategy by which naturally acquired immunity is established through the
natural spread of infectious diseases. Herd immunity is defined as the minimal level of community
protection, through immunisation uptake, for individuals susceptible to infectious agents from their
proximity to and the presence of individuals with acquired immunity (whether through infection or
immunisation) (McNaughton, 2020). McNaughton (2020) argues that herd immunity is better
defined as a ‘fire line’, borrowed from the strategies employed to tackle wildfire by disrupting viral
spread. McNaughton suggests that as with fire lines, where the width has to be determined accord-
ing to the wildfire’s behaviour, fuel and weather conditions (e.g. high winds), herd immunity efforts
have to focus on those individuals who are more likely to be infected and those who are likely to be
exposed in order to ‘smother’ viral spread. Herd immunity requires constant vigilance as the level of
community protection can rapidly decrease with the birth of an estimated 140 million immunologi-
302 cally naive infants and the death of 60 million people, worldwide, every year.

Reflection: essential infectious diseases

knowledge
The public health role of the paramedic is perhaps not an obvious feature of day-to-day clinical practice.
Reflect upon why it is necessary for paramedics to understand essential knowledge on infectious
disease as part of their professional development.

Becoming familiar with vaccine design

to underpin clinical practice knowledge
All vaccines must go through large rigorous clinical trials before they can be fully approved for use
by governmental regulatory bodies responsible for publicly available medicines, such as the
Medicine and Healthcare products Regulatory Authority (UK). Clinical trial methodology ultimately
tests for medicinal safety, quality and effectiveness, but these processes can take time and be costly.
Unlike other drug groups, immunisations are not scientifically studied or understood through the
traditional concepts of pharmacology, i.e. pharmacodynamics and pharmacokinetics, but instead
are studied through the concepts of biotechnology and toxicity.

Vaccine design
Vaccines are pharmacologically designed to prevent or interfere with immunopathogenesis within the
body by lessening the pathogen’s effect through ‘working with’ the body’s immune systems. The vac-
cine’s ‘work’ prompts the body to initiate the innate immunity and activate antigen-presenting cells to
attack one or more antigens (surface proteins) on an infectious pathogen by killing or preventing fur-
ther replication through disablement (Pasquale et al., 2015; PHE, 2021). Immunisations do not provide
an immediate therapeutic effect to patients, but simply put, provide enough immunologically active
material of a particular pathogen to allow the body to produce a ‘learned’ immune response to prevent
Immunisations Chapter 17

serious complication and, ultimately, death. The learning the immune system must undergo can take
from a number of days to several weeks to be immunologically alert and prepared to target future
pathogens. Therefore, the biotechnological engineering of vaccines aims to ultimately create immuni-
sations to behave like infections (or threats) or interact with the immune system to develop a response
and resultant internal development of what is known as immunological memory (Nicholson, 2016).
Josefsberg and Buckland (2012) observe that the evolution of vaccines is correlational to the
advancement of vaccine production methods; methods that evolve as scientific understanding of
immunogenic biology improves. Modern human vaccine development requires significant basic
science knowledge of a target infectious disease, including the natural trajectory, aetiology, epide-
miology and pathogenesis, in order to identify the right immune response to be effective across
immunologically heterogeneous populations (Zepp, 2010). The development of vaccines can take
many years, if not decades, to be rolled out but in a global crisis, this development can be expedited
through political commitment.
The 2013–2016 Ebola outbreak in West Africa caused more than 11 000 deaths and cost the
economy billions of dollars but despite nearly a decade of vaccine development, a vaccine was not
available until after a year of the epidemic (British Society for Immunology, 2020). This vaccine
dilemma can also be observed with the current SARS-CoV-2 pandemic, whereby it took just over a
year for the first available vaccines to be rolled out after the first cases of the novel coronavirus in late
2019 in China.
The European Medicines Agency (EMA) (2005) advises that pharmacokinetic studies are generally
not necessary for vaccine trials as the kinetic properties of antigens within vaccines do not provide
beneficial information for dosing determinations. The EMA does advise that such studies may be
relevant if vaccines contain new adjuvants or excipients. Adjuvants, such as mineral salts, emulsions
and aluminium, are substances added to stimulate amplified inflammatory and immune responses
303
with highly purified antigens that are incapable of such effect (Pasquale et al., 2015); however, not
all vaccines include adjuvants (Josefsberg and Buckland 2012). Vaccines with adjuvants can result in
more frequent and noticeable local reactions, such as a sore arm (Kool et al., 2008).
Table 17.1 illustrates the six main classifications of vaccines.

Vaccine failure
No vaccines can provide 100% protection from infectious diseases and a small number of vaccinated
individuals can end up becoming infected. There are two types of failure: primary and secondary.
Primary failure is defined as when an individual fails to make an immunological response to a vaccine,
whereas secondary failure is when an individual initially immunologically responds to a vaccine, but
their protection fades over time (PHE, 2021).

Appreciating public concerns in the

acceptability and uptake of immunisations
Immunisations present rather different challenges by which the intended effect is not only to
achieve optimal health for individual patients, but more so for the health of the community. Being
given a medicine prophylactically may seem unnecessary or even controversial to some, which can
create public concern about immunisation programmes. Immunisations have many benefits on an
individual level, such as preventing serious disease manifestation or hospitalisation, but the true
and optimal effect of immunisation requires much wider uptake at the population level.
Immunisations can be understood through four different categories of offer in the clinical set-
ting: routine, event-specific, occupational and travel. The majority of routine immunisations are
offered during childhood and then periodically throughout adulthood. The uptake of childhood
immunisations in UK, for example, is considered to be very good but since 2014 there has been a
slow decline, with the uptake of completed courses at around 90%, whilst the goal is a sustained
95% (Bedford, 2020). Immunisation offers are continuously monitored according to infectious
Chapter 17 Immunisations

Table 17.1 Classifications of vaccine biotechnology.

Classification of
vaccine Biotechnology of vaccine Vaccine example
Whole pathogen Use of whole disease-causing pathogen to produce a similar Edward Jenner’s
vaccines effect as seen in natural infection. Potentially dangerous to cowpox vaccine in 1797
individuals due to risk of disease spread and death. This is the
oldest method of vaccine biotechnology and has since been
replaced by more modern vaccines
Live attenuated Contains whole bacteria or viruses that are genetically modified • Rotavirus vaccine
vaccines to ‘weaken’ or attenuate in order to create an immune response • MMR vaccine
but not cause pathogenesis. This type of vaccine biotechnology • Nasal flu vaccine
has a strong and lasting immune response and is considered the • Shingles vaccine
best current vaccine. Caution should be raised with their use in • Chickenpox vaccine
individuals with immune system problems through medication
or underlying illness due to an increased likelihood of
• BCG
TB
vaccine against

pathogenesis • Yellow fever vaccine

• Oral typhoid vaccine
(not the injected
vaccine)
Inactivated
vaccines
Inactivated vaccines are similar to live attenuated vaccines but
contain killed or altered whole bacteria or viruses, so they do not
• Inactivated
Vaccine
polio

replicate. This type of vaccine biotechnology tends not to have as

strong or lasting immune response but is suitable for individuals
• Japanese
encephalitis vaccine
304 with immune system problems through medication or • Hepatitis A vaccine
underlying illness due to an increased likelihood of pathogenesis • Influenza vaccine
• Rabies vaccine
Subunit vaccines Subunit vaccines do not contain any whole bacteria or viruses,
1. Recombinant but instead typically contain one or more specific surface
protein proteins/antigens from the pathogen, sometimes referred to as
vaccines acellular. This type of vaccine biotechnology allows the immune
2. Toxoid vaccines system to focus its attention on a small number of antigen
3. Conjugate targets. Subunit vaccines tend not to have as strong or lasting
vaccines immune response as live attenuated vaccines so may require
further booster doses. Often developed with adjuvants
Recombinant protein vaccines are made using bacterial or yeast • Hepatitis B vaccine
cells to manufacture a vaccine. A small piece of DNA is taken from • HPV vaccine
a bacterium or virus and inserted into manufacturing cells • MenB vaccine
Toxoid vaccines are made of inactivated toxins (poisonous • Diphtheria vaccine
proteins) released by some bacteria. The immune system • Tetanus vaccine
responds in the same way to these toxins as to other surface
antigens of the bacteria. This type of vaccine biotechnology has a
• Pertussis vaccine
strong and lasting immune response.
Conjugate vaccines are joined with polysaccharides (complex • Hib vaccine
sugars on the surface of bacteria) rather than proteins. Often
conjugate vaccines are attached to diphtheria or tetanus toxoid
• MenC vaccine (in
the Hib/MenC
protein to generate a stronger immune response to the vaccine)
polysaccharide • PCV (children’s
pneumococcal
vaccine)
• MenACWY vaccine
(Continued)
Immunisations Chapter 17

Table 17.1 (Continued)

Classification of
vaccine Biotechnology of vaccine Vaccine example
Virus-like particles Virus-like particles vaccines are naturally occurring or synthesised • Hepatitis B vaccine
vaccines
Outer membrane
individual expressions of viral structural proteins and are
non-infectious because they contain no viral genetic material
• HPV vaccine
vesicles vaccines
Outer membrane vesicles vaccines are relatively new type of
vaccine biotechnology; they are a bleb of bacterial outer cell
• MenB vaccine
(meningococcal B
membrane that is non-infectious but stimulates an immune vaccine)
response
Nucleic acid Nucleic acid vaccines are a significantly promising vaccine
vaccines biotechnology. Rather than providing a protein antigen of a
1. RNA vaccines pathogen, they provide genetic instructions of the antigen to the
2. DNA vaccines cells in the body and in turn the cells produce the antigen to
stimulate an immune response
RNA vaccines use messenger RNA (mRNA) inside a lipid
membrane. The lipid membrane protects the mRNA when it
• Pfizer BioNTech and
Moderna Covid-19
enters the body and helps the mRNA get into cells. Once inside vaccines
the cell, the cell translates the mRNA into an antigen protein to
then produce an immune response. The mRNA is then broken
down and eliminated from the body
DNA vaccines are more stable than mRNA vaccines and do not • No licensed DNA 305
need the same initial protection. DNA vaccines are typically vaccines
administered with a technique called electroporation. This uses
low-level electronic waves to allow the body’s cells to take up the
DNA vaccine. DNA must be translated to mRNA within the cell
nucleus before it can subsequently be translated to protein
antigens which stimulate an immune response
Viral vectored Viral vectored vaccines use harmless viruses to deliver the
vaccines genetic code of target vaccine antigens to cells of the body, so
• Replicating that they can produce protein antigens to stimulate an immune
• Non-replicating response. Viral vectored vaccines are significantly cheaper to
produce in most cases compared to nucleic acid vaccines and
many subunit vaccines. This is a newer type of vaccine
biotechnology
Replicating viral vectored vaccines retain the ability to make new
viral particles alongside delivering the vaccine antigen. This type
• Ervebo
(rVSV-ZEBOV)
of vaccine biotechnology has the advantage of a replicating virus Ebola vaccine
that can provide a continuous source of vaccine antigen over an
extended period of time compared to non-replicating vaccines,
and so is likely to produce a stronger immune response
Non-replicating viral vectored vaccines do not retain the ability
to make new viral particles during the process of delivering the
• Oxford-AstraZeneca
Covid-19 vaccine
vaccine antigen to the cell through removing key viral genes. This
has the advantage that the vaccine cannot cause disease, and
adverse events associated with viral vectored replication are
reduced. However, vaccine antigen can only be produced as long
as the initial vaccine remains in infected cells (a few days). This
means the immune response is generally weaker than with
replicating viral vectors and booster doses are likely to be
required

Source: Adapted from Types of Vaccines (Vaccine Knowledge Project, Oxford Vaccine Group, University of Oxford):
https://vk.ovg.ox.ac.uk/vk/types-of-vaccine
Chapter 17 Immunisations

disease threat by governmental health departments or independent advisory expert committees

on immunisations; for example, in the UK, the Joint Committee on Vaccination and Immunisation
provides recommendations on immunisations, vaccine safety and national immunisation sched-
ules to the government (Table 17.2). Routine immunisations are offered and are accessible to
patients with general practitioner (GP) registrations, so paramedics should be mindful of patients

Table 17.2 UK immunisation schedule (PHE 2019b).

Minimum age
according to Administration
vaccine licence Diseases protected against Vaccine given site
8 weeks old Diphtheria, tetanus, pertussis (DTap), polio DTap/IPV/Hib/HepB Thigh
(IPV), Haemophilus influenzae type b (Hib),
hepatitis b (HepB)
Meningococcal group B (MenB) Men B Thigh
Rotavirus Rotavirus By mouth
12 weeks old DTap, IPV, Hib, HepB DTap/IPV/Hib/HepB Thigh
Pneumococcal (13 serotypes) Pneumococcal Thigh
conjugate vaccine
(PCV13)
Rotavirus Rotavirus By mouth
306 16 weeks old DTap, IPV, Hib, HepB DTap/IPV/Hib/HepB Thigh
MenB MenB Thigh
1 year old (or after Hib and meningococcal group C (MenC) Hib/MenC Upper arm/thigh
the child’s first
Pneumococcal (13 serotypes) PCV13 Upper arm/thigh
birthday)
Measles, mumps and rubella (MMR) MMR Upper arm/thigh
(German measles)
MenB MenB booster Thigh
Eligible paediatric Influenza (each year from September) Live attenuated Both nostrils
age groups influenza vaccine
DTap and IPV DTap/IPV Upper arm
MMR MMR (check the first Upper arm
dose given)
3 years 4 months old DTap and IPV DTap/IPV Upper arm
or soon after
MMR MMR (check the first Upper arm
dose given)
Boys and girls aged Cancers caused by human papillomavirus HPV (two doses Upper arm
12–13 years (HPV) types 16 and 18 (and genital warts 6–24 months apart)
caused by types 6 and 11)
14 years old (school Tetanus, diphtheria and IPV Td/IPV (check MMR Upper arm
year 9) status)
Meningococcal groups ACWY disease MenACWY Upper arm
65 years old Pneumococcal (23 serotypes) Pneumococcal Upper arm
polysaccharide vaccine
(PPV)
65 years of age and Influenza (each year from September) Inactivated influenza Upper arm
older vaccine
70 years old Shingles Shingles Upper arm
Source: Modified from PHE (2019b).
Immunisations Chapter 17

who are not registered. Adults with incomplete childhood immunisations can catch up at any point
in their lives via their GP.
In addition to routine immunisations, patients may be eligible for event-specific immunisations
due to ‘dirty’ injuries with the risk of tetanus infection. The tetanus vaccine is required if a patient is
unvaccinated or more than 10 years have passed since their last tetanus vaccine. There is a high
likelihood of paramedics seeing this type of clinical presentation in urgent and emergency care
situations.

Vaccine acceptability
Due to the prophylactic nature of immunisations, the acceptability and uptake can be ethically com-
plex and contextual for a variety of reasons (Bedford, 2020). Vaccine hesitancy can be defined as the
‘delay in acceptance or refusal of vaccines despite availability of vaccine services’ (Bedford, 2020,
p. 302). Bedford (2020) has highlighted a non-exhaustive number of reasons for vaccine hesitancy.

• Complacency (do not perceive need for vaccine).

• Inconvenience (lack of accessibility to vaccines).
• Confidence (do not trust the vaccine or provider).
• Influence of the internet, social media and significant individuals or groups including family,
friends and anti-vaccine (anti-vaxxer) movements.
• Patient-held beliefs about western medicine and anti-vaccine conspiracies.
• Patient attitudes towards vaccine safety and threat of infectious diseases.
Many western countries do not have mandatory vaccine policies so paramedics should only seek to 307
promote essential evidence-based information to patients with ‘anti-vax’ views to avoid disrespect.
If a paramedic is concerned about the safeguarding of a patient’s welfare due to the patient’s/
parent’s/carer’s attitudes about vaccines, they should refer the patient through safeguarding
procedures in line with their employer’s policy.
Paramedics should be mindful of new or re-emerging pandemics which can arise as a direct result
of insufficient immunisation uptake, or indeed infectious diseases without a vaccine. For example,
the measles vaccine has been available from the NHS since 1968, but in 2019 the WHO withdrew the
UK’s ‘measles-free’ status due to an increase in cases, even after the UK had initially eliminated
measles in 2017 (PHE, 2019a). Paramedics should be cognisant of the prevention of seasonal
infectious diseases such as influenza or community-acquired bacterial pneumonias and ‘normalise’
such immunisations through reminding patients of their eligibility.

Clinical consideration: key points when

assessing patients with vaccine hesitancy
Patients with mental capacity must make an autonomous and informed decision before consenting to
receive medical care or intervention. Patients who are not sure if they want to be immunised should not be
forced to receive one. Patients should be advised on the latest evidence base on immunisations as a way of
providing the patient with the essential information required to make an informed decision. If a patient
appears hesitant, with their permission you may wish to consider the following in your consultations.

1. Explain your profession’s commitment to person-centred, evidence-based practice through

empathic communication to establish rapport and trust.
2. Check what information the patient already has regarding the vaccine(s) as well as vaccinations in
general.
3. Ask where the patient has received such information, including credible and unfounded sources of
information.
Chapter 17 Immunisations

4. Explain to the patient the vaccine(s) you wish to administer, including its indications, contraindications,
potential side-effects, potential adverse reactions and the likely immunity cover as well as the concept
of herd immunity/fire lines.
5. Listen and respond carefully to questions from the patient.
6. Remind the patient that they may wish to come back at another time once they have thought about
the decision to vaccinate, unless it is an event-specific vaccination such as tetanus.
7. Patients who lack mental capacity should be referred to their GP. There is no such event as an
‘emergency immunisation’.

Reflection: Immunisation information

and advice opportunities
In your current clinical practice, reflect upon previous opportunities you have had where immunisation
information and advice could have been useful.

308
Recognising the role of the paramedic
in health promotion and immunisation
administration
The nature of paramedic–patient relationships is rapidly changing, with an increasing number of
paramedics working in clinical settings beyond emergency ambulances, such as primary care. Peate
(2015) advises that as paramedics begin to widen their scope of practice, patient safety must remain
the priority. The international literature suggests that paramedics can improve system performance
and patient outcomes in primary care, but more research is required to explain exactly how (Bigham
et al., 2013; Eaton et al., 2020). In light of the little research on paramedics’ clinical practice surround-
ing immunisation, the three previous learning outcomes bring together a solid knowledge base on
immunisations to begin to confirm the role of the paramedic, including conceptualising how infectious
diseases spread, vaccine biotechnology and awareness of more sensitive issues associated with
public concerns surrounding immunisations.

Reflection: the role of the paramedic

How can paramedics contribute to immunisation uptake through health promotion in prehospital care
settings?

Immunisations as prescription-only medicines

In the UK, immunisations are legally defined as prescription-only medicine, with the sale, supply,
administration and prescribing of medicines controlled by three key laws: Medicines Act 1968,
Misuse of Drugs Regulations 2001 and Human Medicines Regulations 2012. Paramedics who have
demonstrable clinical knowledge and competence and are independent prescribers can prescribe
immunisations, but non-prescribing paramedics must follow a ‘written instruction’ by a doctor, den-
tist or non-medical prescriber through a prescription, patient group or patient-specific direction.
Patient-specific directions are written instructions, produced after an individual clinical assessment,
given and signed by a prescriber for another professional (note: not non-registered ambulance staff
Immunisations Chapter 17

or healthcare assistants) to supply or administer medicines to a named patient (HCPC, 2021)

(Figure 17.2). Patient group directions (PGD) are written instructions that are given and signed by a
prescriber for a specific group of patients (with eligibility criteria) that enable the supply or adminis-
tration by named professionals. PGDs are the most common form of written instruction with immu-
nisations (HCPC, 2021) (Figure 17.3). The detailed information that should be present in a PGD can
be found via the MHRA website: www.gov.uk/government/publications/patient-group-directions-
pgds/patient-group-directions-who-can-use-them.

Embedding immunisation history taking in clinical assessment

Paramedics work towards a systems-based assessment in clinical practice, which provides the ideal
framework to embed immunisation history taking. Prior to consenting and administering an immu-
nisation or exploring immunisation options with patients, paramedics should also make sure they
obtain an immunisation history. Patients may be poor historians with regard to their immunisation
history so detailed clinical assessment, with specific questioning for each type of immunisation,

Patient Specific Direction (PSD)

Name of Patient _Richard Brown ________________________________

DOB 01/02/1960

Address __2 Froom Cottages_______________________________

___Hertfordshire____________________________________ 309
___HA10 9JU ______________________

I authorise for the above-named patient to receive the following vaccination:

Name of Vaccination: BNT162b2 Pfizer-BioNTech Covid-19

vaccine

Dose 30µg in 0.3mL

Frequency Twice. Second dose 10–12 weeks after

first dose.

Site of injection/method of IM deltoid region of the upper arm

administration

and that this can be administrated by the Health Care Professional who is suitably
qualified to do so and is employed by this general practice

Signed A Doctor__________________________________

Print Name_______ Alice Doctor________________________

Position/role______General Practitioner_____________________________

Date __________20/10/2021 ________________________

Expiry date of this PSD _______________________31/12/2021 _________

Figure 17.2 Example of a patient-specific direction in general practice.

Chapter 17 Immunisations

To see the complete NHS England PGD for the BNT162b2 Pfizer-BioNTech
COVID-19 vaccine, please visit: https://www.england.nhs.uk/coronavirus/wp-

content/uploads/sites/52/2020/12/C1219-Patient-Group-Direction-for-COVID-19-

mRNA-vaccine-BNT162b2-Pfizer-BioNTech.pdf

To be completed by a Primary Care Paramedic upon administration of the

vaccine

Name of Vaccine administered BNT162b2 Pfizer-BioNTech COVID-19

vaccine

Batch Number 12345678

Expiry Date 08/05/2022

Dose 30µg in 0.3mL

Site of injection/method of IM right deltoid

administration
310

Date vaccine administered 29/10/2021

Contraindications to the vaccine None known.

Notes Patient informed of immunisation, its

indications, contraindications, potential
side effects, potential adverse
reactions, the likely resultant immunity
and to continue to follow COVID-19
rules including social distancing / face
mask wearing. Patient also reminded
about the requirement for a second
dose in 10–12 weeks to complete
immunisation course. Patient is on
warfarin but has not taken this
medication in the last 6 hours.
Patient gave informed verbal
consent.

Signed A. Paramedic_________________________________________

Print Name Adam Paramedic ______________________________

Qualifications______RP____________________________________________

Date _________29/10/2021_____________________________

Figure 17.3 Example of a patient group direction. Source: Based on Public Health England. (2021).
Patient Group Direction for COVID-19 mRNA vaccine BNT162b2 (Pfizer/BioNTech).
Immunisations Chapter 17

should be undertaken, including accessing the patient’s records and asking whether a patient may
have a personally held immunisations record such as the Personal Child Health Record (or ‘red book’)
or an ‘Immunisation Record’ from other countries.
Public Health England (2016) provides an algorithm for individuals with uncertain or incomplete
immunisation status. The algorithm is underpinned by four general principles.

1. Unless there is a documented or reliable verbal vaccine history, individuals should be assumed to
be unimmunised and a full course of immunisations planned.
2. Individuals coming to the UK part way through their immunisation schedule should be
transferred onto the UK schedule and immunised as appropriate for age.
3. If the primary course has been started but not completed, resume the course – no need to repeat
doses or restart course.
4. Plan catch-up immunisation schedule with minimum number of visits and within a minimum
possible timescale – aim to protect individual in shortest time possible.

Not all patients can receive immunisations due to contraindications. It is, however, important to
note that even if patients may feel they are contraindicated, this could be due to self-reported side-
effects of previous immunisations rather than true contraindications, hypersensitivities or adverse
reactions, so careful questioning is required with accurate documentation.
Public Health England (2017) stipulates seven specific situations where vaccination should be
avoided.

• History of confirmed anaphylactic reaction to a previous vaccine dose. 311

• History of confirmed anaphylactic reaction to a component of the vaccine.
• Patients with primary or acquired immunodeficiency (1) or on current or recent immunosuppressive
or immunosuppressive biological therapy (IBT) (2) as well as those in contact with them (3).
• Infants born to a mother who received IBT during pregnancy.
• Pregnant women.
Patients with egg allergies should be offered alternative egg-free/very low ovalbumin vaccines if
possible.

Clinical consideration: consent

The Health and Care Professions Council advises registered practitioners of their duty to gain consent
from patients before beginning an assessment or intervention and explicitly states that accountability
for ensuring a legally competent consent always lies with the practitioner, not the patient.
Failure to ascertain informed consent can lead to both professional and legal action against the
registered practitioner. Immunisation administration requires a qualified practitioner to give patient the
necessary relevant and easy-to-follow information about the immunisation, the indications, the contra-
dictions, potential side-effects, potential adverse reactions and the procedure itself as well as providing
the opportunity for asking questions prior to consenting. This information may need to be provided in a
variety of formats (e.g. verbal, written, Braille) to ensure equity of need. Qualified practitioners should
fully explain the benefits and risks of immunisation, situating immunisations within wider concepts such
as infectious diseases transmission and herd immunity to demonstrate community benefit.
Qualified practitioners should not pressure a patient in any way to receive a vaccine and use health
promotion approaches, such as education or empowerment, to ascertain vaccine acceptability.
Qualified practitioners should explain how the immunisation administration will be documented, in
line with data protection legislation and Caldicott guidance.
The nature of consent, as understood within UK legislation, means that consent is only valid at the time
it is given and is dependent on the offered information that is deemed necessary to make a reasonable
decision. Consent is often subject to case law which can make universal changes to the way practitioners
facilitate consent; for more information, please visit: www.gov.uk/government/publications/reference-
guide-to-consent-for-examination-or-treatment-second-edition
Chapter 17 Immunisations

Clinical consideration: anaphylaxis

Medicines should not be given to patients without the provision of emergency life-saving medications/
equipment to be used in the event of anaphylaxis. The Resuscitation Council UK and Public Health
England (2020) have produced guidance entitled ‘Management of Anaphylaxis in the Vaccination
Setting’ although they advise that anaphylaxis is rare, with less than one anaphylaxis episode per million
vaccine doses in the UK. The onset of anaphylaxis usually occurs within the first 15 minutes but can occur
later. The classic features of anaphylaxis can include:

• itchy skin rash/urticaria (wheals) or swelling (angio-oedema), e.g. lips, face

• airway/breathing problems such as airway swelling, hoarse voice, stridor, shortness of breath,
bronchospasms or persistent cough, tiring with effort of breathing, hypoxic confusion, cyanosis
and respiratory arrest
• tachycardia and hypotension
• a sense of ‘impending doom’, loss of consciousness with no improvement once supine or head
down position.

If anaphylaxis is recognised, urgent ambulance support should be requested (or different in acute
hospital settings) and an anaphylaxis pack should be accessed immediately. Adrenaline (1:1000) should
be administered as soon as possible to older children and adults (500 μg dose) and repeated if the above
clinical features persist. Patients should be continuously monitored and remain lying supine until an
ambulance or extra help arrives as death can occur if a patient stands, walks or sits up too suddenly. An
automated external defibrillator should be available in case of cardiac arrest.
312
All suspected vaccine-induced adverse reactions should be reported via the MHRA’s Yellow Card
scheme and any patient with suspected anaphylaxis should be referred to their local allergy clinic.
For the full RCUK and PHE (2020) guidance, please visit: www.resus.org.uk/about-us/news-and-
events/rcuk-publishes-anaphylaxis-guidance-vaccination-settings

Skills in practice: vaccination care

Paramedics must ensure they practise accountably within their scope of practice when administering
immunisations, as defined by the Health and Care Professions Council, their employer’s policies and
professional indemnity insurance cover.

Before vaccine administration

• Check the clinical setting’s policies and protocols for vaccine administration.
• Ensure vaccines have been stored correctly under cold chain conditions (see the Green Book for
more information).
• Ensure vaccines are correctly labelled and are in their original packaging.
• Ensure vaccines are within their expiry date.
• Wash hands and wear protective personal equipment as required and follow universal
precautions.
• Ensure the correct equipment for drawing the vaccine is available, including sterile syringes,
needles and a sharps bin.
• Draw the vaccine only when it is ready to be administered to the patient. Note that only single-use
needles must be used for drawing up and discarded after each use. When drawing vaccine from a
vial, keep the vial on a firm surface and push the needle down into the vial to minimise needle
stick injury.
• Once a vial has been opened, the following information should be documented on the vial itself.
Immunisations Chapter 17

• Date and time of the reconstitution (if required) or first opened.

• Initials of the health professional who opened the vial/reconstituted the vaccine.
• Date and time the vaccine must be used within.
• Stored correctly once opened but not in use.
Vaccine administration
• Introduce yourself and your role to the patient.
• Check patient details on the appointment/clinical system through asking patients questions to
establish positive identifiers.
• Undertake a clinical assessment to ensure the appropriateness of the patient to receive the vaccine
including all information as outlined in the Clinical consideration: consent box (page 311) to ensure
informed consent.
• Wash/gel hands again.
• Ensure the reconstituted vaccine or vaccine is drawn to the correct dose as per the PSD or PGD and
is administered according to the correct route: intramuscular, oral, nasal or intradermal. The majority
of vaccines are administered intramuscularly in the deltoid area of the upper arm or the anterolateral
aspect of the thigh (see Figures 17.4 and 17.5).
• Ensure that a sharps bin is next to you, so you do not have to travel to dispose of a needle.
• No vaccine should be administered into the same site as a previous vaccine within 7 days in order
to be certain of avoiding adverse reactions.
• Skin preparation is not required if the skin looks visibly clean. If necessary, use water and soap to
clean the skin and ensure it is dry before administration.
313
• If a patient is to have more than one vaccine via injection at the same time, a different limb should
be used for administration for the subsequent vaccines. If only one limb is available, each vaccine
should be administered approximately 25 mm apart.
• Intramuscular injections should be given with the needle at a 90° angle to the skin, with the skin held
taut by using a finger and thumb technique to make a ‘u’ or ‘n’ shape with the non-injecting hand. The
needle should be carefully inserted into the skin, being sure not to over- or underpenetrate. If bone
is felt on needle insertion, the vaccinator should gently pull the needle back a few millimetres and
begin to inject the vaccine. No aspiration of the injection is required to check correct positioning.
• Depending on the vaccine, the needle should remain in place for 10 seconds after pushing the
syringe plunger to ensure no underdosing.
• Gently remove the needle from the patient and place straight into a sharps bin.
• Check the injection site for signs of bleeding, using a small piece of cotton wool if necessary. Use
a small plaster to cover the injection site if the patient is not allergic to plasters.

Postvaccine care
• Continuously observe the patient for any adverse reactions for up to 15 minutes.
• Ensure the patient is comfortable.
• Ensure all patient documentation is completed including:
• the vaccine name, batch number, expiry date
• dose administered
• administration site
• date given
• name and signature of the vaccinator.
Chapter 17 Immunisations

Deltoid muscle

Humerus

Figure 17.4 Location of the deltoid muscle. Source: Peate and Wild (2018).

314

Greater trochanter

Vastus lateralis
injection site

Rectus femoris
injection site

Lateral condyle

Figure 17.5 Location of the rectus femoris and vastus lateralis muscles of the thigh. Source: Peate
and Wild (2018).
Immunisations Chapter 17

Episode of care
Mr Brooks calls 999 following an accident in his garden. He suffered a laceration to his left index finger
whilst attempting to make cuttings from one of his roses with a very old pruning knife; he had originally
felt faint but has since recovered.
Mr Brooks is seen at his home by Hannah Hanbury, an advanced paramedic practitioner in urgent
care, solo working in a rapid response vehicle. Mr Brooks has been gardening all day and has visibly
soiled hands. He is a 68-year-old man and has a firmly set ‘doctor knows best’ attitude to his engagement
with healthcare yet also believes that a ‘bit of dirt won’t hurt you’. Mr Brooks has no significant medical
history and is a retired builder. He lives with his wife in a small village, 15 miles from the nearest health
facility.
Hannah decides that Mr Brooks does not need to attend hospital. She assesses, cleans and sutures Mr
Brooks’ hand and advises him to keep the dressing dry for the next 5 days and to go to the practice nurse
at his general practice for review. Hannah asks Mr Brooks when he last received the tetanus vaccine.
Mr Brooks informs her that he last had an injection when he was a child but knows that he had no ‘child-
hood disease shots’ due to his parents believing ‘a bit of dirt is good for everyone’. Hannah advises Mr
Brooks that due to his reported immunisation history, he would be recommended for the tetanus
vaccine. Hannah recommends this vaccine due to the risk of tetanus infection caused by a bacterium
called Clostridium tetani and the potential entrance of spores of the tetanus bacteria from the garden soil
into his wound. Hannah also advises Mr Brooks of the relevant information about the tetanus vaccine
including the contraindications, potential side-effects and potential adverse reactions.
Hannah advises Mr Brooks to attend the local Minor Injuries Unit (MIU) today to receive the tetanus
vaccine and to inform his GP afterwards so his health records are up to date. On the Patient Report
Form, Hannah documents Mr Brooks’ injury through the ABCDE model and objectively states the 315
advice she gave him regarding the tetanus vaccine with onward signposting to the MIU on discharge.

Conclusion
This chapter has provided an essential overview of the pharmacology of immunisations, and also
presents wider, important disciplinary considerations in relation to the basic epidemiology of
infectious diseases and public concerns about immunisations. Immunisations are integral medicines
to public health and with the increasing numbers of paramedics now working within primary and
urgent care settings, immunisation knowledge is more important than ever before. Without
immunisations, many of the infectious diseases that we do not so often hear about would result in
increased mortality and morbidity in our populations. This chapter should be read in conjunction
with the continuously updated online Green Book, which provides all the latest guidance on
vaccines and vaccination procedures and vaccinatable infectious diseases in the UK: www.gov.uk/
government/collections/immunisation-against-infectious-disease-the-green-book.

The following infectious diseases are a list of conditions that can be prevented or reduced in pathogenic seriousness by
immunisations. Take some time and write notes about each of the conditions. Think about the types of immunisations
that are used to prevent each, including their biotechnological approaches. Remember to include aspects of patient
care. If you are making notes about people you have offered care and support to, you must ensure that you have
adhered to the rules of confidentiality.
The condition Your notes
Influenza infection
Tuberculous infection
Severe acute respiratory syndrome coronavirus
2 infection
Pneumococcal chest infection
Tetanus infection
Chapter 17 Immunisations

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Public Health England (PHE). (2017). Contradictions and special considerations. Chapter 6. The Green Book. https://
assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/655225/
Greenbook_chapter_6.pdf
Public Health England (PHE). (2019a). Measles in England. Public health matters blog. https://publichealthmatters.
blog.gov.uk/2019/08/19/measles-in-england/
Public Health England (PHE). (2019b). UK Immunisation Schedule. Chapter 11. The Green Book. www.gov.uk/
government/publications/immunisation-schedule-the-green-book-chapter-11
Public Health England (PHE). (2021). Immunity and How Vaccines Work. Chapter 1. The Green Book. https://assets.
publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/949797/
Greenbook_chapter_1_Jan21.pdf
Resuscitation Council UK and Public Health England. (2020). Management of Anaphylaxis in the Vaccination Setting.
www.resus.org.uk/about-us/news-and-events/rcuk-publishes-anaphylaxis-guidance-vaccination-settings
Stern, A.M. and Markel, H. (2005). The history of vaccines and immunizations: familiar patterns, new challenges.
Health Affairs 24(3): 611–621.
Sutherst, R.W. (2004). Global change and human vulnerability to vector-borne diseases. Clinical Microbiology
Reviews 17: 136–173.
Zepp, F. (2010). Principles of vaccine design – lessons from nature. Vaccine 28(Suppl 3): C14–C24.
Immunisations Chapter 17

Further reading
Vickers, P.S. (2016). The immune system. In: Fundamentals of Anatomy and Physiology for Nursing and Healthcare
Students (eds I. Peate and M. Nair). Chichester: John Wiley & Sons Ltd.

Multiple-choice questions
1. What is an infectious disease?
(a) A communicable disease that spreads through communities and populations,
regionally, nationally and internationally
(b) Any disease that is perceived to be infectious by the public
(c) A non-communicable disease that spreads through communities and populations,
regionally, nationally and internationally
(d) Any disease that has symptoms of vomiting and diarrhoea
2. How is the horizontal transmission of infectious diseases defined?
(a) The spread of pathogens from individuals from one generation to the next
(b) The societal vulnerabilities of infectious diseases
(c) The spread of pathogens across individuals within the same generation
(d) The spread of infectious diseases that can be foreseen on the horizon
3. Why are social determinants of health important to consider in infectious diseases
spread?
(a) Because social determinants can directly impact on how infectious diseases are 317
spread/controlled
(b) Because people living in poverty are more likely to be in contact with infectious
diseases
(c) Because there is an evidence-based relationship between social determinants
and infectious diseases
(d) All of the above
4. What can dramatically speed up vaccine development?
(a) Political commitment
(b) Social media discourse
(c) A vocal paramedic on social media
(d) A vocal medical doctor on social media
5. How are vaccines broadly designed?
(a) Through attention to biotechnology and toxicity
(b) Through attention to pharmacokinetic studies
(c) Through attention to vaccine acceptability with middle-class individuals
(d) Through attention to how much vaccines cost
6. How many main classifications of vaccines are there?
(a) 1
(b) 3
(c) 6
(d) 12
7. How many routine vaccines is an infant given by the time they reach 6 months old?
(a) 4
(b) 8
(c) 6
(d) 2
8. What is vaccine hesitancy?
(a) Delay in acceptance or refusal of vaccines despite availability of vaccine services
(b) Feeling nervous while receiving a vaccine
Chapter 17 Immunisations

(c) A patient who believes in vaccines but does not attend their appointment
(d) A patient being indecisive about which arm they would like to receive the vaccine
9. What is the best approach to dealing with ‘anti-vaxxers’?
(a) Tell them they are wrong and vaccinate them through force
(b) Provide evidence-based information about vaccines in an objective, neutral
approach with their permission
(c) Pretend the vaccine is another non-vaccine medication and vaccinate them
(d) Provide them with your opinions about vaccines with their permission
10. What is a patient group direction?
(a) A written and signed instruction by a prescriber, produced after an individual
clinical assessment, given by another professional
(b) A written and signed instruction by a prescriber for a specific group of patients
with eligibility criteria, given by another professional
(c) A verbal drug recommendation by a prescriber for a specific patient
(d) A public sign directing patients to a group therapy session
11. How many general principles underpin Public Health England’s (2016) algorithm for
individuals with uncertain or incomplete immunisation status?
(a) 2
(b) 6
(c) 4
(d) 5
318 12. What would be considered the minimum necessary, relevant and easy-to-follow
information alongside the immunisation a patient/client should be given in order to
reach an informed understanding prior to consent?
(a) The indications and adverse effects
(b) The indications, contraindications andpotential adverse reactions
(c) The indications, contraindications, potential side-effects, potential adverse
reactions and an opportunity to ask questions
(d) The indications, contraindications, adverse effects and effects of social media on
immunisations
13. Why do paramedics need to know about immunisations?
(a) Increasing numbers of paramedics are now working in non-ambulance settings
such as primary and urgent care
(b) In case presenting medical complaints are related to vaccinatable infectious diseases
(c) To provide opportunistic health promotion on immunisations through Making
Every Contact Count
(d) All of the above
14. What is the suggested prevalence of anaphylaxis in UK vaccination settings?
(a) Less than nine anaphylaxes per million vaccine doses
(b) Less than five anaphylaxes per million vaccine doses
(c) Less than 24 anaphylaxes per million vaccine doses
(d) Less than one anaphylaxis per million vaccine doses
15. What is the name of the book that provides the latest information on vaccines and
vaccination procedures, for vaccine-preventable infectious diseases in the UK?
(a) The Government Vaccine Book
(b) The Green Book
(c) The Blue Book
(d) The Vaccination Book
Normal Values

There are a variety of techniques that those who analyze blood use in the laboratory to identify the
various components. These techniques can differ from laboratory to laboratory, it is essential that
when assessment of blood results is undertaken, referral to the local laboratory’s normal values is
made. Variation occurs across the UK, Europe, and globally.

Haematology
Full blood count
Haemoglobin (males) 130–180 g/l
Haemoglobin (females) 115–165 g/l
Haematocrit (males) 0.40–0.52
Haematocrit (females) 0.36–0.47
MCV 80–96 fl
MCH 28–32 pg
MCHC 32–35 g/dl
White cell count (4–11) × 109 l
White cell differential
Neutrophils 1.5–7 × 109 l
Lymphocytes 1.5–4 × 109 l
Monocytes 0–0.8 × 109 l
Eosinophils 0.04–0.4 × 109 l
Basophils 0–0.1 × 109 l
Platelet count 150–400 × 109 l
Reticulocyte count (25–85) × 109 l or 0.5–2.4%
Erythrocyte sedimentation rate
Westergren
Under 50 years:
Males 0–15 mm/1st hour
Females 0–20 mm/1st hour
Over 50 years:
Males 0–20 mm/1st hour
Females 0–30 mm/1st hour
Plasma viscosity 1.50–1.72 mPa s1 (at 25 °C)
Coagulation screen
Prothrombin time 11.5–15.5 seconds
International normalized ratio < 1.4
Activated partial thromboplastin time 30–40 seconds
Fibrinogen 1.8–5.4 g/l
Bleeding time 3–8 minutes
Coagulation factors
Factors II, V, VII, VIII, IX, X, XI, XII 50–150 IU/dl

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Normal Values

Factor V Leiden Present or not

320 Von Willebrand factor 45–150 IU/dl
Von Willebrand factor antigen 50–150 IU/dl
Protein C 80–135 IU/dl
Protein S 80–120 IU/dl
Antithrombin III 80–120 IU/dl
Activated protein C resistance 2.12–4.0
Fibrin degradation products <100 mg/l
D‐dimer screen <0.5 mg/l
Hematinics
Serum iron 12–30 μmol/l
Serum iron‐binding capacity 45–75 μmol/l
Serum ferritin 15–300 μg/l
Serum transferrin 2.0–4.0 g/l
Serum B12 160–760 ng/l
Serum folate 2.0–11.0 μg/l
Red cell folate 160–640 μg/l
Serum haptoglobin 0.13–1.63 g/l
Haemoglobin electrophoresis
Haemoglobin A > 95%
Haemoglobin A2 2–3%
Haemoglobin F < 2%
Chemistry
Serum sodium 137–144 mmol/l
Serum potassium 3.5–4.9 mmol/l
Serum chloride 95–107 mmol/l
Serum bicarbonate 20–28 mmol/l
Anion gap 12–16 mmol/l
Serum urea 2.5–7.5 mmol/l
Serum creatinine 60–110 μmol/l
Serum corrected calcium 2.2–2.6 mmol/l
Serum phosphate 0.8–1.4 mmol/l
Serum total protein 61–76 g/l
Serum albumin 37–49 g/l
Serum total bilirubin 1–22 μmol/l
Serum conjugated bilirubin 0–3.4 μmol/l
Serum alanine aminotransferase 5–35 U/l
Serum aspartate aminotransferase 1–31 U/l
Serum alkaline phosphatase 45–105 U/l (over 14 years)
Serum gamma glutamyl transferase 4–35 U/l (<50 U/l in males)
Serum lactate dehydrogenase 10–250 U/l
Serum creatine kinase (males) 24–195 U/l
Serum creatine kinase (females) 24–170 U/l
Creatine kinase MB fraction <5%
Serum troponin I 0–0.4 μg/l
Serum troponin T 0–0.1 μg/l
Serum copper 12–26 μmol/l
Serum caeruloplasmin 200–350 mg/l
Serum aluminum 0–10 μg/l
Serum magnesium 0.75–1.05 mmol/l
Serum zinc 6–25 μmol/l
Serum urate (males) 0.23–0.46 mmol/l
Serum urate (females) 0.19–0.36 mmol/l
Plasma lactate 0.6–1.8 mmol/l
Normal Values

Plasma ammonia 12–55 μmol/l

Serum angiotensin‐converting enzyme 25–82 U/l 321
Fasting plasma glucose 3.0–6.0 mmol/L
Haemoglobin A1 C 3.8–6.4%
Fructosamine <285 μmo/l
Serum amylase 60–180 U/l
Plasma osmolality 278–305 mosmol/kg

Lipids and lipoproteins

Target levels will vary depending on the patient’s overall cardiovascular risk assessment
Serum cholesterol <5.2 mmol/l
Serum LDL cholesterol <3.36 mmol/l
Serum HDL cholesterol >1.55 mmol/l
Fasting serum triglyceride 0.45–1.69 mmol/l

Blood gases (breathing air at sea level)

Blood H+ 35–45 nmol/l
pH 7.36–7.44
PaO2 11.3–12.6 kPa
PaCO2 4.7–6.0 kPa
Base excess ±2 mmol/l

Carboxyhaemoglobin
Non‐smoker <2%
Smoker 3–15%

Immunology/rheumatology
Complement C3 65–190 mg/dl
Complement C4 15–50 mg/dl
Total hemolytic (CH50) 150–250 U/l
Serum C‐reactive protein <10 mg/l

Serum immunoglobulins
IgG 6.0–13.0 g/l
IgA 0.8–3.0 g/l
IgM 0.4–2.5 g/l
IgE <120 kU/l
Serum β2‐microglobulin <3 mg/l
Cerebrospinal fluid
Opening pressure 50–180 mmH2O
Total protein 0.15–0.45 g/l
Albumin 0.066–0.442 g/l
Chloride 116–122 mmol/l
Glucose 3.3–4.4 mmol/l
Lactate 1–2 mmol/l
Cell count ≤5 mL−1
Differential
Lymphocytes 60–70%
Monocytes 30–50%
Neutrophils None
IgG/ALB ≤0.26
IgG index ≤0.88
Urine
Albumin/creatinine ratio (untimed specimen) <3.5 mg/mmol (males)
<2.5 mg/mmol (females)
Glomerular filtration rate 70–140 mL/min
Normal Values

Total protein <0.2 g/24 hours

322 Albumin <30 mg/24 hours
Calcium 2.5–7.5 mmol/24 hours
Urobilinogen 1.7–5.9 μmol/24 hours
Coproporphyrin <300 nmol/24 hours
Uroporphyrin 6–24 nmol/24 hours
δ‐Aminolevulinate 8–53 μmol/24 hours
5‐Hydroxyindoleacetic acid 10–47 μmol/24 hours
Osmolality 350–1000 mosmol/kg
Faeces
Nitrogen 70–140 mmol/24 hours
Urobilinogen 50–500 μmol/24 hours
Fat (on normal diet) <7 g/24 hours
Answers

Chapter 1 Introduction to pharmacology

1. (d); 2. (c); 3. (b); 4. (c); 5. (b); 6. (b); 7. (d); 8. (a); 9. (c); 10. (b); 11. (c); 12. (a); 13. (d);
14. (c); 15. (c)

Chapter 2 How to use pharmaceutical and prescribing reference

guides
1. (a); 2. (a); 3. (c); 4. (c); 5. (a); 6. (b); 7. (a); 8. (a); 9. (c); 10. (d)

Chapter 3 Legal and Ethical Issues.

1. (b); 2. (c); 3. (c); 4. (a); 5. (d); 6. (d); 7. (a); 8. (c); 9. (c); 10. (a); 11. (d); 12. (d); 13. (d);
14. (d); 15. (d)

Chapter 4 Medicines management and the role of the

Paramedic
1. (a); 2. (c); 3. (c); 4. (b); 5. (b); 6. (a); 7. (a); 8. (b); 9. (c); 10. (b); 11. (b); 12. (a); 13. (c);
14. (a); 15. (b)

Chapter 5 Pharmacodynamics and Pharmacokinetics

1. (a); 2. (d); 3. (c); 4. (b); 5. (a); 6. (d); 7. (b); 8. (d); 9. (a); 10. (a); 11. (c); 12. (a); 13. (a);
14. (c); 15. (a)

Chapter 6 Drug Formulations

1. (b); 2. (b); 3. (d); 4. (b); 5. (d); 6. (c); 7. (d); 8. (c); 9. (a); 10. (c); 11. (d); 12. (c); 13. (a); 14. (c); 15. (a)

Chapter 7 Adverse Drug Reactions

1. (a); 2. (c); 3. (b); 4. (c); 5. (a); 6. (b); 7. (a); 8. (d); 9. (d); 10. (a); 11. (a); 12. (a); 13. (c); 14. (c); 15. (d)

Chapter 8 Analgesics
1. (a); 2. (d); 3. (b); 4. (d); 5. (d); 6. (d); 7. (b); 8. (d); 9. (b); 10. (b); 11. (b); 12. (d); 13. (c); 14. (a); 15. (d)

Chapter 9 Antibacterials
1. (b); 2. (d); 3. (b); 4. (c); 5. (a); 6. (d); 7. (d); 8. (d); 9. (a); 10. (a); 11. (a); 12. (b); 13. (d); 14. (d);
15. (b); 16. (c)

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Answers

Chapter 10 Medications used in the cardiovascular system

324 1. (c); 2. (b); 3. (a); 4. (b); 5. (b); 6. (c); 7. (d); 8. (b); 9. (c); 10. (a); 11. (a); 12. (a); 13. (c); 14. (c);
15. (d)

Chapter 11 Medications used in the renal system

1. (c); 2. (a); 3. (a); 4. (d); 5. (c); 6. (b); 7. (d); 8. (c); 9. (a); 10. (c); 11. (d); 12. (b); 13. (a); 14. (a);
15. (b)

Chapter 12 Medications and diabetes mellitus

1. (a); 2. (d); 3. (a); 4. (b); 5. (c); 6. (b); 7. (c); 8. (a); 9. (a); 10. (b); 11. (a)

Chapter 13 Medications used in the respiratory system

1. (b); 2. (a); 3. (b); 4. (d); 5. (a); 6. (b); 7. (a); 8. (b); 9. (c); 10. (d); 11. (b); 12. (d); 13. (b); 14. (c);
15. (c)

Chapter 14 Medications used in the gastrointestinal system

1. (a); 2. (b); 3. (d); 4. (a); 5. (c); 6. (b); 7. (d); 8. (d); 9. (a); 10. (d); 11. (d); 12. (c); 13. (d); 14. (d);
15. (a)

Chapter 15 Medication and the Nervous System

1. (a); 2. (b); 3. (a); 4. (a); 5. (b); 6. (a); 7. (a); 8. (d); 9. (c); 10. (a); 11. (d); 12. (d); 13. (d); 14. (b);
15. (a)

Chapter 16 Medications used in Mental Health

1. (c); 2. (d); 3. (b); 4. (a); 5. (d); 6. (a); 7. (d); 8. (c); 9. (b); 10. (c); 11. (b); 12. (a); 13. (c); 14. (d); 15. (b)

Chapter 17 Immunisations
1. (a); 2. (c); 3. (d); 4. (a); 5. (a); 6. (c); 7. (b); 8. (a); 9. (b); 10. (b); 11. (c); 12. (c); 13. (d); 14. (d);
15. (b)
Index

ABC approach. See Airway, Breathing, reporting of, 119–121 Angiotensin‐converting enzyme
Circulation (ABC) approach signs and symptoms, 114–117 (ACE) inhibitors, 171, 172, 187
Absorption of drug Yellow Card system, 120, 121 Antagonists, 141–142
active transport, 73–74 AEDs. See Antiepileptic drugs (AEDs) Antibacterials
dosage forms, 72 Agomelatine, 284 aminoglycosides, 159–161
enteral, 74 Airway, Breathing, Circulation (ABC) antimicrobial resistance,
parenteral, 74–76 approach, 225 151–152
passive transport, 74 Akathisia, 288 antimicrobial stewardship, 153
route of administration, 72, 73, 75 AKI. See Acute kidney injury (AKI) beta‐lactams, 153–157
Acarbose, 211 Alcohol‐based hand rub, 12 broad‐and narrow‐spectrum
Acetylcholine, 227, 234, 235, Aldosterone‐sensitive sodium antibiotics, 150
262–263, 289 transporter, 190 chloramphenicol, 158–159
Acetylcholinesterase (AChE) Alpha‐1 receptors antagonists, 193, lincosamides, 162–163
inhibitors, 289, 291 196 macrolides, 161–162
Acetyl‐coenzyme A, 174 Alpha‐glucosidase inhibitors, 211 mechanisms of action, 150–151
AChE inhibitors. See Alprazolam, 286 overview of, 149–150
Acetylcholinesterase (AChE) Alteplase, 272, 273 selective toxicity, 150
inhibitors Alzheimer disease, 289, 291, 292 tetracyclines, 157–158
Acidosis, 217 Aminoglycosides, 151, 159–161 treatment, 151
Acts and laws, medical practice, 39 Aminosalicylates (5‐ASAS) drugs, 255 Antibiotic, 150
Acute asthma exacerbation, 100 Amiodarone, 4 Anticholinergics, 235
Acute coronary syndrome (ACS), AMR. See Antimicrobial resistance Antidepressants, 280–281
173–175 (AMR) activated charcoal, 284
Acute kidney injury (AKI), 183–185 AMS. See Antimicrobial stewardship monoamine oxidase inhibitors,
Acute pulmonary oedema, 233 (AMS) 282–283
Adalimumab, 255–256 Analgesia selective serotonin reuptake
Adenosine 5’‐diphosphate (ADP), amitriptyline, 143 inhibitors, 281–282
174 anticonvulsants, 143 serotonin and noradrenaline
ADHD. See Attention deficit‐ antiepileptics, 143 reuptake inhibitors, 283
hyperactivity disorder (ADHD) inhalation anaesthetics, 136–137 serotonin syndrome, 283–284
ADP. See Adenosine 5’‐diphosphate ketamine, 142 stepped care model, 281
(ADP) local anaesthetics, 143–144 Antidiarrhoeals, 254
Adrenaline, 211, 236 magnesium sulfate, 143 Antiemetics, 245
administration, 94 multimodal analgesia, 132 Antiepileptic drugs (AEDs), 267, 268,
concentrations, 13 nefopam, 143 270
dosing guidance, 119 non‐steroidal anti‐inflammatory Antimicrobial resistance (AMR),
Adults lacking capacity, 41 (NSAID), 133–135 151–152
Adverse drug reactions (ADRs) opioids, 137–140 Antimicrobial stewardship (AMS),
causative medications, 113 paracetamol, 133 153
classification of, 111 Anaphylaxis, 114–115, 312 Antipsychotics, 288–289
description, 110–111 management of, 119 Anxiolytics, 285–286
idiosyncratic reactions, 117 symptoms of, 114 ARBs. See Angiotensin receptor
management, 117–119 Angina, 173 blockers (ARBs)
MHRA, 119–121 Angiotensin receptor blockers Aspirin, 4, 134, 174, 273
patient characteristics, 112–113 (ARBs), 171–172, 187 Asthma, 227–231
prevalence of, 111–112 Angiotensin receptor‐neprilysin Atomoxetine, 292
prevention, 117 inhibitor (ARNI), 172 Atrial fibrillation, 170

Fundamentals of Pharmacology for Paramedics, First Edition. Edited by Ian Peate, Suzanne Evans, and Lisa Clegg.
© 2022 John Wiley & Sons Ltd. Published 2022 by John Wiley & Sons Ltd.
Index

Attention deficit‐hyperactivity acute coronary syndrome, 173–175 Cyclic adenosine monophosphate

disorder (ADHD), 292 hypertension and heart failure, (cAMP), 273
326 Autonomic nervous system, 226–227 168–173 Cystic fibrosis, 234
Azathioprine, 255 side‐effects, antipsychotics, 288
Care Quality Commission (CQC) Dapagliflozin, 210
Bacterial cell wall synthesis, outlines, 53 DAPT. See Dual antiplatelet therapy
disruption of, 151 Case law, 38 (DAPT)
Bacterial DNA synthesis inhibition, CCBs. See Calcium channel blockers DBP. See Diastolic blood pressure
151 (CCBs) (DBP)
Bacterial protein synthesis inhibition, Central alerting system (CAS), 65 DCT. See Distal convoluted tubule
151 Central nervous system (CNS), 262, (DCT)
Bendroflumethiazide, pharmacology 268, 279 Dehydration, 256
of, 191, 194–195 Cephalosporins, 154–155 Dementia, 264–265, 289, 291–292
Benzodiazepines, 285, 286 Chemoreceptor trigger zone (CTZ), Deontological ethics/deontology
Benzylpenicillin, 115 246 approach, 42
Benzylpenicillin sodium (Pen G), 153 Chest pain, 175–176 Depression, 280–281
Beta‐2 adrenergic receptor agonists Chloramphenicol, 151, 158–159 Dexamfetamine, 292
(B2‐agonists), 234–235 Cholinesterase inhibitors, 265–267 Diabetes mellitus (DM), 204
Beta‐adrenoceptor antagonists, Chronic bronchitis, 230 alpha‐glucosidase inhibitors, 211
169–170 Chronic hypertension, 168 blood glucose levels (see blood
Beta‐blockers, 169–170, 286 Chronic kidney disease (CKD), 183 glucose levels (BGL))
Beta‐lactams, 151 anaemia, 185 hyperglycaemia, 216–219
carbapenems, 156–157 blood tests, 186 hypoglycaemia, 211–216
cephalosporins, 154–155 calcium abnormalities, 185 incretin mimetics, 210
penicillins, 153–154 categories, 186 insulin replacement therapy, 207–209
BGL. See Blood glucose level (BGL) definition of, 185 ketones measurement, 207
Bilateral tonic clonic seizures (BTCS), treatment of, 187 metformin, 209
268, 269 Chronic obstructive pulmonary monitoring diseases, 205–207
Biologic medicines, 255–256 disease (COPD), 92–93, 228, SGLT‐2 inhibitors, 210–211
Biotechnological engineering, of 230–231, 234, 237–238 sulfonylureas, 209
vaccines, 303 CKD. See Chronic kidney disease (CKD) thiazolidinediones, 211
Blockers, 245 Clarithromycin, 247 Diabetic ketoacidosis (DKA), 207,
Blood glucose level (BGL), 218 Clindamycin, 162, 163 216–217
hormonal control of, 204–205 Clinical assessment, embed Diamorphine (heroin)
measurement, 206 immunisation history taking in, administration, 141
monitoring, 205–206 309–311 metabolism, 140
Blue Card system, 119 Clinical trial methodology, 302 Diarrhoea, 253
Bolam test, 39 Clostridium difficile, 162 Diastolic blood pressure (DBP), 168
British National Formulary (BNF), 32, Computed tomographic Diazepam, 269–270, 286
46, 59 angiography (CTA), 272 Diffusion, 226
British Society for Immunology, 299 Constipation, 249–251 Dihydropyridine CCBs (DHP‐CCBs),
Broad‐spectrum antibiotics, 150 Consumer Medicines Information 172
Bronchoconstriction (CMI), 3 Distal convoluted tubule (DCT), 191
beta‐2 agonists, 234–235 Continuous positive airway pressure Diuretics, 173, 188–190, 233
epinephrine, 236 (CPAP), 233 loop, 190–193, 233, 236
magnesium sulfate, 236 Control of Substances Hazardous to osmotic, 191
muscarinic receptor antagonists, Health Regulations (COSHH), 66 thiazide, 191, 194–195
235 Cor pulmonale, 230 Docusate sodium, 250
BTCS. See Bilateral tonic clonic Coronary artery disease, 167 Donepezil, 291
seizures (BTCS) Corticosteroids, 237, 255 Donepzil, 265
Buccal midazolam, 268–270 COVID‐19 Dopamine, 262–264
Bulk‐forming laxatives, 249 immunisation, 300 Double crewed ambulance (DCA),
Buspirone, 286 mental health disorders, 279 43, 46
Crohn’s disease, 255 Doxazosin, 193, 196
Calcium channel blockers (CCBs), 172 Croup, 231–232 DPP‐4 inhibitors, 210
Calcium sensitisers, 173 CTA. See Computed tomographic Drug absorption, 94
Capsule formulations, 103 angiography (CTA) Drug distribution
Carbapenems, 156–157 CTZ. See Chemoreceptor trigger zone blood–brain barrier, 76
Carbon dioxide molecules, 226 (CTZ) cardiovascular function, 76
Cardiogenic pulmonary oedema, 233 CVD. See Cardiovascular disease placental barrier, 76–77
Cardiovascular disease (CVD), 167 (CVD) protein binding, 76
Index

Drug excretion process, 79 antiepileptic drugs, 268 gastro‐oesophageal reflux disease,

Drug formulations buccal midazolam, 269 251–254
adrenaline administration, 94 diazepam, 268–269 H1 receptor antagonists, 246 327
dosage differences, 105 PNES vs. BTCS, 268, 269 inflammatory bowel disease, 255–257
enteral formulations, 101–105 rectal diazepam, 269–270 laxatives, 249–250
inhaled formulations, 99–101 Epinephrine, 236 nausea and vomiting, 244–245
intradermal administration, 95–96 EPS. See Extrapyramidal symptoms peptic ulcer, 247–248
intramuscular administration, 93, 95 (EPS) serotonin receptor antagonists,
intraosseous administration, 95 Ertugliflozin, 210 246–247
intrathecal administration, 95 Erythromycin, 161–162 Gastro‐oesophageal reflux disease
intravenous administration, 92 ESRD. See End‐stage renal disease (GORD), 251–252
localised injectables, 97 (ESRD) antidiarrhoeals, 254
long‐acting injectables, 97 estimated glomerular filtration drug interventions, 252
needle insertion angles, 96 (eGFR), 185 paramedic practice, 252–254
parenteral administration, 92 Ethical principles and theories General Medical Council (GMC), 43
rectal formulations, 105 autonomy, 40 Geriatric syndrome, 116
route of administration, 91–92 beneficence, 39 Gestational diabetes mellitus (GDM),
subcutaneous administration, 93 deontological ethics/deontology 204
topical formulations, 97–99 approach, 42 Glibenclamide, 209
Drug‐induced renal damage, 188, 189 fidelity, 41 Gliptins, 210
Drugs informed consent approach, 40 Glitizones. See Thiazolidinediones
actions, 6 justice, 40 Global Approach to Lowering
benzodiazepine class, 7, 10 non‐maleficence, 40 Adverse Cardiac outcomes
bloodstream infections, 12 paternalistic care, 40 Through Improving Contractility
dynamic process, 11–13 utilitarian/consequentialism in Heart Failure (GALACTIC‐HF),
enzymes, 7, 9 theory, 42 173
ion channels, 7, 9 veracity, 41 Glucagon, 204, 205, 211, 214–215
naming and classification, 5, 6 virtue ethics focuses, 42 Glucagon‐like peptide‐1 (GLP‐1)
physiological function using, 6–7 Euglycaemic ketoacidosis, 218 receptor agonists, 210
receptors, 7, 8 European Medicines Agency (EMA), Glucocorticoids, 237
route and timing of 303 Glycaemic Emergencies algorithm,
administration, 13 Excitatory neurotransmitters, 279 30
selectivity of binding, 11 Exemptions Glycated haemoglobin (HbA1c), 205
transport molecules, 9–11 cannula flushing, 57 Glyceryl trinitrate (GTN), 46, 104–105,
Dual antiplatelet therapy (DAPT), 174 prescription‐only medicines, 58 117, 174, 233, 236
Dulaglutide, 210 public and patient consultation, 58 Golimumab, 255–256
Duloxetine, 188, 283 student paramedic, 59 GORD. See Gastro‐oesophageal reflux
Dyskinesia, 262–263 Exenatide, 210 disease (GORD)
Extrapyramidal symptoms (EPS), 288 Guanfacine, 292
E. coli, 150 Ezetimibe, 175
Electroconvulsive therapy (ECT), 39 H1 receptor antagonists, 246
Electrolyte replacement, Face, Legs, Activity, Cry and Haematemesis, 248
hyperglycaemia, 218 Consolability (FLACC) score, 131 Haemodialysis, 183
Electrolytes, 236 Family Law Reform Act, 42 Haemorrhagic strokes, 270
Electronic Medicines Compendium Fibrinolytic therapy, 173 HCPC. See Health and care
(EMC), 33–34 First‐generation antipsychotics, 288 professions council (HCPC)
Empagliflozin, 210 ‘Flight or fight’ response, 226 Health and care professions council
Emphysema, 230–231 Flucloxacillin, 153 (HCPC), 71
Endocrine side‐effects, Fluid replacement, hyperglycaemia, performance and ethics, 19–20
antipsychotics, 288 218 proficiency standard, paramedics,
Endogenous insulin, 207 Flurazepam, 286 20
End‐stage renal disease (ESRD), 183 Folate metabolism, interference in, regulatory bodies, 43–44
Enteral formulations 151 standard conduct, 19–20
capsule formulations, 103 Furosemide, 191, 197 Healthcare professional (HCP), 271
liquid formulations, 103–104 Heart failure
oral (PO) administration, 101, Galantamine, 265, 291 definition of, 168
103–104 Gamma‐aminobutyric acid (GABA), drug therapies, 170
tablets, 101–103 285 first‐line pharmacological
Entocort®, 255 Gastrointestinal (GI) system, 244, 245 therapies for, 168
Enzymes, 7, 9 constipation, 249–251 management of, 168–173
Epilepsy, 267 dopamine receptors, 246 myocardial function in, 169
Index

Heart failure with midrange ejection Immunopathogenic mechanisms, meds tab, 32

fraction (HFmEF), 168, 170 300–301 MIMS prescribing guide, 33
328 Heart failure with preserved ejection Immunosuppressive drugs, 255 NHS ambulance services, 22
fraction (HFpEF), 168, 173 Incretin mimetics, 210 Page for Age section, 26–29
Heart failure with reduced ejection Independent prescribing, 59 Pocket Book, 22, 29–30
fraction (HFrEF), 168–173 Infectious diseases, 300–302 resuscitation section, 24
Helicobacter pylori, 247–248 Inflammatory bowel disease (IBD), specific situations, 25
Herd immunity, 302 255–257 trauma section, 25
HHS. See Hyperosmolar Infliximab, 255–256 update analysis, 22
hyperglycaemia state (HHS) Inhalation therapy, 235
Histamine blockade, 282 Inhalational analgesia Ketones, 207
HMG‐CoA. See 3‐hydroxy‐3‐ methoxyflurane, 136–137 Kussmaul breathing, 217
methylglutaryl‐coenzyme A nitrous oxide, 136
(HMG‐CoA) Inhaled formulations LABA. See Long‐acting beta‐agonists
Homeostasis, 244 acute asthma exacerbation, 100 (LABA)
Horizontal transmission, infectious inhalation, 99 Lactic acidosis, 209
diseases, 301 nebulisation, 100 Lactulose, 249
Host–pathogen–environment Inhibitory neurotransmitters, LAMA. See Long‐acting muscarinic
framework, 301 279–280 antagonists (LAMA)
3‐hydroxy‐3‐methylglutaryl‐ Institute of Safe Medication Practices Laxatives, 249–250
coenzyme A (HMG‐CoA), 174–175 (ISMP), Canada, 2 12‐lead ECG, 175
Hyperglycaemia, 204, 219 Insulin, in blood glucose, 204, 205 electrode placement for, 176–177
diabetic ketoacidosis, 216–217 Insulin replacement therapy Left ventricular ejection fraction
electrolyte replacement, 218 administration, 207 (LVEF), 168
euglycaemic ketoacidosis, 218 adverse effects of, 208–209 Left ventricular end‐diastolic
fluid replacement, 218 preparations, 208 pressure (LVEDP), 168
insulin therapy, 218 Insulin therapy, 218 Left ventricular end‐diastolic volume
Hyperkalaemia, 187 Intercollegiate Stroke Working Party (LVEDV), 168
Hyperosmolar hyperglycaemia state (ISWP), 271–273 Legal and ethical standards, 44–45
(HHS), 216–217 Intranasal medication administration, Legal issues, 37
Hypertension 290 Levodopa, 264
beta‐blocker, 13 Intrarenal disease, characteristics of, Lidocaine patch, 143–144
definition of, 168 183, 184 Limbic‐predominant age‐related
drug therapies, 170 Intravenous (IV) glucose, 214–215 TDP‐43 encephalopathy (LATE),
first‐line pharmacological Ion channels, 7, 9 265
therapies for, 168 Ipratropium, 4 Lincosamides, 151, 162–163
management of, 168–173 Ipratropium bromide, 235 Lipid‐lowering therapies, 174
Hypnotics, 286–287 Lipolysis, 216
Hypocalcaemia, 185 Joint Committee on Vaccination and Liquid formulations
Hypoglycaemia, 208, 209, 215–216, Immunisation, 305 solutions/suspensions, 103
274 Joint Formulary Committee, 151 sublingual and buccal
glucagon, 211, 214–215 Joint Royal Colleges Ambulance formulations, 104
iatrogenic, 212 Liaison Committee (JRCALC) Liquid paraffin, 250
risk of, 212 guidelines, 271–273 Liraglutide, 210
signs and symptoms of, 212–213 administering atropine sulfate, 30 Lisdexamfetamine, 292
Hypokalaemia, 187, 190 administering morphine sulfate, Lithium, 287
Hyponatraemia, 187 30 Localised vs. long‐acting injectable
algorithms tab, 30 formulations, 97
Iatrogenic hypoglycaemia, 212 British National Formulary (BNF), Long‐acting benzodiazepines, 286
IBD. See Inflammatory bowel disease 32 Long‐acting beta‐agonists (LABA),
(IBD) CBRNE situation, 31 234
Imipenem, pharmacokinetics of, 156 dashboard, 31 Long‐acting muscarinic antagonists
Immunisations digital app, 22, 30–32 (LAMA), 235
anaphylaxis, 312 Electronic Medicines Compendium Look‐alike sound‐alike (LASA)
consent, 311 (EMC), 33–34 medications, 5–6
description of, 299–300 general guidance section, 23 Loop diuretics, 190–193, 233, 236
infectious diseases, 300–302 maternity care, 25 Loperamide, 254
paramedics, in, 308–315 medical emergencies section, Loprazolam, 286
public concerns, 303, 306–308 24–25 Lorazepam, 286
vaccines, 302–305 medication section, 26–27 Lormetazepam, 286
Immunological memory, 303 medicines, 26 Lower respiratory tract, 226
Index

Macrogols, 249 anxiolytics, 285–286 epilepsy, 267–270

Macrolides, 151, 161–162 attention deficit‐hyperactivity Parkinson disease and
Magnesium sulfate, 236 disorder, 292 parkinsonism, 262–264 329
Magnetic resonance imaging (MRA), dementia, 289, 291–292 strokes and TIAs, 270–274
272 description of, 278–279 Neurogenic signs and symptoms, of
MAO‐B inhibitors, 264 hypnotics, 286–287 hypoglycaemia, 212
MAOIs. See Monoamine oxidase mood‐stabilising medications, Neuroglycopenic signs and symptoms,
inhibitors (MAOIs) 287–288 of hypoglycaemia, 212, 213
Measles vaccine, 307 neurotransmitters, 279–280 Neuroleptic malignant syndrome,
Mechanical ventilation, 225–226 Mesalazine, 255 289
Medical ethics, 45–46 Metabolic (lactic) acidosis, 209 Neuropathic pain, 130
Medication Metabolism (biotransformation) Neurotransmitters, 267, 279–280
administration of, 12 active/inactive form drugs, 77 NHS Business Services Authority
best practice checklist, 29 first‐order reaction, 78 (NHSBSA) analysis, 55
to children, 14 first‐pass effect, 78 NICE. See National Institute for
concentrations and formulations, hepatic first‐pass effect, 79 Health and Care Excellence
13 zero‐order reaction, 78 (NICE)
contraindication, 4 Metformin, 209 Niemann‐Pick C1‐like 1 (NPC1L1),
errors in helathcare, 2 Methotrexate, 255 175
errors in paramedicine, 2 Methoxyflurane, 99–100, 136–137 Nitrates, 236–237
generic medication, 33 Methylphenidate, 292 Nitrazepam, 286
indication, 4 Metoclopramide, 246 Nitroglycerin, 174
look‐alike sound‐alike (LASA), 5–6 Metronidazole, 247 N‐methyl‐D‐aspartate (NMDA)
multi‐incident analysis, 2 Mezavant®, 255 receptor, 292
paramedics, 34 Micro‐organisms, 150 Non‐cardiogenic pulmonary
student paramedic, 59 Mineralocorticoid receptor antagonists, oedema, 233
tricyclic antidepressant (TCA), 143 172 Non‐dihydropyridine CCBs
Medicines and Healthcare products Minerals, 236 (NDHP‐CCBs), 172
Regulatory Agency (MHRA), Mirtazapine, 284 Non‐steroidal anti‐inflammatory
119–121 Misuse of Drugs Act, 59 drugs (NSAIDs), 248, 287
Medicines management Mixed/premixed insulins, 208 acetic acid derivatives, 135
administration procedure, 60 Monoamine oxidase inhibitors COX and LOX enzymes, 134
Controlled Drugs (CDs), 62 (MAOIs), 282–283 enolic acid derivatives, 135
critical medicines, 62 Monotherapy, 268 proprionic acid derivatives, 135
handling and administration Monthly index of medical specialities salicylates, 134
process, 60–64 (MIMS), 33 selective cox‐2 inhibitors, 135
manufacturing, 54–55 Mood‐stabilising medications, Non‐stimulant medication, ADHD,
marketing, 54–55 287–288 292
optimisation, 64–65 Morphine, 103–104, 118, 122, 139 Non‐traumatic pneumothorax, 233
pregnancy and breast feeding, 63 Mucosal atomiser device (MAD), 290 Noradrenaline, 289
prescribing, 59 Mucous membranes, 226 Norepinephrine, 226
prescription‐only medicine (PoM), Muscarinic receptor antagonists, 235 Nursing and Midwifery Council
54 Muscle tremors, 11 (NMC), 43
principles of, 65 Myocardial infarction (MI), 173
procurement and sale, 54–55 Olsalazine, 255
product licensing (PL) number, 55 Narrow therapeutic index (NTI) Opioids, 118, 122
risks of missed medication, 63 drugs, 85 agonists, 137–138
safety, 65 Narrow‐spectrum antibiotics, 150 codeine, 139
selection, 55 Narrow‐spectrum penicillins, 153 diamorphine, 139, 140
side‐effects, 64 Nasal conchae, 226 fentanyl, 140, 141
special care of older people, 63–64 National Health Service (NHS), 21, 53 morphine, 139
storage and disposal, 66 National Institute for Health and Care pharmacokinetics, 140
supply, 55–59 Excellence (NICE), 54, 271–273, receptor binding, 83
Memantine, 265, 292 287 side‐effects, 138
Mental Capacity Act (MCA), 41, 42, 46 guidelines, 21, 153 terminology, 138
Mental health disorders (MHD) Needle insertion angles, 96 Osmotic diuretics, 191
acute behavioural disturbance, Nephron, diuretics in, 190 Osmotic laxatives, 249
289 Nephrotoxic drugs, 184, 188 Oxygen
antidepressants (see Nervous system (NS), 262 devices, 238–239
Antidepressants) cholinesterase inhibitors, 266–267 molecules, 226
antipsychotics, 288–289 dementia, 264–265 therapy, 233
Index

Pain affinity, 82 Primary percutaneous coronary

abnormal pain syndromes, 129 agonist, 82–83 intervention (PPCI), 173
330 assessment of, 131–132 antagonists, 83 Primary spontaneous pneumothorax
categorisation of, 130 clinical considerations, 84 (PSP), 233
definition of, 125 drug administration, 83 Programmes of education and
FLACC score, 131 drug potency and efficacy, 84, 85 training, 71
modulation, 128–129 medication receptors, 81 Prokinetic drugs, 252
non‐pharmacological interventions, medication response, 86 Promotility drugs, 252
126 opiate overdose, 84 Proprotein convertase subtilisin/
pain matrix, 128 opioid by receptor binding, 83 kexin type‐9 (PCSK9) inhibitors,
physiological manifestations, 127 pregnant/lactating patients, 86 175
physiological response, 126 therapeutic index, 84–85 Proton pump inhibitor (PPI), 247, 252
physiology of, 127 Pharmacokinetics Proximal convoluted tubule (PCT),
transmission, 127–128 absorption process, 72–76 210
to treat, 126 aminoglycosides, 159 Psychogenic non‐epileptic seizures
TWEED SASH mnemonic, 126 benzylpenicillin sodium, 153 (PNES), 268, 269
types of, 129–130 cephalosporins, 155 PTSD. See Post‐traumatic stress
Para‐aminobenzoic acid (PABA), 151 chloramphenicol, 158 disorder (PTSD)
Paracetamol, 105, 133 clindamycin, 162 Public Health England, 311
Paramedics, 2, 21, 33, 44, 252–254, distribution process, 76–77 Pulmonary oedema, 233
307 drug administration, 71 P2Y12 receptor inhibitor
administer medications, 71 elimination process, 79 monotherapy, 174
Controlled Drugs, 66 erythromycin, 161
education and training half‐life of medication, 80 Quinolones, 151
programmes, 71 imipenem, 156
effective and safe medicines metabolism, 77–79 RAAS. See Renin‐angiotensin‐
management, 53 opioids, 140 aldosterone system (RAAS)
exemptions, 59 of paracetamol, 80 Rashes and skin eruptions, 115, 116
in health promotion and stages of, 71, 72 Reboxetine, 283
immunisation, 308–315 steady state, 80 Receptors, 7, 8
patient group direction (PGD), 57 termination of action, 81 Recognition of Stroke in the
Parasympathetic nervous systems tetracycline, 157 Emergency room (ROSIER), 271
(PNS), 226, 234 therapeutic range, 81 Rectal diazepam, 269–270
Parathyroid hormone secretion, 185 Pharmacology Rectal formulations, 105
Parliamentary Office of Science and ethical principles and theories, Renal disorders, 115
Technology, 150 39–43 Renal system, 183
Paternalistic care, 40 laws, 38–39 acute kidney injury, 183–185
Pathogens, 150 medication (see medication) chronic kidney disease, 185–187
Patient group direction (PGD), 309, regulatory bodies, 43–44 diuretics, 188–190
310 Plasminogen, 173, 272 drug‐induced renal damage, 188,
legal categories of medicines, 57 PNES. See Psychogenic non‐epileptic 189
paramedics, 57 seizures (PNES) electrolyte abnormalities, 187
unlicensed medicines, 57 Pneumonia, 232 kidneys and sequelae of, 183
Patient information leaflet (PIL), 3, 34 Pneumothorax, 232–233 loop diuretics, 190–193
Patient safety incident (PSI), 65 PNS. See Parasympathetic nervous osmotic diuretics, 191
Patient‐specific direction (PSD), 56, systems (PNS) pre‐renal, intrarenal and postrenal
309, 310 Pocket Book, 22, 29–30 disease characteristics, 184
Peak flow meter, 229 Postrenal disease, characteristics of, thiazide diuretics, 191, 194–195
Penicillins, 153–154 183, 184 urinary retention and
Pentasa®, 255 Post‐traumatic stress disorder (PTSD), incontinence, 187–188, 193,
Peptic ulcer, 247 279 195, 196
Helicobacter pylori, 247–248 PPI. See Proton pump inhibitor (PPI) Renin‐angiotensin‐aldosterone
NSAIDs, 248 Prednisolone, 255 system (RAAS), 171
symptoms of, 248 Pregabalin, 285 Renoprotective agents, 187
Peptidoglycan, 151 Premixed insulins, 208 Research ethics committees (RECs),
Peripheral nervous system (PNS), 262 Pre‐renal disease, characteristics of, 45
Peritoneal dialysis, 183 183, 184 Respiratory system, 225
PGD. See Patient group direction Prescription‐only medicine (PoM), 54 anatomy and physiology, 225–226
(PGD) Pressure gradient, 226 asthma, 227–230
Pharmacodynamics Pressure of carbon dioxide (PCO2), autonomic nervous system,
adverse drug reaction, 85, 87 226 226–227
Index

bronchoconstriction, 234–236 SNS. See Sympathetic nervous T1DM. See Type 1 diabetes mellitus
chronic obstructive pulmonary system (SNS) (T1DM)
disease, 230–231 Sodium valproate, 287–288 T2DM. See Type 2 diabetes mellitus 331
croup, 231–232 Sodium‐glucose cotransporter‐2 (T2DM)
loop diuretics, 236 (SGLT‐2) inhibitors, 210–211 TDP‐43 protein, 265
medical gases, 238 Sodium–potassium–chloride Temazepam, 286
nitrates, 236–237 (Na–K–Cl) cotransporter, 190 Tension pneumothorax, 232–233
oxygen devices, 238–239 Softener laxatives, 249, 250 Tetanus vaccine, 307
pneumonia, 232 SSP. See Secondary spontaneous Tetracyclines, 151, 157–158
pneumothorax, 232–233 pneumothorax (SSP) Thiazide diuretics, 191, 194–195
pulmonary oedema, 233 SSRIs. See Selective serotonin Thiazolidinediones, 211
steroids, 237 reuptake inhibitors (SSRIs) Thrombectomy, 272
‘Rest and digest’ response, 226 Standard and New Antiepileptic Thrombin, 173
Risk minimisation materials (RMMs), Drugs (SANAD), 268 Thrombolysis, 272
34 Statin therapy, 174–175 Thrombophlebitis, 214
Rivastigmine, 265, 291 Status asthmaticus, 228 TIAs. See Transient ischaemic attacks
ROSIER. See Recognition of Stroke in Statute law/Act of Parliament, 38 (TIAs)
the Emergency room (ROSIER) Stepped care model, 281 Tissue plasminogen activator (t‐PA),
Steroids, 232, 237, 255 173
SABA. See Short‐acting beta‐agonists Stimulant laxatives, 249–250 Tofacitinib, 255
(SABA) Stimulants, ADHD, 292 Topical formulations
Sacubitril, 172 Streptokinase, 272 beta‐blockers, 98
Safe administration of medicines, 3 Strokes medications, 98
Salbutamol, 11 assessment of, 271–272 nasal drugs, 98
Salicylates, 273 definition of, 271 ocular drugs, 97
SAMA. See Short‐acting muscarinic haemorrhagic, 270 otic drugs, 98
antagonists (SAMA) hypoglycaemia, 274 transdermal administration, 98–99
Saxagliptin, 210 risk factors, 271 vaginal formulations, 99
Scottish Intercollegiate Guidelines treatment, 272–273 Transient ischaemic attacks (TIAs)
Network (SIGN), 54 ST‐segment elevation myocardial assessment of, 271–272
Secondary spontaneous infarction (STEMI), 173 definition of, 271
pneumothorax (SSP), 233 Students of paramedicine, 3 haemorrhagic, 270
Second‐generation antipsychotics, Subarachnoid haemorrhage (SAH), hypoglycaemia, 274
288 270 risk factors, 271
Selective serotonin reuptake Sulfasalazine, 255 treatment, 272–273
inhibitors (SSRIs), 281–282 Sulfonamides, 151 Traumatic pneumothorax, 232
Selective toxicity, of antimicrobial, Sulfonylureas, 209 Tricyclic antidepressants (TCAs), 143,
150 Summaries of product characteristics 282, 291
Sensory nerve fibres, 128 (SmPCs), 34 Trimethoprim, 151
Serotonin and noradrenaline Supplementary prescribing, 59 Type 1 diabetes mellitus (T1DM), 204,
reuptake inhibitors (SNRIs), 283 Supply medicines management 212
Serotonin (5‐HT3) receptor exemptions, 57–59 Type 2 diabetes mellitus (T2DM), 204,
antagonists, 246–247 patient group direction (PGD), 207, 212
Serotonin syndrome, 283–284, 289 56–57 Tyramine, levels of, 283
Serum sickness, 115, 116 patient‐specific directions (PSD), 56
SGLT‐2 inhibitors. See Sodium‐ prescriptions, 56 UK immunisation schedule, 306
glucose cotransporter‐2 Sympathetic nervous system (SNS), Ulcerative colitis, 255
(SGLT‐2) inhibitors 226 Upper respiratory tract, 226
Shared decision‐making approach, Sympathomimetics, 236 Urea and electrolytes (U&E), 185, 187
40 Systolic blood pressure (SBP), 168 Urinary retention and incontinence,
Short‐acting benzodiazepines, 286 187–188
Short‐acting beta‐agonists (SABA), Tablets drugs used to treat, 193, 195, 196
234, 235 chewable, 103 Utilitarian/consequentialism theory, 42
Short‐acting muscarinic antagonists controlled‐release formulations, 102
(SAMA), 235 dispersible, 102 Vaccines
Simple pneumothorax, 232 enteric coated, 102 acceptability and uptake of, 303,
Sitagliptin, 210 immediate‐release medications, 306–308
16–17 year olds lacking capacity, 42 101 design, 302–305
SNRIs. See Serotonin and Tamsulosin, 193, 196 hesitancy, 307–308
noradrenaline reuptake TCAs. See Tricyclic antidepressants production methods, 303
inhibitors (SNRIs) (TCAs) vaccination care, 312–314
Index

Valsartan, 172 Vortioxetine, 284 World Health Organization (WHO),

Vasodilators, 4 151, 152, 228, 271
332 Vedolizumab, 255–256 Wilderness Medical Society
Venlafaxine, 283 practice guidelines, Yellow Card system, 120, 121
Vertical transmission, infectious 142
diseases, 301 Withdrawal/discontinuation Zolpidem, 287
Vildagliptin, 210 syndrome, 281, 282 Zopiclone, 287
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