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Clinical Pharmacology
for Prescribing
Clinical Pharmacology
for Prescribing

Dr Stevan R. Emmett, MBChB, BSc,

DPM, DPhil (Oxon), MRSB, MFPM
Principal Medical Officer, Defence Science and Technology Laboratories
Consultant Pharmaceutical Physician
Clinical Fellow in Emergency Medicine, Royal United Hospitals NHS Foundation Trust
Senior Research Fellow, Medical School, University of Bristol

Nicola L. Hill, BPharm, PgDip, MSc

Pharmacy Team Leader Portsmouth Hospitals NHS Trust

Dr Federico Dajas-​Bailador, PhD, BSc

Assistant Professor, Faculty of Medicine & Health Sciences,
School of Life Sciences, University of Nottingham

1
 1
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
Oxford University Press is a department of the University of Oxford.
It furthers the University’s objective of excellence in research, scholarship,
and education by publishing worldwide. Oxford is a registered trade mark of
Oxford University Press in the UK and in certain other countries
© Oxford University Press 2020
The moral rights of the authors have been asserted
First Edition published in 2020
Impression: 1
All rights reserved. No part of this publication may be reproduced, stored in
a retrieval system, or transmitted, in any form or by any means, without the
prior permission in writing of Oxford University Press, or as expressly permitted
by law, by licence or under terms agreed with the appropriate reprographics
rights organization. Enquiries concerning reproduction outside the scope of the
above should be sent to the Rights Department, Oxford University Press, at the
address above
You must not circulate this work in any other form
and you must impose this same condition on any acquirer
Published in the United States of America by Oxford University Press
198 Madison Avenue, New York, NY 10016, United States of America
British Library Cataloguing in Publication Data
Data available
Library of Congress Control Number: 2019941441
ISBN 978–​0–​19–​969493–​8
Printed and bound by
CPI Group (UK) Ltd, Croydon, CR0 4YY
Oxford University Press makes no representation, express or implied, that the
drug dosages in this book are correct. Readers must therefore always check
the product information and clinical procedures with the most up-​to-​date
published product information and data sheets provided by the manufacturers
and the most recent codes of conduct and safety regulations. The authors and
the publishers do not accept responsibility or legal liability for any errors in the
text or for the misuse or misapplication of material in this work. Except where
otherwise stated, drug dosages and recommendations are for the non-​pregnant
adult who is not breast-​feeding
Links to third party websites are provided by Oxford in good faith and
for information only. Oxford disclaims any responsibility for the materials
contained in any third party website referenced in this work.
Illustrator

Dr Nick Love, PhD

Post-Sophomore Pathology Fellow
Stanford University School of Medicine
Acknowledgements

The authors would like to thank OUP for believing in the its original conception. Steve also wishes to express his
concept of this book from a very early stage, and for their sincere thanks to co-​authors Nicky and Fed for their be-
continued support and enthusiasm in the editorial team lief in this book and without whom it would have never
through the years it has taken to turn it into a reality. We progressed.
are also highly indebted to all those people that have con- Nicola Hill would like to thank her husband, Martin, and
tributed to the creation of this book and have freely given their two children, Ethan and Isla, for their continued sup-
their time, effort, and knowledge to ensure its contents are port and patience during the writing of this book.
relevant and up to date for the modern prescriber. Federico Dajas-​Bailador would like to thank the con-
Steve Emmett is immeasurably appreciative of his stant support and understanding of his wife, Virginia,
wife, Kelly, and sons, Arthur and Albie, for their patience, and their two children, Maia and Sienna, during the long
understanding, and unswerving love and support over process of researching and writing the many chapters of
the long period of time it has taken to write this text from this book.
Contents

How to interpret the figures x

Abbreviations xi
Contributors xvii
Publisher’s acknowledgement xviii
Advisers xix

Chapter 1 Principles of clinical pharmacology

1.1 Principles of clinical pharmacology 3

Chapter 2 Cardiovascular medicine

2.1 Hypertension 43
2.2 Peripheral vascular disease 58
2.3 Dyslipidaemias 66
2.4 Stable angina 77
2.5 Acute coronary syndrome 90
2.6 Heart failure 102
2.7 Arrhythmias 115
2.8 Venous thromboembolism 132

Chapter 3 Respiratory Medicine

3.1 Asthma 143

3.2 Chronic obstructive pulmonary disease 157

Chapter 4 Endocrinology

4.1 The pituitary gland 167

4.2 The adrenal gland 182
4.3 Thyroid disease 195
4.4 Parathyroid disease 202
4.5 Diabetes mellitus 207
4.6 Female reproduction (abnormal menstruation, contraception,
assisted reproduction) 222
4.7 Androgens, anti-androgens, and anabolic steroids 235

Chapter 5 Renal medicine

5.1 The kidney, drugs, and chronic kidney disease 245

5.2 Acute kidney injury 262
viii Contents

5.3 Disorders of micturition 270

5.4 Erectile dysfunction 279

Chapter 6 Gastroenterology

6.1 Nausea and vomiting 287

6.2 Dyspepsia (peptic ulceration and gastro-​oesophageal reflux disease) 299
6.3 Diarrhoea 309
6.4 Constipation 316
6.5 Irritable bowel syndrome 326
6.6 Inflammatory bowel disease (ulcerative colitis and Crohn’s Disease) 334
6.7 Liver disease 350

Chapter 7 Musculoskeletal medicine

7.1 Osteoarthritis 369

7.2 Inflammatory arthropathies 378
7.3 Gout and hyperuricaemia 390
7.4 Metabolic bone disease (Paget’s, osteoporosis) 397

Chapter 8 Anaesthetics

8.1 General anaesthetics and neuromuscular blockade 409

8.2 Local anaesthetics 424
8.3 Analgesia and pain management 432

Chapter 9 Neurology

9.1 Cerebrovascular disease 449

9.2 Epilepsy (including status epilepticus) 458
9.3 Parkinsonism 477
9.4 Dementia and Alzheimer’s disease 489
9.5 Multiple sclerosis 495
9.6 Myasthenia gravis 504

Chapter 10 Psychiatry

10.1 Anxiety 513

10.2 Depression 523
10.3 Schizophrenia and psychosis 538
10.4 Drug abuse, addiction, and dependence (alcohol, nicotine, opioids) 550

Chapter 11 Infectious disease

11.1 Bacterial infection 559

11.2 Fungal infections 583
11.3 Viral infection 597
11.4 Protozoal and helminth infections 613
 Contents ix

Chapter 12 Non-​malignant haematology and allergy

12.1 Anaemia 627

12.2 Haemoglobinopathies 639
12.3 Allergy 648

Chapter 13 Haemato-​oncology and malignancy

13.1 Haemato-​oncology and malignancy 657

Index 705
How to interpret the figures

Compound X Compound X Y Compound X Z

Figure 0.1 Drugs/​ Figure 0.2 Inhibition/​antagonism Figure 0.3 Activation/​agonism is

pharmaceutical compounds is indicated by a flat ‘hammer’, e.g. indicated by an arrow, e.g. compound X
indicated in light blue ovals. compound X inhibits Y. activates Z.

M1 Enzyme W M2
L1 Receptor H Process G

Figure 0.5 Chemical reactions can also be indicated

Figure 0.4 Molecular interactions, e.g. L1 activates receptor by arrows, e.g. M1 is converted to M2 by enzyme W.
H, whose activity in turn antagonizes process G.

Fats atherosclerosis NO vasodilation vasoconstriction

Figure 0.6 Pathological interactions are Figure 0.7 Therapeutic, antipathophysiological interactions
indicated in dark blue, e.g. fats contribute to or mediators are indicated in light blue, e.g. nitric oxide (NO)
atherosclerosis. inhibits vasoconstriction via vasodilation.

vascular α2-adreno-
5-HT2 naftidrofuryl α2-adreno- receptors
5-HT receptor oxalate receptors agonists
postganglionic
fibres
adrenergic
vasoconstriction
PI3 Phospholipase C PIP2 signalling
by

Ca2+ vasoconstriction noradrenaline sympathetic CNS

Figure 0.9 Example 2: sympathetic CNS outflow causes

Figure 0.8 Example 1: 5-​HT activates the 5-​HT2 receptor, noradreline secretion from sympathetic post-​ganglionic
which then activates phospholipase C, an enzyme that fibres, inducing adrenergic signalling pathways and
catalyses the conversion of PIP2 to PI3. The PI3 molecule thus vasoconstriction. Vascular α2-​adrenoreceptors
then functions to increase intracellular Ca2+, which inhibit sympathetic noradrenaline activity, and thus,
induces vasoconstriction. The drug naftidrofuryl oxalate agonists cause a reduction in sympathetic outflow to the
inhibits 5-​HT2 receptor function, and thereby reduces peripheral vasculature and reduce vasoconstriction.
pathological vasoconstriction.
Abbreviations

6-​CIT six-​item cognitive impairment test APoE apolipoprotein E

6-​MP 6-​mercaptopurine APP amyloid precursor protein
6-​TGN 6-​thioguanine nucleotides AR androgen receptors
AA arachidonic acid ARB angiotensin II receptor blocker
AAS anabolic-​androgenic steroids ARF acute renal failure
ABPA allergic bronchopulmonary aspergillosis ARNI angiotensin II receptor neprilysin inhibitor
ABPM ambulatory ARS anticholinergic risk scores
ABVD adriamycin (doxorubicin), bleomycin, ARV antiretroviral drug
vinblastine dacarbazine AS ankylosing spondylitis
ACE angiotensin-​converting enzyme AT antithrombin
ACh acetylcholine ATN acute tubular necrosis
AChE acetylcholinesterase ATP adenosine triphosphate
ACPA anti-​citrullinated protein antibodies AUDIT Alcohol Use Disorders Identification Test
ACS acute coronary syndrome AV atrioventricular
ACT activated clotting time AVN atrial ventricular node
ACTH adrenocorticotropic hormone AVP arginine vasopressin
AD anti-​arrhythmic drugs AZA azathioprine
ADCC antibody-​dependent cell-​mediated BD twice daily
cytotoxicity Bcl-2 B-cell lymphoma 2
ADH antidiuretic hormone BDNF brain-​derived neurotrophic factor
ADME absorption, distribution, metabolism, and BDP beclomethasone
excretion BEACOPP bleomycin, etoposide, adriamycin
ADP adenosine diphosphate (doxorubicin), cyclophosphamide, oncovin
ADR adrenal receptor (vincristine), procarbazine, prednisolone
AED anti-​epileptic drugs BMD bone mineral density
AIH autoimmune hepatitis BNF British National Formulary
AIHA autoimmune haemolytic anaemia BP blood pressure
AIS androgen insensitivity syndrome BPH benign prostatic hyperplasia
AIT autoimmune thyroiditis BSA body surface area
AKI acute kidney injury CABG coronary artery bypass graft
ALD Alzheimer’s disease CAH congenital adrenal hyperplasia
ALF acute liver failure CAIS complete androgen insensitivity syndrome
ALL acute lymphoblastic leukaemia cAMP cyclic adenosine monophosphate
ALP alkaline phosphatase CaR Ca2+ receptor
ALPD acute laryngopharyngeal dysthaesia cART combination antiretroviral therapy
AML acute myeloid leukaemia CaSR Ca2+-​sensing receptor
AMP adenosine monophosphate CBT cognitive behavioural therapy
AMPK AMP-​activated protein kinase CCB calcium channel blockers
ANP atrial natriuretic peptide CCF congestive cardiac failure
AP activator protein CD controlled drug
APC antigen-​presenting cells CDMS clinically definite multiple sclerosis
xii Abbreviations

CFTR cystic fibrosis transmembrane conductance DIT diiodotyrosine

regulator DKA diabetic ketoacidosis
cGMP guanosine 3',5'-​cyclic monophosphate DLB dementia with Lewy bodies
ChAT choline acetyltransferase DLBCL diffuse large B cell lymphoma
ChIVPP chlorambucil, vinblastine, procarbazine, DM diabetes mellitus
prednisolone DM1 type 1 diabetes mellitus
CINV chemotherapy-​induced nausea and DM2 type 2 diabetes mellitus
vomiting DMARD disease-​modifying anti-​rheumatic drug
CIS clinically isolated syndrome DMT disease-​modifying therapies
CLL chronic lymphocytic leukaemia DOPA 3,4-​dihydroxyphenylalanine
CML chronic myeloid leukaemia DR drug–​receptor interaction
CMV cytomegalovirus DRESS drug rash eosinophilia systemic symptoms
CNS central nervous system DVT deep vein thrombosis
COMT catechol-​O-​methyltransferase DXA dual-​energy X-​ray absorptiometry
COPD chronic obstructive pulmonary disease EAE autoimmune encephalomyelitis
COPDAC cyclophosphamide, Oncovin® (vincristine), EBV Epstein–​Barr virus
prednisolone, dacarbazine EC50 half maximal effective concentration
COPP cyclophosphamide, Oncovin® (vincristine), ECG electrocardiogram
procarbazine, prednisolone ECT electroconvulsive therapy
COX1 cyclo-​oxygenase 1 ED erectile dysfunction
CPAP continuous positive airway pressure EDRF endothelium-​derived relaxing factor
CPE carbapenemase-​producing EEG electroencephalogram
Enterobacteriaceae EF ejection fraction
CK creatine kinase EGFR vascular endothelial growth factor
CD Crohn’s disease EH essential hypertension
CREB cAMP response element-​binding protein EMA European Medicines Agency
CRF corticotrophin-​releasing factor EMT epithelial–​mesenchymal transition
CRH corticotrophin-​releasing hormone EPC endothelial progenitor cell
CRP C-​reactive protein EPO erythropoietin
CRPS complex regional pain syndrome EPS extrapyramidal side effects
CSF cerebrospinal fluid ER oestrogen
CT computed tomography ESA erythropoietin-​stimulating agents
CTPA computed tomography pulmonary ESBL extended-​spectrum beta-​lactamases
angiogram ESR erythrocyte sedimentation rate
CTZ chemoreceptor trigger zone ESRD end-​stage renal disease
CVD cardiovascular disease EWS early warning scores
CXR chest X-​ray FBC full blood count
D drug FcεRI high affinity immunoglobulin E receptor
DA dopamine FDA Food and Drug Administration
DAA direct-​acting antivirals FGA first-​generation antipsychotics
DAG diacylglycerol FH familial hypercholesterolaemia
DAT direct antiglobulin test FSH follicle-​stimulating hormone
DBP diastolic blood pressure FVII factor VII
DCT distal convoluted tubule GA glatiramer acetate
DGH district general hospital GABA gamma-​amino-​butyric acid
DHF dihydrofolate GAD generalized anxiety disorder
DHT 5α-​dihydrotestosterone GDP guanosine diphosphate
DI diabetes insipidus GF growth factor
 Abbreviations xiii

GFR glomerular filtration rate IDO idiopathic detrusor overactivity

GHR growth hormone receptor IFIS intra-​operative floppy iris syndrome
GI gastrointestinal IFNAR interferon-​ α/​β receptor
GLP-​1 glucagon-​like peptide 1 IFRT involved field radiotherapy
GLP-​1R glucagon-like peptide 1 receptor IGE idiopathic generalized epilepsy
GLUT glucose transporters IGF-​1 insulin-​like growth factor
GMC General Medical Council IL interleukins
GM-​CSF granulocyte-​macrophage ILAE International League Against Epilepsy
colony-​stimulating factor IM intramuscular
GnRH gonadotropin-​releasing hormone IMP investigational medicinal products
GORD gastro-​oesophageal reflux disease INI integrase inhibitor
GPhC General Pharmaceutical Council INR international normalized ratio
GR glucocorticoid receptor IRIS immune reconstitution inflammatory
GTC generalized tonic–​clonic seizure syndrome
GTN glyceryl trinitrate IRS insulin receptor substrate
GTP guanosine triphosphate IT intrathecal chemotherapy
GWAS genome-​wide association studies ITP idiopathic thrombocytopenic purpura
HAART highly active anti-​retroviral therapy ITU intensive treatment unit
HAE hereditary angioedema IUD intrauterine device
HAV hepatitis A virus IV intravenous
HBeAg hepatitis B surface antigen JC juxtaglomerular cells
HBPM home blood pressure monitoring JVP jugular venous pressure
HBV hepatitis B virus K equilibrium dissociation constant
HCC hepatocellular carcinoma L ligand
HCV hepatitis C virus LABA long-​acting β2 agonist
HDL-​C high-​density lipoprotein cholesterol LAMA long-​acting muscarinic antagonist
HDU high dependency unit LBBB left bundle branch block
HE hepatic encephalopathy LC locus coeruleus
HF heart failure LDH lactate dehydrogenase
HFpEF heart failure preserved ejection fraction LDL low-​density lipoprotein
HFrEF heart failure reduced ejection fraction LDL-​C low-​density lipoprotein cholesterol
HHV human herpes virus LFT liver function test
HPA hypothalamic–​pituitary axis LH luteinizing hormone
HRT hormone replacement therapy LHRH luteinizing hormone-​releasing hormone
HTN hypertension LMWH low molecular weight heparin
HUS haemolytic uraemic syndrome LNA locked nucleic acid
IA intrinsic activity LRP5 lipoprotein receptor-​related protein 5
IBD inflammatory bowel disease LTOT long-​term oxygen therapy
IBS irritable bowel syndrome LV left ventricular
IBS-​C IBS constipation-​predominant LVEF left ventricular ejection fraction
IBS-​D IBS diarrhoea-​predominant LVF left ventricular failure
IC50 inhibitory concentration MAC minimum alveolar concentration
ICAM-​1 intercellular adhesion molecule 1 MACE amsacrine, cytarabine, and etoposide
ICD impulse control disorder MAHA microangiopathic haemolytic anaemias
ICD-​10 International Classification of Diseases-​10 MALT mucosa-​associated lymphoid tissue
ICH Intracerebral haemorrhage MAOA monoamine oxidase A
ICS inhaled corticosteroid MAOB monoamine oxidase B
IDL intermediate density lipoproteins MAOI monoamine oxidase inhibitors
xiv Abbreviations

MAP mean arterial pressure NNRTI non-nucleoside reverse transcriptase

MAPK mitogen-​activated protein kinase inhibitor
MBP myelin basic protein NNT number needed to treat
mCRC metastatic colorectal cancer NO nitric oxide
MDD major depressive disorder NOAC novel oral anti-​coagulants
MDI metered dose inhaler NOS nitric oxide synthase
MDRD Modification of Diet in Renal Disease NPC National Prescribing Centre
MET mesenchymal–​epithelial transition NPC1L1 Niemann–​Pick C1-​like
MGUS monoclonal gammopathy of unknown N-​REM non-​rapid eye movement
significance NRI NA re-​uptake transporter
MHC major histocompatibility complex NRT Nicotine replacement therapy
MHRA Medicines and Healthcare products NSAID non-​steroidal anti-​inflammatory drugs
Regulatory Agency NSTEMI non-​ST-​elevation myocardial infarction
MI myocardial infarction NYHA New York Heart Association
MIMs Monthly Index of Medical Specialities OA osteoarthritis
MIT monoiodotyrosine OAB overactive bladder syndrome
MMP matrix metalloproteinases OCD obsessive compulsive disorder
MMR measles, mumps, rubella vaccine OD once daily
MMSE Mini Mental State Examination ODV O-​desmethylvenlafaxine
MMX multi-​matrix OEPA Oncovin® (vincristine), etoposide,
MoCA Montreal Cognitive Assessment prednisolone, adriamycin (doxorubicin)
MODY maturity onset diabetes of the young OP osteoporosis
MPTP 1-m
​ ethyl-4
​ -p​ henyl-1​ ,2,3,6-t​ etrahydropyridine OPAT outpatient parenteral antibiotic therapy
MR magnetic resonance OR oestrogen receptor
MRSA meticillin-​resistant Staphylococcus aureus ORS oral rehydration salts
MS multiple sclerosis ORT oral rehydration therapy
MSU midstream specimen of urine PAAP personalized asthma action plan
MTHFR methylenetetrahydrofolate reductase PADH post-​artesunate delayed haemolysis
NA noradrenergic PAF paroxysmal atrial fibrillation
NA nucleoside analogue PAIS partially androgen insensitivity syndrome
NAc nucleus accumbens pANCA perinuclear anti-​neutrophil cytoplasmic
NANC non-​adrenergic-​non-​cholinergic antibodies
NaSSA noradrenaline specific serotonin agonists PASD peripheral artery disease
NCE new chemical entities PBC primary biliary cirrhosis
NDO neurogenic detrusor overactivity PBP penicillin-​binding proteins
NF nuclear factor PCA patient-​controlled analgesia
NFAT nuclear factor of activated T cells PCI percutaneous coronary intervention
NG nasogastric PCL plasma cell leukaemia
NGF nerve growth factors PCOS polycystic ovary syndrome
NGS next-​generation sequencing PJP pneumocystis jiroveci pneumonia
NICE National Institute for Health and PCT proximal convoluted tubule
Care Excellence PD Parkinson’s disease
NIV non-​invasive ventilation PDA patent ductus arteriosis
NMAA nitrogen mustard alkylating agents PDB Pagets disease of bone
NMC Nursing and Midwifery Council PDD Parkinson’s disease dementia
NMDA N-​methyl-​D-​asparate PDE phosphodiesterase
NMJ neuromuscular junction PDE5 phosphodiesterase type 5
NMS neuroleptic malignant syndrome PDGF platelet-​derived growth factor
 Abbreviations xv

PE pulmonary embolism RPLS reversible posterior leukoencephalopathy

PEF peak expiratory flow syndrome
PEP post-​exposure prophylaxis RRT renal replacement therapy
PET positron emission tomography RSI rapid sequence induction
PFC prefrontal cortex RSV respiratory syncitial virus
PG prostaglandins RVF right ventricular failure
PGE prostaglandin E SA sinoatrial
PHE Public Health England SABA short-​acting β2-​adrenoceptor agonist
PI protease inhibitor SAH subarachnoid haemorrhage
Pi3-​k phosphatidylinositol 3-​kinase SAMA short-​acting muscarinic antagonist
PIC pre-​integration complex SAN sino-​atrial node
PIL patient information leaflet SARI serotonin antagonist and reuptake inhibitor
PKA protein kinase A SBP systolic blood pressure
PKC protein kinase C SC subcutaneous
PLC phospholipase C SCD sickle cell anaemia
PML progressive multifocal leukoencephalopathy SCID severe combined immunodeficiency
PNH paroxysmal nocturnal haemoglobinuria syndrome
PONV post-​operative nausea and vomiting SCN suprachiasmatic nucleus
PORC post-​operative residual curarization SERM selective oestrogen receptor modulator
PP paraprotein SERT 5-​HT uptake transporter
PPAR-​α peroxisome proliferator activated SGA second-​generation antipsychotics
receptor alpha SGLT sodium-​glucose co-​transporter
PPI proton pump inhibitor SHBG sex-​hormone-​binding globulin
PPRE peroxisome proliferator response elements SIADH syndrome of inappropriate anti-​diuretic
PR progesterone receptor hormone
PrEP pre-​exposure prophylaxis SLE systemic lupus erythematosus
PRH prolactin hormone SMM smouldering myeloma
PSA prostate specific antigen SN substantia nigra
PSC primary sclerosing cholangitis SNc substantia nigra pars compacta
PT prothrombin time SNRI Serotonin-​noradrenaline reuptake inhibitors
PTH parathyroid hormone SORM selective oestrogen-​receptor modulator
PTP phosphotyrosine phosphatase SOS sinusoidal obstruction syndrome
PTSD post-​traumatic stress disorder SPC summary of product characteristics
PV pharmacovigilance SPECT single-​photon emission computed
PVD peripheral vascular disease tomography
PVL panton-​valentine leucocidin SPRM Selective progesterone receptor modulator
QALY quality-​adjusted life-​year SRI serotonin re-​uptake inhibitor
R receptor SSA somatostatin analogues
RA rheumatoid arthritis SSRI selective serotonin reuptake inhibitor
RANKL receptor activator of nuclear factor STEMI ST-​elevation myocardial infarction
kappa-​B ligand STI sexually transmitted infection
RBC red blood cells SUDEP sudden unexpected death in epilepsy
REM rapid eye movement SUI stress urinary incontinence
RES reticular endothelial system SVR sustained viral response
RF rheumatoid factor TBG thyroxine-​binding globulin
RFA radiofrequency ablation TCA tricyclic antidepressants
RRMS relapsing-​remitting multiple sclerosis TCR T cell receptor
RN raphe nuclei TDS three times a day
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