FASTtrack: Pharmacology

255 Pages·2009·37.18 MB·English

by  Michael D. Randall

Pharmacology
Pharmacology
Michael D Randall
Associate Professor and Reader in Cardiovascular
Pharmacology,
School of Biomedical Sciences,
University of Nottingham Medical School, UK
Stephen PH Alexander
Associate Professor in Molecular Pharmacology,
School of Biomedical Sciences,
University of Nottingham Medical School, UK
and
David A Kendall
Professor of Pharmacology,
School of Biomedical Sciences,
University of Nottingham Medical School, UK
Pharmaceutical Press
London ● Chicago
Published by the Pharmaceutical Press
An imprint of RPS Publishing
1 Lambeth High Street, London SE1 7JN, UK
100 South Atkinson Road, Suite 200, Grayslake, IL 60030-7820, USA
© Pharmaceutical Press 2009
is a trade mark of RPS Publishing
RPS Publishing is the publishing organisation of the Royal Pharmaceutical
Society of Great Britain
First published 2009
Typeset by J&L Composition, Scarborough, North Yorkshire
Printed in Great Britain by by TJ International, Padstow, Cornwall
ISBN 978 0 85369 824 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 written permission of the copyright holder.
The publisher makes no representation, express or implied, with regard
to the accuracy of the information contained in this book and cannot accept
any legal responsibility or liability for any errors or omissions that may be
made.
The rights of Michael Randall, Stephen Alexander and David Kendall to be
identified as the authors of this work have been asserted by them in accordance
with the Copyright, Designs and Patents Act, 1988.
A catalogue record for this book is available from the British Library.
Contents
Introduction to the FASTtrack series ix 5. Quantitative pharmacology . . . . . . . . . . 47
About the authors x Drugs which alter receptor activity 47
Preface xi Agonist activation of receptors: potency
and efficacy 47
1. Pharmacodynamics . . . . . . . . . . . . . . . . 1 Antagonist occupancy of receptors: affinity
Enzymes 2 estimation 53
Structural proteins 4 Radioligand binding 60
Hormones 4 Enzyme–substrate and transporter–
substrate interactions 67
2. Receptors . . . . . . . . . . . . . . . . . . . . . . . 5 Drug selectivity and target identification 68
Superfamilies of receptors 5
7-Transmembrane domain receptors 5 6. Autonomic pharmacology . . . . . . . . . . . 71
Transmitter-gated ion channels 9 Organisation of the autonomic nervous
system 71
Catalytic receptors 13
Pharmacology of the autonomic nervous
Nuclear receptors 17 system 73
3. G-proteins and their downstream 7. Local mediators . . . . . . . . . . . . . . . . . . 79
signalling cascades . . . . . . . . . . . . . . . 21
Histamine 79
Heterotrimeric G-proteins 21
Gasotransmitters 79
Regulation of adenylyl cyclase activity
and cAMP levels by Gs and Gi 23 Eicosanoids 80
nGes-rpvoroutse isny stigenmalling in the sympathetic 25 8. Pmheatramboalcisomkin.e .t i.c .s .a .n .d . d. r.u .g . . . . . . . . . . 87
lGoGefbtv Geacln:is da dtehney rlyelg cuylactlaiosne -oinf dretpineanld ceGntM ePf fects 268 ACFiblresato-rroaprntdicoeenr (kaCinLde) t ibciso aovfa eilaimbilnitay t(ioFn) 8878
Regulation of phospholipase C activity and Rate constant (k) 88
calcium levels by Gq 29 Half-life 89
G12/13–protein-coupled receptor signalling 32 Loading doses 89
Small G-proteins 33 Drug metabolism 90
Posttranslational modifications of
G-proteins 34 9. Gastric pharmacology. . . . . . . . . . . . . . 93
Modulation of G-protein function: GAPs, Control of acid secretion 93
GEFs and GDIs 35 Treatment 93
4. Ion channels and transporters . . . . . . . 37 10. Lower gastrointestinal pharmacology . . 97
Ion channels regulated from inside the Diarrhoea 97
plasma membrane 37
Constipation 99
Voltage-sensitive channels 39
Irritable-bowel syndrome 99
Second messenger-operated ion channels 40
Inflammatory bowel disease 100
Intracellular channels 41
Plasma membrane transporters 41 11. Antiemetics. . . . . . . . . . . . . . . . . . . . 101
ATP-binding cassette transporters 44 Histamine H1-receptor antagonists 101
Intracellular transporters 44 Antimuscarinic agents 101
v
vi Contents
Histamine analogues 101 Decongestants 136
Dopamine receptor antagonists 102 Leukotriene receptor antagonists 136
5-hydroxytryptamine (5HT) receptor Anaphylaxis 136
antagonists 102
Adrenaline 136
Other agents 102
19. Anxiolytics and hypnotics . . . . . . . . . 139
12. Antiarrhythmics. . . . . . . . . . . . . . . . . 103
Benzodiazepines 139
Arrhythmias 103
b-blockers 140
The cardiac action potential 104
Antidepressants as anxiolytics 140
Autonomic control of the heart 104
20. Antidepressants . . . . . . . . . . . . . . . . 143
Antiarrhythmic drugs 104
Serotonin-selective reuptake inhibitors
13. Cardiovascular drugs. . . . . . . . . . . . . 107 (SSRIs) 143
Angiotensin-converting enzyme inhibitors Tricyclic antidepressants 144
(ACEIs) 107
Monoamine oxidase inhibitors 144
Angiotensin (AT ) receptor antagonists 108
1 Selective noradrenaline reuptake inhibitors
Beta-blockers 109 (NARIs) 145
Diuretics 110 Serotonin/noradrenaline reuptake inhibitors
(SNRIs) 145
Calcium channel inhibitors 110
Other drugs 145
Nitrates 111
General features of antidepressant drug
Potassium channel activators 112
therapy 146
Alpha-blockers 112
Centrally acting antihypertensive 112 21. Antiepileptic drugs . . . . . . . . . . . . . . 149
Cardiac glycosides 113 Antiepileptic drugs 149
HMG CoA reductase inhibitors (statins) 114
22. Antipsychotic drugs. . . . . . . . . . . . . . 155
Fibrates 114
Antipsychotic drugs 155
14. Renal and urinary pharmacology . . . . 117
23. Parkinson’s disease . . . . . . . . . . . . . 159
Diuretics 117
Antiparkinsonian drugs 160
Bladder pharmacology 120
24. Analgesics . . . . . . . . . . . . . . . . . . . . 165
15. Antithrombotic agents: anticoagulants
and antiplatelet drugs . . . . . . . . . . . . 123 Opioids 165
Oral anticoagulants 123 Other drugs 167
Injectable anticoagulants 124 Local anaesthetics 168
Antiplatelet drugs 124 Antimigraine drugs 168
Drugs for neuropathic pain treatment 169
16. Antiobesity drugs . . . . . . . . . . . . . . . 127
Drugs for trigeminal neuralgia 169
17. Asthma and chronic obstructive
25. Drugs of abuse . . . . . . . . . . . . . . . . . 171
pulmonary disease . . . . . . . . . . . . . . . 129
Common mechanisms 171
Autonomic control of airways 129
Heroin 172
Asthma 129
Cocaine 172
Bronchodilators 130
Alcohol (ethanol) 173
Anti-inflammatory agents 131
Amphetamines 173
Drugs causing bronchoconstriction 132
Ecstasy (MDMA,
18. Allergy. . . . . . . . . . . . . . . . . . . . . . . . 135 3,4-methylenedioxymethamfetamine) 173
Antihistamines 135 Cannabis 174
Topical corticosteroids 135 Benzodiazepines 174
Contents vii
LSD 174 31. Non-bacterial infections: antiviral,
antifungal and antiparasitic drugs . . . 199
Treatment 175
Antiviral drugs 199
26. General anaesthetics . . . . . . . . . . . . 179
Antifungal agents 200
Mechanisms of general anaesthetics 179
Antimalarial agents 201
Intravenous agents 180
Anthelmintics 202
Gaseous agents 180
Insecticides 202
27. Neuromuscular blocking drugs . . . . . 183
32. Anticancer drugs . . . . . . . . . . . . . . . . 205
Non-depolarising neuromuscular blockers 183 Cancer initiation and prevention 205
Depolarising neuromuscular blockers 184 Anticancer drugs 207
Drugs interfering with DNA and its
28. Thyroid disorders. . . . . . . . . . . . . . . . 187
replication 207
Thioamides 187
Targeted therapies 208
b-blockers 187
Drug resistance 209
Levothyroxine 187
Side-effects of anticancer drugs and
rescue therapy 209
29. Diabetes mellitus . . . . . . . . . . . . . . . 189
Palliative care and additional symptom
Type 1 diabetes 189
control 210
Type 2 diabetes 189
33. Steroids . . . . . . . . . . . . . . . . . . . . . . 211
Diet 190
Steroid nomenclature 211
Biguanides 190
Adrenal steroids 211
Sulphonylureas 190
Gonadal steroids 213
Meglitinide analogues 190
General principles of steroid hormone
Thiazolidinediones (‘glitazones’) 191
receptor activation 216
Glucosidase inhibitors 191
Modulation of incretins 191 34. Biopharmaceuticals. . . . . . . . . . . . . . 219
Monoclonal antibodies 219
30. Antibacterial agents . . . . . . . . . . . . . 193
Recombinant hormones, cytokines and
Penicillins 193
clotting factors 221
Cephalosporins 193
35. Variation in clinical efficacy. . . . . . . . 223
Glycopeptides 194
Tachyphylaxis 223
Tetracyclines 194
Receptor desensitisation 223
Macrolides 194
Tolerance to heroin 225
Clindamycin 194
Receptor densensitisation and
Chloramphenicol 194
downregulation may be clinically useful 225
Aminoglycosides 195
Receptor upregulation 226
Quinolones 195
The pharmacodynamic basis of
Sulphonamides and trimethoprim 195 interindividual variation 226
Metronidazole 195 Answers to self-assessment 229
Antituberculous drugs 195 Index 239
Introduction to the
series
FASTtrack is a new series of revision guides created for undergraduate
pharmacy students. The books are intended to be used in conjunction with
textbooks and reference books as an aid to revision to help guide students
through their exams. They provide essential information required in each
particular subject area. The books will also be useful for pre-registration trainees
preparing for the Royal Pharmaceutical Society of Great Britain’s (RPSGB’s)
registration examination, and to practising pharmacists as a quick reference text.
The content of each title focuses on what pharmacy students really need to
know in order to pass exams. Features include*:
■ concise bulleted information
■ key points
■ tips for the student
■ multiple choice questions (MCQs) and worked examples
■ case studies
■ simple diagrams.
The titles in the FASTtrack series reflect the full spectrum of modules for the
undergraduate pharmacy degree.
Titles include:
Complementary and Alternative Medicine
Managing Symptoms in the Pharmacy
Pharmaceutical Compounding and Dispensing
Pharmaceutics: Dosage Form and Design
Pharmaceutics: Drug Delivery and Targeting
Pharmacology
Physical Pharmacy (based on Florence & Attwood’s Physicochemical Principles
of Pharmacy)
Therapeutics
There is also an accompanying website which includes extra MCQs, further title
information and sample content: www.fasttrackpharmacy.com.
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