Table Of Content

Any screen. Any time. Anywhere. Activate the eBook version of this title at no additional charge. Elsevier eBooks for Medical Education gives you the power to browse and search content, view enhanced images, highlight and take notes—both online and offline. Unlock your eBook today. 1. Visit studentconsult.inkling.com/redeem 2. Scratch box below to reveal your code 3. Type code into “Enter Code” box 4. Click “Redeem” 5. Log in or Sign up 6. Go to “My Library” It’s that easy! Place Peel Off Sticker Here For technical assistance: email [email protected] call 1-800-401-9962 (inside the US) call +1-314-447-8300 (outside the US) Use of the current edition of the electronic version of this book (eBook) is subject to the terms of the nontransferable, limited license granted on studentconsult.inkling.com. Access to the eBook is limited to the first individual who redeems the PIN, located on the inside cover of this book, at studentconsult.inkling.com and may not be transferred to another party by resale, lending, or other means. 2020_ME MEDICAL PHARMACOLOGY THERAPEUTICS & DEDICATION To our families Sixth Edition MEDICAL PHARMACOLOGY THERAPEUTICS & Derek G. Waller, BSc, DM, MB, BS, FRCP Former Consultant Physician and Senior Clinical Lecturer Department of Medicine University Hospital Southampton Southampton United Kingdom Anthony P. Sampson, MA, PhD, FHEA, FBPhS Professorial Fellow in Clinical Pharmacology & Director of Undergraduate Programmes Faculty of Medicine University of Southampton Southampton United Kingdom Andrew W. Hitchings, BSc, MBBS, PhD, FRCP, FFICM, FHEA, FBPhS Reader in Clinical Pharmacology St George’s, University of London Honorary Consultant in Neurointensive Care St George’s University Hospitals NHS Foundation Trust London United Kingdom For additional online content visit StudentConsult.com London New York Oxford Philadelphia St Louis Sydney 2022 ELSEVIER Copyright © 2022 by Elsevier Limited. All rights reserved. First edition 2001 Second edition 2005 Third edition 2010 Fourth edition 2014 Fifth edition 2018 The rights of Derek G. Waller, Anthony P. Sampson and Andrew W. Hitchings to be identified as authors of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notice Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-7020-8159-0 Content Strategist: Alexandra Mortimer Content Development Specialist: Veronika Watkins Project Manager: Joanna Souch Design: Amy L. Buxton Illustration Manager: Anitha Rajarathnam Marketing Manager: Deborah Watkins Printed in Poland Last digit is the print number: 9 8 7 6 5 4 3 2 1 To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter Aptara. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is reviewer(s), Elsevier and typesetter Aptara. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication. confidential until formal publication. Contents Preface, vii SECTION 4 THE RENAL SYSTEM, 218 Drug Dosage and Nomenclature, viii 14. Diuretics, 218 15. Disorders of Micturition, 229 SECTION 1 GENERAL PRINCIPLES, 1 16. Erectile Dysfunction, 236 1. Principles of Pharmacology and Mechanisms of Drug Action, 1 SECTION 5 THE NERVOUS SYSTEM, 242 2. Pharmacokinetics, 32 17. General Anaesthetics, 242 3. Drug Discovery, Safety and Efficacy, 62 18. Local Anaesthetics, 252 4. Neurotransmission and the Peripheral Autonomic Nervous System, 71 19. Opioid Analgesics and the Management of Pain, 258 20. Anxiety, Obsessive-Compulsive Disorder and SECTION 2 THE CARDIOVASCULAR Insomnia, 273 SYSTEM, 89 21. Schizophrenia and Bipolar Disorder, 281 5. Ischaemic Heart Disease, 89 22. Depression, Attention Deficit Hyperactivity 6. Systemic and Pulmonary Hypertension, 108 Disorder and Narcolepsy, 292 7. Heart Failure and Shock, 128 23. Seizures and Epilepsy, 308 8. Cardiac Arrhythmias, 142 24. Extrapyramidal Movement Disorders and Spasticity, 323 9. Cerebrovascular Disease and Dementia, 160 25. Other Neurological Disorders: Multiple Sclerosis, 10. Peripheral Artery Disease, 169 Motor Neuron Disease and Guillain–Barré Syndrome, 336 11. Haemostasis, 175 26. Migraine and Other Headaches, 342 SECTION 3 THE RESPIRATORY SYSTEM, 192 SECTION 6 THE MUSCULOSKELETAL SYSTEM, 350 12. Asthma and Chronic Obstructive Pulmonary Disease, 192 27. The Neuromuscular Junction and Neuromuscular Blockade, 350 13. Respiratory Disorders: Cough, Respiratory Stimulants, Cystic Fibrosis, Idiopathic Pulmonary 28. Myasthenia Gravis, 357 Fibrosis and Neonatal Respiratory Distress Syndrome, 211 29. Nonsteroidal Antiinflammatory Drugs, 361 v 00062-Waller-9780702081590 00062-Waller-9780702081590 These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color figures will appear in color in all electronic versions of this book. figures will appear in color in all electronic versions of this book. To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter Aptara. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is reviewer(s), Elsevier and typesetter Aptara. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication. confidential until formal publication. vi CONTENTS 30. Rheumatoid Arthritis, Other Inflammatory 44. Corticosteroids (Glucocorticoids and Arthritides and Osteoarthritis, 371 Mineralocorticoids), 503 31. Hyperuricaemia, Gout and Pseudogout, 383 45. Female Reproduction, 512 46. Androgens, Antiandrogens and Anabolic Steroids, 530 SECTION 7 THE GASTROINTESTINAL SYSTEM, 389 47. Anaemia and Haematopoietic Colony-Stimulating 32. Nausea and Vomiting, 389 Factors, 535 33. Dyspepsia, Peptic Ulcer Disease and 48. Lipid Disorders, 545 Gastrooesophageal Reflux Disease, 397 34. Inflammatory Bowel Disease, 408 SECTION 10 THE SKIN AND EYES, 558 49. Skin Disorders, 558 35. Constipation, Diarrhoea and Irritable Bowel Syndrome, 415 50. The Eye, 567 36. Liver Disease, 423 37. Obesity, 432 SECTION 11 ANTIMICROBIAL THERAPY, 578 51. Drugs for Infections, 578 SECTION 8 THE IMMUNE SYSTEM, 437 SECTION 12 CANCER, 630 38. The Immune Response and Immunosuppressant Drugs, 437 52. Drugs for Cancer, 630 39. Antihistamines and Allergic Disease, 450 SECTION 13 GENERAL FEATURES: TOXICITY AND PRESCRIBING, 661 SECTION 9 THE ENDOCRINE SYSTEM 53. Drug Toxicity and Overdose, 661 AND METABOLISM, 457 40. Diabetes Mellitus, 457 54. Substance Abuse and Dependence, 677 41. The Thyroid and Control of Metabolic Rate, 473 55. Prescribing, Adherence and Information About Medicines, 693 42. Calcium Metabolism and Metabolic Bone Disease, 480 56. Drug Therapy in Special Situations, 700 43. Pituitary and Hypothalamic Hormones, 491 Index, 712 00062-Waller-9780702081590 00062-Waller-9780702081590 These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color figures will appear in color in all electronic versions of this book. figures will appear in color in all electronic versions of this book. Preface The sixth edition of Medical Pharmacology and Thera- pharmacokinetic properties and unwanted effects peutics has been revised and updated to build upon associated with individual drug classes. Example the strengths and popular approach of previous edi- drugs are covered in depth to illustrate the common tions. Its aim remains to provide a single volume for pharmacological characteristics of their class and to healthcare professionals and students requiring a introduce the reader to those drugs currently in the sound knowledge of the basic principles of clinical most widespread clinical use. pharmacology combined with the practice of drug • A structured approach to the principles of disease prescribing for the management of disease. management, outlining the core principles of drug Medical Pharmacology and Therapeutics relates key choice and planning a therapeutic regimen for many information on basic pharmacology to other relevant common diseases. biomedical sciences in order to underpin the clini- • Drug compendia at the close of each chapter enable cal contexts, and each disease-based chapter is then any drug encountered by the reader in day-to-day structured to reflect the ways that relevant drugs are work or study to be placed within its drug class and used in clinical practice. The chapters covering generic its key features related to the example drugs cov- concepts in pharmacology and therapeutics include ered in the chapter. sections on drug action at a cellular level, pharmaco- • An expanded section of self-assessment questions kinetics, pharmacogenetics, drug development, drug for learning and revision of the concepts and con- toxicity and the principles of prescribing. The sections tent in each chapter, including one-best-answer on clinical management in each disease area have been (OBA), extended-matching-item (EMI), true-false thoroughly revised and updated in line with best prac- and case scenario-based questions. tice and the relevant national guidelines, including on It is our intention that the sixth edition of this book COVID-19. will encourage readers to develop a deeper under- Each chapter in this sixth edition retains the follow- standing of the principles of drug usage that will ing key features: help them to become safe and effective prescribers, • An up-to-date and succinct explanation of the major to enable them to evaluate the findings of basic and pathogenic mechanisms of disease and consequent clinical research, to encourage them to teach and train clinical symptoms and signs, helping the reader to others in their profession, and to develop the skills of put into context the actions of drugs and the conse- lifelong learning that will enable them to tackle chang- quences of their therapeutic use. ing healthcare needs and emerging threats. • A comprehensive review of major drug classes relevant to the disease in question. Basic pharma- DGW cology is described with clear identification of the APS molecular targets, clinical characteristics, important AWH vii Drug Dosage and Nomenclature (epinephrine) and noradrenaline (norepinephrine). In DRUG NOMENCLATURE this book, where the use of these agents as adminis- In the past, the nonproprietary (generic) names of tered drugs is being described, dual names are given. some drugs have varied from country to country, In keeping with European convention, however, adren- leading to potential confusion. Progressively, interna- aline and noradrenaline alone are used when referring tional agreement has been reached to rationalise these to the physiological effects of the naturally occurring variations in names and a single recommended Inter- substances. national Nonproprietary Name (INN) given to all drugs. Where the previously given British Approved DRUG DOSAGES Name (BAN) and the INN have differed, the INN is now the accepted name and is used throughout this Medical knowledge is constantly changing. As new book. information becomes available, changes in treatment, A special case has been made for two medicinal sub- procedures, equipment and the use of drugs become stances: adrenaline (INN: epinephrine) and noradren- necessary. The authors and the publishers have taken aline (INN: norepinephrine). Because of the clinical care to ensure that the information given in the text is importance of these substances and the widespread accurate and up to date. However, readers are strongly European use and understanding of the terms adren- advised to confirm that the information, especially aline and noradrenaline, manufacturers have been with regard to drug usage, complies with the latest asked to continue to dual-label products adrenaline legislation and standards of practice. viii