Pharmacology for Anaesthesia and Intensive Care

372 Pages·2014·2.6 MB·English

by  T. E. Peck

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Pharmacology for Anaesthesia and Intensive Care
FOURTH EDITION
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Pharmacology for Anaesthesia
and Intensive Care
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FOURTH EDITION
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T. E. Peck i
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Consultant Anaesthetist, Royal Hampshire County Hospital, Winchester;
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Honorary Consultant, University Hospital Southampton, UK i
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S. A. Hill
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Consultant Neuroanaest9hetist, University Hospital Southampton, UK
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Cambridge Books Online © Cambridge University Press, 2014
University Printing House, Cambridge CB2 8BS, United Kingdom
Cambridge University Press is part of the University of Cambridge.
It furthers the University’s mission by disseminating knowledge in the pursuit of
education, learning and research at the highest international levels of excellence. G
www.cambridge.org
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Information on this title: www.cambridge.org/9781107657267
© T. E. Peck and S. A. Hill 2014
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his publication is in copyright. Subject to statutory exception
and to the provisions of relevant collective licensing agreements, d
no reproduction of any part may take place without the written
permission of Cambridge University Press. e
First published 2000
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Second edition 2003
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hird edition 2008
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Fourth edition 2014
Printed in the United Kingdom by Clays, St Ives plc U r
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A catalogue record for this publication is available from the British Library .

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Library of Congress Cataloguing in Publicat-ion data
Peck, T. E., author.
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Pharmacology for anaesthesia and intensive care / T. E. Peck, S. A. Hill. – Fourth edition.
9
p. ; cm. n
Includes bibliographical references and index.
9
ISBN 978-1-107-65726-7 (hbk.) a
I. Hill, S. A. (Sue A.), author. II. Title.
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[DNLM: 1. Anesthetics–pharmacology. 2. Cardiovascular Aigents–pharmacology.
i
3. Central Nervous hSystem Agents–pharmacology. 4. Intenssive Care. 5. Peripheral
Nervous System Agents–pharmacology. QV 81]
RD82.2 a r
615.7′81–dc23 e
20140119t56
p
ISBN 978-1-107-65726-7 Hardback
Cambridge University Press has no respon.sibility for the persistence or accuracy of
p
URLs for external or third-party internet websites referred to in this publication,
and does not guarantee that any content on such websites is, or will remain,
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accurate or appropriate.
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Every efort has been made in preparing this book to provide accurate and up-to-date information
which is in accord with accepted standards and practice at the time of publication. Although case
histories are drawn from actual cases, every efort has been made to disguise the identities of the
individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that
the information contained herein is totally free from error, not least because clinical standards are
constantly changing through research and regulation. he authors, editors and publishers therefore
disclaim all liability for direct or consequential damages resulting from the use of material contained
in this book. Readers are strongly advised to pay careful attention to information provided by the
manufacturer of any drugs or equipment that they plan to use.
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CONTENTS
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Preface R page vii
Foreword by Zeev Goldik viii
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SECTION I Basic principles 1
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1 Drug passage across the cell membrane 1
2 Absorption, distribution, metabolism and excreetion 9
3 Drug action 25
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4 Drug interaction i 40
5 Isomerism n 45
6 Pharmacokinetic modelling U r 50
7 Applied pharmacokinetic models i 71
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8 Medicinal chemistry 80
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SECTION II Core drugs in a naesthetic practice s 93
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9 General anaesthetic agents n 93
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10 Analgesics a 126
11 Local anaesthretics 154
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12 Muscle relaixants and reversal agents s 166
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SECTIONa III Cardiovascular drugs 187
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13 Sympathomimetics 187
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14 Adrenoceptor antagonists p 207
15 Anti-arrhythmics . 218
16 Vasodilators p 235
17 Antihypertensives 247
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SECTION IV Other important drugs 257
18 Central nervous system 257
19 Antiemetics and related drugs 270
20 Drugs acting on the gut 280
21 Intravenous luids and minerals 286
22 Diuretics 292
23 Antimicrobials 298
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vi Contents
24 Drugs afecting coagulation 317
25 Drugs used in diabetes 331
26 Corticosteroids and other hormone preparations 336
Index 344
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PREFACE
he style of this fourth edition has remained largely unchanged, as it has proved success-
ful in giving easy access to the contents. In order to keep the overall size similar to previ-
ous editions we have culled some of the drugs that had provided a historical perspective
and reduced the space given to drugs used less commonly. Drugs that had been discon-
tinued or withdrawn, but more recently been reinstated, are now included in order to
remain current. A wide range of drugs that did not exist or were in the trial phase of their
development are now included and further add to the breadth of this book. Section 1
has been developed further with a chapter for applied pharmacokinetic models as the
use of total intravenous anaesthesia becomes more widespread. We trust that this book
will continue to provide current and useful information to the wide readership that it has
attracted thus far in its evolution.
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FOREWORD
he art of anaesthesia includes many diferent facets deeply rooted in medical behaviour:
listening and talking to the patient, evaluating, diagnosing and taking the right decisions.
Drugs are central to patient care in many areas of medical practice and the anaesthetist
as well as all healthcare practitioners need to have a clear understanding of therapeutics.
However, competence in anaesthetic management during the whole perioperative man-
agement of our patients implies good knowledge of pharmacology; it is the bread and
butter of our profession.
he dynamic nature of drug development in this ield compels a continuous updating
of the characteristics of drugs that form such an essential part of our armamentarium.
Pharmacology for Anaesthesia and Intensive Care, edited by T.E. Peck and S.A. Hill,
provides a novel-classic approach to pharmacology.
Drawing on the experience of the authors, who are involved in clinical practice, post-
graduate training and assessments, not only in the United Kingdom but with a pan-Euro-
pean view, the changes and improvements introduced in this fourth edition make this
textbook an appropriate guide not only for trainees at all stages of their training but also
for consultants.
Designed as a refresher textbook, this work is suitable as a reference for daily use as
well as in preparing for various medical assessments and examinations.
Its content is itted to anaesthesia training programmes in pharmacology in many coun-
tries. It covers the pharmacology requirements of the new syllabus in anaesthesia and
intensive care produced by the European Board of Anaesthesiology of the UEMS (Union
of European Medical Specialties) as well that of the Royal College of Anaesthetists.
As for the previous editions, this textbook is part of the recommended bibliography
for examination preparation for the European Diploma in Anaesthesiology and Intensive
Care (EDAIC).
I know that readers will ind this book to be a valuable resource for both examination
preparation and clinical use as a practical guide to pharmacology for anaesthesia and
intensive care.
Zeev Goldik MD MPH
Chairman, Examinations Committee – European Diploma in Anaesthesiology and
Intensive Care
President Elect, European Society of Anaesthesiology
Head of Post Anaesthesia Care Unit and Consultant Anaesthetist, Lady Davis Carmel
Medical Centre, Haifa, Israel
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SECTION I Basic principles
1
Drug passage across the cell
membrane
Many drugs need to pass through one or more cell membranes to reach their site of
action. A common feature of all cell membranes is a phospholipid bilayer, about 10 nm
thick, arranged with the hydrophilic heads on the outside and the lipophilic chains facing
inwards. his gives a sandwich efect, with two hydrophilic layers surrounding the cen-
tral hydrophobic one. Spanning this bilayer or attached to the outer or inner lealets
are glycoproteins, which may act as ion channels, receptors, intermediate messengers
(G-proteins) or enzymes. he cell membrane has been described as a ‘luid mosaic’ as
the positions of individual phosphoglycerides and glycoproteins are by no means ixed
(Figure 1.1). An exception to this is a specialized membrane area such as the neuromus-
cular junction, where the array of postsynaptic receptors is found opposite a motor nerve
ending.
he general cell membrane structure is modiied in certain tissues to allow more spe-
cialized functions. Capillary endothelial cells have fenestrae, which are regions of the
endothelial cell where the outer and inner membranes are fused together, with no inter-
vening cytosol. hese make the endothelium of the capillary relatively permeable; luid
in particular can pass rapidly through the cell by this route. In the case of the renal glom-
erular endothelium, gaps or clefts exist between cells to allow the passage of larger mol-
ecules as part of iltration. Tight junctions exist between endothelial cells of brain blood
vessels, forming the blood–brain barrier (BBB), intestinal mucosa and renal tubules.
hese limit the passage of polar molecules and also prevent the lateral movement of glyc-
oproteins within the cell membrane, which may help to keep specialized glycoproteins
at their site of action (e.g. transport glycoproteins on the luminal surface of intestinal
mucosa) (Figure 1.2).
Methods of crossing the cell membrane
Passive diffusion
his is the commonest method for crossing the cell membrane. Drug molecules move
down a concentration gradient, from an area of high concentration to one of low con-
centration, and the process requires no energy to proceed. Many drugs are weak acids or
weak bases and can exist in either the unionized or ionized form, depending on the pH.
he unionized form of a drug is lipid-soluble and difuses easily by dissolution in the lipid
bilayer. hus the rate at which transfer occurs depends on the pK of the drug in question.
a
Factors inluencing the rate of difusion are discussed below.
1
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