Clinical Pharmacology

806 Pages·2003·83.84 MB·english

by  Bennet

CLINICAL
PHARMACOLOGY
'Nature is not only odder than we think, but it is odder than we
can think.'
J B S Haldane 1893-1964
'Patients may recover in spite of drugs or because of them.'
J H Gaddum 1959
'But know also, man has an inborn craving for medicine ... the
desire to take medicine is one feature which distinguishes man
the animal, from his fellow creatures. It is really one of the most
serious difficulties with which we have to contend ... the doctor's
visit is not thought to be complete without a prescription.'
William Osier 1894
'Morals do not forbid making experiments on one's neighbour or
on one's self ... among the experiments that may be tried on man,
those that can only harm are forbidden, those that are innocent
are permissible, and those that may do good are obligatory.' 'Men
who have excessive faith in their theories or ideas are not only ill
prepared for making discoveries; they make very poor
observations ... they can see in [their] results only a confirmation
of their theory ... This is what made us say that we must never
make experiments to confirm our ideas, but simply to control
them.' 'Empiricism is not the negation of science, as certain
physicians seem to think; it is only its first stage.'
'Medicine is destined to get away from empiricism little by little;
like all other sciences, it will get away by the scientific method.'
'Considered in itself, the experimental method is nothing but
reasoning by whose help we methodically submit our ideas to
experience — the experience of facts.'
Claude Bernard 1865
'I do not want two diseases — one nature-made, one doctor-
made.'
Napoleon Bonaparte 1820
'The ingenuity of man has ever been fond of exerting itself to
varied forms and combinations of medicines.'
William Withering 1785
'All things are poisons and there is nothing that is harmless, the
dose alone decides that something is no poison.'
Paracelsus 1493-1541
'First do no harm.'
'It is a good remedy sometimes to use nothing.'
Hippocrates 460-355 B.C.
CLINICAL
PHARMACOLOGY
P. N. Bennett MD FRCP
Reader in Clinical Pharmacology, University of Bath, and Consultant Physician, Royal United Hospital,
Bath, UK
M. J. Brown MA MSC MD FRCP
Professor of Clinical Pharmacology, University of Cambridge; Consultant
Physician, Addenbrooke's Hospital, Cambridge and Director of Clinical Studies
Gonville and Caius College, Cambridge, UK
NINTH EDITION
CHURCHILL
LIVINGSTONE
EDINBURGH LONDON NEW YORK OXFORD PHILADELPHIA ST LOUIS SYDNEY TORONTO 2003
CHURCHILL LIVINGSTONE Commissioning Editor: Timothy Home
An imprint of Elsevier Science Limited Project Development Manager: Colin Arthur
Copy Editor: Leslie Smillie
© D. R. Laurence 1960,1962,1966,1973 Project Controller: Nancy Arnott
© D. R. Laurence and P. N. Bennett 1980,1987,1992 Designer: Erik Bigland
© D. R. Laurence, P. N. Bennett, M. J. Brown 1997
© P. N. Bennett, M. J. Brown 2003
The right of P N Bennett and M J Brown to be identified as
the authors of this work has been asserted by them in
accordance with the Copyright, Designs and Patents Act
1988.
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First edition 1960 Previous editions translated into
Second edition 1962 Italian, Chinese, Spanish,
Third edition 1966 Serbo-Croat, Russian
Fourth edition 1973
Fifth edition 1980
Sixth edition 1987
Seventh edition 1992
Eighth edition 1997
Standard edition ISBN 0443064806
International Student Edition ISBN 0443064814
British Library Cataloguing in Publication Data
A catalogue record for this book is available from the
British Library
Library of Congress Cataloging in Publication Data
A catalog record for this book is available from the
Library of Congress
The
publisher's
policy is to use
paper manufactured
from sustainable forest!
Printed in Spain
Preface
For your own satisfaction and for mine, please does not always demand wearying solemnity. An
read this preface!1 author, poet and critic said that he judged fiction
thus: 'Could I read it? If I could read it, did I believe
Professor D. R. Laurence was either author or co- it? If I believed it, did I care about it, what was the
author of this textbook from its 1st edition in 1960 to quality of my caring, and did it last?'2 It would be
its 8th in 1997. This is a long life for any textbook. Its presumptuous for us to aspire to satisfy the criteria
achievement bears testimony to a style of pre- for fiction but we have been mindful of them in
sentation that strives to be clear and readable, and producing this book.
to retain the reader's interest whilst imparting All who prescribe drugs would be wise to keep
information about a subject that can be at times in mind that the expectations of patients and of
both complex and confusing. As he withdraws from society in general are becoming ever more exacting
active involvement in the book it is opportune to and that doctors who prescribe casually or ignorantly
pay tribute in this 9th edition to an achievement in now face not only increasing criticism but also civil
authorship sustained over four decades, during (or even criminal) legal charges. The ability to handle
which 'Laurence's pharmacology' became the aid, new developments depends, now more than ever,
advisor and companion to generations of students on comprehension of the principles of pharma-
and doctors seeking guidance in the vital field of cology. These principles are not difficult to grasp
medicinal therapeutics. and are not so many as to defeat even the busiest
doctors who take on themselves the responsibility
of introducing manufactured medicines into the
This book is about the scientific basis and practice of drug
therapy. It is particularly intended for medical students and bodies of their patients.
doctors, and indeed for anyone concerned with evidence-based The principles of pharmacology and drug
drug therapy and prescribing. therapy will be found in chapters 1-8 and they are
applied in the subsequent specialist chapters which
The scope and rate of drug innovation increases. are offered as a reasonably brief solution to the
Doctors are now faced with a professional lifetime problem of combining practical clinical utility with
handling drugs that are new to themselves — drugs some account of the principles on which clinical
that do new things as well as drugs that do old practice rests.
things better; drugs that become familiar during How much practical technical detail to include is
training will be superseded. difficult to decide. In general, where therapeutic
We do not write only for readers who, like us, practices that are complex, potentially dangerous
have a special interest in pharmacology. We try to and commonly up-dated, e.g. anaphylactic shock,
make pharmacology understandable for those whose we provide more detail together with web-sites that
primary interests lie elsewhere but who recognise list the latest advice; less, or even no detail is given
that they need some knowledge of pharmacology if on therapy that is generally conducted only by
they are to meet their moral and legal 'duty of care' specialists, e.g. anticancer drugs and i.v. oxytocin.
to their patients. We try to tell them what they need But always, especially with modern drugs with which
to know without burdening them with irrelevant the prescriber may not be familiar, formularies,
information and we try to make the subject approved guidelines, or the manufacturer's current
interesting. We are very serious, but seriousness literature should be consulted.
1 St Francis of Sales: Preface to Introduction to the devout life
(1609) 2 Philip Larkin: 1922-85
v
PREFACE
Use of the book. Students are, or should be, in particular situations. Similarly, it is assumed that
concerned to understand and to develop a rational, the reader possesses a formulary, local or national,
critical attitude to drug therapy and they should which will provide guidance on the availability,
therefore chiefly concern themselves with how drugs including doses, of a broad range of drugs. But the
act and interact in disease and with how evidence practice of therapeutics by properly educated and
of therapeutic effect is obtained and evaluated. conscientious doctors working in settings com-
To this end they should read selectively and should plicated by intercurrent disease, metabolic differences
not impede themselves by attempts to memorise or personality, involves challenges beyond the rigid
lists of alternative drugs and doses and minor adherence to published recommendations. The role
differences between them, which should never of a textbook is to provide the satisfaction of
be required of them in examinations. Thus the text understanding the basis for a recommended course
has not been encumbered with exhaustive lists of action so that an optimal result may be achieved
of preparations which properly belong in a by informed selection and use of drugs.
formulary, although it is hoped that enough have The guide to further reading at the end of each
been mentioned to cover much routine prescribing, chapter generally comprises a few references to
and many drugs have been included solely for original papers, to referenced editorials and review
identification. articles from a small range of English language
The role and status of a textbook. If a book is to journals that are likely to be available in most hospital
be a useful guide to drug use it must offer clear libraries in order to enable anyone, anywhere, to gain
conclusions and advice. If it is to be of reasonable access to the original literature and to informed
size, alternative acceptable courses of action will opinion, and also to provide interest and sometimes
often have to be omitted. What is recommended amusement. We urge readers to select a title that
should be based on sound evidence where this looks interesting and to read the article. We do not
exists, and on an assessment of the opinions of the attempt to document all the statements we make,
experienced where it does not. which would be impossible in a book of this size.
Increasingly, the selection of drugs is influenced
by guidelines produced by specialist societies and
national bodies. We have provided or made reference Bath, Cambridge P.N.B.,
to these as representing a consensus of best practice 2003 M.J.B.
vi
Farewell
This book originated in 1957 when I, then senior I have seen too many elderly academics become
lecturer in the Department of Pharmacology and in unable, or unwilling, to recognise that they are no
the Department of Medicine at University College longer quite the people that they once were and that
and Medical School London, told the Professor of they have become an embarrassment to their
Medicine that there was no book on Clinical younger colleagues, who are often too kind to
Pharmacology that I could recommend to our enlighten them; though they may murmur behind
medical students. He replied that if that was so then their senior's back. I long ago decided that I must
I should get down to it and write such a book. I not join that group, and I hope I may just have
doubted that I could accomplish the task. He escaped doing so.
marched me off to a nearby medical publisher and a Perhaps my greatest reward has been the
contract was soon signed. Without this pressure kindness of people from all over the world who
and the long-sustained support of Max Rosenheim have taken the trouble to communicate to me that
(later Lord Rosenheim of Camden and President of they have not only profited from, but have actually
the Royal College of Physicians of London) this enjoyed, reading Clinical Pharmacology.
book would not have materialised in its first edition The world of clinical pharmacology has greatly
in 1960. Since that date, both in collaboration and changed since 1957 when I took up my pen, and I
alone, there have been eight editions. I am deeply wish my successors well.
grateful to my collaborators.
Now, after above 40 years with the book, and in D R Laurence, Professor Emeritus of Pharmacology
my eightieth year, the time has come to stand aside. and Therapeutics, University College London
vii
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