Table Of ContentClinical pharmacology
And I will use regimens for the benefit of the ill in accordance with my ability and my judgement.
Hippocrates’ Oath
They used to have a more equitable contract in (ancient) Egypt: for the first three days, the doctor took on the patient at the patient’s risk
and peril: when the three days were up, the risks and perils were the doctor’s. But doctors are lucky: the sun shines on their successes and
the earth hides their failures.
Michael de Montaigne 1533–92
Nature is not only odder than we think, but it is odder than we can think.
JBS Haldane 1893–1964
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 . . .
theycanseein[their]resultsonlyaconfirmationoftheirtheory. . .Thisiswhatmadeussaythatwemustnevermakeexperimentstoconfirm
our ideas, but simply to control them.
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
Commissioning Editor: Jeremy Bowes
Development Editor: Fiona Conn
Project Manager: Andrew Riley
Designer/Design Direction: Russell Purdy
Illustration Manager: Jennifer Rose
Illustrator: Antbits Ltd.
Clinical
pharmacology
11th edition
Peter N Bennett MD FRCP
Formerly Reader in Clinical Pharmacology, University of Bath, and Consultant Physician,
Royal United Hospital, Bath, UK
Morris J Brown MA MSc FRCP FAHA FMedSci
Professor of Clinical Pharmacology, University of Cambridge; Consultant Physician,
Cambridge University Hospitals NHS Foundation Trust, Cambridge; and Director of Clinical Studies,
Gonville and Caius College, University of Cambridge, Cambridge, UK
Pankaj Sharma MD PhD FRCP
Reader in Clinical Neurology at Imperial College London; Consultant Neurologist
at Hammersmith Hospitals, London, UK
Edinburgh
London
New York
Oxford
Philadelphia
St Louis
Sydney
Toronto
2012
# 2012 Dr P N Bennett, Professor Morris J Brown and Dr Pankaj Sharma.
Published by Elsevier Ltd. All rights reserved.
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Third edition 1966
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Sixth edition 1987
Seventh edition 1992
Eighth edition 1997
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ISBN 978-0-7020-4084-9
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden
our understanding, changes in research methods, professional practices, or medical treatment may become
necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating
and using any information, methods, compounds, or experiments described herein. In using such
information or methods they should be mindful of their own safety and the safety of others, including
parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check the most
current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be
administered, to verify the recommended dose or formula, the method and duration of administration,
and contraindications. It is the responsibility of practitioners, relying on their own experience and
knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each
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Contributors
Mark Abrahams MB ChB DA FRCA FFPMRCA
Lead Clinician, Department of Pain Medicine, Cambridge
University Hospitals NHS Foundation Trust, Cambridge, UK
Chapter 18 Pain and analgesics
Graeme Alexander MA MD FRCP
Consultant Hepatologist, Division of Gastroenterology and
Hepatology, Department of Medicine, Cambridge University
Hospitals NHS Foundation Trust, Cambridge UK
Chapter 34 Liver and biliary tract
Sani H Aliyu MBBS FRCP FRCPath
Consultant in Microbiology and Infectious Diseases, Cambridge
University Hospitals NHS Foundation Trust, Cambridge, UK
Chapter 15 Viral, fungal, protozoal and helminthic infections
John Louis-Auguste BA MB ChB MRCP
Specialist Registrar in Gastroenterology, Charing Cross Hospital,
London, UK
Chapter 32 Oesophagus, stomach and duodenum, Chapter 33
Intestines
Trevor Baglin MA MB Ch B PhD FRCP FRCPath
Consultant Haematologist, Cambridge University Hospitals NHS
Foundation Trust, Cambridge University Teaching Hospitals NHS
Trust, Cambridge, UK
Chapter 29 Drugs and haemostasis
Devinder Singh Bansi BM DM FRCP
Consultant Gastroenterologist, Imperial College Healthcare NHS
Trust, London, UK
Chapter 32 Oesophagus, stomach and duodenum, Chapter 33
Intestines
Paul Bentley MA, MRCP, PhD
Clinical Senior Lecturer and Honorary Consultant in Neurology
and Stroke Medicine, Charing Cross Hospital, London, UK
Chapter 21 Neurological disorders - epilepsy, Parkinson’s disease
and multiple sclerosis
Blanca Bolea-Alamanac MD
Consultant Psychiatrist and Honorary Lecturer, University of
Bristol, Bristol, UK
Chapter 20 Psychotropic drugs
Chrysothemis Brown MBBS BA
NIHR Academic Clinical Fellow, Imperial College London, UK
Chapter 39 Vitamins, calcium, bone
Diana C Brown MD MSc FRCP
Consultant Endocrinologist, Cromwell Hospital, London, UK
Chapter 35 Adrenal corticosteroids, antagonists, corticotrophin,
Chapter 37 Thyroid hormones, antithyroid drugs
Simon Davies DM, MBBS, MRCPsych MSc DipEpidemiol
Clinical Lecturer in Psychiatry, University of Bristol, Bristol, UK
Chapter 20 Psychotropic drugs
Wendy N Erber MD DPhil FRCPath FRCPA
Professor of Pathology and Laboratory Medicine University
of Western Australia Western Australia 6009 Australia
Chapter 30 Red blood cell disorders
Mark Evans MD FRCP
University Lecturer, University of Cambridge; Consultant
Physician, Cambridge University Hospitals Foundation Trust,
Cambridge, UK
Chapter 36 Diabetes mellitus, insulin, oral antidiabetes agents,
obesity
Mark Farrington MA MB BChir FRCPath
Consultant Medical Microbiologist, Health Protection Agency,
Cambridge University Hospitals NHS Foundation Trust,
Cambridge, UK
Chapter 12 Chemotherapy of infections, Chapter 13
Antibacterial drugs, Chapter 14 Chemotherapy of bacterial
infections
Andrew Grace PhD FRCP FACC
Research Group Head, University of Cambridge; Consultant
Cardiologist, Papworth Hospital, Cambridge, UK
Chapter 25 Cardiac arrhythmia
Thomas K K Ha MD FRACP FRCP
Consultant Dermatologist, Cambridge University Hospitals NHS
Foundation Trust, Cambridge, UK
Chapter 17 Drugs and the skin
vii
Stephen Haydock PhD FRCP
Consultant Physician, Musgrove Park Hospital, Taunton, UK
Chapter 10 Poisoning, overdose, antidotes, Chapter 11 Drug
dependence
Michael C Lee MBBS FRCA PhD FFPMRCA
Consultant, Churchill Hospital, Oxford, UK
Chapter 18 Pain and analgesics
Justin C Mason PhD FRCP
Professor of Vascular Rheumatology, Imperial College London,
UK
Chapter 16 Drugs for inflammation and joint disease
Karim Meeran MD FRCP FRCPath
Professor of Endocrinology, Faculty of Medicine, Imperial
College London, UK
Chapter 38 Hypothalamic, pituitary and sex hormones
Jerry P Nolan FRCA FCEM FRCP FFICM
Consultant in Anaesthesia & Intensive Care Medicine, Royal
United Hospital, Bath, UK
Chapter 19 Anaesthesia and neuromuscular block
David Nutt, DM FRCP FRCPsych FMedSci
The Edmond J Safra Chair in Neuropsychopharmacology,
Imperial College London, UK
Chapter 20 Psychotropic drugs
Kevin M O’Shaughnessy MA BM BCh DPhil FRCP
Senior Lecturer in Clinical Pharmacology, University of
Cambridge, UK
Chapter 22 Cholinergic and antimuscarinic (anticholinergic)
mechanisms and drugs, Chapter 23 Adrenergic mechanisms and
drugs, Chapter 24 Arterial hypertension, angina pectoris,
myocardial infarction and heart failure, Chapter 26
Hyperlipidaemias, Chapter 27 Kidney and genitourinary tract,
Chapter 28 Respiratory system
Munir Pirmohamed MB CHB PhD FRCP
NHS Chair of Pharmacogenetics, University of Liverpool, UK
Chapter 8 General pharmacology; Pharmacogenomics
June Raine
Chapter 4 Evaluation of drugs in humans, Chapter 6 Official
regulation of medicines
Sir Michael Rawlins MD FRCP FMedSci
Chairman, National Institute for Clinical Excellence (NICE),
London, UK
Chapter 5 Health technology assessment
Sir Peter C Rubin MA DM FRCP
Professor of Therapeutics, University of Nottingham, UK; Chair,
General Medical Council, UK
Chapter 2 Topics in drug therapy: Practical prescribing
Mike Schachter MB BSc FRCP
Senior Lecturer in Clinical Pharmacology, Imperial College,
London, UK
Chapter 1 Clinical pharmacology, Chapter 2 Topics in drug
therapy, Chapter 8 General pharmacology, Chapter 9 Unwanted
effects and adverse drug reactions
Surender K Sharma MD PhD
Chief, Division of Pulmonary, Critical Care and Sleep Medicine;
Head, Department of Medicine; All India Institute of Medical
Sciences, New Delhi, India
Chapter 14 Chemotherapy of bacterial infections
Clare Thornton MA MRCP
Wellcome Trust Clinical Research Fellow, Imperial College
London, UK
Chapter 16 Drugs for inflammation and joint disease
Patrick Vallance
President, Pharmaceuticals R&D GlaxoSmithKline, Brentford UK
Chapter 3 Discovery and development of drugs
Harpreet Wasan MBBS FRCP
Consultant & Reader in Medical Oncology, Hammersmith
Hospital, Imperial College Healthcare NHS trust, London, UK
Chapter 31 Neoplastic disease and immunosuppression
Sue Wilson PhD
Research Fellow, University of Bristol, UK
Chapter 20 Psychotropic drugs
Contributors
viii
Preface
For your own satisfaction and for mine, please read this preface!1
A preface should tell the prospective reader about the subject of a book, its purpose, and its plan.
This book is about the scientific basis and practice of drug therapy. It addresses medical students and
doctors in particular, but also anyone concerned with evidence-based drug therapy and prescribing.
The scope and rate of drug innovation increase. Doctors now face a professional lifetime of hand-
ling drugs that are new to themselves – drugs that do new things as well as drugs that do old things
better; and drugs that were familiar during medical training become redundant.
We write not only for readers who, like us, have a special interest in pharmacology. We try to make
pharmacology understandable for those whose primary interests lie elsewhere but who recognise that
they need some knowledge of pharmacology if they are to meet their moral and legal ‘duty of care’
to their patients. We are aware too, of medical curricular pressures that would reduce the time devoted
to teaching clinical pharmacology and therapeutics, and such diminution is surely a misguided policy
for a subject that is so integral to the successful practice of medicine. Thus, we try to tell readers what
they need to know without burdening them with irrelevant information, and we try to make the sub-
ject interesting. We are very serious, but seriousness does not always demand wearying solemnity.
All who prescribe drugs would be wise to keep in mind the changing and ever more exacting ex-
pectations of patients and of society in general. Doctors who prescribe casually or ignorantly now face
not only increasing criticism but also civil (or even criminal) legal charges. The ability to handle new
developments depends, now more than ever, on comprehension of the principles of pharmacology.
These principles are not difficult to grasp and are not so many as to defeat even the busiest doctors
who take upon themselves the responsibility of introducing manufactured medicines into the bodies
of their patients.
The principles of pharmacology and drug therapy appear in Chapters 1–11 and their application in
the subsequent specialist chapters where we draw on the knowledge and authority of a range of ex-
perts in these fields. The current edition includes new contributions from Sir Michael Rawlins,
Sir Peter Rubin, Professor Munir Pirmohamed and Professor Patrick Vallance. We seek to offer a rea-
sonably brief solution to the problem of combining practical clinical utility with an account of the
principles on which clinical practice rests.
The quantity of practical technical detail to include is a matter of judgment. In general, where ther-
apeutic practices are complex, potentially dangerous, and commonly updated, e.g. anaphylactic
shock, we provide more detail, together with websites for the latest advice; we give less or even no
detail on therapy that specialists undertake, e.g. anticancer drugs. Nevertheless, especially with mod-
ern drugs that are unfamiliar, the prescriber should consult formularies, approved guidelines, or the
manufacturer’s current literature.
Use of the book. Francis Bacon2 wrote that ‘Some books are to be tasted, others to be swallowed,
and some few to be chewed and digested.’ Perhaps elements of each activity can apply to parts of our
text. Students and doctors are, or should be, concerned to understand and to develop a rational,
1St Francis of Sales: Preface to Introduction to the devout life (1609).
2Francis Bacon (1561–1626) Essays (1625) ‘Of studies’. Philosopher and scientist, Bacon introduced the idea of the
experimental or inductive method of reasoning for understanding nature.
ix
critical attitude to drug therapy and they should therefore chiefly address issues of how drugs act and
interact in disease and how evidence of therapeutic effect is obtained and evaluated.
To this end, they should read selectively and should not impede themselves by attempts to mem-
orise lists of alternative drugs and doses and minor differences between them, which should never be
required of them in examinations. Thus, we do not encumber the text with exhaustive lists of prep-
arations, which properly belong in a formulary, although we hope that enough has been mentioned
to cover much routine prescribing, and many drugs have been included solely for identification.
The role and status of a textbook. A useful guide to drug use must offer clear conclusions and
advice. If it is to be of reasonable size, it may often omit alternative acceptable courses of action. What
it recommends should rest on sound evidence, where this exists, and on an assessment of the opin-
ions of the experienced where it does not.
Increasingly, guidelines produced by specialist societies and national bodies have influenced the
selection of drugs. We provide or refer to these as representing a consensus of best practice in partic-
ular situations. Similarly, we assume that the reader possesses a formulary, local or national, that will
provide guidance on the availability, including doses, of a broad range of drugs. Yet the practice of
medicinal therapeutics by properly educated and conscientious doctors working in settings compli-
cated by intercurrent disease, metabolic differences or personality, involves challenges beyond the
rigid adherence to published recommendations. The role of a textbook is to provide the satisfaction
of understanding the basis for a recommended course of action and to achieve an optimal result by
informed selection and use of drugs. As the current edition of the book, initiated and for years main-
tained by Desmond Laurence, now crosses the landmark of 50 years in print, we can but reassert our
belief in this principle.
Bath, Cambridge, London. P.N.B., M.J.B., P.S. 2012
Preface
x
Acknowledgements
It is not possible for three individuals to cover the whole field of drug therapy from their own knowl-
edge and experience. As with previous editions, we invited selected experts to review chapters in their
specialty. They received free rein to add, amend or delete existing text, as they deemed appropriate. We
consider that the book has benefited greatly from the proficiency of these individuals; their names
appear in the list of Contributors alongside their chapters.
Additionally, we express our gratitude to others who have, with such good grace, given us of their
time and energy to supply valuable facts and opinions for this and previous editions; they principally
include: Professor Nigel S Baber, Dr Gerald S Conway, Dr Pippa G Corrie, Dr Francis Hall, Dr Ian
Hudson, the late Professor BNC Pritchard, Dr JPD Reckless, Dr Catriona Reid, Dr Charles Singer.
Much of any merit this book may have is due to the generosity of those referred to above, as well as
others too numerous to mention who have put their knowledge and practical experience of the use of
drugs at our disposal. We hope that this collective acknowledgement will be acceptable. Errors are our
own. We are grateful to readers who alert us to errors and make other suggestions for future editions.
In addition, we thank the authors and publishers who generously granted permission to quote
directly from their writings. If we have omitted any due acknowledgements, we will make amends
as soon as we can.
P.N.B
M.J.B.
P.S.
xi
Chapter | 1 |
Clinical pharmacology
Mike Schachter
SYNOPSIS
Clinical pharmacology comprises all aspects of the scien-
tific study of drugs in humans. Its objective is to optimise
drug therapy and it is justified in so far as it is put to
practical use.
The use of drugs1 to increase human happiness by elim-
ination or suppression of diseases and symptoms and to
improve the quality of life in other ways is a serious matter
and involves not only technical, but also psychosocial con-
siderations. Overall, the major benefits of modern drugs
are on quality of life (measured with difficulty), and exceed
those on quantity of life (measured with ease).2 In some sit-
uations we can attempt both objectives.
Medicines are part of our way of life from birth, when we
may enter the world with the aid of drugs, to death, where
drugs assist (most of) us to depart with minimal distress
and perhaps even with a remnant of dignity. In between
these events we regulate our fertility, often, with drugs.
We tend to take such usages for granted.
But during the intervals remaining, an average family
experiences illness on 1 day in 4 and between the ages
of 20 and 45 years a lower-middle-class man experiences
approximately one life-endangering illness, 20 disabling
(temporarily) illnesses, 200 non-disabling illnesses and
1000 symptomatic episodes: the average person in the
USA can expect to have about 12 years of bad health in
an average lifespan,3 and medicines play a major role:
‘At any time, 40–50% of adults [UK] are taking a prescribed
medicine.’4
Over the centuries humans have sought relief from dis-
comfort in ‘remedies’ concocted from parts of plants, an-
imals and other sources; numerous formularies attest to
their numbers and complexity. Gradually, a more critical
view emerged, recognising the need for proper investiga-
tion of medications. In 1690, John Locke5 was moved
to write, ‘we should be able to tell beforehand that rhu-
barb will purge, hemlock kill, and opium make a man
sleep . . .’.
Yet it was only in the early years of the 20th century that
we began to see the use of specific chemical substances to
achieve particular biological effects; that is, the exact sci-
ence of drug action, which is pharmacology. Subsequently
the discipline underwent a major expansion resulting from
technology that allowed the understanding of molecular
action and the capacity to exploit this. The potential
1A World Health Organization scientific group has defined a drug as ‘any
substance or product that is used or intended to be used to modify or
explore physiological systems or pathological states for the benefit of
the recipient’ (WHO 1966 Technical Report Series no. 341:7). A less
restrictive definition is ‘a substance that changes a biological system by
interacting with it’. (Laurence DR, Carpenter J 1998 A dictionary of
pharmacology and allied topics. Elsevier, Amsterdam, p 106)
A drug is a single chemical substance that forms the active ingredient
of a medicine (a substance or mixture of substances used in restoring or
preserving health). A medicine may contain many other substances to
deliver the drug in a stable form, acceptable and convenient to the
patient. The terms will be used more or less interchangeably in this
book. To use the word ‘drug’ intending only a harmful, dangerous or
addictive substance is to abuse a respectable and useful word.
2Consider, for example, the worldwide total of suffering relieved and
prevented each day by anaesthetics (local and general) and by
analgesics, not forgetting dentistry which, because of these drugs, no
longer strikes terror into even the most stoical as it has done for centuries.
3Quoted in: USA Public Health Service 1995.
4George C F 1994 Prescribers’ Journal 34:7. A moment’s reflection will
bring home to us that this is an astounding statistic which goes a long
way to account for the aggressive promotional activities of the highly
competitive international pharmaceutical industry; the markets for
medicines are colossal.
5Locke J 1690 An Essay Concerning Human Understanding. Clarendon
Press, Oxford, book iv, chapter iii, p. 556. The English philosopher John
Locke (1632–1704) argued that all human knowledge came only from
experience and sensations.
2
consequences for drug therapy are enormous. All cellular
mechanisms (normal and pathological), in their immense
complexity, are, in principle, identifiable. What seems al-
most an infinite number of substances, transmitters, local
hormones, cell growth factors, can be made, modified
and tested to provide agonists, partial agonists, inverse
agonists and antagonists. Moreover, the unravelling of
the human genome opens the way for interference with
disease processes in ways that were never thought possible
before now.
Increasingly large numbers of substances will deserve to
be investigated and used for altering physiology to the ad-
vantage of humans. With all these developments, and
their potential for good, comes capacity for harm, whether
inherent in the substances themselves or resulting from
human misapplication. Successful use of the power con-
ferred (by biotechnology in particular) requires under-
standing of the growing evidence base of the true
consequences of interference. The temporary celebrity of
new drugs is not a new phenomenon. Jean Nicholas
Corvisart6 (1755–1821) reputedly expressed the issue in
the dictum: ‘Here is a new remedy; take it fast, as long
as it still works’.
Clinical pharmacology provides the scientific
basis for:
•
the general aspects of rational, safe and effective
drug therapy
•
drug therapy of individual diseases
•
the safe introduction of new medicines.
The drug and information explosion of the past six de-
cades, combined with medical need, has called into being
a new discipline, clinical pharmacology.7 The discipline
finds recognition as both a health-care and an academic
specialty; indeed, no medical school can be considered
complete without a department or sub-department of clin-
ical pharmacology.
A signal pioneer was Harry Gold8 (1899–1972), of
Cornell University, USA, whose influential studies in the
1930s showed the qualities needed to be a clinical pharma-
cologist. In 1952, he wrote in a seminal article:
a special kind of investigator is required, one whose
training has equipped him not only with the principles
and technics of laboratory pharmacology but also with
knowledge of clinical medicine . . .
Clinical scientists of all kinds do not differ
fundamentally from other biologists; they are set apart
only to the extent that there are special difficulties and
limitations, ethical and practical, in seeking knowledge
from man.9
Willingness to learn the principles of pharmacology,
and how to apply them in individual circumstances of in-
finite variety is vital to success without harm: to maximise
benefit and minimise risk. All of these issues are the
concern of clinical pharmacology and are the subject of
this book.
More detailed aspects comprise:
1.
Pharmacology
•
Pharmacodynamics: how drugs, alone and in
combination, affect the body (young, old, well,
sick).
•
Pharmacokinetics: absorption, distribution,
metabolism, excretion or how the body – well or
sick – affects drugs.
2.
Therapeutic evaluation
•
Whether a drug is of value.
•
How it may best be used.
•
Formal therapeutic trials.
•
Surveillance studies for both efficacy and safety
(adverse effects) – pharmacoepidemiology and
pharmacovigilance.
3.
Control
•
Rational prescribing and formularies.
•
Official regulation of medicines.
•
Social aspects of the use and misuse of medicines.
•
Pharmacoeconomics.
Clinical pharmacology finds expression in concert with
other clinical specialties. Therapeutic success with drugs
is becoming more and more dependent on the user having
at least an outline understanding of both pharmacodynam-
ics and pharmacokinetics. This outline is quite simple and
easy to acquire. However humane and caring doctors may
6He was Emperor Napoleon’s favourite physician.
7The term was first used by Paul Martini (1889–1964). He addressed
issues that are now integral parts of clinical trials, including the use of
placebo, control groups, sample size, relationship between dose and
response, probability of efficacy. His monograph Methodology of
Therapeutic Investigation (Springer, Berlin, 1932), was published in
German and went largely unnoticed by English speakers. (Shelly J H,
Baur M P 1999 Paul Martini: the first clinical pharmacologist? Lancet
353:1870–1873).
8Gold H 1952 The proper study of mankind is man. American Journal of
Medicine 12:619. The title is taken from An Essay on Man by Alexander
Pope (English poet, 1688–1744), which begins with the lines: ‘Know then
thyself, presume not God to scan,/The proper study of mankind is man’.
Indeed, the whole passage is worth appraisal, for it reads as if it were
relevant to modern clinical pharmacology and drug therapy.
9Self-experimentation
has
always
been
a
feature
of
clinical
pharmacology. A survey of 250 members of the Dutch Society of
Clinical Pharmacology evoked 102 responders of whom 55 had carried
out
experiments
on
themselves
(largely
for
convenience)
(van
Everdingen J J, Cohen A F 1990 Self-experimentation by doctors.
Lancet 336:1448). A spectacular example occurred at the 1983
meeting of the American Urological Association at Las Vegas, USA,
during a lecture on pharmacologically induced penile erection, when
the lecturer stepped out from behind the lectern to demonstrate
personally the efficacy of the technique (Zorgniotti A W 1990 Self-
experimentation. Lancet 36:1200).
Clinical pharmacology
Chapter
| 1 |
3
be, they cannot dispense with scientific skill. Knowledge of
clinical pharmacology underpins decisions in therapeutics,
which is concerned with the prevention, suppression or
cure of disease and, from the point of view of society, is
the most vital aspect of medicine.
Pharmacology is the same science whether it investigates
animals or humans. The need for it grows rapidly as not
only scientists, but now the whole community, can see
its promise of release from distress and premature death
over yet wider fields. The concomitant dangers of drugs (fe-
tal deformities, adverse reactions, dependence) only add to
the need for the systematic and ethical application of sci-
ence to drug development, evaluation and use, i.e. clinical
pharmacology.
GUIDE TO FURTHER READING
Baber, N.S., Ritter, J.M., Aronson, J.K.,
2004. Medicines regulation and
clinical pharmacology. Br. J. Clin.
Pharmacol. 58 (6), 569–570 (and
other articles in this issue).
Dollery, C.T., 2006. Clinical
pharmacology – the first 75 years and a
view of the future. Br. J. Clin.
Pharmacol. 61, 650–665.
FitzGerald, G.A., 2007. Clinical
pharmacology or translational
medicine and therapeutics: reinvent
or rebrand and expand? Clin.
Pharmacol. Ther. 81 (1), 19–20.
Honig, P., 2007. The value and future of
clinical pharmacology. Clin.
Pharmacol. Ther. 81 (1), 17–18.
Laurence, D.R., 1989. Ethics and law in
clinical pharmacology. Br. J. Clin.
Pharmacol. 27, 715–722.
Rawlins, M.D., 2005. Pharmacopolitics
and deliberative democracy. Clin.
Med. (Northfield Il) 5, 471–475.
Reidenberg, M.M., 2008. A new look
at the profession of clinical
pharmacology. Clin. Pharmacol. Ther
83 (2), 213–217 (and other articles in
this issue).
Waldman, S.A., Christensen, N.B.,
Moore, J.E., Terzic, A., 2007. Clinical
pharmacology: the science of
therapeutics. Clin. Pharmacol. Ther.
81 (1), 3–6.
Section
| 1 |
General
4
Chapter | 2 |
Topics in drug therapy
Mike Schachter, Sir Peter Rubin
SYNOPSIS
Drug therapy involves considerations beyond the strictly
scientific pharmacological aspects of medicines. These in-
clude numerous issues relating to prescribers and to
patients:
• Practical prescribing.
• The therapeutic situation.
• Treating patients with drugs.
• Iatrogenic disease.
• Benefits and risks.
• Public view of drugs and prescribers.
• Criticisms of modern drugs.
• Drug-induced injury.
• Complementary and alternative medicine.
• Placebo medicines.
• Guidelines, ‘essential’ drugs and prescribing.
• Compliance – patient and doctor.
• Pharmacoeconomics.
5
Practical prescribing
Sir Peter Rubin
First, on this topic, Professor Sir Peter Rubin, Chair of the
General Medical Council, the body that regulates the practice
of medicine by doctors in the UK, writes on the prescribing of
medicines.
Prescribing is a task carried out many times each day and
can seem mundane – a technical process that is far less stim-
ulating and interesting than reaching a diagnosis. However,
there is no such thing as a safe drug and prescribing has the
potential to cause harm or death as well as good. This section
includes some practical advice aimed at identifying common
pitfalls and reducing risk.
The case histories are all real. The data given in the text
and figures come from a study commissioned by the
General Medical Council.1
PRESCRIBING
Getting it right
Good prescribing starts with taking a good history:
•
Does your patient have other medical conditions –
some may be worsened by treatment you would
normally give for their presenting complaint.
•
What drugs is your patient taking now? What are they
for? Are they all still needed? Could they be causing the
symptoms or signs that have brought the patient to
you? Could they interact with whatever you might
think of prescribing?
•
What drugs has your patient taken in the past? Why
were they stopped? Did they cause side-effects?
•
Is the patient allergic to any drugs?
•
Are they taking any non-prescription (over-the-counter)
drugs? If so, could they interact with whatever you might
prescribe (for example, St John’s wort is an enzyme-
inducer)?
Good prescribing means:
•
Making a diagnosis – or at least having a range of
possibilities. Know what it is you are wishing to achieve
and the evidence for the likely efficacy of the drug
treatment you wish to give.
•
Knowing your patient’s kidney and liver function –
most drugs are eliminated by these organs; and some
drugs can damage them.
•
Getting the dose right. For many drugs you will not
know the dose, so do not pretend you do. Never, ever
guess. Never be afraid to ask. Never be too busy to look
up a dose – better to check now than make a trip to the
Coroner’s Court later.
•
Explaining to your patient why you think this treatment
will work,thelikelihoodof it working,the morecommon
side-effects and what your plans are if it does not work.
•
Being alert to the development of adverse drug
reactions. If a patient develops new symptoms after
starting a drug, it is probably the drug. If the adverse
effect is in a fairly new drug – or is not already well
known – you should report the event to the national
body responsible for monitoring and recording adverse
drug reactions.
•
Being very clear about what it is you are prescribing.
•
If using a hand-written prescription, write clearly.
•
If working in a different hospital, remember that the
prescription chart may not be the same as where you
have just been.
•
If using electronic prescribing, beware drop-down
menus and drugs with similar looking names, e.g.
carbimazole and carbamazepine.
Examples of when things went wrong
Focusing on the presenting complaint and
forgetting other medical conditions
A 79-year-old man was admitted to a surgical ward. He told
the admitting doctor that he had long-standing arthritis
which had got worse since his doctor stopped diclofenac
and he asked for it to be re-started. The doctor did so,
but did not notice the patient’s significant renal impair-
ment. The patient went into renal failure and died. A drug
which helps one condition may worsen another!
Forgetting that women get pregnant
A 40-year-old woman is found to be hypertensive. She has
three children, the youngest being 15. Her GP commences
ramipril. Neither the patient nor the doctor suspected that
she was, in fact, in the second trimester of pregnancy. The
baby died at birth from major renal and other abnormali-
ties. Subsequent litigation was settled out of court in the pa-
tient’s favour. Remember that pregnancy is always a possibility
in women of child-bearing age!
Not knowing what you are prescribing
A 29-year-old woman came to the hospital with a urinary
tract infection. The consultant told a young doctor looking
after her to prescribe PenbritinW. She did so and the patient
1http://www.gmc-uk.org/about/research/research_commissioned_4.asp
(accessed 4 October 2011).
Section
| 1 |
General
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