Rang & Dale's Pharmacology

2015·100.35 MB·English

by  Humphrey P. Rang

G
R
V
d
e
t
i
n
U
vip.persianss.ir
G
R
V
RdANG AND DALE’S
Pharmacology
e
t
i
n
U
vip.persianss.ir
G
R
V
d
e
t
i
n
U
Content Strategist: Meghan Ziegler
Content Development Specialist: Alexandra Mortimer
Content Coordinator: Sam Crowe, Trinity Hutton
Project Manager: Joanna Souch
Design: Christian Bilbow
Illustration Manager: Brett MacNaughton
Illustrator: Peter Lamb, Antbits, Jason McAlexander
Marketing Manager: Melissa Darling
vip.persianss.ir
RANG AND DALE’S

Pharmacology
EIGHTH EDITION
G
H P Rang
MB BS MA DPhil Hon FBPharmacolS FMedSci FRS
R
Emeritus Professor of Pharmacology,
University College London, London, UK
V
J M Ritter
DPhil FRCP FBPharmacolS FMedSci
d
Emeritus Professor of Clinical Pharmacology,
King’s College London, and Medicael Research Director, Quintiles,
London, UK
t
R J Flower i
PhD DSc FBPharmacolS FMedSci FRS
n
Professor, Biochemical Pharmacology,
The William Harvey ResU earch Institute,
Barts and the London School of Medicine and Dentistry,
Queen Mary University of London, London, UK
G Henderson
BSc PhD FBPharmacolS FSB
Professor of Pharmacology, University of Bristol, Bristol, UK
For additional online content visit
studentconsult
Student CONSULT
vip.persianss.ir
an imprint of Elsevier Limited
© 2016, Elsevier Ltd. All rights reserved.
First edition 1987
Second edition 1991
Third edition 1995
Fourth edition 1999
Fifth edition 2003
Sixth edition 2007
Seventh edition 2012
The right of H P Rang, J M Ritter, R J Flower and G Henderson 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 G
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 bRy the
Publisher (other than as may be noted herein).
Notices
V
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 experiendce 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
e
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
t
product to be administered, to verify the recommended dose or formula, the method and duration
of administration, and contraindications. It is the reisponsibility of practitioners, relying on their own
experience and knowledge of their patients, to mnake diagnoses, to determine dosages and the best
treatment for each individual patient, and to take all appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors,
assume any liability for any injury and/Uor 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:
Main edition
ISBN-13 978-0-7020-5362-7
International edition
ISBN-13 978-0-7020-5363-4
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
vip.persianss.ir
Rang and Dale’s Pharmacology
Eighth Edition Preface
In this edition, as in its predecessors, we set out not just therapeutic effects; (3) the action of drugs on specific
to describe what drugs do but also to emphasise the mech- organ systems; (4) the action of drugs on the nervous
anisms by which they act. This entails analysis not only system; (5) the action of drugs used to treat infectious
at the cellular and molecular level, where knowledge and diseases and cancer; (6) a range of special topics such as
techniques are advancing rapidly, but also at the level of adverse effects, non-medical uses of drugs, etc. This
physiological mechanisms and pathological disturbances. organisation reflects our belief that drug action needs to
Pharmacology has its roots in therapeutics, where the aim be understood, not as a mere description of the effects of
is to ameliorate the effects of disease, so we have attempted individual drugs and their uses, but as a chemical inter-
to make the link between effects at the molecular and cel- vention that perturbs the network of chemical and cellular
lular level and the range of beneficial and adverse effects signalling that underlies the function of any living organ-
that humans experience when drugs are used for thera- ism. In addition to updating all of the chapters, we have
peutic or other reasons. Therapeutic agents have a high covered the receptor-related topics of biased agonism,
rate of obsolescence, and more than 100 new ones have allosteric modulation and desensitisation in more detail
G
been approved since the last edition of this book. An in Chapters 2 and 3, as well as revamping the section on
appreciation of the mechanisms of action of the class of nuclear receptors. A new Chapter 27 on the pharmacology
drugs to which a new agent belongs provides a good start- of the skin has been added, and Chapters 17 and 18
ing point for understanding and using a new compound on local hormonesR have been revised. Additional material
intelligently. on cognition-enhancing drugs has been included in
Pharmacology is a lively scientific discipline in its own Chapter 48.
right, with an importance beyond that of providing a basis Despite the fact that pharmacology, like other branches
V
for the use of drugs in therapy, and we aim to provide a of biomedical science, advances steadily, with the acquisi-
good background, not only for future doctors but also for tion of new information, the development of new con-
scientists in other disciplines who need to understand cepts and the introduction of new drugs for clinical use,
how drugs act. We have, therefore, where appropriate, wde have avoided making the 8th edition any longer than
described how drugs are used as probes for elucidating its predecessor by cutting out-dated and obsolete mate-
cellular and physiological functions, even when the com- rial, and have made extensive use of small print text to
e
pounds have no clinical use. cover more specialised and speculative information that
Names of drugs and related chemicals are established is not essential to understanding the key message, but
through usage and sometimes there is more thtan one will, we hope, be helpful to students seeking to go into
name in common use. For prescribing purposes, it is greater depth. In selecting new material for inclusion, we
i
important to use standard names, and we follow, as far as have taken into account not only new agents but also
n
possible, the World Health Organization’s list of recom- recent extensions of basic knowledge that presage further
mended international non-proprietary names (rINN). drug development. And where possible, we have given a
Sometimes these conflict with the familiar names of drugs brief outline of new treatments in the pipeline. Reference
U
(e.g. amphetamine becomes amfetamine in the rINN list), lists are largely restricted to guidance on further reading,
and the endogenous mediator prostaglandin I – the together with review articles that list key original papers.
2
standard name in the scientific literature – becomes ‘epo-
prostenol’ – a name unfamiliar to most scientists – in
the rINN list. In general, we use rINN names as far as
possible in the context of therapeutic use, but often use
the common name in describing mediators and familiar
drugs. Sometimes English and American usage varies
(as with adrenaline/epinephrine and noradrenaline/
norepinephrine). Adrenaline and noradrenaline are the
official names in EU member states and relate clearly to
terms such as ‘noradrenergic’, ‘adrenoceptor’ and ‘adrenal
gland’ and we prefer them for these reasons.
Drug action can be understood only in the context of
what else is happening in the body. So at the beginning
of most chapters, we briefly discuss the physiological and
biochemical processes relevant to the action of the drugs
described in that chapter. We have included the chemical
structures of drugs only where this information helps in
understanding their pharmacological and pharmacoki-
netic characteristics, secure in the knowledge that chemi-
cal structures are readily available online.
The overall organisation of the book has been retained,
with sections covering: (1) the general principles of drug
action; (2) the chemical mediators and cellular mecha-
nisms with which drugs interact in producing their xv
vip.persianss.ir
G
R
V
d
e
t
i
n
U
ACKNOWLEDGEMENTS
We would like to thank the following for their help
and advice in the preparation of this edition: Dr Alistair
Corbett, Dr Hannah Gill, Professor Eamonn Kelly,
Professor Alastair Poole, Dr Emma Robinson, Dr Maria
Usowicz and Professor Federica Marelli-Berg. We would
like to put on record our appreciation of the team at
Elsevier who worked on this edition: Meghan Ziegler
(commissioning editor), Alexandra Mortimer (develop-
ment editor), Joanna Souch (project manager), Brett
MacNaughton (illustration manager), Peter Lamb, Antbits
and Jason McAlexander (freelance illustrators), Elaine
Leek (freelance copyeditor), Marcela Holmes (freelance
proofreader) and Innodata Inc. (freelance indexing
services).
London 2014 H. P. Rang
J. M. Ritter
R. J. Flower
G. Henderson
vip.persianss.ir
GENERAL PRINCIPLES    SECTION 1
1
What is pharmacology?
pharmacopoeias were written, and the apothecaries’ trade 
OVERVIEW
flourished. However, nothing resembling scientific prin-
ciples was applied to therapeutics, which was known at 
In this introductory chapter we explain how phar-
that time as materia medica.2 Even Robert Boyle, who laid 
macology came into being and evolved as a scien-
the scientific foundations of chemistry in the middle of the 
tific discipline, and describe the present day structure
17th century, was content, when dealing with therapeu-
of the subject and its links to other biomedical
tics (A Collection of Choice Remedies, 1692), to recommend 
sciences. The structure that has emerged forms the
concoctions of worms, dung, urine and the moss from a 
basis of the organisation of the rest of the book.
dead man’s skull. The impetus for pharmacology came 
Readers in a hurry to get to the here-and-now of
G
pharmacology can safely skip this chapter. from the need to improve the outcome of therapeutic 
intervention by doctors, who were at that time skilled at 
clinical observation and diagnosis but broadly ineffectual 
WHAT IS A DRUG? when it came to treatment.3 Until the late 19th century, 
R
knowledge of the normal and abnormal functioning of the 
For the purposes of this book, a drug can be defined as a body was too rudimentary to provide even a rough basis 
chemical substance of known structure, other than a nutrient for understanding drug effects; at the same time, disease 
or an essential dietary ingredient,1 which, when administered and deathV were regarded as semisacred subjects, appro-
to a living organism, produces a biological effect. priately dealt with by authoritarian, rather than scientific, 
A few points are worth noting. Drugs may be synthetic  doctrines. Clinical practice often displayed an obedience 
chemicals, chemicals obtained from plants or animals, or  tod authority and ignored what appear to be easily ascer-
products of genetic engineering. A medicine is a chemical  tainable facts. For example, cinchona bark was recognised 
preparation, which usually, but not necessarily, contains  as a specific and effective treatment for malaria, and a 
one or more drugs, administered with the intention oef  sound protocol for its use was laid down by Lind in 1765. 
producing a therapeutic effect. Medicines usually contain  In 1804, however, Johnson declared it to be unsafe until 
other  substances  (excipients,  stabilisers,  solvents,  etc.)  the fever had subsided, and he recommended instead the 
besides the active drug, to make them more convetnient to  use of large doses of calomel (mercurous chloride) in  
use. To count as a drug, the substance must bie adminis- the early stages – a murderous piece of advice that was 
tered as such, rather than released by physionlogical mech- slavishly followed for the next 40 years.
anisms. Many substances, such as insulin or thyroxine, are  The motivation for understanding what drugs can and 
endogenous hormones but are also drugs when they are  cannot do came from clinical practice, but the science 
administered intentionally. Many drUugs are not used in  could be built only on the basis of secure foundations in 
medicines but are nevertheless useful research tools. In  physiology, pathology and chemistry. It was not until 
everyday parlance, the word drug is often associated with  1858 that Virchow proposed the cell theory. The first use 
addictive, narcotic or mind-altering substances – an unfor- of a structural formula to describe a chemical compound 
tunate negative connotation that tends to bias uninformed  was in 1868. Bacteria as a cause of disease were discovered 
opinion against any form of chemical therapy. In this book  by Pasteur in 1878. Previously, pharmacology hardly had 
we focus mainly on drugs used for therapeutic purposes  the legs to stand on, and we may wonder at the bold 
but also describe important examples of drugs used as  vision of Rudolf Buchheim, who created the first pharma-
experimental tools. Although poisons fall strictly within  cology institute (in his own house) in Estonia in 1847.
the definition of drugs, they are not covered in this book. In its beginnings, before the advent of synthetic organic 
chemistry,  pharmacology  concerned  itself  exclusively 
with  understanding  the  effects  of  natural  substances, 
ORIGINS AND ANTECEDENTS
mainly plant extracts – and a few (mainly toxic) chemicals 
such as mercury and arsenic. An early development in 
Pharmacology can be defined as the study of the effects 
chemistry was the purification of active compounds from 
of drugs on the function of living systems. As a science, 
plants. Friedrich Sertürner, a young German apothecary, 
it was born in the mid-19th century, one of a host of new 
purified morphine from opium in 1805. Other substances 
biomedical sciences based on principles of experimenta-
quickly followed, and, even though their structures were 
tion  rather  than  dogma  that  came  into  being  in  that 
unknown, these compounds showed that chemicals, not 
remarkable period. Long before that – indeed from the 
magic or vital forces, were responsible for the effects that 
dawn of civilisation – herbal remedies were widely used, 
2The name persists today in some ancient universities, being attached to 
1Like most definitions, this one has its limits. For example, there are a  chairs of what we would call clinical pharmacology.
number of essential dietary constituents, such as iron and various  3Oliver Wendell Holmes, an eminent physician, wrote in 1860: ‘[I] 
vitamins, that are used as medicines. Furthermore, some biological  firmly believe that if the whole materia medica, as now used, could be 
products (e.g. epoietin) show batch-to-batch variation in their chemical  sunk to the bottom of the sea, it would be all the better for mankind 
1
constitution that significantly affects their properties. and the worse for the fishes’ (see Porter, 1997).
vip.persianss.ir
1
SECTION 1 GENERAL PRINCIPLES
plant extracts produced on living organisms. Early phar- and therapeutics. Biochemistry also emerged as a distinct 
macologists focused most of their attention on such plant- science early in the 20th century, and the discovery of 
derived drugs as quinine, digitalis, atropine, ephedrine,  enzymes and the delineation of biochemical pathways 
strychnine and others (many of which are still used today  provided yet another framework for understanding drug 
and will have become old friends by the time you have  effects. The picture of pharmacology that emerges from 
finished reading this book).4 this brief glance at history (Fig. 1.1) is of a subject evolved 
from ancient prescientific therapeutics, involved in com-
merce from the 17th century onwards, and which gained 
PHARMACOLOGY IN THE 20TH AND
respectability by donning the trappings of science as soon 
21ST CENTURIES as this became possible in the mid-19th century. Signs of 
its carpetbagger past still cling to pharmacology, for the 
Beginning in the 20th century, the fresh wind of synthetic 
pharmaceutical industry has become very big business 
chemistry  began  to  revolutionise  the  pharmaceutical 
and  much  pharmacological  research  nowadays  takes 
industry, and with it the science of pharmacology. New 
place in a commercial environment, a rougher and more 
synthetic drugs, such as barbiturates and local anaesthet- pragmatic place than the glades of academia.5 No other 
ics, began to appear, and the era of antimicrobial chemo-
biomedical ‘ology’ is so close to Mammon.
therapy began with the discovery by Paul Ehrlich in 1909 
of  arsenical  compounds  for  treating  syphilis.  Further 
ALTERNATIVE THERGAPEUTIC PRINCIPLES
breakthroughs came when the sulfonamides, the first anti-
bacterial drugs, were discovered by Gerhard Domagk in  Modern medicine relies heavily on drugs as the main  
1935, and with the development of penicillin by Chain  tool of therapeutics. Other therapeutic procedures, such 
and Florey during the Second World War, based on the  as surgery, diet, exercise, psychological treatments etc., 
R
earlier work of Fleming. are  also  important,  of  course,  as  is  deliberate  non-
These few well-known examples show how the growth  intervention, but none is so widely applied as drug-based 
of synthetic chemistry, and the resurgence of natural  therapeutics.
product chemistry, caused a dramatic revitalisation of  BefoVre the advent of science-based approaches, repeated 
therapeutics in the first half of the 20th century. Each new  attempts were made to construct systems of therapeutics, 
drug class that emerged gave pharmacologists a new chal- many of which produced even worse results than pure 
lenge, and it was then that pharmacology really estab- dempiricism. One of these was allopathy, espoused by James 
lished its identity and its status among the biomedical  Gregory (1735–1821). The favoured remedies included 
sciences. blood letting, emetics and purgatives, which were used 
In parallel with the exuberant proliferation of theraepeu- until the dominant symptoms of the disease were sup-
tic molecules – driven mainly by chemistry – which gave  pressed. Many patients died from such treatment, and it 
pharmacologists so much to think about, physiology was  was in reaction against it that Hahnemann introduced the 
t
also making rapid progress, particularly in relation to  practice  of  homeopathy  in  the  early  19th  century.  The 
chemical mediators, which are discussed iin depth else- implausible guiding principles of homeopathy are:
where in this book. Many hormones, nneurotransmitters 
• like cures like
and  inflammatory  mediators  were  discovered  in  this 
• activity can be enhanced by dilution.
period, and the realisation that chemical communication 
plays a central role in almost everUy regulatory mechanism  The system rapidly drifted into absurdity: for example, 
that our bodies possess immediately established a large  Hahnemann recommended the use of drugs at dilutions 
area of common ground between physiology and phar- of 1 : 1060, equivalent to one molecule in a sphere the size 
macology, for interactions between chemical substances  of the orbit of Neptune.
and living systems were exactly what pharmacologists  Many other systems of therapeutics have come and 
had been preoccupied with from the outset. The concept  gone, and the variety of dogmatic principles that they 
of ‘receptors’ for chemical mediators, first proposed by  embodied have tended to hinder rather than advance sci-
Langley in 1905, was quickly taken up by pharmacologists  entific progress. Currently, therapeutic systems that have 
such as Clark, Gaddum, Schild and others and is a con- a basis that lies outside the domain of science are actually 
stant theme in present-day pharmacology (as you will  gaining ground under the general banner of ‘alternative’ 
soon discover as you plough through the next two chap- or  ‘complementary’  medicine.  Mostly,  they  reject  the 
ters). The receptor concept, and the technologies devel- ‘medical model’, which attributes disease to an underlying 
oped from it, have had a massive impact on drug discovery  derangement of normal function that can be defined in 
biochemical or structural terms, detected by objective 
means, and influenced beneficially by appropriate chemi-
4A handful of synthetic substances achieved pharmacological  cal or physical interventions. They focus instead mainly 
prominence long before the era of synthetic chemistry began. Diethyl 
on subjective malaise, which may be disease-associated or 
ether, first prepared as ‘sweet oil of vitriol’ in the 16th century, and 
nitrous oxide, prepared by Humphrey Davy in 1799, were used to liven 
up parties before being introduced as anaesthetic agents in the 
mid-19th century (see Ch. 41). Amyl nitrite (see Ch. 21) was made in  5Some of our most distinguished pharmacological pioneers made 
1859 and can claim to be the first ‘rational’ therapeutic drug; its  their careers in industry: for example, Henry Dale, who laid the 
therapeutic effect in angina was predicted on the basis of its  foundations of our knowledge of chemical transmission and the 
physiological effects – a true ‘pharmacologist’s drug’ and the smelly  autonomic nervous system (Ch. 12); George Hitchings and Gertrude 
forerunner of the nitrovasodilators that are widely used today. Aspirin  Elion, who described the antimetabolite principle and produced  
(Ch. 26), the most widely used therapeutic drug in history, was first  the first effective anticancer drugs (Ch. 56); and James Black, who 
synthesised in 1853, with no therapeutic application in mind. It was  introduced the first β-adrenoceptor and histamine H-receptor 
2
2 rediscovered in 1897 in the laboratories of the German company Bayer,  antagonists (Chs 13 and 17). It is no accident that in this book, where 
who were seeking a less toxic derivative of salicylic acid. Bayer  we focus on the scientific principles of pharmacology, most of our 
commercialised aspirin in 1899 and made a fortune. examples are products of industry, not of nature.
vip.persianss.ir
1
WhAt IS PhARmACoLoGy?
(cid:36)(cid:83)(cid:83)(cid:85)(cid:82)(cid:91)(cid:76)(cid:80)(cid:68)(cid:87)(cid:72)(cid:3)(cid:71)(cid:68)(cid:87)(cid:72)(cid:86)
(cid:33)(cid:22)(cid:19)(cid:19)(cid:19)(cid:3)(cid:37)(cid:38) (cid:55)(cid:75)(cid:72)(cid:85)(cid:68)(cid:83)(cid:72)(cid:88)(cid:87)(cid:76)(cid:70)(cid:86)
(cid:48)(cid:68)(cid:74)(cid:76)(cid:70)(cid:68)(cid:79)(cid:3)(cid:83)(cid:82)(cid:87)(cid:76)(cid:82)(cid:81)(cid:86)
(cid:43)(cid:72)(cid:85)(cid:69)(cid:68)(cid:79)(cid:3)(cid:85)(cid:72)(cid:80)(cid:72)(cid:71)(cid:76)(cid:72)(cid:86)
(cid:97)(cid:20)(cid:25)(cid:19)(cid:19)(cid:3)(cid:36)(cid:39) (cid:38)(cid:82)(cid:80)(cid:80)(cid:72)(cid:85)(cid:70)(cid:72)
(cid:36)(cid:83)(cid:82)(cid:87)(cid:75)(cid:72)(cid:70)(cid:68)(cid:85)(cid:76)(cid:72)(cid:86)
(cid:38)(cid:75)(cid:72)(cid:80)(cid:76)(cid:86)(cid:87)(cid:85)(cid:92)
(cid:97)(cid:20)(cid:27)(cid:19)(cid:19)
(cid:49)(cid:68)(cid:87)(cid:88)(cid:85)(cid:68)(cid:79) (cid:37)(cid:76)(cid:82)(cid:80)(cid:72)(cid:71)(cid:76)(cid:70)(cid:68)(cid:79)
(cid:83)(cid:85)(cid:82)(cid:71)(cid:88)(cid:70)(cid:87)(cid:86) (cid:86)(cid:70)(cid:76)(cid:72)(cid:81)(cid:70)(cid:72)(cid:86)
(cid:51)(cid:68)(cid:87)(cid:75)(cid:82)(cid:79)(cid:82)(cid:74)(cid:92) G (cid:51)(cid:75)(cid:68)(cid:85)(cid:80)(cid:68)(cid:70)(cid:72)(cid:88)(cid:87)(cid:76)(cid:70)(cid:68)(cid:79)
(cid:51)(cid:75)(cid:68)(cid:85)(cid:80)(cid:68)(cid:70)(cid:82)(cid:79)(cid:82)(cid:74)(cid:92) (cid:76)(cid:81)(cid:71)(cid:88)(cid:86)(cid:87)(cid:85)(cid:92)
(cid:38)(cid:75)(cid:72)(cid:80)(cid:76)(cid:70)(cid:68)(cid:79) (cid:51)(cid:75)(cid:92)(cid:86)(cid:76)(cid:82)(cid:79)(cid:82)(cid:74)(cid:92)
(cid:86)(cid:87)(cid:85)(cid:88)(cid:70)(cid:87)(cid:88)(cid:85)(cid:72)
R
(cid:54)(cid:92)(cid:81)(cid:87)(cid:75)(cid:72)(cid:87)(cid:76)(cid:70)
(cid:97)(cid:20)(cid:28)(cid:19)(cid:19) (cid:70)(cid:75)(cid:72)(cid:80)(cid:76)(cid:86)(cid:87)(cid:85)(cid:92) (cid:37)(cid:76)(cid:82)(cid:70)(cid:75)(cid:72)(cid:80)(cid:76)(cid:86)(cid:87)(cid:85)(cid:92) (cid:54)(cid:92)(cid:81)(cid:87)(cid:75)(cid:72)(cid:87)(cid:76)(cid:70)
V (cid:71)(cid:85)(cid:88)(cid:74)(cid:86)
(cid:48)(cid:82)(cid:79)(cid:72)(cid:70)(cid:88)(cid:79)(cid:68)(cid:85)
(cid:97)(cid:20)(cid:28)(cid:26)(cid:19)
(cid:69)(cid:76)(cid:82)(cid:79)(cid:82)(cid:74)(cid:92)
(cid:37)(cid:76)(cid:82)(cid:83)(cid:75)(cid:68)(cid:85)(cid:80)(cid:68)(cid:70)(cid:72)(cid:88)(cid:87)(cid:76)(cid:70)(cid:68)(cid:79)(cid:86)
d
(cid:21)(cid:19)(cid:19)(cid:19) (cid:51)(cid:75)(cid:68)(cid:85)(cid:80)(cid:68)(cid:70)(cid:82)(cid:79)(cid:82)(cid:74)(cid:92)
Fig. 1.1  The development of pharmacology.  e
t
i
not. Abandoning objectivity in defining and measuring  duced into the body, are very different from those of 
n
disease goes along with a similar departure from scientific  drug-based therapeutics and will require a different con-
principles in assessing therapeutic efficacy and risk, with  ceptual framework, which texts such as this will increas-
the result that principles and practicesU can gain acceptance  ingly need to embrace if they are to stay abreast of modern 
without satisfying any of the criteria of validity that would  medical treatment.
convince a critical scientist, and that are required by law 
to be satisfied before a new drug can be introduced into  PHARMACOLOGY TODAY
therapy. Demand for ‘alternative’ therapies by the general 
public, alas, has little to do with demonstrable efficacy.6 As with other biomedical disciplines, the boundaries of 
pharmacology  are  not  sharply  defined,  nor  are  they  
constant. Its exponents are, as befits pragmatists, ever 
THE EMERGENCE OF BIOTECHNOLOGY
ready to poach on the territory and techniques of other 
Since the 1980s, biotechnology has emerged as a major  disciplines.  If  it  ever  had  a  conceptual  and  technical  
source of new therapeutic agents in the form of antibod- core that it could really call its own, this has now dwindled 
ies, enzymes and various regulatory proteins, including  almost to the point of extinction, and the subject is defined 
hormones, growth factors and cytokines (see Buckel, 1996;  by its purpose – to understand what drugs do to living 
Walsh, 2003). Although such products (known as biophar- organisms, and more particularly how their effects can  
maceuticals) are generally produced by genetic engineer- be applied to therapeutics – rather than by its scientific 
ing rather than by synthetic chemistry, the pharmacological  coherence.
principles are essentially the same as for conventional  Figure 1.2 shows the structure of pharmacology as it 
drugs. Looking further ahead, gene- and cell-based thera- appears today. Within the main subject fall a number of 
pies (Ch. 59), although still in their infancy, will take  compartments (neuropharmacology, immunopharmacol-
therapeutics into a new domain. The principles governing  ogy, pharmacokinetics, etc.), which are convenient, if not 
the design, delivery and control of functioning artificial  watertight,  subdivisions.  These  topics  form  the  main 
genes introduced into cells, or of engineered cells intro- subject matter of this book. Around the edges are several 
interface disciplines, not covered in this book, which form 
important two-way bridges between pharmacology and 
6The UK Medicines and Healthcare Regulatory Agency (MHRA)  other fields of biomedicine. Pharmacology tends to have 
requires detailed evidence of therapeutic efficacy based on controlled  more of these than other disciplines. Recent arrivals on 
clinical trials before a new drug is registered, but no clinical trials data  the fringe are subjects such as pharmacogenomics, phar- 3
for homeopathic products or for the many herbal medicines that were 
on sale before the Medicines Act of 1968. macoepidemiology and pharmacoeconomics.
vip.persianss.ir