Dictionary of Pharmacology and Allied Topics

383 Pages·1998·20.32 MB·English

by  Laurence

A Dictionary of
Pharmacology and
Allied Topics
D.R. Laurence MD FRCP
Professor Emeritus of Pharmacology and Therapeutics,
University College London, UK
with contributions from
J.R. Carpenter BSc PhD
Honorary Fellow, and lately Lecturer in Pharmacology,
University of Manchester.
Senior Medical Editor, Gar diner- Caldwell Communications L td,
Macclesfield. UK
“If language is not correct, what is said is not what is meant”
(Confucius: Chinese philosopher, 551-479 BCE)
1998
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PREFACE
Please read this preface; it is an important part of the book
Pharmacology is a science with its own distinctive attitudes and practices.
It is also a science that links many others in the massive enterprise of devel-
oping chemicals that affect living tissues to the benefit of humankind. The
most prominent of these activities is the development of new medicines, but
there are many others.
It is important that pharmacologists understand these other disciplines with
which they are involved, and that the latter understand pharmacology, for all
are engaged in enterprises fundamental to human happiness and to the good
of society.
Hence the discursive title of this book.
Who this book is intended for:
- Pharmacologists, basic and clinical,
- All people engaged in clinical drug evaluation, whether or not they would
describe themselves as pharmacologists,
- Those who write about drugs, medicines and clinical drug evaluation,
- Other people whose interests require that they have access to the world of
drugs and medicines.
We invite them all to browse in it as well as to use it for reference, for “A dic-
tionary [is not] a bad book to read. There is no cant in it, no excess of expla-
nation, and it is full of suggestion” (Ralph Walda E,?orson, 1803-1882, poet
and essayist, USA).
The scope of pharmacology (see main entry in the text).
Pharmacology is a discipline that, although having its own territory and termi-
nology, also ‘trespasses’ extensively into virtually all branches of medicine,
as well as into allied sciences, such as physiology and biochemistry, and into
law and social policy. It is the basis for an efficient and powerful research-
based industry.
Pharmacologists need to understand each other and other scientists, and to
be themselves understood by scientific, medical and social policy-makers.
Because pharmacology is such a highly diverse discipline we have kept
browsers particularly in mind throughout, for leisurely browsing is a comfort-
able way of assimilating information.
The need for clarity.
0
“Most men think indistinctly and therefore cannot speak with exactness”, and
“Language is only the instrument of science, and words are but the signs of
ideas”. Thus, in 1755, wrote Dr Samuel Johnson in the preface to his great
work, the first comprehensive Dictionary of the English Language; and his
statements remain true today.
vi
The need for lucidity in speech and writing has never been greater than it is
now. On a practical personal level, failure to communicate effectively can be
a major barrier to career success. If words are not used with precision and in
accordance with their currently accepted meaning, “what is said is not what is
meant” (Confucius).
The meaning of words.
The meaning of words changes with time (semantic change), and the ped-
ant’s belief that the first recorded use of a word must remain its correct
meaning is erroneous (etymological fallacy). Language alteration with time
may be abrupt or gradual. Change cannot be successfully resisted except for
some scientific jargon (terminology) where it is in the interest of practitioners
of the science and of its application to social purposes that certain meanings
remain constant (lawyers in particular are familiar with this necessity); or
changed only by intellectual consensus; or by regulation in the cases of
statutory authorities, e.g. official medicines regulation. Similar considerations
apply to the invention of new terms.
Definitions are needed.
We find support for our enterprise from philosophers and scientists, for ex-
ample:
Voltaire (1694-1778): “If you wish to converse with me, define your terms.”
RW Emerson (18 03-1 882): “He that can define ... is the best man.”
L Wittgensfein (1880-1951): “If language is to be a means of communication
there must be agreement not only in definitions but also (queer as this may
sound) in judgements.”
U Trendelenburg (1983): “The clarity of our nomenclature should concern us
deeply, and not only from the point of view of pedantic linguistics. After all,
scientists have to rely on language to formulate their hypotheses and theo-
ries, express their view and describe their insights into the workings of na-
ture. Moreover, a considerable percentage of them have to rely on a foreign
language (known as basic English, scientific English or simply poor English).
Without a precisely defined nomenclature, all our attempts to master this for-
eign language are doomed to failure, and we are quite unable to convey to
others our own insights and thoughts.”
We also find support from politicians, who, it is no surprise to learn, have
never favoured precision of language:
8 Disraeli(1804-1881): “I hate definitions.”
E Burke (1724-1779): “1 have no great opinion of a definition, the celebrated
remedy of [uncertainty and confusion].”
Some philosophers, however, can seem ambivalent. Karl Popper (19 02-
1994) (see science in pharmacology) said that any special interest in defini-
tions leads to ‘empty verbalism’ and that he had tried for decades to combat
the ‘superstition’ [his word] that if we want to be precise we have to define
our terms. However, he appears not to have been referring to practising sci-
entists seeking data that may be put to use in the relief of real disease in real
people in the real world, but rather to armchair philosophers of the Humpty
vii
Dumpty persuasion, “‘When I use a word,’ Humpty Dumpty said in a rather
scornful tone, ‘it means just what I choose it to mean - neither more nor
less”’ (Lewis Carroll, 1832-1898). But Popper also said that nothing is so irn-
portant as language.
Yet there are scientists (often ultra-specialists working at the growing edge of
knowledge in their field) who disapprove of attempts to generate standard or
model nomenclature as adversely restricting their intellectual and scientific
freedom. Their restricted view is comprehensible, but it shows lack of under-
standing, of consideration, and even of compassion for the broader commu-
nity of scientists in which they themselves live; and, in particular, for students
(as all of them once were), who need to know what is being said as precisely
as possible. We agree with the International Union of Pharmacology
(IUPHAR) Committee on Receptor Nomenclature and Drug Classification
that: “The literature of pharmacology presents many inconsistencies in the
use of nomenclature and symbols. These are particularly common in opera-
tional studies in which receptors are characterized by quantitative measure-
ments of receptor-mediated function and of ligand binding. The problem is
compounded by the fact that sometimes a given term is used in quite differ-
ent senses. For these reasons, it would, we believe, be helpful to adhere to
(as far as is practicable and reasonable) a common terminology, set of defi-
nitions, and symbol usage. These issues have been addressed in most other
biological and physical sciences ...” The committee consulted widely and,
“These consultations notwithstanding, the recommendations ... are to be re-
garded as provisional in nature. Their aim is to aid communication and ease
of comprehension without being rigidly prescriptive, and they will certainly re-
quire periodic revision and updating as new ideas and information arise.”
“It should be added that variations from the suggested notation and usage
may well be desirable under particular circumstances ...”
“The only essential is that the new terms are clearly defined‘ (Pharmacologi-
cal Reviews 1995;47:255). We consider this good advice.
The lexicographer.
Dr Johnson (in 1755) described the lexicographer or “writer of dictionaries”
as “the slave of science” and as “a harmless drudge that busies himself in
tracing the original, and detailing the significance of words”. He added that
although “Every other authour may aspire to praise, a lexicographer can only
hope to escape reproach, and even this negative recompence has been yet
granted to very few”. In concluding his preface he addresses his critics with a
little less than his customary self-assurance: “In this work, when it shall be
found that much is omitted, let it not be forgotten that much likewise is per-
formed.” We, after our so much more modest endeavours, know how he felt.
The reasons why this book has been compiled.
0
We have undertaken this enterprise because we think the need for it is in-
creasingly apparent. We include words and terms that are met and used by
pharmacologists beyond the strictly technical terms of the discipline. Our
decades of joint experience of practice and teaching have taught us the de-
sirability of thus broadening the scope of the book. We invite anyone who
dissents to question students about the meaning of the words they use. In-
viii
deed, we recommend questioning professional colleagues - by those willing
to risk the unpopularity and resentment that is apt to ensue. But, ... philo-
“
sophical problems arise when language goes on holiday” (L Witfgenstein).
“To say that a word has meaning is not to say that those who use the word
correctly have ever thought out what the meaning is” (B Russell, 1872-1970).
We all get by thus in daily talk, but a more rigorous approach is necessary in
scientific communication and debate.
The benefits of a broad view of pharmacology.
0
The reasons why we emphasize that we treat ‘allied topics’ and offer this
book for browsing as well as for reference are that we think that current cir-
cumstances of education, training and practice of pharmacology, plus the in-
creasingly competitive scramble for resources, create conditions that inevita-
bly have a narrowing intellectual effect at all levels; and this is enhanced by
exploding technological advance and information overload.
Practice of individuals must unavoidably be circumscribed, but a broad view
remains important if pharmacology is to flourish and so to be enabled to fulfil
its potential for massive relief of suffering and for practical gains to society
(including the economy), everywhere.
Choice of entries.
0
Our choice of entries from the enormous range of appropriate topics is nec-
essarily idiosyncratic and we make no apology for this. Also, the space allot-
ted to each has no inherent validity - we have been guided by the general
accessibility of other sources of information. For example, the legions of indi-
vidual drugs and classes of drugs are accessibly and comprehensively listed
in innumerable textbooks, pharmacopoeias and formularies, and we include
only those relatively few that seem to have a special claim for one reason or
another, sadly, sometimes, for the harm they have done. This book is not a
dictionary of drugs. Because relevant aspects of the publications of official
and semi-official bodies, such as regulatory authorities, the World Health Or-
ganization, World Medical Association, European Community/Union, Interna-
tional Committee of Medical Journal Editors and the International Union of
Pharmacology, never seem to be at hand when wanted, we quote selectively
from these.
D.R. LAURENCE J.R. CARPENTER
Contents
Notes ix
Preface v
α - Ayurvedic medicine 1
'backtracking booze' - bush teas 36
(C ) - cytotoxic drug, handling precautions 50
1 max
DALY - dystonia 91
EC - ex vivo 114
fact - fuzzy logic 136
GABA - guidelines and regulations 146
habituation - hysteresis 156
iatrogenic disease - IUPHAR 170
jackknife method (statistical) - just society 187
K - knowledge 189
a
label (radioactive) - lysosome 191
MAb - mydriatic 206
n = 1 clinical trial - nyctohemeral 225
objective - oxytocic 238
p value - pyrexia, pyretic, pyrogen 246
QALY - quotation and permission to quote 282
racemate - run-in period 285
safety - systemic availability 309
t½ - tyramine 343
uncertainty principle (in therapeutic research) - utility measurement 361
valid - volunteer 363
warnings to patients - women as subjects in early tests of new drugs 368
xanthine-containing drinks - xylocholine 371
Yates's correction - yohimbine 372
Zelen randomization - zwitterion 373
A 1
a See maximal agonist effect (a)
abbreviations (L. ab, away from; brevis, brief, short)
See alphabetic entries, acronym
abortifacient (L. ab, away, from; oriri, to appear; faciens, doing)
- Substance that causes abortion. Some contraceptives act by preventing im-
plantation or by causing early abortion rather than by preventing conception
(fertilization). See teratothanasia
ABPI
- Association of the British Pharmaceutical Industry.
abridged application (for a licenceharketing application)
(L. abbreviare, to shorten)
- Plainly, the full research and development procedures for new active sub-
stances are inappropriate in the case of medicinal products of well estab-
lished medicinal use, e.g. insulin, aspirin. But regulatory authorities have a
legitimate concern for pharmaceutical quality including bioequivalence. They
provide for this situation by allowing appropriately shortened (abridged) appli-
cations.
absorption (L. ab, away, from; sorbere, to suck)
- The process by which one substance penetrates or enters another. In relation
to drugs, the process by which a drug is taken up from its site of administra-
tion. See adsorption
abstinence syndrome (L. ab, away, from; fenere, to hold;
Gr. sun, with; drome, run)
See withdrawal syndrome
abuse and misuse of drugs (L. ab, away; uti, to use; missa, divergen)
A distinction may be made between the two words:
- Abuse is non-medical use without therapeutic intent, e.g. to get intoxi-
cated. Also, the use of a drug to an extent that seriously interferes with
health and social or economic functioning of the individual.
See recreational (use) drugs
- Misuse is over-prescribing by a doctor, i.e. for too many people or of too
much or for too long; or inappropriate choice, i.e. the wrong drug or a drug
when no drug would be better. Also excessive self-medication.
See substance abuse
abuse liability (of drugs)
- An imprecise concept concerning the proclivity of a drug or class of drugs to
induce drug-seeking behaviour.
- The events that precede or accompany strong drug-seeking behaviour as it
2
relates to the social context in clinical studies and to the operant schedule in
animal studies (Scott E Lukas).
academic (academy) (etymol, see academic freedom)
- The original (16th century) use of the term implies guardianship of standards
in reasoning, including a questioning (sceptical) attitude to facts and the
soundness of inferences, that forms the basis of the intellectual attitudes of a
university.
- Since 1886 the term has acquired an added derogatory (or pejorative) over-
tone meaning: unpractical, merely theoretical, having no practical application.
Academics understandably don’t like this, but they are prgbably going to have
to live with it.
- USA English does not distinguish between academic (as a noun) and acade-
mician (member of an Academy)
See academic usage/English, academic freedom
academic freedom (Gr. academe, from Academus, an ancient Greek hero
who made himself useful to the captured daughter of Jupiter)
- Plato (d 348 BCE) set up his school of philosophy in Academus’ pleasure
garden. The school concentrated so solemnly on literature that laughter was
forbidden - so much for freedom.
- “One of the problems in writing about academic freedom is that the phrase is
much misused, sometimes out of sheer woolly-mindedness but more often by
those who wish to conceal dubious actions under a high-minded disguise.
- “Academic freedom is the right of any scholar, within his field of expertise, to
think about and do research on any problem that interests him, to make pub-
lic his conclusions, and to teach what he sincerely believes to be true.” [But it
does not mean that the community has a duty to pay for the implementation
of all academics’ research interests].
- To this may be added, “without placing themselves in jeopardy of losing their
jobs and any privileges they may have at their institutions.”
- But academic freedom has an ‘enemy within’, i.e. “those who say that aca-
demic freedom is an unchallengeable right and deduce from this that they are
not answerable to anyone for the way in which they carry out their duties - or
even for their failure to carry them out at all” (after P Swinnerton-Dyer, The
importance of academic freedom. Nature 1995;373:186).
academic usage/English
- An elevated and often complex style associated with concern for accuracy,
objectivity and dispassionate comment and characterized by:
- Qualifying expressions, e.g. may, usually.
- Parenthetical asides, e.g. as far as can be determined at this point in time.
- Passive constructions, serving to minimize or remove personality, e.g. ‘it’
was found that, instead of ‘we’ found, or (horror!) ‘I’ found (after Oxford
Companion to the English Language 7992). The result of this ‘stultifying
convention’ is that reading most scientific papers has become ‘tedious
drudgery’ (ND Mermin, ibidem) (L. ibidem, in the same place).
See academic
3
acceptable daily intake (ADI) (L. ac, ad, before, to; capere, to take)
- A term used in evaluation of an environmental chemical to which the human
population is expected to be exposed. It is expressed in mg kg-’ day”. “It has
proved the most practicable approach for establishing the acceptable levels
of intentional and unintentional food additives, pesticide residues, food and
environmental contaminants” (Risk assessment; Royal Society of London,
1983).
acceptance range See area under the curve (AUC)
acceptor site (L. ac, ad, before, to; capere, to take; situs, placed)
- A binding site for a molecule that does not mediate a biological effect di-
rectly via that site.
accident (L. ac, ad, before, to; cidere, to fall)
- Unexpected event.
- Unintended misfortune.
- In discussing whether or not the victim of a drug accident during routine ther-
apy should be compensated by society or by the person or organization re-
sponsible for the injury or not at all, it is relevant to distinguish whether or not
there has been fault.
- Drug accidents affecting thousands of people include thalidomide. stilbes-
trol, practolol and clioquinol. See compensation, liability, injury
accumulatiodcumulation (of drugs) (L. accumulare, to heap up:
cumulus, a heap)
- A progressive increase in the amount of drug in the body due to the rate of
administration (intake) exceeding the rate of metabolism or elimination.
- In isolated tissue preparations: serial additions of drug without the usual
washouts between doses - hence cumulative dose-response curves.
accuracy (L. ac, ad, before, to; cura, care)
- The closeness of agreement of a determined value with a true (or accepted)
reference value. See precision
ACE
- Angiotensin-converting enzyme. (Gr. angeion, vessel; L. tensio, stretched)
acetylcholine (L. acetum, vinegar; Gr. khole, bile)
- A neurotransmitter, the effects of which are classically divided into:
- Nicotinic effects: actions of acetylcholine (mimicked by nicotine) at
acetylcholine receptors (previously known as cholinoceptors) on the post-
synaptic membrane of the following structures:
- autonomic ganglion cells, causing depolarization of the postsynaptic
nerve (fast excitatory postsynaptic potential). These effects are blocked
by hexamethonium (ion channel block), tetraethylammonium, meca-
rnylarnine.