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Introduction to Pharmacology
© 1997, 2003 Taylor & Francis
In the ocean depths off Madagascar, obsolete fish keep their laggard appointments.
In the depths of the human mind, obsolete assumptions go their daily rounds. And
there is little difference between the two, except that the fish do no harm.
Robert Ardrey
African Genesis, 1967
That which in the beginning may be just like poison, but at the end is like nectar,
and which awakens one to self-realization, is said to be happiness in the mode of
goodness.
Bhagavad Gita
Nothing in life is to be feared, it is only to be understood.
Marie Curie
© 1997, 2003 Taylor & Francis
Introduction to Pharmacology
Second Edition
Mannfred A. Hollinger, Ph.D.
Professor Emeritus,
Department of Medical
Pharmacology and Toxicology
University of California, Davis
© 1997, 2003 Taylor & Francis
First published 1997 by Taylor & Francis
Second edition published 2003 by Taylor & Francis
11 New Fetter Lane, London EC4P 4EE
Simultaneously published in the USA and Canada
by Taylor & Francis Inc,
29 West 35th Street, New York, NY 10001
Taylor & Francis is an imprint of the Taylor & Francis Group
© 1997, 2003 Taylor & Francis
Typeset in 10/12 pt Sabon by Graphicraft Limited, Hong Kong
Printed and bound in Great Britain by TJ International Ltd, Padstow, Cornwall
All rights reserved. No part of this book may be reprinted or reproduced or
utilised in any form or by any electronic, mechanical, or other means, now
known or hereafter invented, including photocopying and recording, or in any
information storage or retrieval system, without permission in writing from
the publishers.
Every effort has been made to ensure that the advice and information in this
book is true and accurate at the time of going to press. However, neither the
publisher nor the authors can accept any legal responsibility or liability for any
errors or omissions that may be made. In the case of drug administration, any
medical procedure or the use of technical equipment mentioned within this
book, you are strongly advised to consult the manufacturer’s guidelines.
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
Hollinger, Mannfred A.
Introduction to pharmacology / Mannfred A. Hollinger.—2nd ed.
p. cm.
Includes bibliographical references and index.
1. Pharmacology. I. Title.
[DNLM: 1. Pharmacology. 2. Pharmaceutical Preparations. QV 4 H74li
2003]
RM300 .H65 2003
615′.1—dc21 2002072005
ISBN 0-415-28033-8 (hbk)
ISBN 0-415-28034-6 (pbk)
© 1997, 2003 Taylor & Francis
Contents
Acknowledgements vii
Preface to the first edition viii
Preface to the second edition x
PART 1
Fundamentals of pharmacokinetics 1
1 Introduction 3
2 Absorption and distribution 23
3 Metabolism and elimination 44
4 Drug interactions 61
PART 2
Fundamentals of pharmacodynamics and
toxicodynamics 73
5 Drug receptors 75
6 Dose–response relationship 90
7 Drug toxicity 101
8 Treating drug overdose 137
PART 3
Drugs that replace, cure, or treat symptoms 147
9 Hormones 149
10 Chemotherapeutic agents 164
11 Drug treatment of symptoms: neuropharmacology and
substance abuse 181
12 Cardiovascular drugs 241
© 1997, 2003 Taylor & Francis
PART 4
Drug development 265
13 Drug discovery by the pharmaceutical industry 267
14 Pharmaceutical development of drugs and the FDA 299
15 Animals in research 316
16 Alternative medicine 341
Appendix: The History of drug abuse laws in the United States 351
Glossary 376
Answers to questions 393
vi Contents
© 1997, 2003 Taylor & Francis
Acknowledgements
The author would like to express his thanks for the continuing support of his wife
Georgia throughout this project. In addition, the always-present commiseration of
sons Randy and Chris served as a never-ending source of insight and intellectual
stimulation. The author would also like to acknowledge the excellent graphic design
provided by Tsunami Graphics, Sacramento, CA.
Much of the Appendix has been reproduced with kind permission from PJD Publica-
tions Limited, Westbury, NY 11590, USA, from M. A. Hollinger, Res. Commun Alc.
Sbst. Abuse, vol. 16, pp. 1–23, 1995. Copyright 1995 by PJD Publications Ltd.
© 1997, 2003 Taylor & Francis
Preface to the first edition
The topic of pharmacology usually escapes the attention of many college students by
virtue of the fact that pharmacology itself is rarely taught on the undergraduate level.
It generally is reserved for postbaccalaureate students who are enrolled in health
curricula associated with medicine, dentistry, nursing, and the veterinary sciences;
however, certain upper level undergraduates are interested in the subject. This book
is the product of teaching undergraduates the principles of pharmacology over the
last 20 years. During that period the author continually searched for an appropriate
textbook for students who normally had some background in biochemistry and physio-
logy. Medical school texts were of no use since their coverage is far too extensive.
Alternatively, “softer” texts tended to overemphasize certain areas, such as drug
abuse, which were often the driving force behind their creation. Although both types
of texts were good in their own right, they missed the mark. Students frequently
expressed a desire for more “hard” science that would not inundate them with boiler
plate text. It is because I agree with this sentiment that this book was created. The
goal of this book is not to be a mini-medical school pharmacology text. Rather, it is
intended to address a wider audience of advanced undergraduate students who have
an interest in learning about the diverse aspects of pharmacology in society—not
simply about the curative aspects of drugs. It is hoped that not only students in the
biological sciences but also those in the social sciences will find some, if not all, of the
book’s contents informative and useful.
This book has been organized to provide a logical continuum of information relat-
ing to drugs, beginning with the inevitable historical discovery of drugs in food. With
this background, important pharmacological principles will be considered relating to
drug absorption, distribution, metabolism, and elimination. This material forms the
corpus of the chapters that constitute Part 1. In essence, the emphasis is placed upon
pharmacokinetic aspects of drug action. Having gained access to the body, how
do drugs produce an effect and how can the effect be quantified for comparative
purposes? In Part 2, the student is exposed to the concepts of drug–receptor inter-
action and the transduction of drug binding into pharmacodynamic or toxicodynamic
responses. Factors influencing drug toxicity, as well as underlying principles of man-
aging drug overdose, also will be presented as the inevitable “other side of the coin.”
Part 3 reiterates, in more detail, the concept introduced in Part 1 that drugs can be
classified into four broad categories: (1) drugs that replace physiological inadequa-
cies, (2) drugs that cure, (3) drugs that treat symptoms, and (4) drugs that alter mood
or behavior. In this regard, hormones, antibiotics, and neuroactive agents provide
© 1997, 2003 Taylor & Francis
examples, respectively, in their own chapters. In addition, the pharmacology of sub-
stance abuse as well as the evolution of drug abuse laws and the use of drugs in
sports are also discussed. In Part 4, the final three chapters deal with the development
of drugs by the pharmaceutical industry and the challenges they face in new drug
discovery as well as dealing with the FDA. The section concludes with a discussion of
the controversial use of experimental animals in research, an area often neglected in
the study of pharmacology.
Mannfred A. Hollinger
Davis, California
Preface to the first edition ix
© 1997, 2003 Taylor & Francis
Preface to the second edition
Since the publication of the first edition I have reevaluated the content of the book as
well as its purpose. It became clear over the years that certain important areas that
had been omitted in the first edition needed to be included in a revision, if a revision
was to be meaningful. Therefore, additional areas added to the second edition include
cardiovascular drugs, anticancer drugs, neuroleptics, designer drugs, bioterrorism,
placebos, recombinant DNA technology, apoptosis, gaseous anesthetics, local
anesthetics, vitamins, and the cigarette industry Master Settlement Agreement. In the
intervening period since the publication of the first edition, the issue of alternative
medicine has also become very topical, and a new chapter on this subject has been
added.
Although identifying areas of omission was relatively straightforward, the question
of how to make the book more attractive to my intended audience was more illusive.
It has always been my goal to reach upper-level undergraduate students beyond those
in the traditional “hard” science paths. Surely there must be students and faculties in
the humanities, in fields such as sociology and psychology, for example, who would
find certain aspects of the study of drugs interesting and perhaps even provocative?
Areas such as animal experimentation, the development of drug laws, drugs in sports,
the drug discovery process, and bioterrorism are not typical subjects expanded upon
in graduate level texts. These are stand-alone subjects that do not require mastery
of pharmacokinetics and pharmacodynamics, which are covered essentially in the
introductory chapters in Parts 1 and 2.
In order to assist the student in evaluating his/her progress in dealing with the
subject matter, I have included a set of 10 self-assessment questions at the end of each
chapter (answers are provided at the back of the book). These questions are intended
to emphasize the important facts, principles, and personalities that the student should
become familiar with in the field of pharmacology. To further enhance the teaching
power of the book the new edition contains 41 new tables and 33 new figures.
Finally, in the hope of helping students and faculty, wherever, I encourage con-
structive input and am willing to try to answer any questions. My email is
mahollinger@ucdavis.edu.
Mannfred A. Hollinger
Oro Valley, Arizona
© 1997, 2003 Taylor & Francis
[...]... Another of Baer’s contributions to the field involved a method to sterilize the maggots Today, commercial and research laboratories produce sterile larvae The ability of maggots to promote healing of lacerations on skin wounds is the result of their secretion of the chemical allantoin A less offensive source of allantoin is the synthetic form Synthetic allantoin is available today to accelerate wound healing... libido (presumably structurally related to either estrogen or progesterone) Mistletoe has, of course, become a contemporary symbol to Yuletide merrymakers as a license to kiss The Celts, and others, also used mistletoe for medical purposes The Roman historian Pliny the Younger wrote that mistletoe was “deemed a cure for epilepsy; carried about by women it assisted them to conceive, and it healed ulcers most... preparations of the late 1800s (see Appendix) In addition to providing drugs, plants have also been recently utilized for ecological purposes via the process of phytoremediation Phytoremediation refers to the ability of some plants to remove toxic compounds from the soil, concentrate them in their own tissues, and thus, achieve a certain degree of detoxification Current interest has specifically focused on... product—Salivart®), artificial tears, placebos, or tetrodotoxin drugs? However, with this official orientation behind us, we may now proceed to investigate the world(s) of drugs and their diverse influences on the human experience BACKGROUND The roots of pharmacology extend backward in time to our earliest Pleistocene hominid ancestors on the African savanna, approximately five to ten million years ago These primitive... heart attacks to prevent further damage, investigators noticed that patients who took placebo pills regularly had a lower death rate than patients who took placebos sporadically Therefore, the placebo effect is not unique to psychiatric illness Conversely, what types of patients are not really amenable to a placebo effect? If you are a type I (insulin-dependent) diabetic (Chapter 9) who goes into hypoglycemic... Haitians do not fear zombies, they fear being turned into one According to one theory, victims are “converted” into a zombie in a two-step process Initially, the intended victim is treated with the nerve toxin tetrodotoxin applied surreptitiously to an open wound As the toxin does its work, the victim presents with all the symptoms of death Often not realizing this error in diagnosis, the victim is... job is to reduce the level of the toxin so that the meal is not fatal but retains enough of the toxin to produce some of its effects These include a mild numbing or tingling of the tongue and lips, sensations of warmth, a flushing of the skin, and a general feeling of euphoria If the dose is too high, difficulty in breathing occurs and a coma-like state develops In some cases, people have seemed to have... pharmacoepidemiology e pharmacoeconomics 9 Extracts from which of the following were believed to confer the gift of flight? a mistletoe b tobacco c tomatoes d thorn apple e cannabis 10 Which of the following produces a steroid precursor that was used in the synthesis of progesterone? a mistletoe b coca plant c North American potatoes d Southwestern mushrooms e Mexican yam © 1997, 2003 Taylor & Francis Chapter 2... usually have to gain entrance into the body in order to produce an effect, the exception being those that produce a topical (skin) effect Today, there are a number of methods that can be used to introduce a drug into the body Because of its convenience, the most common delivery system is the oral route However, sometimes the oral route is not the most appropriate In addition to the oral route, some of the... inflammatory mediators Modern pharmacology owes part of its development to Friedrich Worler, who inaugurated the field of synthetic organic chemistry in 1828 with the synthesis of urea This achievement catalyzed the formation of an entire industry (the German dye industry), which ultimately led to the synthesis of NCEs, many of which were subsequently introduced as possible therapeutic agents Prior to this . & Francis
Introduction to Pharmacology
Second Edition
Mannfred A. Hollinger, Ph.D.
Professor Emeritus,
Department of Medical
Pharmacology and Toxicology
University. Francis
Contents
Acknowledgements vii
Preface to the first edition viii
Preface to the second edition x
PART 1
Fundamentals of pharmacokinetics 1
1 Introduction 3
2 Absorption
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