THIEME FLEXIBOOK Heinz Ullmann Klaus Mohr Albrecht Ziegler Detlef Bieger Color Atlas of Pharmacology 2nd edition, revised and expanded Thieme
Color Atlas of Pharmacology 2nd edition, revised and expanded Albrecht Ziegler, Ph. D mycology Department of Pharmacology University of Kiel Germany Klaus mohr. M. D Detlef Bieger, M.D acology Division of Basic Medical Science Faculty of Medicine Memorial University of University of Bonn Germany St John,s, Newfoundland anada 164 color plates by jurgen Wirth Thieme Stuttgart· New York·2000 LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
re K III Color Atlas of Pharmacology 2nd edition, revised and expanded Heinz Lüllmann, M. D. Professor Emeritus Department of Pharmacology University of Kiel Germany Klaus Mohr, M. D. Professor Department of Pharmacology and Toxicology Institute of Pharmacy University of Bonn Germany Albrecht Ziegler, Ph. D. Professor Department of Pharmacology University of Kiel Germany Detlef Bieger, M. D. Professor Division of Basic Medical Sciences Faculty of Medicine Memorial University of Newfoundland St. John’s, Newfoundland Canada 164 color plates by Jürgen Wirth Thieme Stuttgart · New York · 2000 Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
Library of Congress Cataloging-in-Publication English. Heinz Ullmann.[et al. ] color ed, rev. and expanded. Rev. and expanded translation of: Taschenatlas der Pharmakologie BN3-13-781702-1(GTV-SBN086577-843-4(TN 1. Pharmacology At 2. Pharmacology Handbooks, manuals, etc. NLM: 1. Pharmacology Atlases. 2. Pharmacology Handbooks. M301.12T38131999 for Library of Congress 99-33662 Illustrated by Jurgen Wirth, Darmstadt, Ger- panded tra and copyrighted 1996 by dition ticular c on of the 3rd Taschenatlas der Pharmakologie erences are in accordance with the state of Some of the product names, patents and regis- knowledge at the time of production of the fact registered trademarks or proprieta 5mx121 representation by the publisher that it is in the public domain. including all parts the ying each drug an d by ts set by copyright legislation, without the prosecution. This applies in particular to pho- Such tant with drugs that cessing and storage. sers own risk 02000 Georg Thieme Verlag. Rudigerstrasse 14. thors and publishers request every user to re port to the publishers any discrepancies or in- Thieme New York. 333 Seventh Avenue. New accuracies noticed. ork, NY 10001, USA Typesetting by Gulde Druck, Tubingen Printed in Germany by Staudigl, Donauworth SBN3-13-781702-1(GT ISBN0-86577-8434(TNY)123456 LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
Library of Congress Cataloging-in-Publication Data Taschenatlas der Pharmakologie. English. Color atlas of pharmacology / Heinz Lullmann … [et al.] ; color plates by Jurgen Wirth. — 2nd ed., rev. and expanded. p. cm. Rev. and expanded translation of: Taschenatlas der Pharmakologie. 3rd ed. 1996. Includes bibliographical references and indexes. ISBN 3-13-781702-1 (GTV). — ISBN 0-86577-843-4 (TNY) 1. Pharmacology Atlases. 2. Pharmacology Handbooks, manuals, etc. I. Lullmann, Heinz. II. Title. [DNLM: 1. Pharmacology Atlases. 2. Pharmacology Handbooks. QV 17 T197c 1999a] RM301.12.T3813 1999 615’.1—dc21 DNLM/DLC for Library of Congress 99-33662 CIP IV Illustrated by Jürgen Wirth, Darmstadt, Germany This book is an authorized revised and expanded translation of the 3rd German edition published and copyrighted 1996 by Georg Thieme Verlag, Stuttgart, Germany. Title of the German edition: Taschenatlas der Pharmakologie Some of the product names, patents and registered designs referred to in this book are in fact registered trademarks or proprietary names even though specific reference to this fact is not always made in the text. Therefore, the appearance of a name without designation as proprietary is not to be construed as a representation by the publisher that it is in the public domain. This book, including all parts thereof, is legally protected by copyright. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher’s consent, is illegal and liable to prosecution. This applies in particular to photostat reproduction, copying, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage. ©2000 Georg Thieme Verlag, Rüdigerstrasse14, D-70469 Stuttgart, Germany Thieme New York, 333 Seventh Avenue, New York, NY 10001, USA Typesetting by Gulde Druck, Tübingen Printed in Germany by Staudigl, Donauwörth ISBN 3-13-781702-1 (GTV) ISBN 0-86577-843-4 (TNY) 123456 Important Note: Medicine is an ever-changing science undergoing continual development. Research and clinical experience are continually expanding our knowledge, in particular our knowledge of proper treatment and drug therapy. Insofar as this book mentions any dosage or application, readers may rest assured that the authors, editors and publishers have made every effort to ensure that such references are in accordance with the state of knowledge at the time of production of the book. Nevertheless this does not involve, imply, or express any guarantee or responsibility on the part of the publishers in respect of any dosage instructions and forms of application stated in the book. Every user is requested to examine carefully the manufacturers’ leaflets accompanying each drug and to check, if necessary in consultation with a physician or specialist, whether the dosage schedules mentioned therein or the contraindications stated by the manufacturers differ from the statements made in the present book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Every dosage schedule or every form of application used is entirely at the user’s own risk and responsibility. The authors and publishers request every user to report to the publishers any discrepancies or inaccuracies noticed. Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
Preface The present second edition of the Color Atlas of Pharmacology goes to print six years after the first edition. Numerous revisions were needed, highlighting the dramatic continuing progress in the drug sciences. In particular, it appeared necessary to in- clude novel therapeutic principles, such as the inhibitors of platelet aggregation from the group of integrin GPIIB/IIIA antagonists, the inhibitors of viral protease,or the non-nucleoside inhibitors of reverse transcriptase. Moreover, the re-evaluation and expanded use of conventional drugs, e.g. in congestive heart failure, bronchial asthma, or rheumatoid arthritis, had to be addressed. In each instance. the primary mphasis was placed on essential sites of action and basic pharmacological princi ples Details and individual drug properties were deliberately omitted in the interest of making drug action more transparent and affording an overview of the pharmaco- logical basis of drug therapy The authors wish to reiterate that the Color Atlas of Pharmacology cannot replace a textbook of pharmacology, nor does it aim to do so. Rather, this little book is desi ned to arouse the curiosity of the pharmacological novice: to help students of me- dicine and pharmacy gain an overview of the discipline and to review certain bits of information in a concise format; and, finally, to enable the experienced therapist to recall certain factual data, with perhaps some Our cordial thanks go to the many readers of the multilingual editions Atlas for their suggestions. We are indebted to Prof Ulrike Holzgrabe Doc Achim MeiBner, Kiel, Prof. Gert-Hinrich Reil, Oldenburg. Prof Reza Tal Mr Christian Klein, Bonn, and Mr Christian Riedel, Kiel, for providing stimula- discussions and technical support, as well as to Dr. Liane Platt- and Dr. David Frost, New York, for their editorial and stylistic gui nz Ullmann Jurgen Wirth Fall 1999 LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
V Preface The present second edition of the Color Atlas of Pharmacology goes to print six years after the first edition. Numerous revisions were needed, highlighting the dramatic continuing progress in the drug sciences. In particular, it appeared necessary to include novel therapeutic principles, such as the inhibitors of platelet aggregation from the group of integrin GPIIB/IIIA antagonists, the inhibitors of viral protease, or the non-nucleoside inhibitors of reverse transcriptase. Moreover, the re-evaluation and expanded use of conventional drugs, e.g., in congestive heart failure, bronchial asthma, or rheumatoid arthritis, had to be addressed. In each instance, the primary emphasis was placed on essential sites of action and basic pharmacological principles. Details and individual drug properties were deliberately omitted in the interest of making drug action more transparent and affording an overview of the pharmacological basis of drug therapy. The authors wish to reiterate that the Color Atlas of Pharmacology cannot replace a textbook of pharmacology, nor does it aim to do so. Rather, this little book is designed to arouse the curiosity of the pharmacological novice; to help students of medicine and pharmacy gain an overview of the discipline and to review certain bits of information in a concise format; and, finally, to enable the experienced therapist to recall certain factual data, with perhaps some occasional amusement. Our cordial thanks go to the many readers of the multilingual editions of the Color Atlas for their suggestions. We are indebted to Prof. Ulrike Holzgrabe, Würzburg, Doc. Achim Meißner, Kiel, Prof. Gert-Hinrich Reil, Oldenburg, Prof. Reza Tabrizchi, St. John’s, Mr Christian Klein, Bonn, and Mr Christian Riedel, Kiel, for providing stimulating and helpful discussions and technical support, as well as to Dr. Liane PlattRohloff, Stuttgart, and Dr. David Frost, New York, for their editorial and stylistic guidance. Heinz Lüllmann Klaus Mohr Albrecht Ziegler Detlef Bieger Jürgen Wirth Fall 1999 Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
Contents History of Pharmacology Drug Administration 12468 Dosage Forms for Oral, and Nasal Applications osage Forms for Parenteral Pulmonary ectal or Vaginal, and Cutaneous Application Drug Administration by Inhalation Cellular Sites of Actic Potential Targets of Drug Action Distribution in the bod External Barriers of the Body ossible Modes of Drug Distribution Binding to Plasma Proteins Drug elimination The Liver as an Excretory Organ 32 Biotransformation of Drugs enterohepatic Cycle The Kidney as Excretory Organ Elimination of Lipophilic and Hydrophilic Substances Pharmacokinetics Drug Concentration in the body as a Function of Time. Time Course of Drug Concentration in Plasma Time Course of Drug Plasma Levels During Repeated Accumulation: Dose, Dose Interval, and Plasma Level Fluctuation Change in Elimination Characteristics During Drug Therap Quantification of Drug Action Concentration-Effect Relationship- Effect Curves Concentration-Binding Curves Drug-Receptor Interaction Types of Binding Forces enantioselectivity of Drug Action 64 lode of Operation of G-Protein-Coupled Receptors Time Course of plasma Concentration and Effect Adverse Drug Effects LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
Contents General Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 History of Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Drug Sources Drug and Active Principle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Drug Administration Dosage Forms for Oral, and Nasal Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Dosage Forms for Parenteral Pulmonary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Rectal or Vaginal, and Cutaneous Application . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Drug Administration by Inhalation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Dermatalogic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 From Application to Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Cellular Sites of Action Potential Targets of Drug Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Distribution in the Body External Barriers of the Body . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Blood-Tissue Barriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 Membrane Permeation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Possible Modes of Drug Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 Binding to Plasma Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Drug Elimination The Liver as an Excretory Organ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Biotransformation of Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Enterohepatic Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 The Kidney as Excretory Organ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Elimination of Lipophilic and Hydrophilic Substances . . . . . . . . . . . . . . . . . . . . . 42 Pharmacokinetics Drug Concentration in the Body as a Function of Time. First-Order (Exponential) Rate Processes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Time Course of Drug Concentration in Plasma . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Time Course of Drug Plasma Levels During Repeated Dosing and During Irregular Intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 Accumulation: Dose, Dose Interval, and Plasma Level Fluctuation . . . . . . . . . . 50 Change in Elimination Characteristics During Drug Therapy . . . . . . . . . . . . . . . 50 Quantification of Drug Action Dose-Response Relationship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Concentration-Effect Relationship – Effect Curves . . . . . . . . . . . . . . . . . . . . . . . . 54 Concentration-Binding Curves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Drug-Receptor Interaction Types of Binding Forces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Agonists-Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Enantioselectivity of Drug Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Receptor Types . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Mode of Operation of G-Protein-Coupled Receptors . . . . . . . . . . . . . . . . . . . . . . 66 Time Course of Plasma Concentration and Effect . . . . . . . . . . . . . . . . . . . . . . . . . 68 Adverse Drug Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 VI Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license