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
Contents vIl Drug Allergy Drug Toxicity in Pregnancy and Lactation Drug-independent Effects Placebo- Homeopathy Systems Pharmacology he Sympathetic Nervous System mpathetic Nervous System 80 tructure of the Sympathetic Nervous System Adrenoceptor Subtypes Catecholamine actions Structure- Activity Relationship of Sympathomimetic -Sympathomimetics, a-Sympatholytics Types of B-Blockers Drugs Acting on the Parasympathetic Nervous System Parasympathetic Nervous System Cholinergic Synapse Parasympathomimetics Parasympatholytic Ganglionic Transmission Effects of Nicotine on Body Function Consequences of Tobacco Smoking 112 Biogenic amines Biogenic Amines- Actions and harmacological Implications 14 Vasodilators 118 Inhibitors of the RAA Sy Drugs Acting on Smooth Muscle Drugs Used to Influence Smooth Muscle Organs Overview of Modes of Action cardiac Glycoside Electrophysiological Actions of Antiarrhythmics of the Na*-Channel Blocking Type lros &s for the Treatment of Anemias Prophylaxis and Therapy of Thromboses arin Derivatives- Heparin Formation, Activation, and Aggregation of Platelets LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
Contents VII Drug Allergy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Drug Toxicity in Pregnancy and Lactation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Drug-independent Effects Placebo – Homeopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Systems Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Drug Acting on the Sympathetic Nervous System Sympathetic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Structure of the Sympathetic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 Adrenoceptor Subtypes and Catecholamine Actions . . . . . . . . . . . . . . . . . . . . . . 84 Structure – Activity Relationship of Sympathomimetics . . . . . . . . . . . . . . . . . . . 86 Indirect Sympathomimetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 α-Sympathomimetics, α-Sympatholytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 β-Sympatholytics (β-Blockers) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Types of β-Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Antiadrenergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 Drugs Acting on the Parasympathetic Nervous System Parasympathetic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Cholinergic Synapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Parasympathomimetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 Parasympatholytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104 Nicotine Ganglionic Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108 Effects of Nicotine on Body Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110 Consequences of Tobacco Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 Biogenic Amines Biogenic Amines – Actions and Pharmacological Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Serotonin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Vasodilators Vasodilators – Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 Organic Nitrates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 Calcium Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 Inhibitors of the RAA System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Drugs Acting on Smooth Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Drugs Used to Influence Smooth Muscle Organs . . . . . . . . . . . . . . . . . . . . . . . . . . 126 Cardiac Drugs Overview of Modes of Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128 Cardiac Glycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 Antiarrhythmic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134 Electrophysiological Actions of Antiarrhythmics of the Na+-Channel Blocking Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 136 Antianemics Drugs for the Treatment of Anemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138 Iron Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140 Antithrombotics Prophylaxis and Therapy of Thromboses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 Coumarin Derivatives – Heparin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 144 Fibrinolytic Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Intra-arterial Thrombus Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148 Formation, Activation, and Aggregation of Platelets . . . . . . . . . . . . . . . . . . . . . . . 148 Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
VIll Contents Inhibitors of Platelet Aggregat systemic Effect of Acetylsalicylic Acid dverse Effects of Antiplatelet Drugs Drugs used in Hyperlipoproteinemias Diuretic Nacl Reabsorption in the Kidney Diuretics of the Sulfonamide Type tassium-Sparing Diuretics antidiuretic Hormone(ADH)and Derivatives Drugs for Gastric and Duodenal Ulcers Laxatives rugs Affecting Motor Function polarizing Muscle Relaxants Antiparkinsonian Drugs Drugs for the Suppression of Pain, Analgesics, Pain Mechanisms and Pathways 94 tic An Antipyretic Analgesics and Antiinflammatory Drugs steroidal Antiinflammatory Thermoregulation and Antipyretics Local Anesthetics Morphine Type General Anesthetic Drugs eneral Anesthesia and general Anesthetic drugs Injectable Anesthetics porifics, Hypnotics p-Wake Cycle and Hypnotics Therapy of Schizophreni 240 LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
Inhibitors of Platelet Aggregation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Presystemic Effect of Acetylsalicylic Acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Adverse Effects of Antiplatelet Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 150 Plasma Volume Expanders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 Drugs used in Hyperlipoproteinemias Lipid-Lowering Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 Diuretics Diuretics – An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 158 NaCI Reabsorption in the Kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 Osmotic Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 Diuretics of the Sulfonamide Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162 Potassium-Sparing Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 Antidiuretic Hormone (/ADH) and Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . 164 Drugs for the Treatment of Peptic Ulcers Drugs for Gastric and Duodenal Ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 166 Laxatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 Antidiarrheals Antidiarrheal Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178 Other Gastrointestinal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180 Drugs Acting on Motor Systems Drugs Affecting Motor Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 Muscle Relaxants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 184 Depolarizing Muscle Relaxants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 Antiparkinsonian Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 188 Antiepileptics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 190 Drugs for the Suppression of Pain, Analgesics, Pain Mechanisms and Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 Antipyretic Analgesics Eicosanoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 Antipyretic Analgesics and Antiinflammatory Drugs Antipyretic Analgesics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 Antipyretic Analgesics Nonsteroidal Antiinflammatory (Antirheumatic) Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 Thermoregulation and Antipyretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 Local Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 204 Opioids Opioid Analgesics – Morphine Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 210 General Anesthetic Drugs General Anesthesia and General Anesthetic Drugs . . . . . . . . . . . . . . . . . . . . . . . . 216 Inhalational Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218 Injectable Anesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 Hypnotics Soporifics, Hypnotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222 Sleep-Wake Cycle and Hypnotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224 Psychopharmacologicals Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 226 Pharmacokinetics of Benzodiazepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 Therapy of Manic-Depressive Illnes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 Therapy of Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 236 Psychotomimetics (Psychedelics, Hallucinogens) . . . . . . . . . . . . . . . . . . . . . . . . . 240 VIII Contents Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
ContentsⅨ Hormones 242 Thyroid Hormone Therapy Hyperthyroidism and Antithyroid Drugs 246 Follicular Growth and Ovulation, Estrogen and estin pr Treatment of Insulin-Dependent iabetes mellitus Treatment of Maturity-Onset(Type ll) 262 Drugs for Maintaining Calcium Homeostasis Antibacterial Drug hibitors of Tetrahydrofolate Synthesis hibitors of dNa function Drugs for Treating Mycobacterial Infections Antifungal Drugs Antin &s used in the Treatment of Fungal Infection Chemotherapy of Viral Infection Drugs for Treatment of AIDS 288 Disinfectants and Antiseptics Drugs for Treating Endo-and Ectoparasitic Infestations 292 Anticancer Drugs py of Malignant Tumors hibition of Immune Responses Antidotes Therapy of Acute Myocardial Infarction Hypotension Emesis LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
Contents IX Hormones Hypothalamic and Hypophyseal Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242 Thyroid Hormone Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 Hyperthyroidism and Antithyroid Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 Glucocorticoid Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248 Androgens, Anabolic Steroids, Antiandrogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . 252 Follicular Growth and Ovulation, Estrogen and Progestin Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254 Oral Contraceptives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 256 Insulin Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258 Treatment of Insulin-Dependent Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 Treatment of Maturity-Onset (Type II) Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 Drugs for Maintaining Calcium Homeostasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264 Antibacterial Drugs Drugs for Treating Bacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266 Inhibitors of Cell Wall Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268 Inhibitors of Tetrahydrofolate Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272 Inhibitors of DNA Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274 Inhibitors of Protein Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276 Drugs for Treating Mycobacterial Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280 Antifungal Drugs Drugs Used in the Treatment of Fungal Infection . . . . . . . . . . . . . . . . . . . . . . . . . 282 Antiviral Drugs Chemotherapy of Viral Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 284 Drugs for Treatment of AIDS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288 Disinfectants Disinfectants and Antiseptics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290 Antiparasitic Agents Drugs for Treating Endo- and Ectoparasitic Infestations . . . . . . . . . . . . . . . . . . . 292 Antimalarials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294 Anticancer Drugs Chemotherapy of Malignant Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 Immune Modulators Inhibition of Immune Responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 300 Antidotes Antidotes and treatment of poisonings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 302 Therapy of Selected Diseases Angina Pectoris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 Antianginal Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 308 Acute Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310 Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 Hypotension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 Gout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316 Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 318 Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320 Migraine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 322 Common Cold . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 Allergic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326 Bronchial Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 Emesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
X Contents Further Reading LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
Further Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 Drug Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 X Contents Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license
2 History of Pharmacolog Since time immemorial. medicaments have been used for treating disease in humans and animals. The herbals of an- quity describe the therapeutic powers f certain plants and minerals. Belief in he curative powers of plants and cer- traditional knowledge, that is, empirical information not subjected to critical icine. He prescribed chemically defined fessional en re poison, nothing is without poison; the dose alone causes a thing not to be poi- Claudius Galen(129-200 A D )first at ackground of p ology Both the- ribute equally to the rational use of medicines through interpretation of ob- rved and experienced results. experience. We, however, maintain that it is found in part by experience, in part by theory. Neither experience nor the lone is apt to discover all. Theophrastus von Hohenheim(1493- Johann Jakob Wepfer (1620-1695 began to was the first to verify by animal experi- quesiton doctrines handed down from mentation assertions about pharmaco- active ingredient(s)in prescribed reme. "Pondered at length. Finally I resolved to es, while rejecting the irrational co rify the matter by experiments. coctions and mixtures of medieval med- LOllmann, Color Atlas of Pharmacology e 2000 Thieme All rights reserved Usage subject to terms and conditions of license
History of Pharmacology Since time immemorial, medicaments have been used for treating disease in humans and animals. The herbals of antiquity describe the therapeutic powers of certain plants and minerals. Belief in the curative powers of plants and certain substances rested exclusively upon traditional knowledge, that is, empirical information not subjected to critical examination. The Idea Claudius Galen (129–200 A.D.) first attempted to consider the theoretical background of pharmacology. Both theory and practical experience were to contribute equally to the rational use of medicines through interpretation of observed and experienced results. “The empiricists say that all is found by experience. We, however, maintain that it is found in part by experience, in part by theory. Neither experience nor theory alone is apt to discover all.” The Impetus Theophrastus von Hohenheim (1493– 1541 A.D.), called Paracelsus, began to quesiton doctrines handed down from antiquity, demanding knowledge of the active ingredient(s) in prescribed remedies, while rejecting the irrational concoctions and mixtures of medieval medicine. He prescribed chemically defined substances with such success that professional enemies had him prosecuted as a poisoner. Against such accusations, he defended himself with the thesis that has become an axiom of pharmacology: “If you want to explain any poison properly, what then isn‘t a poison? All things are poison, nothing is without poison; the dose alone causes a thing not to be poison.” Early Beginnings Johann Jakob Wepfer (1620–1695) was the first to verify by animal experimentation assertions about pharmacological or toxicological actions. “I pondered at length. Finally I resolved to clarify the matter by experiments.” 2 History of Pharmacology Lüllmann, Color Atlas of Pharmacology © 2000 Thieme All rights reserved. Usage subject to terms and conditions of license