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BRS Pharmacology Pharmacology Gary C. Rosenfeld, Ph.D. Professor Department of Integrated Biology and Pharmacology and Graduate School of Biomedical Sciences Assistant Dean for Education Programs University of Texas Medical School at Houston Houston, Texas David S. Loose, Ph.D. Associate Professor Department of Integrated Biology and Pharmacology and Graduate School of Biomedical Sciences University of Texas Medical School at Houston Houston, Texas With special contributions by Medina Kushen, M.D. William Beaumont Hospital Royal Oak, Michigan Todd A. Swanson, M.D., Ph.D. William Beaumont Hospital Royal Oak, Michigan Acquisitions Editor: Charles W. Mitchell Product Manager: Stacey L. Sebring Marketing Manager: Jennifer Kuklinski Production Editor: Paula Williams Copyright C 2010 Lippincott Williams & Wilkins 351 West Camden Street Baltimore, Maryland 21201-2436 USA 530 Walnut Street Philadelphia, PA 19106 All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner. The publisher is not responsible (as a matter of product liability, negligence or otherwise) for any injury resulting from any material contained herein. This publication contains information relating to general principles of medical care which should not be construed as specific instructions for individual patients. Manufacturers’ product information and package inserts should be reviewed for current information, including contraindications, dosages and precautions. Printed in the United States of America Library of Congress Cataloging-in-Publication Data Rosenfeld, Gary C. Pharmacology / Gary C. Rosenfeld, David S. Loose ; with special contributions by Medina Kushen, Todd A. Swanson. — 5th ed. p. ; cm. — (Board review series) Includes index. ISBN 978-0-7817-8913-4 (soft cover : alk. paper) 1. Pharmacology—Examinations, questions, etc. I. Loose, David S. II. Title. III. Series: Board review series. [DNLM: 1. Pharmacology—Examination Questions. QV 18.2 R813p 2010] RM301.13.R67 2010 6150.1076—dc22 2009010547 The publishers have made every effort to trace the copyright holders for borrowed material. If they have inadvertently overlooked any, they will be pleased to make the necessary arrangements at the first opportunity. We’d like to hear from you! If you have comments or suggestions regarding this Lippincott Williams & Wilkins title, please contact us at the appropriate customer service number listed below, or send correspondence to [email protected]. If possible, please remember to include your mailing address, phone number, and a reference to the book title and author in your message. To purchase additional copies of this book call our customer service department at (800) 638-3030 or fax orders to (301) 824-7390. International customers should call (301) 714-2324. Preface to the Fifth Edition This concise review of medical pharmacology is designed for medical students, dental stu- dents, and others in the health care professions. It is intended primarily to help students prepare for licensing examinations, such as the United States Medical Licensing Exami- nation Step 1 (USMLE) or other similar examinations. This book presents condensed and succinct descriptions of relevant and current Board-driven information pertaining to phar- macology without the usual associated details. It is not meant to be a substitute for the comprehensive presentation of information and difficult concepts found in standard phar- macology texts. ORGANIZATION The fifth edition begins with a chapter devoted to the general principles of drug action, fol- lowed by chapters concerned with drugs acting on the major body systems. Other chapters discuss autocoids, ergots, anti-inflammatory and immunosuppressive agents, drugs used to treat anemias and disorders of hemostasis, infectious diseases, cancer, and toxicology. Each chapter includes a presentation of specific drugs with a discussion of their gen- eral properties, mechanism of action, pharmacologic effects, therapeutic uses, and adverse effects. A drug list, tables, and figures summarize essential drug information included in all chapters. Clinically oriented, USMLE-style review questions and answers with explanations fol- low each chapter to help students assess their understanding of the information. Similarly, a comprehensive examination consisting of USMLE-style questions is included at the end of the book. This examination serves as a self-assessment tool to help students determine their fund of knowledge and diagnose any weaknesses in pharmacology. Key Features n Updated with current drug information n End-of-chapter review tests feature updated USMLE-style questions n 2-color tables and figures summarize essential information for quick recall n Updated drug lists for each chapter n Additional USMLE-style comprehensive examination questions and explanations Gary C. Rosenfeld, Ph.D. David S. Loose, Ph.D. v Acknowledgments The authors acknowledge and thank our colleagues for their support and contributions to this book and our medical students for being our harshest critics. vi Contents Preface v Acknowledgments vi 1. GENERAL PRINCIPLES OF DRUG ACTION 1 I. Dose–Response Relationships 1 II. Drug Absorption 6 III. Drug Distribution 9 IV. Drug Elimination and Termination of Action 10 V. Biotransformation (Metabolism) of Drugs 11 VI. Excretion of Drugs 14 VII. Pharmacokinetics 15 Review Test 19 2. DRUGS ACTING ON THE AUTONOMIC NERVOUS SYSTEM 26 I. The Peripheral Efferent Nervous System 26 II. Parasympathomimetic Drugs 31 III. Muscarinic-Receptor Antagonists 35 IV. Ganglion-Blocking Drugs 38 V. Skeletal Muscle Relaxants 38 VI. Sympathomimetic Drugs 41 VII. Adrenergic Receptor Antagonists 47 Review Test 52 3. DRUGS ACTING ON THE RENAL SYSTEM 60 I. Diuretics 60 II. Nondiuretic Inhibitors of Tubular Transport 66 Review Test 68 vii viii Contents 4. DRUGS ACTING ON THE CARDIOVASCULAR SYSTEM 72 I. Agents Used to Treat Congestive Heart Failure (CHF) 72 II. Antiarrhythmic Drugs 78 III. Antianginal Agents 83 IV. Antihypertensive Drugs 85 V. Drugs that Lower Plasma Lipids 91 Review Test 95 5. DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM 100 I. Sedative–Hypnotic Drugs 100 II. Antipsychotic (Neuroleptic) Drugs 105 III. Antidepressant Drugs 109 IV. Lithium 114 V. Opioid Analgesics and Antagonists 115 VI. Antiparkinsonian Drugs and Drugs Used to Treat Alzheimer’s Disease 121 VII. Antiepileptic Drugs 125 VIII. General Anesthetics 128 IX. Local Anesthetics 133 X. Drugs of Abuse 136 Review Test 145 6. AUTOCOIDS, ERGOTS, ANTI-INFLAMMATORY AGENTS, AND IMMUNOSUPPRESSIVE AGENTS 150 I. Histamine and Antihistamines 150 II. Serotonin and Serotonin Antagonists 154 III. Ergots 155 IV. Eicosanoids 157 V. Nonsteroidal Antiinflammatory Drugs (NSAIDs) 159 VI. Drugs Used for Gout 167 VII. Immunosuppressive Agents 168 Review Test 172 7. DRUGS USED IN ANEMIA AND DISORDERS OF HEMOSTASIS 175 I. Drugs Used in the Treatment of Anemias 175 II. Drugs Acting on Myeloid Cells 179 III. Drugs Used in Hemostatic Disorders 179 Review Test 186 Contents ix 8. DRUGS ACTING ON THE GASTROINTESTINAL TRACT 191 I. Antiemetics 191 II. Anorexigenics and Appetite Enhancers 193 III. Agents Used for Upper GI Tract Disorders 193 IV. Prokinetic Agents 197 V. Drugs Used to Dissolve Gallstones 197 VI. Digestive Enzyme Replacements 198 VII. Agents that Act on the Lower GI Tract 198 Review Test 202 9. DRUGS ACTING ON THE PULMONARY SYSTEM 206 I. Introduction to Pulmonary Disorders 206 II. Agents Used to Treat Asthma and Other Bronchial Disorders 206 III. Drugs Used to Treat Rhinitis and Cough 212 Review Test 214 10. DRUGS ACTING ON THE ENDOCRINE SYSTEM 216 I. Hormone Receptors 216 II. The Hypothalamus 216 III. The Anterior Pituitary 220 IV. The Posterior Pituitary 222 V. Drugs Acting on the Gonadal and Reproductive System 223 VI. The Adrenal Cortex 232 VII. The Thyroid 236 VIII. The Pancreas and Glucose Homeostasis 238 IX. The Calcium Homeostatic System 243 X. Retinoic Acid and Derivatives 246 Review Test 249 11. DRUGS USED IN TREATMENT OF INFECTIOUS DISEASES 252 I. Infectious Disease Therapy 252 II. Antibacterials 253 III. Antimycobacterial Agents 265 IV. Antifungal Agents 269 V. Antiparasitic Drugs 271 VI. Antiviral Drugs 275 Review Test 282 x Contents 12. CANCER CHEMOTHERAPY 287 I. Principles of Cancer Chemotherapy 287 II. Alkylating Agents 288 III. Antimetabolites 292 IV. Natural Products 295 V. Miscellaneous Agents 298 VI. Steroid Hormone Agonists and Antagonists and Related Drugs 300 VII. Adjunct Agents 302 Review Test 304 13. TOXICOLOGY 309 I. Principles and Terminology 309 II. Air Pollutants 311 III. Solvents 313 IV. Insecticides and Herbicides 313 V. Fumigants and Rodenticides 315 VI. Heavy Metal Poisoning and Management 315 VII. Drug Poisoning 319 Review Test 321 Comprehensive Examination 324 Index 341 chapter General Principles of 1 Drug Action I. DOSE–RESPONSE RELATIONSHIPS A. Drug effects are produced by altering the normal functions of cells and tissues in the body via one of four general mechanisms: 1. Interaction with receptors, naturally occurring target macromolecules that mediate the effects of endogenous physiologic substances such as neurotransmitters and hormones a. Figure 1-1 illustrates the four major classes of drug–receptor interactions, using specific examples of endogenous ligands. (1) Ligand-activated ion channels. Figure 1-1A illustrates acetylcholine interacting with a nicotinic receptor
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