Brenner and Stevens’ Pharmacology [5th Edition] 9780323391733, 9780323391726, 9780323391689

Table of contents :
Front Cover......Page 1
Inside Front Cover......Page 2
Brenner and Stevens Pharmacology......Page 3
Copyright Page......Page 6
Preface......Page 7
Table Of Contents......Page 9
Section 1_text......Page 11
Pharmacology and Its Subdivisions......Page 13
Pharmacy and Related Sciences......Page 14
Pure Drug Compounds......Page 15
Ointments, Creams, Lotions, and Suppositories.......Page 16
Enteral Administration......Page 17
Drug Names......Page 18
Review Questions......Page 19
Drug Distribution......Page 21
Role of Drug Biotransformation......Page 22
Formation of Active Metabolites......Page 23
Oxidative Reactions.......Page 24
Variations in Acetyltransferase Activity......Page 26
Biliary Excretion and Enterohepatic Cycling......Page 27
Bioavailability......Page 29
Interpretation of the Volume of Distribution......Page 30
Elimination Half-Life......Page 32
Zero-Order Kinetics......Page 33
Maintenance Dose......Page 34
Summary of Important Points......Page 35
Review Questions......Page 36
Receptor Classification......Page 37
Signal Transduction......Page 38
G Protein–Coupled Receptors (GPCRs)......Page 39
Membrane-Bound Enzymes......Page 40
Receptor Regulation and Drug Tolerance......Page 41
Quantal Dose-Response Relationship......Page 42
Review Questions......Page 43
Clinical Trials......Page 45
Amendments to the Food, Drug, and Cosmetic Act.......Page 47
Excessive Pharmacologic Effects......Page 48
Hematopoietic Toxicity......Page 49
Idiosyncratic Reactions......Page 50
Altered Drug Biotransformation......Page 51
Age......Page 53
Pregnancy and Lactation......Page 54
Review Questions......Page 55
Treatment of Poisoning......Page 57
Herbicides......Page 58
Botanical Pesticides......Page 59
Lead......Page 60
Arsenic......Page 61
Chelators......Page 62
Regulations to Prevent Toxic Workplace Exposure......Page 63
Summary of Important Points......Page 64
Review Questions......Page 65
Section 2_text......Page 67
Autonomic Nervous System......Page 69
Neurotransmitters......Page 70
Cholinergic Neurotransmission......Page 72
Muscarinic Receptors......Page 73
Cardiac Effects.......Page 74
Acetylcholine......Page 75
Edrophonium.......Page 76
Management of Organophosphate Poisoning.......Page 78
Adverse Effects and Interactions......Page 80
Indications......Page 81
Review Questions......Page 82
Pharmacologic Effects.......Page 83
Gastrointestinal and Urinary Tract Effects.......Page 84
Dicyclomine, Oxybutynin, Solifenacin, and Related Drugs......Page 85
Mechanisms and Effects.......Page 86
Indications.......Page 87
Depolarizing Neuromuscular Blocking Agents......Page 88
Review Questions......Page 89
Drugs Modulating the Baroreceptor Reflex......Page 91
Adrenoceptor Agonists......Page 92
α-Adrenoceptors......Page 93
Direct-Acting Adrenoceptor Agonists......Page 94
Chemistry and Pharmacokinetics......Page 95
Cardiovascular Effects......Page 96
Adverse Effects.......Page 97
Noncatecholamines......Page 98
Mechanisms, Effects, and Indications.......Page 99
Pharmacokinetics.......Page 100
Review Questions......Page 101
Mechanisms, Effects, and Indications.......Page 103
Pharmacokinetics.......Page 104
Mechanisms, Effects, and Indications.......Page 105
Pharmacokinetic Properties......Page 106
Mechanisms and Effects......Page 107
Summary of Important Points......Page 109
Review Questions......Page 110
Section 3_text......Page 111
Hypertension......Page 113
Sites and Effects of Antihypertensive Drug Action......Page 114
Thiazide and Related Diuretics......Page 115
Potassium-Sparing Diuretics......Page 117
Sympatholytic Drugs......Page 118
Centrally Acting Drugs......Page 119
Mechanism of Action......Page 120
Indications......Page 121
Angiotensin Receptor Blockers......Page 122
Fenoldopam......Page 123
Hypertensive Emergencies and Urgencies......Page 124
Review Questions......Page 125
Mechanisms and Effects of Antianginal Drugs......Page 127
Amyl Nitrite......Page 129
Calcium Channel Blockers......Page 130
Mechanisms and Pharmacologic Effects......Page 131
Ivabradine......Page 132
Management of Angina Pectoris......Page 133
Review Questions......Page 134
Pathophysiology of Heart Failure......Page 135
Digoxin......Page 137
Electrophysiologic and Electrocardiographic Effects.......Page 138
Indications.......Page 139
Dobutamine......Page 140
Angiotensin Receptor Blockers......Page 141
Βeta-Adrenoceptor Antagonists......Page 142
Management of Heart Failure......Page 143
Review Questions......Page 144
Loop of Henle......Page 145
Collecting Duct......Page 146
Mechanisms and Pharmacologic Effects.......Page 148
Indications.......Page 149
Chemistry and Pharmacokinetics.......Page 150
Amiloride and Triamterene......Page 151
Mechanisms, Pharmacologic Effects, and Indications.......Page 152
Management of Edema......Page 153
Review Questions......Page 154
Cardiac Action Potentials and Electrocardiographic Findings......Page 155
Abnormal Impulse Formation......Page 156
Drug-Induced Dysrhythmias......Page 158
Drug Properties......Page 159
Disopyramide......Page 160
Flecainide......Page 161
Propafenone......Page 162
Chemistry and Pharmacokinetics.......Page 163
Ibutilide and Dofetilide......Page 164
Magnesium Sulfate......Page 165
Atrial Fibrillation and Flutter......Page 166
Summary of Important Points......Page 167
Review Questions......Page 168
Chylomicrons......Page 169
High-Density Lipoproteins......Page 170
Guidelines for Management of Hypercholesterolemia......Page 172
Lifestyle Changes......Page 173
Chemistry and Pharmacokinetics......Page 174
Indications......Page 175
Adverse Effects and Interactions......Page 176
Chemistry and Pharmacokinetics......Page 177
Indications......Page 178
Summary of Important Points......Page 179
Review Questions......Page 180
Pathologic Thrombus Formation......Page 181
Pharmacokinetic and Pharmacologic Effects......Page 182
Adverse Effects and Interactions......Page 183
Indications......Page 184
Pharmacokinetic and Pharmacologic Effects......Page 186
Indications.......Page 187
Aspirin......Page 188
Indications......Page 189
Pharmacokinetics......Page 190
Vorapaxar......Page 191
Clinical Use......Page 192
Summary of Important Points......Page 193
Review Questions......Page 194
Oral Iron Preparations......Page 195
Parenteral Iron Preparations......Page 196
Vitamin B12......Page 197
Erythropoiesis-Stimulating Agents......Page 198
Colony-Stimulating Factors......Page 199
Review Questions......Page 200
Section 4_text......Page 201
Excitatory and Inhibitory Neurotransmission......Page 203
Fast Versus Slow Signals......Page 204
Glycine.......Page 205
Glutamate and Aspartate.......Page 206
Dopamine.......Page 207
Other Neurotransmitters......Page 209
Memory......Page 210
Emotional Processing......Page 211
Review Questions......Page 212
Neurologic Basis of Anxiety......Page 215
Insomnia......Page 216
Pharmacokinetics.......Page 217
Mechanism of Action.......Page 219
Pharmacologic Effects.......Page 220
Adverse Effects.......Page 221
Specific Agents......Page 223
Specific Agents......Page 224
Buspirone......Page 225
Review Questions......Page 226
Classification of Seizures......Page 227
Treatment of Seizure Disorders......Page 228
Mechanisms and Effects.......Page 231
Eslicarbazepine......Page 232
Interactions.......Page 234
Gabapentin......Page 235
Vigabatrin......Page 236
Clonazepam and Other Drugs......Page 237
Summary of Important Points......Page 238
Review Questions......Page 239
Chemistry and Pharmacokinetics......Page 241
Pharmacologic Effects......Page 242
Iontophoresis.......Page 243
Spinal Intrathecal Anesthesia.......Page 244
Pharmacokinetics.......Page 245
Pharmacologic Effects.......Page 247
Adverse Effects.......Page 248
Parenteral Anesthetics......Page 249
Summary of Important Points......Page 250
Review Questions......Page 251
Overview......Page 253
Pharmacologic Effects......Page 254
Adverse Effects......Page 256
Adverse Effects.......Page 257
Risperidone.......Page 259
Biogenic Amine Hypothesis......Page 260
Tricyclic Antidepressants......Page 262
Specific Drugs......Page 263
Serotonin and Norepinephrine Reuptake Inhibitors......Page 264
Mirtazapine......Page 265
Treatment Considerations......Page 266
Mechanism of Action......Page 267
Specific Drugs......Page 268
Summary of Important Points......Page 269
Review Questions......Page 270
Pain and Analgesic Agents......Page 271
Classification......Page 273
Central Nervous System.......Page 274
Morphine......Page 275
Fentanyl and Its Derivatives......Page 276
Other Opioid Agonists......Page 277
Specific Drugs......Page 278
Acute Pain......Page 279
Chronic Pain......Page 280
Review Questions......Page 281
Overview......Page 283
Mechanisms and Pharmacologic Effects.......Page 284
Adverse Effects.......Page 285
Carbidopa......Page 286
Dopamine Receptor Agonists......Page 287
Treatment Considerations......Page 289
Other Agents......Page 290
Treatment......Page 291
Treatment......Page 292
Summary of Important Points......Page 293
Review Questions......Page 294
Drug Dependence......Page 295
Physical Dependence.......Page 296
Pharmacokinetics.......Page 297
Central Nervous System Effects, Mechanisms, and Interactions.......Page 298
Other Alcohols and Glycols......Page 299
Opioids......Page 300
Methamphetamine......Page 301
Nicotine......Page 302
Cannabis and Its Derivatives......Page 303
Prescription Drug Abuse......Page 304
Treatment of Drug Dependence......Page 305
Summary of Important Points......Page 306
Review Questions......Page 307
Section 5_text......Page 309
Histamine Biosynthesis and Release......Page 311
Mechanisms and Pharmacokinetics......Page 312
First-Generation Antihistamines......Page 313
Intranasal Antihistamines.......Page 314
Serotonin Agonists......Page 315
Eicosanoid Receptors and Effects......Page 316
Prostaglandin E1 and Prostaglandin E1 Derivatives......Page 318
Summary of Important Points......Page 319
Review Questions......Page 320
Asthma......Page 321
Corticosteroids......Page 322
Lodoxamide and Nedocromil......Page 324
Adverse Effects and Interactions.......Page 325
β2-Adrenoceptor Agonists......Page 326
Pharmacokinetics......Page 328
Management of Asthma......Page 329
Viral Rhinitis......Page 330
Summary of Important Points......Page 331
Review Questions......Page 332
Drugs for Peptic Ulcer Disease......Page 333
Adverse Effects and Interactions......Page 334
Chemistry and Pharmacokinetics......Page 335
Gastric Antacids......Page 336
Aminosalicylates......Page 337
Laxatives......Page 338
Opioid Drugs......Page 339
Agents for IBS With Diarrhea......Page 340
Pharmacokinetics and Indications......Page 341
Adverse Effects and Interactions......Page 342
Summary of Important Points......Page 343
Review Questions......Page 344
Characteristics and Pathogenesis of Migraine Headaches......Page 345
Antiepileptic Drugs and Antidepressants......Page 346
Nonsteroidal Antiinflammatory Drugs......Page 347
Interactions.......Page 348
Prophylactic Treatment of Migraines......Page 349
Summary of Important Points......Page 350
Review Questions......Page 351
Rheumatoid Arthritis......Page 353
Prostaglandin Effects......Page 354
Cyclooxygenase Isozymes......Page 355
Nonselective Cyclooxygenase Inhibitors......Page 356
Adverse Effects.......Page 357
Pharmacokinetics.......Page 358
Pharmacokinetics.......Page 359
Celecoxib, Rofecoxib, and Valdecoxib......Page 360
Methotrexate......Page 361
Tumor Necrosis Factor α (TNFα) Blocking Agents.......Page 362
Xanthine Oxidase Inhibitors......Page 363
Summary of Important Points......Page 365
Review Questions......Page 366
Section 6_text......Page 367
Hormones Released From the Anterior Lobe of the Pituitary......Page 369
Clinical Uses of Hypothalamic and Pituitary Hormones......Page 370
Growth Hormone–Inhibiting Hormone Preparations......Page 371
Gonadotropin Preparations......Page 372
Oxytocin and Related Drugs......Page 373
Summary of Important Points......Page 374
Review Questions......Page 375
Thyroid Disorders......Page 377
Hyperthyroidism......Page 378
Pharmacokinetics......Page 379
Liothyronine......Page 380
Iodide Salts......Page 381
Summary of Important Points......Page 382
Review Questions......Page 383
Physiologic Effects of Adrenal Steroids......Page 385
Glucocorticoids......Page 387
Antiinflammatory Effects......Page 388
Cushing Syndrome......Page 389
Systemic Administration and Pharmacokinetics......Page 390
DHEA Use in Older Men......Page 391
Review Questions......Page 392
Biosynthesis of Gonadal Steroids......Page 393
Mechanism of Action......Page 395
Preparations and Disposition......Page 396
Adverse Effects......Page 397
Therapeutic Effects......Page 398
Contraceptives......Page 399
Administration......Page 400
Interactions......Page 401
Emergency Contraceptives......Page 402
Mechanisms and Indications......Page 403
Antiprogestins......Page 404
Gonadotropin-Releasing Hormone Analogs......Page 405
Summary of Important Points......Page 406
Review Questions......Page 407
Physiologic Effects......Page 409
Pathophysiology......Page 410
Short-Acting Insulin......Page 413
Mechanisms and Pharmacologic Effects.......Page 414
Mechanisms and Pharmacologic Effects.......Page 416
Incretin Mimetics......Page 417
Renal Glucose Reabsorption Inhibitors......Page 418
Insulin Requirements and Administration Schedules......Page 419
Summary of Important Points......Page 420
Review Questions......Page 421
Bone Disorders......Page 423
Pharmacokinetics.......Page 425
Indications.......Page 426
Adverse Effects......Page 427
Mechanism of Action.......Page 428
Indications.......Page 429
Hypercalcemia......Page 430
Review Questions......Page 431
Section 7_text......Page 433
Bactericidal or Bacteriostatic Effect......Page 435
Laboratory Tests for Microbial Sensitivity......Page 437
Mechanisms of Resistance......Page 439
Host Factors......Page 440
Pharmacokinetic Properties......Page 441
Combination Drug Therapy......Page 442
Prevention of Infection Caused by Invasive Procedures......Page 444
Review Questions......Page 445
Cytoplasmic and Outer Membranes......Page 447
Other Drugs......Page 448
Penicillins......Page 449
Spectrum and Indications......Page 450
Bacterial Resistance......Page 453
Clinical Use......Page 454
Carbapenems......Page 455
Summary of Important Points......Page 456
Review Questions......Page 457
Aminoglycosides......Page 459
Bacterial Resistance......Page 461
Adverse Effects......Page 462
Adverse Effects......Page 463
Spectrum and Indications......Page 464
Chloramphenicol......Page 465
Summary of Important Points......Page 466
Review Questions......Page 467
Spectrum, Indications, and Bacterial Resistance......Page 469
Spectrum and Indications......Page 471
Spectrum and Indications......Page 472
Bacterial Resistance......Page 473
Rifaximin......Page 474
Review Questions......Page 475
Drug Regimens......Page 477
Mechanism of Action and Resistance.......Page 478
Ethambutol......Page 480
Chemistry and Pharmacokinetics.......Page 481
New Drugs for Tuberculosis......Page 482
Summary of Important Points......Page 483
Review Questions......Page 484
Clinical Uses and Mechanisms of Antifungal Drugs......Page 485
Pharmacokinetics.......Page 486
Spectrum and Indications.......Page 487
Azole Derivatives......Page 489
Specific Drugs......Page 490
Griseofulvin......Page 491
Review Questions......Page 492
Drugs for Herpesvirus Infections......Page 493
Acyclovir, Famciclovir, and Valacyclovir......Page 494
Ganciclovir, Valganciclovir, and Cidofovir......Page 496
Sites of Drug Action......Page 497
Chemistry and Pharmacokinetics......Page 498
Specific Drugs......Page 499
Fusion and Entry Inhibitors......Page 500
Neuraminidase Inhibitors......Page 501
Drugs for Hepatitis and Other Viral Infections......Page 502
Adverse Effects and Interactions......Page 503
Summary of Important Points......Page 504
Review Questions......Page 505
Chemistry and Pharmacokinetics......Page 507
Drugs for Infections Caused by Blood- and Tissue-Dwelling Protozoa......Page 510
Chloroquine and Quinine......Page 511
Drugs for Toxoplasmosis......Page 512
Drugs for Other Protozoan Infections......Page 513
Diethylcarbamazine......Page 514
Drugs for Infestations Caused by Ectoparasites......Page 515
Review Questions......Page 516
Overview......Page 517
Treatment Regimens and Schedules......Page 518
Drug Toxicity......Page 519
Pharmacokinetics.......Page 522
DNA Cross-linking and Related Drugs......Page 523
Nitrogen Mustards......Page 524
Anthracycline Drugs......Page 525
Dactinomycin......Page 526
Mitotic Inhibitors......Page 527
Enzyme and Proteasome Inhibitors......Page 528
Monoclonal Antibodies.......Page 529
Drugs for Breast Cancer.......Page 531
Calcineurin and mTOR Inhibitors......Page 532
Review Questions......Page 533
Chapter 3......Page 535
Chapter 6......Page 536
Chapter 8......Page 537
Chapter 10......Page 538
Chapter 13......Page 539
Chapter 15......Page 540
Chapter 18......Page 541
Chapter 19......Page 542
Chapter 22......Page 543
Chapter 24......Page 544
Chapter 26......Page 545
Chapter 29......Page 546
Chapter 31......Page 547
Chapter 34......Page 548
Chapter 36......Page 549
Chapter 38......Page 550
Chapter 41......Page 551
Chapter 44......Page 552
Chapter 45......Page 553
A......Page 555
B......Page 558
C......Page 559
D......Page 561
E......Page 563
G......Page 564
H......Page 565
I......Page 566
L......Page 567
M......Page 568
N......Page 570
P......Page 571
R......Page 573
S......Page 574
T......Page 576
W......Page 577
Z......Page 578
Inside Back Cover......Page 579

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PHARMACOLOGY FIFTH EDITION

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PHARMACOLOGY FIFTH EDITION

George M. Brenner, PhD Professor Emeritus of Pharmacology Oklahoma State University Center for Health Sciences Tulsa, Oklahoma

Craig W. Stevens, PhD Professor of Pharmacology Oklahoma State University Center for Health Sciences Tulsa, Oklahoma

1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 19103-2899

Pharmacology, ed. 5 ISBN: 978-0-323-39166-5 Copyright © 2018 by Elsevier, Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Previous editions copyrighted 2013, 2010, 2006, and 2000 by Saunders, an imprint of Elsevier Inc. Library of Congress Cataloging-in-Publication Data Names: Brenner, George M., author. | Stevens, Craig W., author. Title: Pharmacology / George M. Brenner, Craig W. Stevens. Description: Fifth edition. | Philadelphia, PA : Elsevier, [2018] | Includes   bibliographical references and index. Identifiers: LCCN 2017020406 | ISBN 9780323391665 (pbk. : alk. paper) Subjects: | MESH: Pharmacological Phenomena | Pharmaceutical Preparations |   Drug Therapy Classification: LCC RM300 | NLM QV 4 | DDC 615/.1–dc23 LC record available at https://lccn.loc.gov/2017020406

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Preface Medical pharmacology is primarily concerned with the mechanisms by which drugs treat disease processes, relieve symptoms, and counteract the molecular manifestations of disease. Pharmacology is also concerned with the factors that determine the time course of drug action, including drug absorption, distribution, metabolism, and excretion. Students are often overwhelmed by the vast amount of pharmacological information available today. This textbook provides the essential concepts and information that students need to be successful in their courses without an overwhelming amount of detail. This text is primarily intended for students who are taking their first course in pharmacology, but it will also be useful for those who are preparing to take medical board or licensing examinations. Because of the large number of drugs available today, this text emphasizes the general properties of drug categories and prototypical drugs. Chapters begin with a drug classification box to familiarize students with drug categories, subcategories, and specific drugs to be discussed in the chapter. In the four years since the publication of the previous edition of Pharmacology by Brenner and Stevens, major trends in the development and marketing of new medications and new formulations were apparent. First, there was an explosion of combination drugs released onto the market in recent years. This is a good thing, as there is often pharmacological synergy between combined agents, but also because patient compliance is improved. It is easier to take one pill than two, or three, or four. The usual product combines two successful and effective single agents for the treatment of a disorder. These newly approved combination drugs are included in this 5th edition of Brenner & Stevens’ Pharmacology. Second, the market is flush with a number of new immunopharmacology products. Immunopharmacology is now a well-ripened field and the fruits of this discipline are apparent to both the physician and consumer by the new immunopharmacology drugs touted in TV commercials. Pharmaceutical manufacturing of monoclonal antibodies that target receptors or other proteins is a rapidly growing sector of biologics. Many therapeutic classes of pharmacological agents now have one or two drugs that work via antibodies or that target immune system factors. This edition contains a number of such new immunopharmacology drugs. However, the FDA approval of monoclonal antibody drugs and other biologics often comes with a number of serious warnings and adverse outcomes. Third, during the last four years, the rampant use of prescription opioids and the resultant opioid overdose epidemic were fully recognized. The appropriate response from the pharmaceutical manufacturers was to develop new agents and

formulations for the treatment of opioid dependence. The expanded class of these opioid medications is fully described in Chapter 23, “Opioid Analgesic and Antagonists.” Fourth, the epidemic of type 2 diabetes across the USA, and the tremendous market for product, brought drug developers back into the lab to work on antidiabetes medications. There were eight FDA-approved antidiabetes medications released into the market in the last two years. Many of these new medications target recently discovered mechanisms of action, like blocking sugar uptake at the kidneys. These new drugs and mechanisms of action for treating diabetes are updated in Chapter 35, “Drugs for Diabetes.” The book now in your hands was extensively revised for the 5th edition to include all the new drugs on the market, and to exclude older drugs that were withdrawn from the market since the last edition of this textbook. The figures that were retained were updated and new figures added, with an emphasis on illustrating drug mechanisms of action. A modern graphic style was developed for the figures to improve understanding and to entice the eye. The reader of this book will know some drugs better by their trade names. With the incessant marketing of new pharmaceuticals, many trade names of new drugs become common. As all medications are indexed under both their generic and brand name, this book is also a valuable reference for a quick review of drugs encountered in the reader’s personal or professional life. We thank our spouses and offspring for their encouragement and patience while we worked on this book. Much appreciation goes to our “significant others” (P