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Basic and Clinical Pharmacology PDF

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G R V d e t i n U - 9 9 r i h a t 1 S C H E D U L E O F C O N T R O L L E D D R U G S SCHEDULE I Depressants: Schedule II barbiturates in mixtures with noncontrolled drugs or in (All nonresearch use illegal under federal law.) suppository dosage form Flunitrazepam (Rohypnol) Barbiturates (butabarbital [Butisol], butalbital [Fiorinal]) Narcotics: Ketamine (Ketalar) Heroin and many nonmarketed synthetic narcotics Cannabinoids: Hallucinogens: Dronabinol (Marinol) LSD Anabolic Steroids: Fluoxymesterone (Androxy), Methyltestosterone MDA, STP, DMT, DET, mescaline, peyote, bufotenine, ibogaine, (Android, Testred, Methitest), Nandrolone decanoate (Deca- psilocybin, phencyclidine (PCP; veterinary drug only) Durabolin) Non US, Nandrolone phenpropionate (Durabolin) Non Marijuana US, Oxandrolone (Oxandrin), Oxymetholone (Androl-50), Stanozolol Methaqualone (Winstrol), Testolactone (Teslac), Testosterone and its esters SCHEDULE II SCHEDULE IV (No telephone prescriptions, no refills.)2 (Prescription must be rewritten after 6 months or five refills; differs from Opioids: Schedule III in penalties for illegal possession.) Opium Opioids: Opium alkaloids and derived phenanthrene alkaloids: codeine, Butorphanol (Stadol) morphine (Avinza, Kadian, MSContin, Roxanol), hydrocodone and Difenoxin 1 mg + atropine 25 mcg (Motofen) hydrocodone combinations (Zohydro ER, Hycodan, Vicodin, Pentazocine (Talwin) Lortab), hydromorphone (Dilaudid), oxymorphone (Exalgo), Stimulants: oxycodone (dihydroxycodeinone, a component of Oxycontin, Armodafinil (Nuvigil) Percodan, Percocet, Roxicodone, Tylox) Diethylpropion (Tenuate) not in US Designated synthetic drugs: meperidine (Demerol), methadone, levorphanol (Levo-Dromoran), fentanyl (Duragesic, Actiq, Modafinil (Provigil) Fentora), alfentanil (Alfenta), sufentanil (Sufenta), remifentanil Phentermine (Ionamin, Adipex-P) (Ultiva), tapentadol (Nycynta) Depressants: Stimulants: Benzodiazepines: Alprazolam (Xanax), Chlordiazepoxide (Librium), Coca leaves and cocaine Clonazepam (Klonopin), Clorazepate (Tranxene), Diazepam Amphetamines: Amphetamine complex (Biphetamine), (Valium), Estazolam (ProSom), Flurazepam (Dalmane), Halazepam Amphetamine salts (Adderall), Dextroamphetamine (Dexedrine, (Paxipam), Lorazepam (Ativan), Midazolam (Versed), Oxazepam Procentra), Lisdexamfetamine (Vyvanse), Methamphetamine (Serax), Prazepam (Centrax), Quazepam (Doral), Temazepam (Desoxyn), Methylphenidate (Ritalin, Concerta, Methylin, (Restoril) Triazolam (Halcion) Daytrana, Medadate), Above in mixtures with other controlled or Chloral hydrate (Somnote) uncontrolled drugs Eszopiclone (Lunesta) Cannabinoids: Lacosamide (Vimpat) Nabilone (Cesamet) Meprobamate (Equanil, Miltown, etc) Depressants: Methobarbital (Mebaral) Amobarbital (Amytal) Methohexital (Brevital) Pentobarbital (Nembutal) Paraldehyde Secobarbital (Seconal) Phenobarbital Zaleplon (Sonata) SCHEDULE III Zolpidem (Ambien) (Prescription must be rewritten after 6 months or five refills.) Opioids: SCHEDULE V Buprenorphine (Buprenex, Subutex) (As any other nonopioid prescription drug) Mixture of above Buprenorphine and Naloxone (Suboxone) Codeine: 200 mg/100 mL The following opioids in combination with one or more active Difenoxin preparations: 0.5 mg + 25 mcg atropine non-opioid ingredients, provided the amount does not exceed that shown: Dihydrocodeine preparations: 10 mg/100 mL Codeine and dihydrocodeine: not to exceed 1800 mg/dL or 90 mg/ Diphenoxylate (not more than 2.5 mg and not less than 0.025 mg of tablet or other dosage unit atropine per dosage unit, as in Lomotil) Opium: 500 mg/dL or 25 mg/5 mL or other dosage unit (paregoric) Ethylmorphine preparations: 100 mg/100 mL Stimulants: Opium preparations: 100 mg/100 mL Benzphetamine (Didrex) Pregabalin (Lyrica) Phendimetrazine (Bontril) Pyrovalerone (Centroton, Thymergix) 1See http://www.usdoj.gov/dea/pubs/scheduling.html for additional details. 2Emergency prescriptions may be telephoned if followed within 7 days by a valid written prescription annotated to indicate that it was previously placed by telephone. Katzung_insidecover.indd 1 25/10/14 5:06 PM a LANGE medical book Basic & Clinical Pharmacology G Thirteenth Edition R V d Edited by e t Bertram G. Katzung, MD, PhD i n Professor Emeritus Department of Cellular & Molecular PharmU acology University of California, San Francisco Associate Editor - Anthony J. Trevor, 9PhD 9 Professor Emeritus Department of Cellular r& Molecular Pharmacology University of Californiia, San Francisco h a t New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto Katzung-FM_p001-012.indd 1 10/24/14 4:00 PM Copyright © 2015 by McGraw-Hill Education. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher, with the exception that the program listings may be entered, stored, and executed in a computer system, but they may not be reproduced for publication. ISBN: 978-0-07-182641-9 MHID: 0-07-182641-6 The material in this eBook also appears in the print version of this title: ISBN: 978-0-07-182505-4, MHID: 0-07-182505-3. eBook conversion by codeMantra Version 1.0 All trademarks are trademarks of their respective owners. Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark. Where such designations appear in this book, they have been printed with initial caps. McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corporate training programs. To contact a representative, please visit the Contact Us page at www.mhprofessional.com. Notice Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. TERMS OF USE This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work. Use of this work is subject to these terms. Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s prior consent. You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited. Your right to use the work may be terminated if you fail to comply with these terms. THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. McGraw-Hill Education and its licensors do not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free. Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom. McGraw-Hill Education has no responsibility for the content of any information accessed through the work. Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, puni- tive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages. This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise. Contents Preface vii Authors ix I 10. Adrenoceptor Antagonist Drugs S E C T I O N David robertson, MD, & italo Biaggioni, MD 152 Basic PrinciPles 1 III G S E C T I O N 1. Introduction: The Nature of Drugs & Drug CArDiovASCULARr-rENAL Development & Regulation DrUgS 169 Bertram G. Katzung, MD, PhD 1 V 11. Antihypertensive Agents 2. Drug Receptors & Pharmacodynamics d neal l. Benowitz, MD 169 Mark von Zastrow, MD, PhD 20 e 3. Pharmacokinetics & Pharmacodynamics: 12. Vtasodilators & the Treatment Rational Dosing & the Time Course iof Angina Pectoris n Bertram G. Katzung, MD, PhD 191 of Drug Action nicholas H. G. Holford, MB, chB, FracP 41 U 13. Drugs Used in Heart Failure 4. Drug Biotransformation Bertram G. Katzung, MD, PhD 209 - Maria almira correia, PhD 56 14. Agents Used in Cardiac Arrhythmias 9 Joseph r. Hume, PhD, & augustus O. 5. Pharmacogenomics Grant, MD, PhD 224 Jennifer e. Hibma, PharmD, 9 & Kathleen M. Giacomini, PhD 74 r 15. Diuretic Agents II hi ramin sam, MD, David Pearce, MD, & S E C T I O N Harlan e. ives, MD, PhD 249 a aUTOnOMic DrUGs 87 IV t S E C T I O N 6. Introduction to Autonomic Pharmacology DrUgS WiTH iMPorTANT ACTioNS Bertram G. Katzung, MD, PhD 87 oN SMooTH MUSCLE 271 7. Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs 16. Histamine, Serotonin, & the Ergot Alkaloids achilles J. Pappano, PhD 105 Bertram G. Katzung, MD, PhD 271 8. Cholinoceptor-Blocking Drugs 17. Vasoactive Peptides achilles J. Pappano, PhD 121 ian a. reid, PhD 294 9. Adrenoceptor Agonists & 18. The Eicosanoids: Prostaglandins, Sympathomimetic Drugs Thromboxanes, Leukotrienes, & Related italo Biaggioni, MD, & David robertson, MD 133 Compounds emer M. smyth, PhD, & Garret a. FitzGerald, MD 313 iii Katzung-FM_p001-012.indd 3 10/24/14 4:00 PM iivv CCooNNTTEENNTTSS 19. Nitric Oxide 32. Drugs of Abuse samie r. Jaffrey, MD, PhD 329 christian lüscher, MD 552 20. Drugs Used in Asthma VI S E C T I O N Joshua M. Galanter, MD, & Homer a. Boushey, MD 336 DrUgS USED To TrEAT DiSEASES oF V THE BLooD, iNFLAMMATioN, S E C T I O N & goUT 567 DrUgS THAT ACT iN THE 33. Agents Used in Cytopenias; Hematopoietic CENTrAL NErvoUS SYSTEM 355 Growth Factors James l. Zehnder, MD 567 21. Introduction to the Pharmacology of CNS Drugs 34. Drugs Used in Disorders of Coagulation John a. Gray, MD, PhD, & James l. Zehnder, MD 584 roger a. nicoll, MD 355 35. Agents Used in Dyslipidemia 22. Sedative-Hypnotic Drugs Mary J. Malloy, MD, & John P. Kane, MD, PhD 602 anthony J. Trevor, PhD 369 36. Nonsteroidal Anti-Inflammatory Drugs, 23. The Alcohols Disease-Modifying Antirheumatic Drugs, susan B. Masters, PhD, & Nonopioid Analgesics, & Drugs Used anthony J. Trevor, PhD 384 in Gout 24. Antiseizure Drugs nabeel H. Borazan, MD, & Daniel e. Furst, roger J. Porter, MD, & MD 618 Brian s. Meldrum, MB, PhD 396 VII S E C T I O N 25. General Anesthetics ENDoCriNE DrUgS 643 Helge eilers, MD, & spencer Yost, MD 421 26. Local Anesthetics 37. Hypothalamic & Pituitary Hormones Kenneth Drasner, MD 440 roger K. long, MD, & Hakan cakmak, MD 643 27. Skeletal Muscle Relaxants 38. Thyroid & Antithyroid Drugs Marieke Kruidering-Hall, PhD, & Betty J. Dong, PharmD, FasHP, FccP, & Francis s. lundy campbell, MD 455 Greenspan, MD, FacP 663 28. Pharmacologic Management of Parkinsonism 39. Adrenocorticosteroids & Adrenocortical & Other Movement Disorders Antagonists Michael J. aminoff, MD, Dsc, FrcP 472 George P. chrousos, MD 680 29. Antipsychotic Agents & Lithium 40. The Gonadal Hormones & Inhibitors charles DeBattista, MD 490 George P. chrousos, MD 696 30. Antidepressant Agents 41. Pancreatic Hormones & Antidiabetic Drugs charles DeBattista, MD 510 Martha s. nolte Kennedy, MD, & Umesh Masharani, MBBs, MrcP (UK) 723 31. Opioid Agonists & Antagonists 42. Agents That Affect Bone Mineral Homeostasis Mark a. schumacher, PhD, MD, allan i. Basbaum, PhD, & ramana K. naidu, MD 531 Daniel D. Bikle, MD, PhD 747 Katzung-FM_p001-012.indd 4 10/24/14 4:00 PM CCooNNTTEENNTTSS vv VIII 54. Cancer Chemotherapy S E C T I O N edward chu, MD, & alan c. sartorelli, PhD 918 CHEMoTHErAPEUTiC DrUgS 767 55. Immunopharmacology 43. Beta-Lactam & Other Cell Wall- & Douglas F. lake, PhD, & Membrane-Active Antibiotics adrienne D. Briggs, MD 946 Daniel H. Deck, PharmD, & IX lisa G. Winston, MD 769 S E C T I O N ToXiCoLogY 971 44. Tetracyclines, Macrolides, Clindamycin, Chloramphenicol, Streptogramins, 56. Introduction to Toxicology: Occupational & Oxazolidinones & Environmental G Daniel H. Deck, PharmD, & Daniel T. Teitelbaum, MD 971 lisa G. Winston, MD 788 R 57. Heavy Metal Intoxication & Chelators 45. Aminoglycosides & Spectinomycin Daniel H. Deck, PharmD, & Michael J. KosneVtt, MD, MPH 987 lisa G. Winston, MD 799 58. Managemdent of the Poisoned Patient 46. Sulfonamides, Trimethoprim, Kent r. Olson, MD 1001 e & Quinolones t X Daniel H. Deck, PharmD, & S EiC T I O N lisa G. Winston, MD 807 n SPECiAL ToPiCS 1013 47. Antimycobacterial Drugs U 59. Special Aspects of Perinatal & Daniel H. Deck, PharmD, & lisa G. Winston, MD 815 Pediatric Pharmacology - Gideon Koren, MD 1013 48. Antifungal Agents 9 Don sheppard, MD, & 60. Special Aspects of Geriatric Pharmacology Harry W. lampiris, MD 825 9 Bertram G. Katzung, MD, PhD 1024 r 49. Antiviral Agents 61. Dermatologic Pharmacology i sharon safrin, MD 835 h Dirk B. robertson, MD & Howard i. Maibach, MD 1033 a 50. Miscellaneous Antimicrobial Agents; Disinfectants, Atntiseptics, & Sterilants 62. Drugs Used in the Treatment of Daniel H. Deck, PharmD, & Gastrointestinal Diseases lisa G. Winston, MD 865 Kenneth r. McQuaid, MD 1052 51. Clinical Use of Antimicrobial Agents 63. Therapeutic & Toxic Potential of Harry W. lampiris, MD, & Daniel s. Maddix, Over-the-Counter Agents PharmD 873 robin l. corelli, PharmD 1084 52. Antiprotozoal Drugs 64. Dietary Supplements & Herbal Medications Philip J. rosenthal, MD 886 cathi e. Dennehy, PharmD, & candy Tsourounis, PharmD 1094 53. Clinical Pharmacology of the Antihelminthic Drugs Philip J. rosenthal, MD 908 Katzung-FM_p001-012.indd 5 10/24/14 4:00 PM vi CoNTENTS 65. Rational Prescribing & Prescription Writing Appendix: Vaccines, Immune Globulins, Paul W. lofholm, PharmD, & & Other Complex Biologic Products Bertram G. Katzung, MD, PhD 1108 Harry W. lampiris, MD, & Daniel s. Maddix, PharmD 1133 66. Important Drug Interactions & Their Mechanisms index 1141 John r. Horn, PharmD, FccP 1118 Katzung-FM_p001-012.indd 6 10/24/14 4:00 PM Preface The thirteenth edition of Basic & Clinical Pharmacology continues development and regulation material previously covered in the important changes inaugurated in the eleventh edition, with Chapter 5 has been incorporated into Chapter 1. extensive use of full-color illustrations and expanded coverage of • A generic name–trade name table appears at the conclusion of  transporters, pharmacogenomics, and new drugs. Case studies most chapters, providing a rapid reference for these names. accompany most chapters and answers to questions posed in the • Many revised illustrations in full Gcolor provide significantly  case studies appear at the end of each chapter. As in prior editions, more information about drug mechanisms and effects and help to clarify important concepts. the book is designed to provide a comprehensive, authoritative, R • Major revisions of the chapters on sympathomimetic, diuretic,  and readable pharmacology textbook for students in the health antipsychotic, antidepressant, antidiabetic, anti-inflammatory, sciences. Frequent revision is necessary to keep pace with the rapid and antiviral drugs, pVrostaglandins, nitric oxide, hypothalamic changes in pharmacology and therapeutics; the 2–3 year revision and pituitary hormones, central nervous system neurotrans- cycle of the printed text is among the shortest in the field and the mitters, immundopharmacology, and toxicology. availability of an online version provides even greater currency. • Continued expansion of the coverage of general concepts relat- The book also offers special features that make it a useful reference ing to neewly discovered receptors, receptor mechanisms, and for house officers and practicing clinicians. drug transporters. Information is organized according to the sequence used in • Desctriptions  of  important  new  drugs  released  through  i many pharmacology courses and in integrated curricula: basic prin- nAugust 2014. ciples; autonomic drugs; cardiovascular-renal drugs; drugs with An important related educational resource is Katzung & Trevor’s important actions on smooth muscle; central nervous system drugs; U Pharmacology: Examination & Board Review, tenth edition (Trevor drugs used to treat inflammation, gout, and diseases of the blood; AJ, Katzung BG, & Masters SB: McGraw-Hill, 2013). This book endocrine drugs; chemotherapeutic drugs; toxicology; and sp ecial provides a succinct review of pharmacology with approximately topics. This sequence builds new information on a founda-tion of one thousand sample examination questions and answers. It is information already assimilated. For example, early pres entation of 9 especially helpful to students preparing for board-type examina- autonomic nervous system pharmacology allows students to inte- tions. A more highly condensed source of information suitable for grate the physiology and neuroscience they have learned elsewhere 9 review purposes is USMLE Road Map: Pharmacology, second with the pharmacology they are learning and prepares them to edition (Katzung BG, Trevor AJ: McGraw-Hill, 2006). understand the autonomic effects of other rdrugs. This is especially This edition marks the 32th year of publication of Basic & important for the cardiovascular and cientral nervous system drug h Clinical Pharmacology. The widespread adoption of the first twelve groups. However, chapters can be used equally well in courses and editions indicates that this book fills an important need. We curricula that present these topics in a different sequence. a believe that the thirteenth edition will satisfy this need even more Within each chapter, emphasis is placed on discussion of drug groups and prototypes rathter than offering repetitive detail about successfully. Spanish, Portuguese, Italian, French, Indonesian, individual drugs. Selection of the subject matter and the order of Japanese, Korean, Turkish, and Ukrainian translations are avail- its presentation are based on the accumulated experience of teach- able. Translations into other languages are under way; the pub- ing this material to thousands of medical, pharmacy, dental, lisher may be contacted for further information. podiatry, nursing, and other health science students. I wish to acknowledge the prior and continuing efforts of my Major features that make this book particularly useful in inte- contributing authors and the major contributions of the staff at grated curricula include sections that specifically address the clini- Lange Medical Publications, Appleton & Lange, and McGraw-Hill, cal choice and use of drugs in patients and the monitoring of their and of our editors for this edition, Donna Frassetto and Rachel effects—in other words, clinical pharmacology is an integral part of D’Annucci Henriquez. I also wish to thank Alice Camp and this text. Lists of the trade and generic names of commercial Katharine Katzung for their expert proofreading contributions. preparations available are provided at the end of each chapter for Suggestions and comments about Basic & Clinical Pharmacology easy reference by the house officer or practitioner writing a chart are always welcome. They may be sent to me in care of the publisher. order or prescription. Bertram G. Katzung, MD, PhD San Francisco Significant revisions in this edition include: December, 2011 • Addition of a chapter on pharmacogenomics, an area of  increasing importance in all aspects of pharmacology. The drug vii Katzung-FM_p001-012.indd 7 10/24/14 4:00 PM This page intentionally left blank

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