MC GRAW-HILL Medical Publishing Division
S i x t h E d i t i o n
PHARMACOTHERAPY
A Pathophysiologic Approach
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 editors 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 editors 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.
S i x t h E d i t i o n
PHARMACOTHERAPY
A Pathophysiologic Approach
Editors
Joseph T. DiPiro, PharmD, FCCP
Professor and Executive Dean, South Carolina College of Pharmacy, University of South Carolina, Columbia, and Medical University of South Carolina, Charleston
Robert L. Talbert, PharmD, FCCP, BCPS
Professor, College of Pharmacy, University of Texas at Austin; Professor, Departments of Medicine and Pharmacology, University of Texas Health Science Center at San Antonio, Texas
Gary C. Yee, PharmD, FCCP
Professor and Chair, Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska
Gary R. Matzke, PharmD, FCP, FCCP
Professor, Department of Pharmacy and Therapeutics, School of Pharmacy, Renal-Electrolyte Division, School of Medicine,
University of Pittsburgh, Pittsburgh, Pennsylvania
Barbara G. Wells, PharmD, FASHP, FCCP, BCPP
Dean and Professor, School of Pharmacy, The University of Mississippi, University, Mississippi
L. Michael Posey, BS Pharm
President, PENS Pharmacy Editorial and News Services, Athens, Georgia
M C GRAW-HILL
Medical Publishing Division
New York Chicago San Francisco Lisbon
London Madrid Mexico City Milan New Delhi
Pharmacotherapy: A Pathophysiologic Approach, Sixth Edition C
Copyright 2005, 2002 by The McGraw-Hill Companies, Inc. All rights reserved. Printed in the United States of America. 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.C Previous editions copyright 1999, 1997, 1993 by Appleton & Lange.
1 2 3 4 5 6 7 8 9 0 DOWDOW 0 9 8 7 6 5 Set ISBN 0-07-141613-7 Book p/n 0-07-146392-5
E-book download access card p/n 0-07-146393-3 and sticker p/n 0-07-146394-1
E-book ISBN 0-07-146390-9This book is sold with codes for access to an Online Learning Center and
an e-book version of the text. This book is not returnable unless the shrink-wrap and the scratch-off coating on the codes are intact.Please tell the authors and publisher what you think of this book by sending
your comments to pharmacotherapy@mcgraw-hill.com. Please put the author
and title of the book in subject line. This book was set in Times Roman by TechBooks, Inc. The editors were Michael Brown, Andrew Hall, Karen G. Edmonson, and Peter J. Boyle. The production supervisor was Richard Ruzycka. The text designer was Joan O’Connor. The cover designer was Elizabeth Pisacreta. Barbara Littlewood prepared the index. RR Donnelley was printer and binder. This book is printed on acid-free paper.C Cover images copyright 1999 by Obi-Tabot Tabe. The images used on the
′ ′
cover and spine are taken from a 9 × 4-1/2 oil painting by Obi-Tabot Tabe, PharmD, a painter, graphic designer, scientific illustrator, and pharmacist.Dr. Tabe, originally from Cameroon, is a graduate of the University of Pittsburgh, School of Pharmacy. The painting incorporates the artist’s
impressions of concepts introduced in the pharmacy curriculum. The painting
can be seen in the student lounge of Salk Hall at the university.
Cataloging-in-publication data is on file for this title at the Library of Congress.
Dedication
To those pharmacists who had the courage and perseverance to pioneer the
development of the clinical practice of pharmacy.
To the contemporary pharmaceutical care practitioners who continue to expand
their impact on patient outcomes and thereby serve as role models for their
colleagues and students while clinging tenaciously to the highest standards of
practice.
To our mentors, whose vision provided educational and training programs that
encouraged our professional growth and challenged us to be innovators in our
patient care, research, and educational endeavors.
To our faculty colleagues for their efforts and support for our mission to provide a
comprehensive and challenging educational foundation for the clinical pharmacists
of the future.
And finally to our families for the time that they have sacrificed so that this
sixth edition would become a reality.
C ONTENTS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
14. Heart Failure . . . . . . . . . . . . . . . . 219 Robert B. Parker J. Herbert Patterson Julie A. Johnson
DISORDERS . . . . . . . . . . . 149 Robert L. Talbert, Section Editor
11. Cardiovascular Testing . . . . . . . . . . .
149 Robert L. Talbert
12. Cardiopulmonary Resuscitation . . . . . . .
171 Jeffrey F. Barletta
13. Hypertension . . . . . . . . . . . . . . .
185 Joseph J. Saseen Barry L. Carter
15. Ischemic Heart Disease . . . . . . . . . . 261 Robert L. Talbert
115 Andy Stergachis Thomas K. Hazlet
16. Acute Coronary Syndromes . . . . . . . . 291 Sarah A. Spinler Simon de Denus
17. Arrhythmias . . . . . . . . . . . . . . . .
321 Jerry L. Bauman Marieke Dekker Schoen
18. Diastolic Heart Failure and the Cardiomyopathies
. . . . . . . . . . .
357 Jean M. Nappi Michael R. Zile
19. Venous Thromboembolism . . . . . . . . . 373 Stuart T. Haines Mario Zeolla
10. Clinical Toxicology . . . . . . . . . . . . 125 Peter A. Chyka
9. Pharmacoepidemiology . . . . . . . . . .
Foreword . . . . . . . . . . . . . . . . . . . . . xv
Preface . . . . . . . . . . . . . . . . . . . . . . xix Contributors . . . . . . . . . . . . . . . . . . . xxi Guiding Principles of Pharmacotherapy . . . . . xxxiii
Foreword to the First Edition . . . . . . . . . . . xvii
SECTION 2. CARDIOVASCULAR
75 Larisa H. Cavallari Y. W. Francis Lam
1 Lisa A. Sanchez 2. Health Outcomes and Quality of Life . . . .
91 Milap C. Nahata Carol Taketomo
7. Pediatrics . . . . . . . . . . . . . . . . . .
SECTION 1: BASIC CONCEPTS . . . . . . . . .
1 L. Michael Posey, Section Editor
1. Pharmacoeconomics: Principles, Methods, and Applications . . . . . . . . . . . . . . .
17 Stephen Joel Coons
6. Pharmacogenetics . . . . . . . . . . . . . .
3. Evidence-Based Medicine . . . . . . . . . .
Catherine I. Lindblad Shelly L. Gray David R. P. Guay Emily R. Hajjar Teresa C. McCarthy
4. Documentation of Pharmacy Services . . . . . . . . . . . . . . . . . .
39 George E. MacKinnon, III Neil J. MacKinnon
5. Clinical Pharmacokinetics and Pharmacodynamics . . . . . . . . . . .
51 Larry A. Bauer
27 Elaine Chiquette L. Michael Posey
8. Geriatrics . . . . . . . . . . . . . . . . . 103
viii
20. Stroke . . . . . . . . . . . . . . . . . . . 415 Susan C. Fagan David C. Hess
SECTION 4. GASTROINTESTINAL DISORDERS
22. Peripheral Arterial Disease . . . . . . . . . 453 Barbara J. Hoeben Robert L. Talbert
36. Diarrhea, Constipation, and Irritable Bowel Syndrome
33. Peptic Ulcer Disease . . . . . . . . . . . .
629 Rosemary R. Berardi Lynda S. Welage
34. Inflammatory Bowel Disease . . . . . . . .
649 Joseph T. DiPiro Robert R. Schade
35. Nausea and Vomiting . . . . . . . . . . . . 665 Cecily V. DiPiro
A. Thomas Taylor
. . . . . . . . . . . . . .
32. Gastroesophageal Reflux Disease . . . . . .
677 William J. Spruill William E. Wade
37. Portal Hypertension and Cirrhosis . . . . .
693 Edward G. Timm James J. Stragand
38. Drug-Induced Liver Disease . . . . . . . .
713 William R. Kirchain Mark A. Gil
39. Pancreatitis . . . . . . . . . . . . . . . . 721 Rosemary R. Berardi Patricia A. Montgomery
40. Viral Hepatitis . . . . . . . . . . . . . . . 737 Manjunath P. Pai Renee-Claude Mercier Marsha A. Raebel
613 Dianne B. Williams Robert R. Schade
31. Evaluation of the Gastrointestinal Tract . . . . . . . . . . . . . . . . . . . 605 Marie A. Chisholm Mark W. Jackson
23. Use of Vasopressors and Inotropes in the Pharmacotherapy of Shock . . . . . . . . . 461 Maria I. Rudis Joseph F. Dasta
26. Asthma . . . . . . . . . . . . . . . . . .
24. Hypovolemic Shock . . . . . . . . . . . . 479 Brian L. Erstad
SECTION 3. RESPIRATORY DISORDERS . . . . . . . . . . .
495 Robert L. Talbert, Section Editor
25. Introduction to Pulmonary Function Testing
. . . . . . . . . . . . . . . . . .
495 Jay I. Peters Stephanie M. Levine
503
21. Hyperlipidemia . . . . . . . . . . . . . . 429 Robert L. Talbert
H. William Kelly Christine A. Sorkness
27. Chronic Obstructive Pulmonary Disease . . 537 Sharya V. Bourdet Dennis M. Williams
28. Acute Respiratory Distress Syndrome . . . .
557 Peter Gal J. Laurence Ransom
29. Drug-Induced Pulmonary Diseases . . . . .
577 Hengameh H. Raissy Michelle Harkins Patricia L. Marshik
30. Cystic Fibrosis . . . . . . . . . . . . . . . 591 Gary Milavetz Jeffrey J. Smith
. . . . . . . . . . . 605 Joseph T. DiPiro, Section Editor
ix SECTION 5. RENAL DISORDERS . . . . . . . 761
. . . . . . . . . . . . . . . . . .
1003 Susan C. Fagan Fenwick T. Nichols
53. Multiple Sclerosis . . . . . . . . . . . .
1007 Jacquelyn L. Bainbridge John R. Corboy
54. Epilepsy . . . . . . . . . . . . . . . . .
1023 Barry E. Gidal William R. Garnett
55. Status Epilepticus . . . . . . . . . . . . . 1049 Stephanie J. Phelps Collin A. Hovinga Bradley A. Boucher
56. Acute Management of the Brain Injury Patient
1061 Bradley A. Boucher Stephanie J. Phelps Shelly D. Timmons
SECTION 6. NEUROLOGIC DISORDERS . . 1003 Barbara G. Wells, Section Editor
57. Parkinson’s Disease . . . . . . . . . . . .
1075 Merlin V. Nelson Richard C. Berchou Peter A. LeWitt
58. Pain Management . . . . . . . . . . . . . 1089 Terry J. Baumann
59. Headache Disorders . . . . . . . . . . . . 1105 Deborah S. King Katherine C. Herndon
SECTION 7. PSYCHIATRIC DISORDERS . .
1123 Barbara G. Wells, Section Editor
60. Evaluation of Psychiatric Illness . . . . . .
52. Evaluation of Neurologic Illness . . . . . .
51. Acid-Base Disorders . . . . . . . . . . . . 983 Gary R. Matzke Paul M. Palevsky
Gary R. Matzke, Section Editor
47. Glomerulonephritis . . . . . . . . . . . .
41. Quantification of Renal Function . . . . . . 761 Thomas C. Dowling Thomas J. Comstock
42. Acute Renal Failure . . . . . . . . . . . . 781 Bruce A. Mueller
43. Chronic Kidney Disease: Progression- Modifying Therapies . . . . . . . . . . . . 799 Melanie S. Joy Abhijit Kshirsagar James Paparello
44. Chronic Kidney Disease: Therapeutic Approach for the Management of Complications . . . . . . . . . . . . . . . 821
Joanna Q. Hudson Kunal Chaudhary
45. Hemodialysis and Peritoneal Dialysis . . . . 851 Rowland J. Elwell Edward F. Foote
46. Drug-Induced Kidney Disease . . . . . . . 871 Thomas D. Nolin Jonathan Himmelfarb Gary R. Matzke
891 Alan H. Lau
967 Donald F. Brophy Todd W. B. Gehr
48. Drug Therapy Individualization for Patients with Renal Insufficiency
. . . . . . . . . .
919 Reginald F. Frye Gary R. Matzke
49. Disorders of Sodium, Water, Calcium, and Phosphorus Homeostasis
. . . . . . . . . .
937 Melanie S. Joy Gerald A. Hladik
50. Disorders of Potassium and Magnesium Homeostasis
. . . . . . . . . . . . . . . .
1123 Patricia A. Marken Mark E. Schneiderhan Stuart Munro
x
SECTION 8. ENDOCRINOLOGIC DISORDERS
. . . . . . . . . . . . . .
1369 Robert L. Talbert
74. Adrenal Gland Disorders . . . . . . . . . 1391 John G. Gums John M. Tovar
75. Pituitary Gland Disorders . . . . . . . . .
1407 Amy M. Heck Jack A. Yanovski Karim Anton Calis
. . . 1425 Barbara G. Wells, Section Editor
76. Pregnancy and Lactation: Therapeutic Considerations
1425 Denise L. Walbrandt Pigarelli Connie K. Kraus Beth E. Potter
72. Diabetes Mellitus . . . . . . . . . . . . . 1333 Curtis L. Triplitt Charles A. Reasner William L. Isley
77. Contraception . . . . . . . . . . . . . .
1443 Lori M. Dickerson Kathryn K. Bucci
78. Menstruation-Related Disorders . . . . . . 1465 Martha P. Fankhauser Marlene P. Freeman
79. Endometriosis . . . . . . . . . . . . . .
1485 Deborah A. Sturpe Alkesh D. Patel
80. Hormone Therapy in Women . . . . . . . 1493 Sophia N. Kalantaridou Susan R. Davis Karim Anton Calis
73. Thyroid Disorders . . . . . . . . . . . .
. . . . . . . . . . . 1333 Robert L. Talbert, Section Editor
61. Childhood Disorders . . . . . . . . . . . 1133 Julie A. Dopheide Karen A. Theesen Michael Malkin
65. Substance-Related Disorders: Alcohol, Nicotine, and Caffeine . . . . . . . . . . 1193 Paul L. Doering
62. Eating Disorders . . . . . . . . . . . . .
1147 Patricia A. Marken Roger W. Sommi
63. Alzheimer’s Disease . . . . . . . . . . .
1157 Jennifer D. Faulkner Jody Bartlett Paul Hicks
64. Substance-Related Disorders: Overview and Depressants, Stimulants, and Hallucinogens . . . . . . . . . . . . . .
1175 Paul L. Doering
66. Schizophrenia . . . . . . . . . . . . . .
71. Sleep Disorders . . . . . . . . . . . . . . 1321 Cherry W. Jackson Judy L. Curtis
1209 M. Lynn Crismon Peter F. Buckley
SECTION 9. GYNECOLOGIC AND OBSTETRIC DISORDERS
67. Depressive Disorders . . . . . . . . . . .
1235 Judith C. Kando Barbara G. Wells Peggy E. Hayes
68. Bipolar Disorder . . . . . . . . . . . . . 1257 Martha P. Fankhauser Marlene P. Freeman
69. Anxiety Disorders I: Generalized Anxiety, Panic, and Social Anxiety Disorders . . . . 1285 Cynthia K. Kirkwood Sarah T. Melton
70. Anxiety Disorders II: Posttraumatic Stress Disorder and Obsessive-Compulsive Disorder . . . . . . . . . . . . . . . . .
1307 Cynthia K. Kirkwood Eugene H. Makela Barbara G. Wells
xi . . . 1515
89. Rheumatoid Arthritis . . . . . . . . . . . 1671 SECTION 10. UROLOGIC DISORDERS
L. Michael Posey, Section Editor Arthur A. Schuna
81. Erectile Dysfunction . . . . . . . . . . . 1515
90. Osteoarthritis . . . . . . . . . . . . . . . 1685 Mary Lee
Karen E. Hansen Mary Elizabeth Elliott
82. Management of Benign Prostatic . . . . . . . . .
91. Gout and Hyperuricemia 1705 Hyperplasia . . . . . . . . . . . . . . . 1535 David W. Hawkins Mary Lee Daniel W. Rahn . . . . . . . . . . .
83. Urinary Incontinence 1547 Eric S. Rovner
SECTION 13. DISORDERS OF THE Jean Wyman
EYES, EARS, NOSE, Thomas Lackner . . . . . . . . .
AND THROAT 1713 David Guay
L. Michael Posey, Section Editor
92. Glaucoma . . . . . . . . . . . . . . . . 1713 SECTION 11. IMMUNOLOGIC
Timothy S. Lesar DISORDERS . . . . . . . . . . 1565
Richard G. Fiscella Gary C. Yee, Section Editor
Deepak Edward
84. Function and Evaluation of the Immune
93. Allergic Rhinitis . . . . . . . . . . . . . 1729 . . . . . . . . . . . . . . . . . . System 1565
J. Russell May Philip D. Hall Philip H. Smith Mary S. Hayney
85. Systemic Lupus Erythematosus and Other SECTION 14. DERMATOLOGIC . . . . . . . .
Collagen-Vascular Diseases 1581 . . . . . . . . . .
DISORDERS 1741 L. Michael Posey, Section Editor
Jeffrey C. Delafuente Kimberly A. Cappuzzo
94. Dermatologic Drug Reactions, Self-Treatable Skin Disorders, and Skin
86. Allergic and Pseudoallergic Drug . . . . . . . . . . . . . . . . . .
Cancer 1741 . . . . . . . . . . . . . . . . . Reactions 1599
Nina H. Cheigh Joseph T. DiPiro Dennis R. Ownby
95. Acne Vulgaris . . . . . . . . . . . . . . 1755 Dennis P. West . . . . . . .
87. Solid-Organ Transplantation 1613 Lee E. West Heather J. Johnson Maria Letizia Musumeci Kristine S. Schonder Giuseppe Micali
96. Psoriasis . . . . . . . . . . . . . . . . . 1769 SECTION 12. BONE AND JOINT Dennis P. West . . . . . . . . . .
DISORDERS 1645 Lee E. West L. Michael Posey, Section Editor Laura Scuderi
Giuseppe Micali . . . . . .
88. Osteoporosis and Osteomalacia 1645 . . . . . . . . . . . . .
97. Atopic Dermatitis 1785 Mary Beth O’Connell Terry L. Seaton
Nina H. Cheigh
xii SECTION 15. HEMATOLOGIC DISORDERS . . . . . . . . . . 1793
2081 Elizabeth A. Coyle Randall A. Prince
111. Gastrointestinal Infections and Enterotoxigenic Poisonings
. . . . . . . .
2035 Steven Martin Rose Jung
112. Intraabdominal Infections . . . . . . . . .
2055 Joseph T. DiPiro Thomas R. Howdieshell
113. Parasitic Diseases . . . . . . . . . . . . . 2067 JV Anandan
114. Urinary Tract Infections and Prostatitis . .
115. Sexually Transmitted Diseases . . . . . . 2097 Leroy C. Knodel
1997 Michael A. Crouch Angie Veverka
116. Bone and Joint Infections . . . . . . . . .
2119 Edward P. Armstrong Leslie L. Barton
117. Sepsis and Septic Shock . . . . . . . . . 2131 S. Lena Kang-Birken Joseph T. DiPiro
118. Superficial Fungal Infections . . . . . . .
2145 Thomas E. R. Brown Thomas W. F. Chin
119. Invasive Fungal Infections . . . . . . . . .
2161 Peggy L. Carver
120. Infections in Immunocompromised Patients . . . . . . . . . . . . . . . . . . 2191 Douglas N. Fish S. Diane Goodwin
110. Tuberculosis . . . . . . . . . . . . . . . 2015 Charles A. Peloquin
109. Infective Endocarditis . . . . . . . . . . .
Gary C. Yee, Section Editor
108. Skin and Soft Tissue Infections . . . . . . 1977 Susan L. Pendland Douglas N. Fish Larry H. Danziger
98. Hematopoiesis . . . . . . . . . . . . . . 1793 William P. Petros Solveig Ericson
99. Anemias . . . . . . . . . . . . . . . . . 1805 Beata Ineck Barbara J. Mason
E. Gregory Thompson
106. Lower Respiratory Tract Infections . . . .
1923 Elizabeth D. Hermsen John C. Rotschafer
105. Central Nervous System Infections . . . .
104. Antimicrobial Regimen Selection . . . . . 1909 David S. Burgess Betty J. Abate
103. Laboratory Tests to Direct Antimicrobial Pharmacotherapy . . . . . . . . . . . . . 1891 Michael J. Rybak Jeffrey R. Aeschlimann
1943 Mark L. Glover Michael D. Reed
SECTION 16. INFECTIOUS DISEASES . . .
1875 S. Jay Weaver Thomas E. Johns
C. Y. Jennifer Chan Reginald Moore 102. Drug-Induced Hematologic Disorders . . .
1855
101. Sickle Cell Disease . . . . . . . . . . . .
1833 Betsy Bickert Janet L. Kwiatkowski
100. Coagulation Disorders . . . . . . . . . .
107. Upper Respiratory Tract Infections . . . .
1963 Yasmin Khaliq Sarah Forgie George Zhanel
1891 Joseph T. DiPiro, Section Editor
xiii 121. Antimicrobial Prophylaxis in Surgery . . . 2217
2591 Todd W. Mattox Pamela D. Reiter
. . . . . . . . . . . . . .
2541 Janelle B. Perkins Gary C. Yee
SECTION 18. NUTRITIONAL DISORDERS . . . . . . . . . .
2559 Gary R. Matzke, Section Editor
135. Assessment of Nutrition Status and Nutrition Requirements . . . . . . . . . . 2559 Katherine Hammond Chessman Vanessa J. Kumpf
136. Prevalence and Significance of Malnutrition . . . . . . . . . . . . . . . 2579 Gordon Sacks Pamela D. Reiter
137. Parenteral Nutrition . . . . . . . . . . . .
138. Enteral Nutrition . . . . . . . . . . . . .
133. Melanoma . . . . . . . . . . . . . . . . 2525 Rowena N. Schwartz
2615 Vanessa J. Kumpf Katherine Hammond Chessman
139. Nutritional Considerations in Major Organ Failure
. . . . . . . . . . .
2635 Renee M. DeHart Sunshine J. Yocum
140. Obesity . . . . . . . . . . . . . . . . . . 2659 John V. St. Peter Mehmood A. Khan
Glossary . . . . . . . . . . . . . . . . . . . .
2677 Index . . . . . . . . . . . . . . . . . . . . . .
134. Hematopoietic Stem Cell Transplantation
132. Chronic Leukemias . . . . . . . . . . . . 2513 Timothy R. McGuire Steven Z. Pavletic
Salmaan Kanji John W. Devlin 122. Vaccines, Toxoids, and Other Immunobiologics . . . . . . . . . . . . . 2231
126. Lung Cancer . . . . . . . . . . . . . . .
Mary S. Hayney 123. Human Immunodeficiency Virus Infection
. . . . . . . . . . . . . . . . .
2255 Courtney V. Fletcher Thomas N. Kakuda
SECTION 17. ONCOLOGIC DISORDERS . .
2279 Gary C. Yee, Section Editor
124. Cancer Treatment and Chemotherapy . . . 2279 Carol McManus Balmer Amy Wells Valley Andrea Iannucci
125. Breast Cancer . . . . . . . . . . . . . . 2329 Celeste Lindley Laura Boehnke Michaud
2365 Rebecca S. Finley Jeannine S. McCune
2485 Helen L. Leather Betsy Bickert
127. Colorectal Cancer . . . . . . . . . . . . .
2383 Patrick J. Medina Lisa E. Davis
128. Prostate Cancer . . . . . . . . . . . . . .
2421 Jill M. Kolesar
129. Lymphomas . . . . . . . . . . . . . . . 2439 Val R. Adams Gary C. Yee
130. Ovarian Cancer . . . . . . . . . . . . . . 2467 William C. Zamboni Laura L. Jung Margaret E. Tonda
131. Acute Leukemias . . . . . . . . . . . . .
2695 Color plates appear between pages 1740 and 1741.
F OREWORD
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Drug therapy often represents the best treatment for human diseases and illnesses, and the spectrum of effective medications continues to improve at a remarkable pace. This is likely to continue over the com- ing years, as our understanding of disease pathogenesis and molecular pharmacology rapidly expands, fueling the discovery of new classes of medication. This, coupled with impressive advances in technology and our understanding of the human genome, promises to usher in a new wave of targeted therapies and individualized medicine that may further improve the efficacy and reduce the toxicity of medications. However, most of the highly effective medications currently available for clinical use emerged from classical pharmacology and chemistry, on a foundation of incomplete knowledge of disease mechanisms. This may contribute in part to the propensity of many medications to produce adverse drug effects or to exhibit limited efficacy in a subset of patients with a given diagnosis. These imperfect medications will remain the mainstay of therapeutics for years to come.
The limited efficacy and potential toxicity of many of today’s medications, coupled with the rapidly expanding portfolio of medi- cations for disease treatment and prevention, creates enormous com- plexity in selecting optimal medications for individual patients. Thus, the expertise of clinically educated and trained pharmacists is increas- ingly important if we are to ensure patients receive the most effective medications in the doses and combinations that are optimal for them and their illnesses.
The sixth edition of Pharmacotherapy: A Pathophysiologic
Approach contains a wealth of information that will be an invaluable
resource to students and practitioners who work to expand their knowledge of pharmacotherapy and translate it into better drug ther- apy for individual patients. In a perfect world, every patient would benefit from the collective talents of a health care team that is fully able to integrate knowledge of disease pathogenesis and pharmacotherapy, thereby optimizing drug therapy for each individual. Such a team is incomplete without a clinical pharmacist.
How many clinical pharmacists does it take in this day and age? Can one justify 25 pharmacists for a 58-bed hospital? That’s the real- ity at St. Jude Children’s Research Hospital, where I have worked for the last 25 years. And this wasn’t even seriously challenged when the “health care consultants” rolled into town 10 years ago. Why not? The reasons are multiple, yet simple in the end: Pharmacists are integrally involved in the pharmacotherapy of every patient. The medical staff would not have it any other way, and the patients deserve no less.
That’s as it should be everywhere, in hospitals and clinics and com- munity pharmacies. Moreover, pharmacists have become integral to the process of defining the future state of pharmacotherapy, by bring- ing unique expertise to the research enterprise. That must continue as well. The pharmacists of the present and future must integrate phar- macology, pathophysiology, therapeutics, and, increasingly, genetics into complex treatment decisions.
Pharmacotherapy: A Pathophysiologic Approach is an impor-
tant tool to this end. By providing pharmacy students and practicing pharmacists (plus physicians and nurses) with a comprehensive and definitive source of information about diseases and their drug treat- ment, it is a conduit to the clinical use of pharmacotherapeutic princi- ples by pharmacists, which is the sine qua non of pharmacy practice in the twenty-first century.
Health care in the United States and other developed countries nities to improve the way these advances are deployed, especially drug therapy. Studies have shown that even when there are clear guidelines for appropriate use of medications for specific diseases, too many pa- tients receive suboptimal drug therapy for too long. This is caused in part by far more drug therapy choices than most clinicians can master and also by aggressive marketing—to physicians, pharmacists, and directly to consumers—which can inappropriately shape prescribing habits. Who is to intervene in the name of rational therapeutics? The well-armed pharmacist, for one!
Reality is even more alarming when one also considers adverse drug effects. A 2000 Institute of Medicine (IOM) report documented that adverse drug effects are common in the United States, represent- ing the sixth leading cause of death according to published meta- analyses. This is staggering news. Yet even if overstated by 100% it is an enormous concern for patients. Pharmacists must intervene and make definitive strides to reduce the adverse effects of medications, and they must be armed with pharmacotherapeutic knowledge and given time in their clinical practice to do so. This textbook serves as a source of such knowledge for those who are devoted to this end, whether they are matriculating toward their pharmacy degree or striv- ing to advance their contributions in a busy clinical practice.
A 2001 IOM report documented a substantial gap in health care between those who receive the best and those who receive the average in health care in the United States. Recent studies have also documented that when patients exceed their cap in prescription drug coverage, they often discontinue medications or take fewer doses of prescribed therapy, even when adverse consequences can result if chronic diseases are left untreated. The cost-consequences of inade- quate prescription drug coverage may well exceed the cost-savings of capping or limiting prescription drug benefits.
How might pharmacists change this equation for the better? Per- haps one approach would be to avoid the use of unnecessarily ex- pensive medications when less expensive medications are equally effective. Another would be to help minimize the adverse economic and health care impact of adverse drug effects. The pages of this text are filled with information that could simultaneously translate into greater efficacy, lower toxicity, and more cost-effective use of medica- tions. Pharmacists who translate this knowledge to everyday treatment decisions can play a vital role in showing not only that the best drug therapy can be safe and cost-effective, but that it does not always require the newest medication on the market. This will require a wealth of knowledge and determination by pharmacists, if they are to offset the power of marketing prescription drugs to prescribers and directly to the public. Pharmacotherapy: A Pathophysiologic Approach is a comprehensive scholarly effort by leading practitioners and educators who have created a definitive and unbiased resource that is based on a wealth of clinical experience and academic expertise. It offers a solid foundation for the education of future clinicians and for the practice of pharmacotherapy today, loaded with ammunition to fight the forces of irrational prescribing.
William E. Evans, PharmD Professor of Pharmacy and Pediatrics University of Tennessee Colleges of Pharmacy and Medicine Director and CEO St. Jude Children’s Research Hospital
F OREWORD TO THE F
Suspecting that other professions in other times must have faced similar quests for recognition of their unique knowledge and skills I once searched the literature for an example that might parallel phar- macy’s modern-day aspirations. Writing in the Philadelphia Medical
for recognition of the pharmacotherapy specialist. The utterances of a maturing profession as revealed in the contents of this book, and the intraprofessional recognition and acceptance of a higher level of responsibility in the safe, effective, and economical use of drugs and drug products, bode well for the future of the profession and for the improvement of patient care with drugs.
apy: A Pathophysiologic Approach with ACCP’s petitioning of BPS
It is fortuitous—the coinciding of the release of Pharmacother-
It has been my experience that, given the opportunity for one-on- one, collaborative practice with physicians and other health profes- sionals, pharmacy practitioners who have been educated and trained to perform at the level of pharmacotherapeutics specialists almost invariably have convinced the former that “the importance of their work will not be lessened, but enhanced, by the increased safety and dispatch with which” individualized problems of drug therapy could be managed in collaboration with clinical pharmacy practitioners.
The anesthetizer will have to make his own place in medicine: the profession will not make a place for him, and not until he has demonstrated the value of his services will it concede him the position which the importance of his duties entitles him to occupy. He will be obliged to define his own rights, duties and privileges, and he must not expect that his own estimate of the importance of his position will be conceded without opposition. There are many surgeons who are unwilling to share either the credit or the emoluments of their work with anyone, and their opposition will be overcome only when they are shown that the importance of their work will not be lessened, but enhanced, by the increased safety and dispatch with which operations may be done. . . .
for specialty training and practice in a field of medicine lacking such expertise at that time. In an article entitled “The Anesthetizer as a Speciality,” Galloway commented:
Journal, May 27, 1899, D. H. Galloway, MD, reflected on the need
The recognition by BPS of pharmacotherapy as an area of spe- cialty practice in pharmacy will serve as an important statement by the profession that we have matured sufficiently to be competent and willing to take unprecedented responsibilities in the collaborative, pharmacotherapeutic management of patient-specific problems. It commits pharmacy to an intention that will not be uniformly or rapidly accepted within the established health care community. Nonetheless, this formal action places us on the road to an avowed goal, and acceptance will be gained as the pharmacotherapists proliferate and establish their importance in the provision of optimal, cost-effective drug therapy.
IRST E DITION
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Because of the growing complexity of pharmacotherapeutic agents, their dosing regimens, and techniques for delivery, pharmacy is obligated to produce, recognize, and remunerate specialty practi- tioners who can fulfill the profession’s responsibilities to society for service expertise where the competence required in a particular case exceeds that of the general practitioner. It simply is a component of our covenant with society and is as important as any other facet of that relationship existing between a profession and those it serves.
Within this book one will find the scientific foundation for the essential knowledge required of one who may aspire to specialty prac- tice as a pharmacotherapist. As is the case with any such publication, its usefulness to the practitioner or the future practitioner is limited to providing such a foundation. To be socially and professionally responsible in practice, the pharmacotherapist’s foundation must be continually supplemented and complemented by the flow of informa- tion appearing in the primary literature. Of course this is not unique to the general or specialty practice of pharmacy; it is essential to the fulfillment of obligations to clients in any occupation operating under the code of professional ethics.
In 1987, the Board of Pharmaceutical Specialties (BPS), in deny- ing the petition filed by the American College of Clinical Pharmacy (ACCP) to recognize “clinical pharmacy” as a specialty, conceded nonetheless that the petitioning party had documented in its petition a specialist who does in fact exist within the practice of pharmacy and whose expertise clearly can be extricated from the performance char- acteristics of those in general practice. A refiled petition from ACCP requests recognition of “pharmacotherapy” as a Specialty Area of Pharmacy Practice. While the BPS had issued no decision when this book went to press, it is difficult to comprehend the basis for a rejec- tion of the second petition.
tured practitioner who is able to call upon unique knowledge and skills so as to function as an appropriately confident, independently competent pharmacotherapeutics expert.
A Pathophysiologic Approach, pharmacy’s utterances bespeak a ma-
Within a period of perhaps 15 or 20 years, we have witnessed a profound maturation within the profession of pharmacy. The utter- ances of the profession, as projected in its literature, have evolved from mostly self-centered and self-serving issues of trade protection to a composite of expressed professional interests that prominently include responsible explorations of scientific/technological questions and ethical issues that promote the best interests of the clientele served by the profession. With the publication of Pharmacotherapy:
Evidence of the maturity of a profession is not unlike that character- izing the maturity of an individual; a child’s utterances and behavior typically reveal an unrealized potential for attainment, eventually, of those attributes characteristic of an appropriately confident, inde- pendently competent, socially responsible, sensitive, and productive member of society.
Charles A. Walton, PhD San Antonio, Texas
P REFACE
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Pharmacists and other health care professionals who evaluate, de- sign, and recommend pharmacotherapy for the management of their patients face many new and exciting challenges in these early years of the twenty-first century. As we complete our work on the sixth edition of Pharmacotherapy: A Pathophysiologic Approach, we rec- ognize just how much our tasks as editors have become equally com- plicated, trying to balance the need to provide accurate, thorough, and unbiased information about the treatment of diseases against the hard publishing realities of deadlines, word counts, and book length. We thus strive to keep foremost in our minds the precepts that first led us to embark on this endeavor: r
Advance the quality of patient care through optimal medication management based on sound pharmacotherapeutic principles. r Stimulate the student to achieve higher levels of learning. r Motivate young practitioners to enhance the breadth, depth, and quality of care they can provide to each of their patients. r Challenge established pharmacists and other primary-care providers to learn the new concepts and refine their understanding of the basic tenets of pathophysiology and therapeutics. r Inform the pharmacy and medical communities about the standards of medication therapy management toward which we all should strive and which all patients will one day expect and, yes, demand. While our emphasis in past editions has been on how to incor- porate diseases that were previously untreatable with pharmacologic agents, new features in this sixth edition are focused more on the real- ities of teaching entry-level doctor of pharmacy students and meeting their postgraduate needs. We have incorporated a number of new pedagogical devices into chapters that will enable students and prac- titioners to more quickly grasp the important concepts and find related passages in the text. The addition of more features to disease-oriented chapters and the inclusion of more design elements give this edition a striking new look: r