Pharmacotherapy Handbook

Pharmacotherapy Handbook Seventh Edition

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.

Pharmacotherapy Handbook Seventh Edition Barbara G. Wells, PharmD, FASHP, FCCP, BCPP Dean and Professor Executive Director, Research Institute of Pharmaceutical Sciences School of Pharmacy, The University of Mississippi Oxford, Mississippi

Joseph T. DiPiro, PharmD, FCCP Professor and Executive Dean South Carolina College of Pharmacy Medical University of South Carolina, Charleston, and University of South Carolina, Columbia

Terry L. Schwinghammer, PharmD, FCCP, FASHP, BCPS Professor and Chair, Department of Clinical Pharmacy School of Pharmacy, West Virginia University Morgantown, West Virginia

Cecily V. DiPiro, PharmD Consultant Pharmacist Mount Pleasant, South Carolina

New York Chicago San Francisco Lisbon London Madrid Mexico City Milan New Delhi San Juan Seoul Singapore Sydney Toronto

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Contents

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .x To the Reader . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

SECTION 1: BONE AND JOINT DISORDERS Edited by Terry L. Schwinghammer

1. 2. 3. 4.

Gout and Hyperuricemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1 Osteoarthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9 Osteoporosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18 Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

SECTION 2: CARDIOVASCULAR DISORDERS Edited by Terry L. Schwinghammer

5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

Acute Coronary Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43 Arrhythmias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .60 Cardiopulmonary Arrest. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74 Heart Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .82 Hyperlipidemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .98 Hypertension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .111 Ischemic Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .130 Shock. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143 Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .156 Venous Thromboembolism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .163

SECTION 3: DERMATOLOGIC DISORDERS Edited by Terry L. Schwinghammer

15. Acne Vulgaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .179 16. Psoriasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .186 17. Skin Disorders and Cutaneous Drug Reactions . . . . . . . . . . . . . . . . . .196 SECTION 4: ENDOCRINOLOGIC DISORDERS Edited by Terry L. Schwinghammer

18. Adrenal Gland Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .203 19. Diabetes Mellitus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .210 20. Thyroid Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .227 v

Contents

SECTION 5: GASTROINTESTINAL DISORDERS Edited by Joseph T. DiPiro and Terry L. Schwinghammer

21. 22. 23. 24. 25. 26. 27. 28. 29.

Cirrhosis and Portal Hypertension. . . . . . . . . . . . . . . . . . . . . . . . . . . . Constipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Gastroesophageal Reflux Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hepatitis, Viral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

239 250 256 263 273

Inflammatory Bowel Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nausea and Vomiting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Pancreatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Peptic Ulcer Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

282 294 305 314

SECTION 6: GYNECOLOGIC AND OBSTETRIC DISORDERS Edited by Barbara G. Wells

30. Contraception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 31. Hormone Therapy in Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341 32. Pregnancy and Lactation: Therapeutic Considerations . . . . . . . . . . . 353 SECTION 7: HEMATOLOGIC DISORDERS Edited by Cecily V. DiPiro

33. Anemias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 34. Sickle Cell Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371 SECTION 8: INFECTIOUS DISEASES Edited by Joseph T. DiPiro

35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. vi

Antimicrobial Regimen Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 Central Nervous System Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 Endocarditis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399 Fungal Infections, Invasive . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 412 Gastrointestinal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 426 Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 Influenza . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Intraabdominal Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Respiratory Tract Infections, Lower. . . . . . . . . . . . . . . . . . . . . . . . . . . Respiratory Tract Infections, Upper. . . . . . . . . . . . . . . . . . . . . . . . . . . Sepsis and Septic Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sexually Transmitted Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

450 456 465 478 487 493

Contents

47. 48. 49. 50. 51.

Skin and Soft-Tissue Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .509 Surgical Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .522 Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .532 Urinary Tract Infections and Prostatitis . . . . . . . . . . . . . . . . . . . . . . . .544 Vaccines, Toxoids, and Other Immunobiologics . . . . . . . . . . . . . . . . .556

SECTION 9: NEUROLOGIC DISORDERS Edited by Barbara G. Wells

52. 53. 54. 55. 56.

Epilepsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .577 Headache: Migraine and Tension-Type . . . . . . . . . . . . . . . . . . . . . . . .599 Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .614 Parkinson’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .629 Status Epilepticus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .637

SECTION 10: NUTRITIONAL DISORDERS Edited by Cecily V. DiPiro

57. 58. 59. 60.

Assessment and Nutrition Requirements . . . . . . . . . . . . . . . . . . . . . . .647 Enteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .655 Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .663 Parenteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .669

SECTION 11: ONCOLOGIC DISORDERS Edited by Cecily V. DiPiro

61. 62. 63. 64. 65.

Breast Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .679 Colorectal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .689 Lung Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .699 Lymphomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .704 Prostate Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .713

SECTION 12: OPHTHALMIC DISORDERS Edited by Cecily V. DiPiro

66. Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .719 SECTION 13: PSYCHIATRIC DISORDERS Edited by Barbara G. Wells

67. Alzheimer’s Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .727 68. Anxiety Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .735 69. Bipolar Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .756 vii

Contents

70. 71. 72. 73.

Major Depressive Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sleep Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Substance-Related Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

778 799 814 823

SECTION 14: RENAL DISORDERS Edited by Cecily V. DiPiro

74. 75. 76. 77. 78.

Acid–Base Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acute Renal Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chronic Kidney Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Drug Dosing in Renal Insufficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . Electrolyte Homeostasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

839 849 858 875 881

SECTION 15: RESPIRATORY DISORDERS Edited by Terry L. Schwinghammer

79. Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 897 80. Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 906 81. Chronic Obstructive Pulmonary Disease. . . . . . . . . . . . . . . . . . . . . . . 921 SECTION 16: UROLOGIC DISORDERS Edited by Cecily V. DiPiro

82. Benign Prostatic Hyperplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 931 83. Erectile Dysfunction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 936 84. Urinary Incontinence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 944 APPENDICES Edited by Barbara G. Wells

Appendix Appendix Appendix Appendix Appendix Appendix

1. Allergic and Pseudoallergic Drug Reactions. . . . . . . . . . . 2. Geriatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Drug-Induced Hematologic Disorders . . . . . . . . . . . . . . . 4. Drug-Induced Liver Disease . . . . . . . . . . . . . . . . . . . . . . . 5. Drug-Induced Pulmonary Disorders . . . . . . . . . . . . . . . . 6. Drug-Induced Kidney Disease . . . . . . . . . . . . . . . . . . . . . .

951 955 958 962 965 971

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 975

viii

Preface

This seventh edition of the pocket companion to Pharmacotherapy: A Pathophysiologic Approach, seventh edition, is designed to provide practitioners and students with critical information that can be easily used to guide drug therapy decision making in the clinical setting. To ensure brevity and portability, the bulleted format provides the user with essential textual information, key tables and figures, and treatment algorithms. Corresponding to the major sections in the main text, disorders are alphabetized within the following sections: Bone and Joint Disorders, Cardiovascular Disorders, Dermatologic Disorders, Endocrinologic Disorders, Gastrointestinal Disorders, Gynecologic and Obstetric Disorders, Hematologic Disorders, Infectious Diseases, Neurologic Disorders, Nutritional Disorders, Oncologic Disorders, Ophthalmic Disorders, Psychiatric Disorders, Renal Disorders, Respiratory Disorders, and Urologic Disorders. Drug-induced conditions associated with allergic and pseudoallergic reactions, hematologic disorders, liver disease, pulmonary disorders, and kidney disease appear in five tabular appendices. In the seventh edition, information on the management of pharmacotherapy in the elderly has been added as an appendix. Also in the seventh edition, chapters have been added on adrenal gland disorders and influenza. Carrying over a popular feature from Pharmacotherapy, each chapter is organized in a consistent format: • • • •

Disease state definition Concise review of relevant pathophysiology Clinical presentation Diagnosis

• Desired outcome • Treatment • Monitoring

The treatment section may include nonpharmacologic therapy, drug selection guidelines, dosing recommendations, adverse effects, pharmacokinetic considerations, and important drug–drug interactions. When more in-depth information is required, the reader is encouraged to refer to the primary text, Pharmacotherapy: A Pathophysiologic Approach, seventh edition. It is our sincere hope that students and practitioners find this book helpful as they continuously strive to deliver highest quality patient-centered care. We invite your comments on how we may improve subsequent editions of this work. Barbara G. Wells Joseph T. DiPiro Terry L. Schwinghammer Cecily V. DiPiro Please provide your comments about this book, Wells et al., Pharmacotherapy Handbook, seventh edition, to its Authors and Publisher by writing to [email protected]. Please indicate the author and title of this handbook in the subject line of your e-mail.

ix

Acknowledgments

The editors wish to express their sincere appreciation to the authors whose chapters in the seventh edition of Pharmacotherapy: A Pathophysiologic Approach served as the basis for this book. The dedication and professionalism of these outstanding practitioners, teachers, and clinical scientists are evident on every page of this work. The authors of the chapters from the seventh edition are acknowledged at the end of each respective Handbook chapter.

x

To the Reader

Basic and clinical research provides a continuous flow of biomedical information that enables practitioners to use medications more effectively and safely. The editors, authors, and publisher of this book have made every effort to ensure accuracy of information provided. However, it is the responsibility of all practitioners to assess the appropriateness of published drug therapy information, especially in light of the specific clinical situation and new developments in the field. The editors and authors have taken care to recommend dosages that are consistent with current published guidelines and other responsible literature. However, when dealing with new and unfamiliar drug therapies, students and practitioners should consult several appropriate information sources.

xi

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SECTION 1

BONE AND JOINT DISORDERS

CHAP TER

Edited by Terry L. Schwinghammer

1

Gout and Hyperuricemia

DEFINITIONS • The term gout describes a disease spectrum including hyperuricemia, recurrent attacks of acute arthritis associated with monosodium urate crystals in leukocytes found in synovial fluid, deposits of monosodium urate crystals in tissues (tophi), interstitial renal disease, and uric acid nephrolithiasis. • Hyperuricemia may be an asymptomatic condition, with an increased serum uric acid concentration as the only apparent abnormality. A urate concentration greater than 7.0 mg/dL is abnormal and associated with an increased risk for gout.

PATHOPHYSIOLOGY • In humans, uric acid is the end product of the degradation of purines. It serves no known physiologic purpose and is regarded as a waste product. The size of the urate pool is increased severalfold in individuals with gout. This excess accumulation may result from either overproduction or underexcretion. • The purines from which uric acid is produced originate from three sources: dietary purine, conversion of tissue nucleic acid to purine nucleotides, and de novo synthesis of purine bases. • Abnormalities in the enzyme systems that regulate purine metabolism may result in overproduction of uric acid. An increase in the activity of phosphoribosyl pyrophosphate (PRPP) synthetase leads to an increased concentration of PRPP, a key determinant of purine synthesis and thus uric acid production. A deficiency of hypoxanthine–guanine phosphoribosyl transferase (HGPRT) may also result in overproduction of uric acid. HGPRT is responsible for the conversion of guanine to guanylic acid and hypoxanthine to inosinic acid. These two conversions require PRPP as the cosubstrate and are important reutilization reactions involved in nucleic acid synthesis. A deficiency in the HGPRT enzyme leads to increased metabolism of guanine and hypoxanthine to uric acid and more PRPP to interact with glutamine in the first step of the purine pathway. Complete absence of HGPRT results in the childhood Lesch-Nyhan syndrome, characterized by choreoathetosis, spasticity, mental retardation, and markedly excessive production of uric acid. • Uric acid may also be overproduced as a consequence of increased breakdown of tissue nucleic acids, as with myeloproliferative and lymphoproliferative disorders. Cytotoxic drugs used to treat these disorders can 1

SECTION 1

|

Bone and Joint Disorders

also result in overproduction of uric acid due to lysis and breakdown of cellular matter. Dietary purines play an unimportant role in the generation of hyperuricemia in the absence of some derangement in purine metabolism or elimination. About two-thirds of the uric acid produced each day is excreted in the urine. The remainder is eliminated through the GI tract after enzymatic degradation by colonic bacteria. A decline in the urinary excretion of uric acid to a level below the rate of production leads to hyperuricemia and an increased miscible pool of sodium urate. Drugs that decrease renal clearance of uric acid through modification of filtered load or one of the tubular transport processes include diuretics, nicotinic acid, salicylates (less than 2 g/day), ethanol, pyrazinamide, levodopa, ethambutol, cyclosporine, and cytotoxic drugs. The average human produces 600 to 800 mg of uric acid daily and excretes less than 600 mg in urine. Individuals who excrete more than 600 mg after being on a purine-free diet for 3 to 5 days are considered overproducers. Hyperuricemic individuals who excrete less than 600 mg of uric acid per 24 hours on a purine-free diet are defined as underexcretors of uric acid. On a regular diet, excretion of more than 1,000 mg per 24 hours reflects overproduction; less than this is probably normal. Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, increased vascular permeability, complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling. Uric acid nephrolithiasis occurs in 10% to 25% of patients with gout. Predisposing factors include excessive urinary excretion of uric acid, acidic urine, and highly concentrated urine. In acute uric acid nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of uric acid crystals in the collecting ducts and ureters. This syndrome is a wellrecognized complication in patients with myeloproliferative or lymphoproliferative disorders and results from massive malignant cell turnover, particularly after initiation of chemotherapy. Chronic urate nephropathy is caused by the long-term deposition of urate crystals in the renal parenchyma. Tophi (urate deposits) are uncommon in gouty subjects and are a late complication of hyperuricemia. The most common sites of tophaceous deposits in patients with recurrent acute gouty arthritis are the base of the great toe, helix of the ear, olecranon bursae, Achilles tendon, knees, wrists, and hands.

•

•

•

•

•

•

•

•

CLINICAL PRESENTATION • Acute attacks of gouty arthritis are characterized by rapid onset of excruciating pain, swelling, and inflammation. The attack is typically monoarticular 2

Gout and Hyperuricemia

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CHAPTER 1

at first, most often affecting the first metatarsophalangeal joint (podagra), and then, in order of frequency, the insteps, ankles, heels, knees, wrists, fingers, and elbows. Attacks commonly begin at night, with the patient awakening from sleep with excruciating pain. The affected joints are erythematous, warm, and swollen. Fever and leukocytosis are common. Untreated attacks may last from 3 to 14 days before spontaneous recovery. • Although acute attacks of gouty arthritis may occur without apparent provocation, attacks may be precipitated by stress, trauma, alcohol ingestion, infection, surgery, rapid lowering of serum uric acid by ingestion of uric acid–lowering agents, and ingestion of certain drugs known to elevate serum uric acid concentrations.

DIAGNOSIS • The definitive diagnosis is accomplished by aspiration of synovial fluid from the affected joint and identification of intracellular crystals of monosodium urate monohydrate in synovial fluid leukocytes. • When joint aspiration is not a viable option, a presumptive diagnosis of acute gouty arthritis may be made on the basis of the presence of the characteristic signs and symptoms, as well as the response to treatment.

DESIRED OUTCOME • The goals in the treatment of gout are to terminate the acute attack, prevent recurrent attacks of gouty arthritis, and prevent complications associated with chronic deposition of urate crystals in tissues.

TREATMENT ACUTE GOUTY ARTHRITIS (Fig. 1-1) Nonpharmacologic Therapy • Patients may be advised to reduce their intake of foods high in purines (e.g., organ meats), avoid alcohol, increase fluid intake, and lose weight if obese. • Joint rest for 1 to 2 days should be encouraged, and local application of ice may be beneficial. Nonsteroidal Antiinflammatory Drugs • Nonsteroidal antiinflammatory drugs (NSAIDs) are the mainstay of therapy because of their excellent efficacy and minimal toxicity with shortterm use. There is little evidence to support one NSAID as more efficacious than another, and three drugs (indomethacin, naproxen, and sulindac) have FDA approval for this indication (Table 1-1). • Therapy should be initiated with maximum recommended doses for gout at the onset of symptoms and continued for 24 hours after complete resolution of an acute attack, then tapered quickly over 2 to 3 days. Acute attacks generally resolve within 5 to 8 days after initiating therapy. 3

SECTION 1

|

Bone and Joint Disorders Contraindication to NSAID?

Acute gouty arthritis

NO

YES

Onset of symptoms 1

Joint accessible to injection?

YES

Contraindication to systemic corticosteroids?

NO

Intraarticular corticosteroid

Analgesics and joint rest +/− oral colchicine

YES

NO

Parenteral or oral corticosteroid +/− intraarticular corticosteroid

FIGURE 1-1. Treatment algorithm for acute gouty arthritis. (NSAID, nonsteroidal antiinflammatory drug.)

4

Gout and Hyperuricemia TABLE 1-1

|

CHAPTER 1

Dosage Regimens of Nonsteroidal Antiinflammatory Drugs for Treatment of Acute Gouty Arthritis

Generic Name

Dosage and Frequency

Etodolac Fenoprofen Ibuprofen Indomethacin Ketoprofen Naproxen Piroxicam Sulindac

300 mg twice daily 300–600 mg three to four times daily 800 mg four times a day 25–50 mg four times a day for 3 days, then taper to twice daily for 4–7 days 75 mg four times a day 500 mg twice daily for 3 days, then 250–500 mg daily for 4–7 days 20 mg once daily or 10 mg twice daily 200 mg twice daily for 7–10 days

• The most common adverse effects involve the GI system (gastritis, bleeding, and perforation), kidneys (renal papillary necrosis, reduced creatinine clearance [CLcr]), cardiovascular system (sodium and fluid retention, increased blood pressure), and CNS (impaired cognitive function, headache, dizziness). • Although the risk of GI complications is relatively small with short-term therapy, coadministration with a proton pump inhibitor should be considered in elderly patients and others at increased GI risk. NSAIDs should be used with caution in individuals with a history of peptic ulcer disease, heart failure, uncontrolled hypertension, renal insufficiency, coronary artery disease, or if they are receiving anticoagulants concurrently. • The efficacy and safety of cyclooxygenase-2 (COX-2) selective inhibitors (e.g., celecoxib) have not been fully assessed in gouty arthritis, but they are more costly than conventional NSAIDs and are unlikely to result in fewer GI complications because of the short duration of therapy. Colchicine • Colchicine is an antimitotic drug that is highly effective in relieving acute gout attacks but has a low benefit-toxicity ratio. When colchicine is started within the first 24 hours of an acute attack, about two-thirds of patients respond within several hours. The likelihood of success decreases substantially if treatment is delayed longer than 48 hours after symptom onset. • Oral colchicine causes dose-dependent GI adverse effects (nausea, vomiting, and diarrhea) in 50% to 80% of patients before relief of the attack. Non-GI adverse effects include neutropenia and axonal neuromyopathy, which may be worsened in patients taking other myopathic drugs (e.g., statins) or in those with renal insufficiency. Colchicine should not be used concurrently with macrolide antibiotics (especially clarithromycin) because reduced biliary excretion may lead to increased plasma colchicine levels and agranulocytosis. • Colchicine should be reserved for patients with insufficient relief, intolerance, or contraindications to NSAIDs. • The usual oral colchicine dose is 1 mg initially, followed by 0.5 mg every 1 hour until the joint symptoms subside, the patient develops abdominal discomfort or diarrhea, or a total dose of 8 mg has been given. 5

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Bone and Joint Disorders

• IV colchicine should be avoided because it is associated with serious adverse effects (e.g., bone marrow suppression, tissue necrosis from local extravasation, disseminated intravascular coagulation, hepatocellular toxicity, and renal failure). If considered necessary, the recommended initial IV dose is 2 mg (if renal function is normal) diluted in 10 to 20 mL of normal saline administered slowly over 10 to 20 minutes in a secure, freeflowing IV line to avoid extravasation. This may be followed by two additional doses of 1 mg each at 6-hour intervals, with the total dose not exceeding 4 mg. After a full IV course, patients should not receive colchicine by any route for at least 7 days. Corticosteroids • Corticosteroids may be used to treat acute attacks of gouty arthritis, but they are reserved primarily for patients with a contraindication or who are unresponsive to NSAID or colchicine therapy. Patients with multiple-joint involvement may also benefit. • The recommended dose is prednisone 30 to 60 mg (or an equivalent dose of another corticosteroid) orally once daily for 3 to 5 days. Because rebound attacks may occur upon steroid withdrawal, the dose should be gradually tapered in 5-mg increments over 10 to 14 days and discontinued. • A single intramuscular injection of a long-acting corticosteroid (e.g., methylprednisolone acetate) can be used as an alternative to the oral route if patients are unable to take oral therapy. If not contraindicated, low-dose colchicine can be used as adjunctive therapy to injectable corticosteroids to prevent rebound flare-ups. • Intraarticular administration of triamcinolone hexacetonide 20 to 40 mg may be useful for acute gout limited to one or two joints. • Adrenocorticotropic hormone (ACTH) gel, 40 to 80 USP units, may be given intramuscularly every 6 to 8 hours for 2 to 3 days and then discontinued. Studies with ACTH are limited, and it should be reserved for patients with contraindications to first-line therapies (e.g., heart failure, chronic renal failure, history of GI bleeding).

PROPHYLACTIC THERAPY OF INTERCRITICAL GOUT General Approach • Prophylactic treatment can be withheld if the first episode of acute gouty arthritis was mild and responded promptly to treatment, the patient’s serum urate concentration was only minimally elevated, and the 24-hour urinary uric acid excretion was not excessive (less than 1,000 mg/24 hours on a regular diet). • If the patient had a severe attack of gouty arthritis, a complicated course of uric acid lithiasis, a substantially elevated serum uric acid (greater than 10 mg/dL), or a 24-hour urinary excretion of uric acid of more than 1,000 mg, then prophylactic treatment should be instituted immediately after resolution of the acute episode. • Prophylactic therapy is cost-effective for patients with frequent attacks of gouty arthritis (i.e., two or more attacks per year) even if the serum uric acid concentration is normal or only minimally elevated. 6

Gout and Hyperuricemia

|

CHAPTER 1

Colchicine • Colchicine given in low oral doses (0.5 to 0.6 mg twice daily) may be effective in preventing recurrent arthritis in patients with no evidence of visible tophi and a normal or slightly elevated serum urate concentration. The oral dose should be reduced to no more than 0.6 mg daily or every other day in patients with renal or hepatic dysfunction. Treated patients who sense the onset of an acute attack should increase the dose to 1 mg every 2 hours; in most instances, the attack aborts after 1 or 2 mg. Discontinuation of prophylaxis may be attempted if the serum urate concentration remains normal and the patient is symptom-free for 1 year. Uric Acid–Lowering Therapy • Patients with a history of recurrent acute gouty arthritis and a significantly elevated serum uric acid concentration are probably best managed with uric acid–lowering therapy. • Colchicine, 0.5 mg twice daily, is sometimes given during the first 6 to 12 months of antihyperuricemic therapy to minimize the risk of acute attacks that may occur during initiation of uric acid–lowering therapy. • The therapeutic objective of antihyperuricemic therapy is to achieve and maintain a serum uric acid concentration less than 6 mg/dL, and preferably below 5 mg/dL. Xanthine Oxidase Inhibitor • Allopurinol and its major metabolite, oxypurinol, are xanthine oxidase inhibitors and impair the conversion of hypoxanthine to xanthine and xanthine to uric acid. Allopurinol also lowers the intracellular concentration of PRPP. Because of the long half-life of its metabolite, allopurinol can be given once daily orally. It is typically initiated at a dose of 100 mg/day and increased by 100 mg/day at 1-week intervals to achieve a serum uric acid level of 6 mg/dL or less. Serum levels can be checked about 1 week after starting therapy or modifying the dose. Although typical doses are 100 to 300 mg daily, occasionally doses of 600 to 800 mg/day are necessary. The dose should be reduced in patients with renal insufficiency (200 mg/day for CLcr 60 mL/min or less, and 100 mg/day for CLcr 30 mL/min or less). • Allopurinol is the antihyperuricemic drug of choice in patients with a history of urinary stones or impaired renal function, in patients who have lymphoproliferative or myeloproliferative disorders and need pretreatment with a xanthine oxidase inhibitor before initiation of cytotoxic therapy to protect against acute uric acid nephropathy, and in patients with gout who are overproducers of uric acid. • The major side effects of allopurinol are skin rash, urticaria, leukopenia, GI problems, headache, and increased frequency of acute gouty attacks with the initiation of therapy. An allopurinol hypersensitivity syndrome characterized by fever, eosinophilia, dermatitis, vasculitis, and renal and hepatic dysfunction occurs rarely but is associated with a 20% mortality rate. Uricosuric Drugs • Probenecid and sulfinpyrazone increase the renal clearance of uric acid by inhibiting the renal tubular reabsorption of uric acid. They should only be 7

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Bone and Joint Disorders

used in patients with documented underexcretion of uric acid. Therapy with uricosuric drugs should be started at a low dose to avoid marked uricosuria and possible stone formation. Maintenance of adequate urine flow and alkalinization of the urine with sodium bicarbonate or Shohl’s solution during the first several days of uricosuric therapy further diminish the possibility of uric acid stone formation. • Probenecid is given initially at a dose of 250 mg twice daily for 1 to 2 weeks, then 500 mg twice daily for 2 weeks. Thereafter, the daily dose is increased by 500-mg increments every 1 to 2 weeks until satisfactory control is achieved or a maximum dose of 2 g/day is reached. • The initial dose of sulfinpyrazone is 50 mg twice daily for 3 to 4 days, then 100 mg twice daily, increasing the daily dose by 100-mg increments each week up to 800 mg/day. • The major side effects associated with uricosuric therapy are GI irritation, rash and hypersensitivity, precipitation of acute gouty arthritis, and stone formation. These drugs are contraindicated in patients who are allergic to them and in patients with impaired renal function (CLcr 65 years • Comorbid medical conditions • Oral glucocorticoid use • History of peptic ulcer disease • History of upper GI bleed • Oral anticoagulant use Select: COX-2 inhibitor or NSAID + PPI or NSAID + misoprostol or COX-2 inhibitor + PPI

Trial 1–2 weeks for pain; 2–4 weeks if inflammation persists Adequate response? Yes

No

Continue therapy

Try another NSAID Yes

Adequate response? No

Consider opioid analgesics, hyaluronate injections (IA), and evaluate for surgery

FIGURE 2-1. Treatment for osteoarthritis. (COX, cyclooxygenase; IA, intraarticular; NSAID, nonsteroidal antiinflammatory drug; OA, osteoarthritis; PPI, proton pump inhibitor.)

13

SECTION 1

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TABLE 2-1

Bone and Joint Disorders Medications Commonly Used in the Treatment of Osteoarthritis

Medication Oral analgesics Acetaminophen Tramadol Acetaminophen/codeine Acetaminophen/oxycodone Topical analgesics Capsaicin 0.025% or 0.075% Nutritional supplements Glucosamine sulfate/chondroitin sulfate Nonsteroidal antiinflammatory drugs (NSAIDs) Carboxylic acids Acetylated salicylates Aspirin, plain, buffered, or enteric-coated Nonacetylated salicylates Salsalate Diflunisal Choline salicylateb Choline magnesium salicylate Acetic acids Etodolac Diclofenac Indomethacin Ketorolac c Nabumetoned Propionic acids Fenoprofen Flurbiprofen Ibuprofen Ketoprofen Naproxen Naproxen sodium Oxaprozin Fenamates Meclofenamate Mefenamic acide Oxicams Piroxicam Meloxicam Coxibs Celecoxib

Dosage and Frequency 325–650 mg every 4–6 hours or 1 g three to four times/day 50–100 mg every 4–6 hours 300–1,000 mg/15–60 mg every 4 hours as needed 325–650 mg/2.5–10 mg every 6 hours as needed

4,000

Apply to affected joint three to four times/day

—

500 mg/400 mg three times/day

1,500/1,200

325–650 mg every 4–6 hours for pain; antiinflammatory doses start at 3,600 mg/day in divided doses

3,600a

500–1,000 mg two to three times/day 500–1,000 mg two times/day 500–1,000 mg two to three times/day 500–1,000 mg two to three times/day

3,000a 1,500 3,000a 3,000a

800–1,200 mg/day in divided doses 100–150 mg/day in divided doses 25 mg two to three times/day; 75 mg SR once daily 10 mg every 4–6 hours 500–1,000 mg one to two times/day

1,200 200 200; 150 40 2,000

300–600 mg three to four times/day 200–300 mg/day in 2–4 divided doses 1,200–3,200 mg/day in 3–4 divided doses 150–300 mg/day in 3–4 divided doses 250–500 mg twice a day 275–550 mg twice a day 600–1,200 mg daily

3,200 300 3,200 300 1,500 1,375 1,800

200–400 mg/day in 3–4 divided doses 250 mg every 6 hours

400 1,000

10–20 mg daily 7.5 mg daily

20 15

100 mg twice daily or 200 mg once daily

200 (400 for RA)

RA, rheumatoid arthritis; SR, sustained-release. aMonitor serum salicylate levels over 3–3.6 g/day. b Only available as a liquid; 870 mg salicylate/5 mL. c Not approved for treatment of OA for more than 5 days. d Nonorganic acid but metabolite is an acetic acid. e Not approved for treatment of OA.

14

Maximum Dosage (mg/day)

400 4,000/360 4,000/40

Osteoarthritis

|

CHAPTER 2

• All NSAIDs have the potential to cause gastric and duodenal ulcers and bleeding through direct (topical) or indirect (systemic) mechanisms. Risk factors for NSAID-associated ulcers and ulcer complications (perforation, gastric outlet obstruction, GI bleeding) include increased age, comorbid medical conditions (e.g., cardiovascular disease), concomitant corticosteroid or anticoagulant therapy, and history of peptic ulcer disease or upper GI bleeding. • For OA patients who need an NSAID but are at high risk for GI complications, the ACR recommendations include either a COX-2 selective inhibitor or a nonselective NSAID in combination with either a proton pump inhibitor or misoprostol. • NSAIDs may also cause kidney diseases, hepatitis, hypersensitivity reactions, rash, and CNS complaints of drowsiness, dizziness, headaches, depression, confusion, and tinnitus. All nonselective NSAIDs inhibit COX-1-dependent thromboxane production in platelets, thereby increasing bleeding risk. NSAIDs should be avoided in late pregnancy because of the risk of premature closure of the ductus arteriosus. • The most potentially serious drug interactions include the concomitant use of NSAIDs with lithium, warfarin, oral hypoglycemics, high-dose methotrexate, antihypertensives, angiotensin-converting enzyme inhibitors, βblockers, and diuretics. Topical Therapies • Capsaicin, an extract of red peppers that causes release and ultimately depletion of substance P from nerve fibers, has been beneficial in providing pain relief in OA when applied topically over affected joints. It may be used alone or in combination with oral analgesics or NSAIDs. • To be effective, capsaicin must be used regularly, and it may take up to 2 weeks to work. It is well tolerated, but some patients experience temporary burning or stinging at the site of application. Patients should be warned not to get the cream in their eyes or mouth and to wash their hands after application. • Application of the cream, gel, or lotion is recommended four times daily, but tapering to twice-daily application may enhance long-term adherence with adequate pain relief. • Topical diclofenac in a dimethyl sulfoxide carrier (Pennsaid) is a safe and effective treatment for OA pain. It is thought to act primarily by local inhibition of COX-2 enzymes. The product was under review by the U.S. FDA at the time of this writing. • Topical rubefacients containing methyl salicylate, trolamine salicylate, and other salicylates may have modest, short-term efficacy for treating acute pain associated with OA. Glucosamine and Chondroitin • Glucosamine and chondroitin are dietary supplements that were shown to stimulate proteoglycan synthesis from articular cartilage in vitro. Although their excellent safety profile makes them appealing for patients at high risk of adverse drug events, enthusiasm waned after results of a large, well-controlled, National Institutes of Health-sponsored clinical trial demonstrated no significant clinical response to glucosamine alone, chon15

SECTION 1

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Bone and Joint Disorders

droitin alone, or combination therapy when compared to placebo across all patients. In subgroup analyses, patients with moderate to severe knee pain showed a response to combination glucosamine–chondroitin therapy superior to placebo, but this finding did not reach the predetermined threshold for pain reduction. • Because of their relative safety, a trial of glucosamine–chondroitin may be reasonable in patients considering alternatives to traditional OA treatment. Dosing should be at least glucosamine sulfate 1,500 mg/day and chondroitin sulfate 1,200 mg/day in divided doses. • Glucosamine adverse effects are mild and include GI gas, bloating, and cramps; it should not be used in patients with shellfish allergies. The most common adverse effect of chondroitin is nausea. Corticosteroids • Systemic corticosteroid therapy is not recommended in OA, given the lack of proven benefit and the well-known adverse effects with long-term use. • Intraarticular corticosteroid injections can provide relief, particularly when a joint effusion is present. Average doses for injection of large joints in adults are methylprednisolone acetate 20 to 40 mg or triamcinolone hexacetonide 10 to 20 mg. After aseptic aspiration of the effusion and corticosteroid injection, initial pain relief may occur within 24 to 72 hours, with peak relief occurring in about 1 week and lasting for 4 to 8 weeks. The patient should minimize joint activity and stress on the joint for several days after the injection. Therapy is generally limited to three or four injections per year because of the potential systemic effects of the drugs and because the need for more frequent injections indicates poor response to therapy. Hyaluronate Injections • High-molecular-weight hyaluronic acid is a constituent of normal cartilage that provides lubrication with motion and shock absorbency during rapid movements. Because the concentration and molecular size of endogenous hyaluronic acid decrease in OA, exogenous administration has been studied in an attempt to reconstitute synovial fluid and reduce symptoms. • Hyaluronic acid injections temporarily and modestly increase synovial fluid viscosity and were reported to decrease pain, but many studies were short term and poorly controlled with high placebo response rates. • Four intraarticular hyaluronic acid preparations are available for treating pain associated with OA of the knee: sodium hyaluronate (Hyalgan 20 mg/2 mL; Supartz 25 mg/2.5 mL), hylan polymers (Synvisc 16 mg/2 mL), and hyaluronan (Orthovisc 30 mg/2 mL). Hyalgan and Supartz are administered once weekly for five injections, whereas Synvisc and Orthovisc are administered once weekly for three injections. • Injections are well tolerated, but acute joint swelling and local skin reactions (e.g., rash, ecchymoses, or pruritus) have been reported. • These products may be beneficial for OA of the knee that is unresponsive to other therapy, but they are expensive because treatment includes both drug and administration costs.

16

Osteoarthritis

|

CHAPTER 2

Opioid Analgesics • Low-dose opioid analgesics (e.g., oxycodone) may be useful for patients who experience no relief with acetaminophen, NSAIDs, intraarticular injections, or topical therapy. • They are particularly useful in patients who cannot take NSAIDs because of renal failure, or for patients in whom all other treatment options have failed and who are at high surgical risk, precluding joint arthroplasty. • Low-dose opioids should be used initially, usually in combination with acetaminophen. Sustained-release compounds usually offer better pain control throughout the day and are used when simple opioids are ineffective. Tramadol • Tramadol with or without acetaminophen has modest analgesic effects in patients with OA. It may also be effective as add-on therapy in patients taking concomitant NSAIDs or COX-2 selective inhibitors. As with opioids, tramadol may be helpful for patients who cannot take NSAIDs or COX-2 selective inhibitors. • Tramadol should be initiated at a lower dose (100 mg/day in divided doses) and may be titrated as needed for pain control to a dose of 200 mg/ day. It is available in a combination tablet with acetaminophen and as a sustained-release tablet. • Opioid-like adverse effects such as nausea, vomiting, dizziness, constipation, headache, and somnolence are common.

EVALUATION OF THERAPEUTIC OUTCOMES • To monitor efficacy, the patient’s baseline pain can be assessed with a visual analog scale, and range of motion for affected joints can be assessed with flexion, extension, abduction, or adduction. • Depending on the joint affected, measurement of grip strength and 50-feet walking time can help assess hand and hip/knee OA, respectively. • Baseline radiographs can document the extent of joint involvement and follow disease progression with therapy. • Other measures include the clinician’s global assessment based on the patient’s history of activities and limitations caused by OA, the Western Ontario and McMaster Universities Arthrosis Index, Stanford Health Assessment Questionnaire, and documentation of analgesic or NSAID use. • Patients should be asked if they are having adverse effects from their medications. They should also be monitored for any signs of drug-related effects, such as skin rash, headaches, drowsiness, weight gain, or hypertension from NSAIDs. • Baseline serum creatinine, hematology profiles, and serum transaminases with repeat levels at 6- to 12-month intervals are useful in identifying specific toxicities to the kidney, liver, GI tract, or bone marrow.

See Chap. 95, Osteoarthritis, authored by Lucinda M. Buys and Mary Elizabeth Elliott, for a more detailed discussion of this topic.

17

3

CHAP TER

Osteoporosis

DEFINITION • Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing individuals to an increased fracture risk. • Categories of osteoporosis include: (1) postmenopausal osteoporosis, (2) agerelated osteoporosis, and (3) secondary osteoporosis.

PATHOPHYSIOLOGY • Bone loss occurs when bone resorption exceeds bone formation, usually from high bone turnover when the number and/or depth of bone resorption sites greatly exceed the rate and ability of osteoblasts to form new bone. • In addition to reduced bone mineral density (BMD), bone quality and structural integrity are impaired because of the increased quantity of immature bone that is not yet adequately mineralized. • Men and women begin to lose a small amount of bone mass starting in the third or fourth decade as a consequence of reduced bone formation. Estrogen deficiency during menopause increases proliferation, differentiation, and activation of new osteoclasts and prolongs survival of mature osteoclasts; this increases bone resorption more than formation. Men do not undergo a period of accelerated bone resorption similar to menopause. The etiology of male osteoporosis is multifactorial; secondary causes and aging are the most common contributing factors. • Age-related osteoporosis occurs mainly because of hormone, calcium, and vitamin D deficiencies leading to accelerated bone turnover and reduced osteoblast formation. • Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents.

CLINICAL PRESENTATION • Many patients are unaware that they have osteoporosis and only present after fracture. Fractures can occur after bending, lifting, or falling, or independent of any activity. • The most common osteoporosis-related fractures involve the vertebrae, proximal femur, and distal radius (wrist or Colles’ fracture). Two-thirds of patients with vertebral fractures are asymptomatic; the remainder present with moderate to severe back pain that radiates down a leg after a new vertebral fracture. The pain usually subsides significantly after 2 to 4 weeks, but residual, chronic, low-back pain may persist. Multiple vertebral fractures decrease height and sometimes curve the spine (kyphosis or lordosis) with or without significant back pain. 18

Osteoporosis

|

CHAPTER 3

• Patients with a nonvertebral fracture frequently present with severe pain, swelling, and reduced function and mobility at the fracture site.

DIAGNOSIS • A patient history should be obtained to identify history of adult fractures, comorbidities, surgeries, falls, and the presence of risk factors for osteoporosis. • Major risk factors include current smoker, low body weight (3 months, treatment options include a taxane, gemcitabine, topotecan, irinotecan, CAV (cyclophosphamide, doxorubicin, and vincristine), and vinorelbine. • Patients with SCLC that recurs within 3 months of first-line chemotherapy are considered refractory to chemotherapy and unlikely to respond to a second-line regimen.

EVALUATION OF THERAPEUTIC OUTCOMES • Efficacy of induction therapy for SCLC should be determined after two to three cycles of chemotherapy. If there is no response or progressive disease, therapy can be discontinued or changed to a non–cross-resistant regimen. If responsive to chemotherapy, the induction regimen should be administered for four to six cycles. • Intensive therapeutic monitoring is required for all lung cancer patients to avoid drug-related and radiotherapy-related toxicities. These patients frequently have numerous concurrent medical problems requiring close attention. • References should be consulted for management of common toxicities associated with the aggressive chemotherapy regimens used for lung cancer.

See Chap. 132, Lung Cancer, authored by Jeannine S. McCune and Deborah A. Frieze, for a more detailed discussion of this topic. 703

64

CHAP TER

Lymphomas

DEFINITION • Lymphomas are a heterogenous group of malignancies that arise from immune cells residing predominantly in lymphoid tissues. Differences in histology have led to classification as Hodgkin’s and non-Hodgkin’s lymphoma (HL and NHL, respectively), which are addressed separately in this chapter.

HODGKIN’S LYMPHOMA PATHOPHYSIOLOGY • Current hypotheses indicate that B-cell transcriptional processes are disrupted, which prevent expression of B-cell surface markers and production of immunoglobulin messenger RNA. Alterations in the normal apoptotic pathways favor cell survival and proliferation. • Malignant Reed-Sternberg cells overexpress nuclear factor-κ B, which is associated with cell proliferation and anti-apoptotic signals. Infections with viral and bacterial pathogens upregulate nuclear factor-κ B. EpsteinBarr virus is found in many, but not all, HL tumors.

CLINICAL PRESENTATION • Most patients with HL present with a painless, rubbery lymph node. Adenopathy is usually localized to the cervical region but can also occur in the mediastinal, hilar, and retroperitoneal regions. • Constitutional, or “B,” symptoms (e.g., fever, night sweats, weight loss, and pruritus) are present at diagnosis in approximately 25% of patients with HL.

DIAGNOSIS AND STAGING • Diagnosis requires the presence of Reed-Sternberg cells in the lymph node biopsy. • Staging is performed to provide prognostic information and to guide therapy. Clinical staging is based on noninvasive procedures such as history, physical examination, laboratory tests, and radiography. Pathologic staging is based on biopsy findings of strategic sites (e.g., muscle, bone, skin, spleen, abdominal nodes) using an invasive procedure (e.g., laparoscopy). • Approximately half of the patients have localized disease (stages I, II, and IIE). The other half has advanced disease at diagnosis, of which 10% to 15% is stage IV. • Prognosis predominantly depends on age and stage; patients older than 65 to 70 years are 50% as likely to be cured as younger patients. Patients with limited stage disease (stages I to II) have a 90% to 95% cure rate, whereas those with advanced disease (stages III to IV) have a 65% to 75% cure rate. 704

Lymphomas

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CHAPTER 64

TREATMENT SUMMARY • The treatment goal for HL is to maximize curability while minimizing treatment-related complications. • Treatment options include radiation therapy, chemotherapy, or both (combined-modality therapy). The therapeutic role of surgery is limited, regardless of stage. • Combination chemotherapy is the primary treatment modality for most HL patients. • Radiation therapy is an integral part of treatment and can be used alone for selected patients with early-stage disease, although most patients will receive chemotherapy and radiation. Involved-field radiation therapy targets a single field of HL. Extended-field or subtotal nodal radiation targets the involved field and an uninvolved area. Total nodal radiation therapy targets all areas. • Long-term complications of radiotherapy, chemotherapy, and chemoradiotherapy include gonadal dysfunction, secondary malignancies, and cardiac disease. Patients treated for HL are at increased risk of developing leukemia, GI tumors, lung cancer, and breast cancer.

TABLE 64-1

General Treatment Recommendations for Hodgkin’s Lymphomaa,b

Early-stage disease Favorable prognosis (CS I or II with no risk factors) Unfavorable prognosis (CS I or II with risk factors [e.g., B symptoms, extranodal disease, bulky disease, three or more sites of nodal involvement, or an erythrocyte sedimentation rate >50]) Advanced-stage disease Favorable prognosis (CS III or IV) Unfavorable prognosis (CS III or IV with four or more poor prognostic factors [e.g., low serum albumin, low hemoglobin, male gender, age ≥45 years, high white blood cell count]) Relapsed disease Relapse after radiation

Relapse after primary chemotherapyc

Extended-field radiation or two cycles of Stanford V or four cycles of ABVD followed by involved-field radiation 2–4 cycles of ABVD plus involved-field radiation

6–8 cycles of ABVD plus radiation to residual lymphoma or sites of bulky disease 6–8 cycles of escalated-dose BEACOPP plus radiation to residual lymphoma or sites of bulky disease

6–8 cycles of chemotherapy with or without radiation (treat as if this were primary advanced disease) Salvage chemotherapy at conventional doses or high-dose chemotherapy and autologous hematopoietic stem cell transplantation

ABVD, Adriamycin, bleomycin, vinblastine, and dacarbazine; BEACOPP, bleomycin, etoposide, Adriamycin, cyclophosphamide, Oncovin, procarbazine, and prednisone; CS, clinical stage. aPatients should be considered for clinical trials when possible. bIn general, patients with large mediastinal adenopathy should be treated with chemotherapy followed by radiation to the mediastinum. cA standard regimen or approach does not exist. See Table 64-2 for details of chemotherapy regimens.

705

SECTION 11

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Oncologic Disorders

Initial Chemotherapy • Two to 8 cycles of chemotherapy should be administered, depending on the stage of disease and presence of risk factors (Tables 64-1 and 64-2). Salvage Chemotherapy • Response to salvage therapy depends on the extent and site of recurrence, previous therapy, and duration of first remission. Choice of salvage therapy should be guided by response to initial therapy and a patient’s ability to tolerate therapy. • Patients who relapse after an initial complete response can be treated with the same regimen, a non–cross-resistant regimen, radiation therapy, or highdose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT). • Lack of complete remission after initial therapy or relapse within one year after completing initial therapy is associated with poor prognosis. Patients with these prognostic factors are candidates for high-dose chemotherapy and HSCT.

NON-HODGKIN’S LYMPHOMA PATHOPHYSIOLOGY • Chromosomal translocations have become a hallmark of many lymphomas and are helpful in the diagnosis and classification of lymphoid malignancies. NHL often involves extranodal sites and does not spread through contiguous lymph nodes. • NHLs are derived from monoclonal proliferation of B or, less commonly, T lymphocytes and their precursors. Two categories of B- and T-cell neoplasms are “precursor” neoplasms corresponding to the earliest stages of differentiation, and “peripheral” neoplasms corresponding to the more differentiated cell stages.

CLINICAL PRESENTATION • Patients present with a variety of symptoms, which depend on the site of involvement and whether it is nodal or extranodal. • Adenopathy can be localized or generalized. Involved nodes are painless, rubbery, and discrete and are usually located in the cervical and supraclavicular regions. Mesenteric or GI involvement can cause nausea, vomiting, obstruction, abdominal pain, palpable abdominal mass, or GI bleeding. Bone marrow involvement can cause symptoms related to anemia, neutropenia, or thrombocytopenia. • Forty percent of patients with NHL present with B symptoms—fever, night sweats, and weight loss.

DIAGNOSIS AND STAGING • Diagnosis is established by biopsy of an involved lymph node. • Diagnostic workup of NHL is generally similar to that of HL. • Systems for classifying NHLs continue to evolve. Lymphomas can be classified by degree of aggressiveness. Slow-growing or indolent lympho706

Lymphomas TABLE 64-2

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CHAPTER 64

Combination Chemotherapy Regimens for Hodgkin’s Lymphoma

Drug MOPP Mechlorethamine Vincristine Procarbazine Prednisone Repeat every 21 days ABVD Adriamycin (doxorubicin) Bleomycin Vinblastine Dacarbazine Repeat every 28 days MOPP/ABVD Alternating months of MOPP and ABVD MOPP/ABV hybrid Mechlorethamine Vincristine Procarbazine Prednisone Doxorubicin Bleomycin Vinblastine Repeat every 28 days Stanford V Doxorubicin Vinblastine Mechlorethamine Etoposide Vincristine Bleomycin Prednisone One course (12 weeks) BEACOPP (baseline) Bleomycin Etoposide Adriamycin (doxorubicin) Cyclophosphamide Oncovin (vincristine) Procarbazine Prednisone Repeat every 21 days BEACOPP (escalated) Bleomycin Etoposide Adriamycin (doxorubicin) Cyclophosphamide Oncovin (vincristine) Procarbazine

Dosage (mg/m2)

Route

Days

6 1.4 100 40

IV IV Oral Oral

1, 8 1, 8 1–14 1–14

25 10 6 375

IV IV IV IV

1, 15 1, 15 1, 15 1, 15

6 1.4 100 40 35 10 6

IV IV Oral Oral IV IV IV

1 1 1–7 1–14 8 8 8

25 6 6 60 1.4a 5 40

IV IV IV IV IV IV Oral

Weeks 1, 3, 5, 7, 9, 11 Weeks 1, 3, 5, 7, 9, 11 Weeks 1, 5, 9 Weeks 3, 7, 11 Weeks 2, 4, 6, 8, 10, 12 Weeks 2, 4, 6, 8 Every other day for 12 weeks; begin tapering at week 10

10 100 25 650 1.4a 100 40

IV IV IV IV IV Oral Oral

8 1–3 1 1 8 1–7 1–14

10 200 35 1,250 1.4a 100

IV IV IV IV IV Oral

8 1–3 1 1 8 1–7 (continued)

707

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Oncologic Disorders Combination Chemotherapy Regimens for Hodgkin’s Lymphoma (Continued)

Drug Prednisone Granulocyte colony-stimulating factor Repeat every 21 days

Dosage (mg/m2) 40

Route

Days

Oral Subcutaneously

1–14 8+

a

Vincristine dose capped at 2 mg.

mas are favorable (untreated survival measured in years), whereas rapidgrowing or aggressive lymphomas are unfavorable (untreated survival measured in weeks to months). • Prognosis depends on histologic subtype and clinical risk factors (e.g., age more than 60 years, performance status of 2 or more, elevated lactic dehydrogenase, extranodal involvement, and stage III or IV disease). These risk factors are used to calculate the International Prognostic Index. • A newer prognostic index uses similar risk factors except that poor performance status is replaced with low hemoglobin (less than 12 g/dL). Current research is focused on the prognostic importance of phenotypic and molecular characteristics of NHL.

DESIRED OUTCOME • The primary treatment goals for NHL are to relieve symptoms and, whenever possible, cure the patient of disease without causing unacceptable toxicity.

TREATMENT General Principles • Appropriate therapy for NHL depends on many factors including patient age, histologic type, stage and site of disease, presence of adverse prognostic factors, and patient preference. • Treatment is divided into two categories: limited disease (e.g., localized disease; Ann Arbor stages I and II) and advanced disease (e.g., Ann Arbor stage III or IV and stage II patients with poor prognostic features). • Treatment options include radiation therapy, chemotherapy, and biologic agents. • Radiation therapy is rarely suitable for remission induction because NHL is rarely localized at diagnosis. Radiation therapy is used more commonly in advanced disease, mainly as a palliative measure. • Effective chemotherapy ranges from single-agent therapy for indolent lymphomas to aggressive, complex combination regimens for aggressive lymphomas. Paradoxically, indolent or favorable lymphomas are rarely curable, whereas aggressive or unfavorable lymphomas are potentially curable. • Treatment strategies are summarized for the most common NHLs as examples of how to treat indolent (i.e., follicular) and aggressive (i.e., 708

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diffuse large B-cell) lymphomas. Strategies are also summarized for acquired immune deficiency syndrome (AIDS)–related lymphoma. Indolent Lymphomas • Follicular lymphomas occur in older adults with a majority having advanced disease at diagnosis. The clinical course is generally indolent, with median survival of 8 to 10 years. The natural history of follicular lymphoma is unpredictable with spontaneous regression of objective disease seen in 20% to 30% of patients. Localized Follicular Lymphoma • Options for stage I and II follicular lymphoma include locoregional radiation therapy, chemotherapy followed by radiation therapy, and extended-field radiation therapy. • Radiation therapy is the standard treatment and is usually curative. Chemotherapy is not recommended, unless the patient has high-risk, stage II disease. Advanced Follicular Lymphoma • Management of stages III and IV indolent lymphoma is controversial because standard approaches are not curative. Time to relapse is only 18 to 36 months. After relapse, response can be reinduced; however, response rates and durations decrease with each retreatment. • Therapeutic options are diverse and include watchful waiting, single-agent therapy, combination chemotherapy, biologic therapy, radioimmunotherapy, and combined-modality therapy. Immediate aggressive therapy does not improve survival compared with conservative therapy (i.e., watchful waiting followed by single-agent chemotherapy, rituximab or radiation therapy, only when needed). • Oral alkylating agents, chlorambucil, 0.1 to 0.2 mg/kg, or cyclophosphamide, 1.5 to 2.5 mg/kg (adjusted to white blood cell and platelet counts), are the mainstay of treatment. These single agents are as effective as combination regimens and produce minimal toxicity, but secondary acute myelogenous leukemia (AML) is a concern. Fludarabine and cladribine produce high response rates without secondary AML, but they are more myelosuppressive. • Rituximab, a chimeric monoclonal antibody directed at the CD20 molecule on B cells, has become one of the most widely used therapies for follicular lymphoma. Rituximab is approved for first-line therapy either alone or combined with chemotherapy and as maintenance therapy for patients with stable disease or with partial or complete response following induction chemotherapy. • The rituximab dosage is 375 mg/m2 weekly for 4 weeks. Maintenance schedules include 375 mg/m2 weekly for 4 weeks every 6 months for 2 years or 375 mg/m2 every 2 to 3 months for 1 to 2 years. Maintenance rituximab significantly prolongs progression-free and overall survival as compared with observation or initiation of rituximab at the time of disease progression. • Adverse effects are usually infusion related, especially after the first infusion of rituximab. Adverse effects include fever, chills, respiratory 709

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•

•

•

•

•

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Oncologic Disorders

symptoms, fatigue, headache, pruritus, and angioedema. Patients should receive acetaminophen, 650 mg, and diphenhydramine, 50 mg, 30 minutes before the infusion. Anti-CD20 radioimmunoconjugates are mouse antibodies linked to radioisotopes (e.g., 131I-tositumomab and 90Y-ibritumomab tiuxetan). They have the advantage of delivering radiation to tumor cells expressing the CD20 antigen and to adjacent tumor cells that do not express it. They have the disadvantage of damaging adjacent normal tissue (e.g., bone marrow). Radioimmunotherapy was initially used as salvage therapy and is being evaluated as first-line therapy in combination with CHOP (cyclophosphamids, doxorubicin, vincristine, and prednisone). Radioimmunotherapy is generally well tolerated. Toxicities include infusion-related reactions, myelosuppression, and possibly myelodysplastic syndrome or AML. 131I-tositumomab can cause thyroid dysfunction. The decision to use radioimmunotherapy requires consideration of the complexity, risks, and cost. The ideal candidate has limited bone marrow involvement and adequate blood cell counts. High-dose chemotherapy followed by HSCT is an option for relapsed follicular lymphoma. The recurrence rate is lower after allogeneic than after autologous HSCT, but the benefit is offset by increased treatmentrelated mortality. The ideal candidate is young and does not have serious comorbidities.

Aggressive Lymphomas • Diffuse large B-cell lymphomas are the most common lymphoma in patients of all ages but most commonly seen in the seventh decade. Extranodal disease is present at diagnosis in 30% to 40% of patients. The International Prognostic Index score correlates with prognosis. Diffuse aggressive lymphomas are sensitive to chemotherapy with cure achieved in some patients. Early-Stage Diffuse Large B-Cell Lymphoma • Stage I and nonbulky stage II should be treated with three to four cycles of rituximab and CHOP (R-CHOP) (Table 64-3) followed by locoregional radiation therapy. • Patients with at least one adverse risk factor should receive six to eight cycles of R-CHOP followed by locoregional radiation therapy. TABLE 64-3

a b

Combination Chemotherapy for Non-Hodgkin’s Lymphoma (CHOP)a,b

Drug

Dose (mg/m2)

Route

Days

Cyclophosphamide Doxorubicin Vincristine Prednisone

750 50 1.4 100

IV IV IV Oral

1 1 1 1–5

Cycle should be repeated every 21 days. Rituximab 375 mg/m2 on day 1 is commonly added (R-CHOP).

710

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Advanced Diffuse Large B-Cell Lymphoma Disease • Bulky stage II and stages III and IV lymphoma should be treated with RCHOP or rituximab and CHOP-like chemotherapy until achieving complete response (usually four cycles). Two or more additional cycles should be given following complete response for a total of six to eight cycles. Maintenance therapy following a complete response does not improve survival. • High-dose chemotherapy with autologous HSCT should be considered in high-risk patients who respond to standard chemotherapy and are candidates for autologous HSCT. • Although historically, elderly adults have lower complete response and survival rates than younger patients, full dose R-CHOP is recommended as initial treatment for aggressive lymphoma in the elderly. Salvage Therapy for Aggressive Lymphoma • Approximately one-third of patients with aggressive lymphoma will require salvage therapy at some point. Salvage therapy is more likely to induce response if the response to initial chemotherapy was complete (chemosensitivity) than if it was primarily or partially resistant to chemotherapy. • High-dose chemotherapy with autologous HSCT is the therapy of choice for younger patients with chemosensitive relapse. • Salvage regimens incorporate drugs not used as initial therapy. Commonly used regimens include DHAP (dexamethasone, high-dose cytarabine, and cisplatin), ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin), and MINE (mesna, ifosfamide, mitoxantrone, and etoposide). None is clearly superior to the others. • ICE (ifosfamide, carboplatin, and etoposide) appears to be better tolerated than cisplatin-containing regimens, especially in elderly adults. • Rituximab is being evaluated in combination with many salvage regimens. Non-Hodgkin’s Lymphoma in Acquired Immune Deficiency Syndrome • Patients with AIDS have more than a 100-fold increased risk of developing NHL, which is usually aggressive. • Treatment of AIDS-related lymphoma is difficult because underlying immunodeficiency increases the risk of treatment-related myelosuppression. • Standard combination regimens (e.g., CHOP) yield disappointing results. Newer approaches including dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), and rituximabcontaining combination chemotherapy are promising. • Antiretroviral therapy and prophylactic antibiotics should be continued during chemotherapy.

EVALUATION OF THERAPEUTIC OUTCOMES • The primary outcome to be identified is tumor response, which is based on physical examination, radiologic evidence, and other baseline findings. Complete response is desirable because it yields the only chance for cure. 711

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• Patients are evaluated for response at the end of four cycles or, if treatment is shorter, at the end of treatment. • Optimal outcomes for most types of lymphoma may require delivery of full doses on time. Hematopoietic growth factors and other supportive care measures are often needed to achieve this goal. • To optimize chemotherapy administration, the clinician must identify, monitor, treat, and prevent or minimize treatment-related toxicity. Pertinent laboratory data and other procedures should be reviewed to establish a baseline for monitoring purposes. Major organ and system toxicities to be monitored include hematologic, neurologic, skin, pulmonary, GI, renal, and cardiac.

See Chap. 135, Lymphomas, authored by Val R. Adams and Gary C. Yee, for a more detailed discussion of this topic.

712

CHAP TER

65

Prostate Cancer

DEFINITION • Prostate cancer is a malignant neoplasm that arises from the prostate gland. Prostate cancer has an indolent course; localized prostate cancer is curable by surgery or radiation therapy but advanced prostate cancer is not yet curable.

PATHOPHYSIOLOGY • The normal prostate is composed of acinar secretory cells that are altered when invaded by cancer. The major pathologic cell type is adenocarcinoma (more than 95% of cases). • Prostate cancer can be graded. Well-differentiated tumors grow slowly, whereas poorly differentiated tumors grow rapidly and have a poor prognosis. • Metastatic spread can occur by local extension, lymphatic drainage, or hematogenous dissemination. Skeletal metastases from hematogenous spread are the most common sites of distant spread. The lung, liver, brain, and adrenal glands are the most common sites of visceral involvement, but these organs are not usually involved initially.

CLINICAL PRESENTATION • Localized prostate cancer is usually asymptomatic. • Locally invasive prostate cancer is associated with ureteral dysfunction or impingement, such as alterations in micturition (e.g., urinary frequency, hesitancy, dribbling). • Patients with advanced disease commonly present with back pain and stiffness due to osseous metastases. Untreated spinal cord lesions can lead to cord compression. Lower extremity edema can occur as a result of lymphatic obstruction. Anemia and weight loss are nonspecific signs of advanced disease.

SCREENING • Screening for prostate cancer is controversial. The American Cancer Society recommends baseline prostate-specific antigen (PSA) and digital rectal exam (DRE) beginning at age 50 years for men of normal risk. Earlier testing is recommended for men at higher risk for prostate cancer. • DRE is commonly employed for screening of prostate cancer. It has the advantages of specificity, low cost, safety, and ease of performance. DRE has the disadvantages of relative insensitivity and of inter-observer variability. • PSA is a glycoprotein produced and secreted by the epithelial cells of the prostate gland. Acute urinary retention, acute prostatitis, and benign prostatic hypertrophy (BPH) influence PSA, therefore limiting the usefulness of PSA alone for early detection. PSA is a useful marker for monitoring response to therapy. 713

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TREATMENT CHEMOPREVENTION • The risk of prostate cancer was reduced 25% in patients taking finasteride for treatment of BPH. • Prostate cancer diagnosed in patients on finasteride is more aggressive, making its use in men without BPH controversial.

GENERAL APPROACH TO TREATMENT • The initial treatment for prostate cancer depends on the disease stage, Gleason score, presence of symptoms, and patient’s life expectancy. The most appropriate therapy for early-stage prostate cancer is unknown. • Expectant management, also known as observation or watchful waiting, involves monitoring the course of the disease and initiating treatment if disease progresses or the patient becomes symptomatic. PSA and DRE are performed every 6 months. • Radical prostatectomy and radiation therapy are generally considered equivalent for localized prostate cancer, and neither has been shown to be superior to observation alone. • Men with disease confined to the prostate (T1 or T2a), no symptoms, Gleason score of 2 to 6, or PSA of less than 10 ng/mL are at low risk for recurrence and have a high 10-year survival rate. If life expectancy is less than 10 years, options are expectant management or radiation therapy. If life expectancy is more than 10 years, options are expectant management, radiation, or radical prostatectomy. • Men with disease involving more than one-half of one lobe or both lobes (T2bc), Gleason score of 7, or PSA of 10 to 20 ng/mL are at intermediate risk for recurrence. If life expectancy is less than 10 years, options are expectant management, radiation therapy, or radical prostatectomy. If life expectancy is more than 10 years, options are prostatectomy or radiation therapy. • Men with disease localized to the periprostatic area (T3), Gleason score of 8 to 10, or PSA of more than 20 ng/mL are at high risk for recurrence and should be treated with androgen ablation for 2 to 3 years combined with radiation therapy. Radical prostatectomy can be considered in patients with low tumor volume. • Men with disease fixed or invading adjacent structures other than the seminal vesicles (T4) are at very high risk for recurrence. Androgen ablation should be initiated at diagnosis instead of waiting for the onset of symptoms. • The major initial treatment modality for advanced prostate cancer is androgen ablation (e.g., orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonists with or without antiandrogens). After disease progression, secondary hormonal manipulations, cytotoxic chemotherapy, and supportive care are used.

SURGERY AND RADIATION THERAPY • Prostatectomy and radiation therapy are potentially curative but are associated with complications that must be weighed against expected 714

Prostate Cancer

•

• • •

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CHAPTER 65

benefit. Consequently, many patients postpone therapy until the onset of symptoms. Complications of radical prostatectomy include blood loss, stricture formation, incontinence, lymphocele, fistula formation, anesthetic risk, and impotence. Nerve-sparing techniques facilitate return of sexual potency after prostatectomy. Acute complications of radiation therapy include cystitis, proctitis, hematuria, urinary retention, penoscrotal edema, and impotence. Chronic complications of radiation therapy include proctitis, diarrhea, cystitis, enteritis, impotence, urethral stricture, and incontinence. Bilateral orchiectomy rapidly reduces circulating androgen levels. Many patients are not surgical candidates owing to advanced age or perceived unacceptability. Nonetheless, orchiectomy is the preferred initial treatment for patients with impending spinal cord compression or ureteral obstruction.

HORMONAL THERAPY • The rationale for hormonal therapy is based on the effect of androgens on the growth and differentiation of the normal prostate (Fig. 65-1).

Hypothalamus LHRH LH FSH

Pituitary

ACTH

LH FSH

Testes

Adrenal glands PROL GH

Testosterone

Testosterone

+ R

Androgens

Androgens

DHT

DHT

R

DNA RNA DHT

R

Prostate cell

mRNA

FIGURE 65-1. Hormonal regulation of the prostate gland. (ACTH, adrenocorticotropic hormone; DHT, dihydrotestosterone; FSH, follicle-stimulating hormone; GH, growth hormone; LH, luteinizing hormone; LHRH, luteinizing hormone-releasing hormone; mRNA, messenger RNA; PROL, prolactin; R, receptor.)

715

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• The testes and the adrenal glands are the major sources of androgens, specifically dihydrotestosterone (DHT). • LHRH from the hypothalamus stimulates the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. • LH complexes with receptors on the Leydig cell testicular membrane and stimulates the production of testosterone and small amounts of estrogen. • FSH acts on testicular Sertoli cells to promote maturation of LH receptors and produce an androgen-binding protein. • Circulating testosterone and estradiol influence the synthesis of LHRH, LH, and FSH by a negative-feedback loop at the hypothalamic and pituitary level. • Only 2% of total plasma testosterone is present in the active unbound state that penetrates the prostate cell, where it is converted to DHT by 5 αreductase. DHT subsequently binds with a cytoplasmic receptor and is transported to the cell nucleus where transcription and translation of stored genetic material occur. Luteinizing Hormone-Releasing Hormone Agonists • LHRH agonists provide response rates of approximately 80%, which is similar to that of orchiectomy, and have the advantage of being reversible. • There are no comparative trials of LHRH agonists, so the choice is usually based on cost (Table 65-1) and on patient and physician preference. Leuprolide acetate is administered daily. Leuprolide depot and goserelin acetate implant can be administered monthly, or every 12 or 16 weeks. • The most common adverse effects of LHRH agonists are disease flare-up during the first week of therapy (e.g., increased bone pain, urinary symptoms), hot flashes, erectile impotence, decreased libido, and injection-site reactions. Antiandrogens • Monotherapy with flutamide, bicalutamide, and nilutamide is no longer recommended due to decreased survival as compared with patients treated with LHRH agonist therapy or orchiectomy. Antiandrogens are indicated for advanced prostate cancer only when combined with an LHRH agonist (flutamide and bicalutamide]) or orchiectomy (nilutamide). In combination, antiandrogens can reduce the LHRH agonist-induced flare. • The adverse effects of antiandrogens are gynecomastia, hot flushes, GI disturbances, liver function test abnormalities, and breast tenderness. GI disturbances consist of diarrhea for flutamide and bicalutamide and nausea or constipation for nilutamide. Flutamide is also associated with methemoglobinemia, whereas nilutamide causes visual disturbances (impaired dark adaptation), alcohol intolerance, and interstitial pneumonitis. Combined Hormonal Blockade • The role of combined hormonal therapy, also referred to as maximal androgen deprivation or total androgen blockade, continues to be evaluated. • Randomized trial results are mixed when candidates for second-line therapy are treated with combinations of antiandrogens plus either LHRH 716

Prostate Cancer TABLE 65-1

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CHAPTER 65

Comparative Costs of Hormonal Therapy for Advanced Prostate Cancer

Drug

Dose

Annual Cost (Based on AWP)

Leuprolide depot Leuprolide depot Leuprolide depot Goserelin implant Goserelin implant Triptorelin depot Triptorelin LA depot Flutamide Bicalutamide Nilutamide

7.5 mg/mo 22.5 mg/12 wks 30 mg/16 wks 3.6 mg every 28 days 10.8 mg/12 wks 3.75 mg q 28 day 11.25 mg q 84 day 750 mg/day 50 mg/day 300 mg/day for first month then 150 mg/day

$709.20/mo; $8,510/yr $2,127.59/12 wks; $8,510/yr $2,836.79/16 wks; $8,510/yr $469.99/mo; $5,640/yr $1,409.98/12 wks; $5,640/yr $582.00/mo; $6,984/yr $1,746.00/84; $6,984/yr $376.60/mo; $4,519/yr $484.44/mo; $5,813/yr $728.80 for first month, then $364.40/mo; $4,373.80/yr for chronic therapy

Combined Androgen Blockade Leuprolide depot 22.5 mg/12 wks + flutamide 750 mg/day + bicalutamide 50 mg/day + nilutamide 150 mg/day Goserelin depot 10.8 mg/12 wks + flutamide 750 mg/day + bicalutamide 50 mg/day + nilutamide 150 mg/day Triptorelin LA depot 11.25 mg every 84 days + flutamide 750 mg/day + bicalutamide 50 mg/day + nilutamide 150 mg/day

Cost Per 3 Months of Therapy (Based on AWP) $3,257 $3,581 $3,221 $2,540 $2,863 $2,503 $2,876 $3,199 $2,839

AWP, average wholesale price; LA, long-acting. Compiled from Thomson PDR, Red Book, Montvale, NJ, 2006.

agonists or orchiectomy. The most recent metaanalysis showed only a slight survival benefit at 5 years for maximal androgen blockade with flutamide or nilutamide (27.6%) compared with conventional medical or surgical castration alone (24.7%). • Some investigators consider combined androgen blockade to be the initial hormonal therapy of choice for newly diagnosed patients because the major benefit is seen in patients with minimal disease. Some argue that treatment should not be delayed because combined androgen deprivation trials demonstrate a survival advantage for young patients with good performance status and minimal disease who were initially treated with hormonal therapy. • Until definitive trials are published, it is appropriate to use either LHRH agonist monotherapy or combined androgen blockade as initial therapy for metastatic prostate cancer.

SALVAGE THERAPY • The selection of salvage therapy depends on what was used as initial therapy. Radiotherapy can be used after radical prostatectomy. Androgen ablation can be used after radiation therapy or radical prostatectomy. 717

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• If testosterone levels are not suppressed (i.e., greater than 20 ng/dL) after initial LHRH agonist therapy, an antiandrogen or orchiectomy may be indicated. If testosterone levels are suppressed, the disease is considered androgen independent and should be treated with palliative therapy. • If initial therapy consisted of an LHRH agonist and antiandrogen, then androgen withdrawal should be attempted. Mutations of the androgen receptor may allow antiandrogens to become agonists. Withdrawal produces responses lasting 3 to 14 months in up to 35% of patients. • Androgen synthesis inhibitors provide symptomatic, but brief, relief in approximately 50% of patients. Aminoglutethimide causes adverse effects in 50% of patients, such as lethargy, ataxia, dizziness, and self-limiting rash. The adverse effects of ketoconazole are GI intolerance, transient increases in liver and renal function tests, and hypoadrenalism. • Bisphosphonates such as pamidronate and zoledronic acid may prevent skeletal morbidity, such as pathologic fractures and spinal code compression, when used for hormone-refractory prostate cancer in patients with clinically significant bone loss. Usual dosages are pamidronate, 90 mg every month, and zoledronic acid, 4 mg every 3 to 4 weeks. • After hormonal options are exhausted, palliation can be achieved with strontium-89 or samarium-153 lexidronam for bone-related pain, analgesics, glucocorticoids, local radiotherapy, or chemotherapy.

CHEMOTHERAPY • Docetaxel, 75 mg/m2 every 3 weeks, combined with prednisone, 5 mg twice daily, has been shown to prolong survival in hormone-refractory metastatic prostate cancer. The most common adverse events were nausea, alopecia, and myelosuppression. Docetaxel can also cause fluid retention and peripheral neuropathy. • The combination of estramustine 280 mg by mouth three times daily on days 1 to 5 and docetaxel 60 mg/m2 on day 2 of a 21-day cycle also improves survival in hormone-refractory metastatic prostate cancer. Estramustine causes a decrease in testosterone and a corresponding increase in estrogen, which results in an increase in thromboembolic events, gynecomastia, and decreased libido.

EVALUATION OF THERAPEUTIC OUTCOMES • For definitive, curative therapy, objective parameters to monitor include primary tumor size, involved lymph nodes, and tumor markers such as PSA. PSA level is checked every 6 months for the first 5 years, and then annually. • With metastatic disease, clinical benefit can be documented by evaluating performance status, weight, quality of life, analgesic requirements, and PSA or DRE at 3-month intervals. • Patients should be monitored for treatment-related adverse events, especially events that are amenable to intervention.

See Chap. 134, Prostate Cancer, authored by Jill M. Kolesar, for a more detailed discussion of this topic. 718

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OPHTHALMIC DISORDERS

CHAP TER

Edited by Cecily V. DiPiro

66

Glaucoma

DEFINITION • Glaucomas are ocular disorders characterized by changes in the optic nerve head (optic disk) and by loss of visual sensitivity and field.

PATHOPHYSIOLOGY • There are two major types of glaucoma: open-angle glaucoma, which accounts for most cases and is therefore the focus of this chapter, and closed-angle glaucoma. • In open-angle glaucoma, the specific cause of optic neuropathy is unknown. Increased intraocular pressure (IOP) was historically considered to be the sole cause. Additional contributing factors include increased susceptibility of the optic nerve to ischemia, reduced or dysregulated blood flow, excitotoxicity, autoimmune reactions, and other abnormal physiologic processes. • Although IOP is a poor predictor of which patients will have visual field loss, the risk of visual field loss increases with increasing IOP. IOP is not constant; it changes with pulse, blood pressure, forced expiration or coughing, neck compression, and posture. • The balance between the inflow and outflow of aqueous humor determines IOP. Inflow is increased by β-adrenergic agents and decreased by α2-, α-, and β-adrenergic blockers; dopamine blockers; carbonic anhydrase inhibitors (CAIs); and adenylate cyclase stimulators. Outflow is increased by cholinergic agents, which contract the ciliary muscle and open the trabecular meshwork, and by prostaglandin analogs and β- and α2-adrenergic agonists, which affect uveoscleral outflow. • Secondary open-angle glaucoma has many causes including exfoliation syndrome, pigmentary glaucoma, systemic diseases, trauma, surgery, lens changes, ocular inflammatory diseases, and drugs. Secondary glaucoma can be classified as pretrabecular (normal meshwork is covered and prevents outflow of aqueous humor), trabecular (meshwork is altered or material accumulates in the intertrabecular spaces), or posttrabecular (episcleral venous blood pressure is increased). • Many drugs can increase IOP (Table 66-1). The potential to induce or worsen glaucoma depends on the type of glaucoma and on whether it is adequately controlled. • Closed-angle glaucoma occurs when there is a physical blockage of the trabecular meshwork, resulting in increased IOP. 719

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TABLE 66-1

Ophthalmic Disorders Drugs That May Induce or Potentiate Increased Intraocular Pressure

Open-angle glaucoma Ophthalmic corticosteroids (high risk) Systemic corticosteroids Nasal/inhaled corticosteroids Fenoldopam Ophthalmic anticholinergics Succinylcholine Vasodilators (low risk) Cimetidine (low risk) Closed-angle glaucoma Topical anticholinergics Topical sympathomimetics Systemic anticholinergics Heterocyclic antidepressants Low-potency phenothiazines Antihistamines Ipratropium Benzodiazepines (low risk) Theophylline (low risk) Vasodilators (low risk) Systemic sympathomimetics (low risk) Central nervous system stimulants (low risk) Selective serotonin reuptake inhibitors Imipramine Venlafaxine Topiramate Tetracyclines (low risk) Carbonic anhydrase inhibitors (low risk) Monoamine oxidase inhibitors (low risk) Topical cholinergics (low risk)

CLINICAL PRESENTATION • Open-angle glaucoma is slowly progressive and is usually asymptomatic until the onset of substantial visual field loss. Central visual acuity is maintained, even in late stages. • In closed-angle glaucoma, patients typically experience intermittent prodromal symptoms (e.g., blurred or hazy vision with halos around lights and occasionally, headache). Acute episodes produce symptoms associated with a cloudy, edematous cornea; ocular pain; nausea, vomiting, and abdominal pain; and diaphoresis.

DIAGNOSIS • The diagnosis of open-angle glaucoma is confirmed by the presence of characteristic optic disk changes and visual field loss, with or without increased IOP. Normal tension glaucoma refers to disk changes, visual field loss, and IOP of less than 21 mm Hg. Ocular hypertension refers to IOP of more than 21 mm Hg without disk changes or visual field loss. 720

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• For closed-angle glaucoma, the presence of a narrow angle is usually visualized by gonioscopy. IOP is generally markedly elevated (e.g., 40 to 90 mm Hg) when symptoms are present. Additional signs include hyperemic conjunctiva, cloudy cornea, shallow anterior chamber, and occasionally edematous and hyperemic optic disk.

DESIRED OUTCOME • The goal of drug therapy in patients with glaucoma is to preserve visual function by reducing the IOP to a level at which no further optic nerve damage occurs.

TREATMENT OF OCULAR HYPERTENSION AND OPEN-ANGLE GLAUCOMA • Treatment is indicated for ocular hypertension if the patient has a significant risk factor such as IOP greater than 25 mm Hg, vertical cup-disk ratio greater than 0.5, or central corneal thickness less than 555 micrometers. Additional risk factors to be considered include family history of glaucoma, black race, severe myopia, and presence of only one eye. • Treatment is indicated for all patients with elevated IOP and characteristic optic disk changes or visual field defects. • Drug therapy is the most common initial treatment and is initiated in a stepwise manner, starting with a single well tolerated topical agent (Table 66-2). Historically, β-blockers (e.g., timolol) were the treatment of choice and continue to be used if there are no contraindications to potential βblockade caused by systemic absorption. β-Blockers have the advantage of low cost owing to generic formulations. • Newer agents are also suitable for first-line therapy. Prostaglandin analogs (e.g., latanoprost, bimatoprost and travoprost) have the advantage of strong potency, unique mechanism suitable for combination therapy, good safety profile, and once-a-day dosing. Brimonidine has the theoretical advantage of neuroprotection, which has not yet been demonstrated in humans. Topical CAIs are also suitable for first-line therapy. • Pilocarpine and dipivefrin, a prodrug of epinephrine, are used as thirdline therapies because of adverse events or reduced efficacy as compared with newer agents. • Carbachol, topical cholinesterase inhibitors, and oral CAIs (e.g., acetazolamide) are used as last-resort options after failure of less toxic options. • The optimal timing of laser or surgical trabeculectomy is controversial, ranging from initial therapy to after failure of third- or fourth-line drug therapy. Antiproliferative agents such as fluorouracil and mitomycin C are used to modify the healing process and maintain patency.

TREATMENT OF CLOSED-ANGLE GLAUCOMA • Acute closed-angle glaucoma with high IOP requires rapid reduction of IOP. Iridectomy is the definitive treatment, which produces a hole in the 721

TABLE 66-2

Topical Drugs Used in the Treatment of Open-Angle Glaucoma Pharmacologic Properties

Common Brand Names

Dose Form

Strength (%)

Usual Dosea

Mechanism of Action

Generic Betoptic-S Generic

Solution Suspension Solution

0.5 0.25 1

1 drop twice a day 1 drop twice a day 1 drop twice a day

All reduce aqueous production of ciliary body

Betagan OptiPranolol Timoptic, Betimol, Istalol Timoptic-XE

Solution Solution Solution Gelling solution

0.25, 0.5 0.3 0.25, 0.5 0.25, 0.5

1 drop twice a day 1 drop twice a day 1 drop one to two times a day 1 drop every day a

Propine

Solution

0.1

1 drop twice a day

Increased aqueous humor outflow

Iopidine Alphagan P

Solution Solution

0.5, 1 0.15, 0.1

1 drop two to three times a day 1 drop two to three times a day

Both reduce aqueous humor production; brimonidine known to also increase uveoscleral outflow

Cholinergic agonists direct acting Carbachol Irreversible

Carboptic, Isopto Carbachol

Solution

1.5, 3

1 drop two to three times a day

All increase aqueous humor outflow through trabecular meshwork

Pilocarpine

Isopto Carpine, Pilocar

Solution

0.25, 0.5, 1, 2, 4, 6, 8, 10

Pilopine HS

Gel

4

1 drop two to three times a day 1 drop four times a day Every 24 hours at bedtime

Drug

β-Adrenergic blocking agents Betaxolol Relative β1-selective Carteolol Levobunolol Metipranolol Timolol

Nonselective, intrinsic sympathomimetic activity Nonselective Nonselective Nonselective

Nonspecific adrenergic agonists Dipivefrin Prodrug α2-Adrenergic agonists Apraclonidine Specific α2-agonists Brimonidine

Irreversible

Cholinesterase inhibitors Echothiophate Carbonic anhydrase inhibitors Topical Brinzolamide Carbonic anhydrase type II inhibition Dorzolamide Systemic Acetazolamide

Phospholine Iodide

Solution

0.125

Once or twice a day

Azopt Trusopt

Suspension Solution

1 2

Two to three times a day Two to three times a day

Generic Diamox Sequels Generic

Tablet Injection Capsule Tablet

125 mg, 250 mg 500 mg/vial 500 mg 25 mg, 50 mg

125–250 mg two to four times a day 250–500 mg 500 mg twice a day 25–50 mg two to three times a day

Xalatan Lumigan

Solution Solution

0.005 0.03

1 drop every night 1 drop every night

Travoprost Combinations Timolol-dorzolamide

Travatan, Travatan Z

Solution

0.004

1 drop every night

Cosopt

Solution

Timolol 0.5% dorzolamide 2%

1 drop twice daily

Timolol-brimonidine

Combigan

Solution

Timolol 0.5% brimonide 0.2%

1 drop twice daily

Methazolamide Prostaglandin analogs Latanoprost Prostaglandin F2α analog Bimatoprost Prostamide analog

a

Use of nasolacrimal occlusion will increase number of patients successfully treated with longer dosage intervals.

All reduce aqueous humor production of ciliary body

Increases aqueous uveoscleral outflow and to a lesser extent trabecular outflow

SECTION 12

•

• •

• •

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Ophthalmic Disorders

iris that permits aqueous flow to move directly from the posterior to the anterior chamber. Drug therapy of an acute attack typically consists of an osmotic agent and secretory inhibitor (e.g., β-blocker, α2 agonist, latanoprost, or CAI), with or without pilocarpine. Osmotic agents are used because they rapidly decrease IOP. Examples include glycerin, 1 to 2 g/kg orally, and mannitol, 1 to 2 g/kg IV. Although traditionally the drug of choice, pilocarpine use is controversial as initial therapy. Once IOP is controlled, pilocarpine should be given every 6 hours until iridectomy is performed. Topical corticosteroids can be used to reduce ocular inflammation and synechiae. Epinephrine should be used with caution because it can precipitate acute closed-angle glaucoma, especially when used with a β-blocker.

EVALUATION OF THERAPEUTIC OUTCOMES • Successful outcomes require identifying an effective, well-tolerated regimen; closely monitoring therapy; and patient adherence. Whenever possible, therapy for open-angle glaucoma should be started as a single agent in one eye to facilitate evaluation of drug efficacy and tolerance. Many drugs or combinations may need to be tried before the optimal regimen is identified. • Monitoring therapy for open-angle glaucoma should be individualized. IOP response is assessed every 4 to 6 weeks initially, every 3 to 4 months after IOPs become acceptable, and more frequently after therapy is changed. The visual field and disk changes are monitored annually, unless glaucoma is unstable or worsening. • Patients should be monitored for tachyphylaxis, especially with β-blockers or apraclonidine. Treatment can be temporarily discontinued to monitor its benefit. • There is no specific target IOP because the correlation between IOP and optic nerve damage is poor. Typically, a 25% to 30% reduction is desired. • The target IOP also depends on disease severity and is generally less than 21 mm Hg for early visual field loss or optic disk changes, with progressively lower targets for greater damage. Targets as low as less than 10 mm Hg are desired for very advanced disease, continued damage at higher IOPs, normal tension glaucoma, and pretreatment pressures in the low- to mid-teens. • Using more than one drop per dose increases the risk of adverse events and cost, but not efficacy. • Patients should be educated about possible adverse effects and methods for preventing them. • Patients should be taught how to administer topical therapy. With a forefinger pulling down the lower eyelid to form a pocket, the patient should place the dropper over the eye, look at the tip of the bottle, and then look up and place a single drop in the eye. To maximize topical activity and minimize systemic absorption, the patient should close the lid for 1 to 3 minutes after instillation and place the index finger over the nasolacrimal drainage system in the inner corner of the eye. 724

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• If more than one topical drug is required, instillation should be separated by 5 to 10 minutes to provide optimal ocular contact. • Adherence to drug therapy should be monitored because it is commonly inadequate and a cause of therapy failure.

See Chap. 97, Glaucoma, authored by Richard G. Fiscella, Timothy S. Lesar, and Deepak P. Edward, for a more detailed discussion of this topic.

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SECTION 13

PSYCHIATRIC DISORDERS

CHAP TER

Edited by Barbara G. Wells

67

Alzheimer’s Disease

DEFINITION • Alzheimer’s disease (AD) is a progressive dementia affecting cognition, behavior, and functional status with no known cause or cure. Patients eventually lose cognitive, analytical, and physical functioning, and the disease is ultimately fatal.

PATHOPHYSIOLOGY • The signature findings are intracellular neurofibrillary tangles (NFTs), extracellular neuritic plaques, degeneration of neurons and synapses, and cortical atrophy. • Mechanisms proposed for these changes are: ✓ β-Amyloid protein aggregation, leading to formation of plaques ✓ Hyperphosphorylation of tau protein, leading to intracellular NFT development and collapse of microtubules ✓ Inflammatory processes—levels of multiple cytokines and chemokines are elevated in AD brains ✓ Neurovasculature dysfunction ✓ Oxidative stress ✓ Mitochondrial dysfunction • Neuritic plaques are lesions found in brain and cerebral vasculature. • Whether genetic variations promote a primary β-amyloidosis in the majority of AD patients is unresolved. • Density of NFTs correlates with severity of dementia. • While there is a variety of neurotransmitter deficits, loss of cholinergic activity is most prominent and correlates with AD severity. • It is clear that replacement of acetylcholine activity cannot compensate for all the changes that take place in AD. • Deficits that exist in other pathways are: ✓ Serotonergic neurons of the raphe nuclei and noradrenergic cells of the locus ceruleus are lost ✓ Monoamine oxidase type B activity is increased ✓ Glutamate pathways of the cortex and limbic structures are abnormal • Excitatory neurotransmitters, including glutamate, have been implicated as potential neurotoxins in AD. • Risk factors for AD are hypertension, elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and diabetes.

727

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TABLE 67-1 Mild (MMSE score 26–18)

Moderate (MMSE score 17–10)

Severe (MMSE score 9–0)

Psychiatric Disorders Stages of Alzheimer’s Disease Patient has difficulty remembering recent events. Ability to manage finances, prepare food, and carry out other household activities declines. May get lost while driving. Begins to withdraw from difficult tasks and to give up hobbies. May deny memory problems. Patient requires assistance with activities of daily living. Frequently disoriented with regard to time (date, year, season). Recall for recent events is severely impaired. May forget some details of past life and names of family and friends. Functioning may fluctuate from day to day. Patient generally denies problems. May become suspicious or tearful. Loses ability to drive safely. Agitation, paranoia, and delusions are common. Patient loses ability to speak, walk, and feed self. Incontinent of urine and feces. Requires care 24 hours a day, 7 days a week.

MMSE, Mini-Mental State Examination. Data from Alzheimer’s Association. http://www.alz.org/; Rubin CD. The primary care of Alzheimer’s disease. Am J Med Sci 2006;332:314– 333; and Grossberg GT, Desai AK. Management of Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2003;58A:331–353.

CLINICAL PRESENTATION • The onset of AD is almost imperceptible, but deficits progress over time. Cognitive decline is gradual, and behavioral disturbances may be present in moderate stages. Table 67-1 shows the stages of AD.

SYMPTOMS • Table 67-2 shows the clinical presentation of AD and recommended laboratory and diagnostic tests.

DIAGNOSIS • The definitive diagnosis of AD is made by examining brain tissue. Useful diagnostic criteria and guidelines are provided by: ✓ The Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision ✓ The Agency for Healthcare Research and Quality ✓ The American Academy of Neurology ✓ The National Institute of Neurological and Communicative Disorders and Stroke ✓ Alzheimer’s Disease and Related Disorders Association • Patients with suspected AD should have a history and physical examination with appropriate laboratory and other diagnostic tests, neurologic and psychiatric examinations, standardized rating assessments, functional evaluation, and a caregiver interview. • Information about prescription drug use; alcohol or other substance use; family medical history; and history of trauma, depression, or head injury should be obtained. It is important to rule out medication use as a contributor or cause of symptoms (e.g., anticholinergics, sedatives, hypnotics, opioids, antipsychotics, and anticonvulsants) as contributors to dementia symptoms. Other medications may contribute to delirium, e.g., 728

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Clinical Presentation of Alzheimer’s Disease

General The patient may have vague memory complaints initially, or the patient’s significant other may report that the patient is “forgetful.” Cognitive decline is gradual over the course of illness. Behavioral disturbances may be present in moderate stages. Loss of daily function is common in advanced stages. Symptoms Cognitive Memory loss (poor recall and losing items) Aphasia (circumlocution and anomia) Apraxia Agnosia Disorientation (impaired perception of time and unable to recognize familiar people) Impaired executive function Noncognitive Depression, psychotic symptoms (hallucinations and delusions) Behavioral disturbances (physical and verbal aggression, motor hyperactivity, uncooperativeness, wandering, repetitive mannerisms and activities, and combativeness) Functional Inability to care for self (dressing, bathing, toileting, and eating) Laboratory tests Rule out vitamin B12 and folate deficiency Rule out hypothyroidism with thyroid function tests Blood cell counts, serum electrolytes, liver function tests Other diagnostic tests CT or MRI scans may aid diagnosis CT, computed tomography; MRI, magnetic resonance imaging.

digoxin, nonsteroidal antiinflammatory drugs, histamine2 receptor antagonists, amiodarone, antihypertensives, and corticosteroids. • The Folstein Mini-Mental State Examination (MMSE) can help to establish a history of deficits in two or more areas of cognition and establish a baseline against which to evaluate change in severity. The average expected decline in an untreated patient is 2 to 4 points per year.

DESIRED OUTCOME • The primary goal of treatment in AD is to maintain patient functioning as long as possible. Secondary goals are to treat the psychiatric and behavioral sequelae.

TREATMENT NONPHARMACOLOGIC THERAPY • Sleep disturbances, wandering, urinary incontinence, agitation, and aggression should be managed with behavioral interventions whenever possible. • On initial diagnosis, the patient and caregiver should be educated on the course of illness, available treatments, legal decisions, changes in lifestyle that will be necessary with disease progression, and other quality of life issues. 729

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Psychiatric Disorders Treatment Options for Cognitive Symptoms in Alzheimer’s Disease

• In mild–moderate disease, consider therapy with a cholinesterase inhibitor. • Donepezil, or • Rivastigmine, or • Galantamine • Titrate to recommended maintenance dose as tolerated. • In moderate to severe disease, consider adding antiglutamatergic therapy. • Memantine • Titrate to recommended maintenance dose as tolerated. • Alternatively, consider memantine or cholinesterase inhibitor therapy alone. • Behavioral symptoms may require additional pharmacologic approaches. Data from Desai AK, Grossberg GT. Diagnosis and treatment of Alzheimer’s disease. Neurology 2005;64(Suppl 3):S34–S39; Lyketsos CG, Colenda CC, Beck C, et al. Position statement of the American Association for Geriatric Psychiatry regarding principles of care for patients with dementia resulting from Alzheimer’s disease. Am J Geriatr Psychiatry 2006;14:561–573; and Lleó A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med 2006;57:513–533.

• The Alzheimer’s Association recommends staying physically, mentally, and socially active, adopting a low-fat/low-cholesterol diet rich in dark vegetables and fruit, and managing body weight.

PHARMACOTHERAPY OF COGNITIVE SYMPTOMS • Managing blood pressure, cholesterol, and blood sugar may reduce the risk of developing AD and may prevent the worsening of dementia in patients with AD. • Current pharmacotherapeutic interventions are primarily symptomatic attempts to improve or maintain cognition. Table 67-3 may be used as an algorithm for managing cognitive symptoms in AD. • Successful treatment reflects a decline of less than 2 points each year on the MMSE score. Cholinesterase Inhibitors • Table 67-4 summarizes the clinical pharmacology of the cholinesterase inhibitors. • No direct comparative trials have assessed the effectiveness of one agent over another. Donepezil, rivastigmine, and galantamine are indicated in mild to moderate AD, while donepezil is also indicated in severe AD. • If the decline in MMSE score is more than 2 to 4 points after treatment for 1 year with the initial agent, it is reasonable to change to a different cholinesterase inhibitor. Otherwise, treatment should be continued with the initial medication throughout the course of the illness. • The most frequent adverse effects are mild to moderate GI symptoms (nausea, vomiting, and diarrhea), urinary incontinence, dizziness, headache, syncope, bradycardia, muscle weakness, salivation, and sweating. Abrupt discontinuation can cause worsening of cognition and behavior in some patients. • Donepezil (Aricept) is a piperidine derivative with specificity for inhibition of acetylcholinesterase rather than butyrylcholinesterase. 730

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CHAPTER 67

Clinical Pharmacology of the Cholinesterase Inhibitors Donepezil

Rivastigmine

Galantamine

Brand name Dosage forms

Aricept Tablet Orally disintegrating tablet

Exelon Capsule Oral solution Patch

Starting dose

5 mg daily at bedtime

Maintenance dose

5–10 mg daily

Meals Half-life Protein binding Metabolism

No effect of food 70 hours 96% Substrate (minor) of CYP2D6 and 3A4 Glucuronidation Yes

1.5 mg twice a day 4.6 mg/day (patch) 3–6 mg twice a day 9.5 mg/day (patch) Take with food 1.5 hours 40% Cholinesterase-mediated hydrolysis — Major pathway

Razadyne Tablet Oral solution Extended-release (ER) capsule 4 mg twice a day (8 mg daily for ER) 8–12 mg twice a day (16–24 mg daily for ER) Take with food 7 hours 18% Substrate (minor) of CYP2D6 and 3A4 Glucuronidation Yes

Renal elimination

CYP, cytochrome P450. Data from Namenda (memantine hydrochloride) package insert. St. Louis, MO: Forest Laboratories, 2005; Aricept (donepezil hydrochloride) package insert. Teaneck, NJ: Eisai Co, Ltd., 2006; Exelon (rivastigmine tartrate) package insert. East Hanover, NJ: Novartis Pharmaceuticals, 2006; Razadyne (galantamine hydrobromide) package insert. Titusville, NJ: Ortho-McNeil Neurologics, 2006; and Exelon (rivastigmine) Patch package insert. East Hanover, NJ: Novartis Pharmaceutical, 2007.

• Rivastigmine has central activity at acetylcholinesterase and butyrylcholinesterase sites, but low activity at these sites in the periphery. • Galantamine is a cholinesterase inhibitor that also has activity as a nicotinic receptor agonist. • Tacrine was the first cholinesterase inhibitor approved for the treatment of AD, but it has been replaced by safer drugs which are better tolerated. Other Drugs • Memantine (Namenda) blocks glutamatergic neurotransmission by antagonizing N-methyl-D-aspartate receptors, which may prevent excitotoxic reactions. It is used as monotherapy, and data suggest that when it is combined with a cholinesterase inhibitor, there is improvement in cognition and activities of daily living. ✓ It is indicated for treatment of moderate to severe AD. ✓ It is not metabolized by the liver, but is primarily excreted unchanged in the urine (half-life of elimination = 60 to 80 hours). ✓ It is usually well tolerated, and side effects include constipation, confusion, dizziness, hallucinations, headache, cough, and hypertension. ✓ It is initiated at 5 mg/day and increased weekly by 5 mg/day to the effective dose of 10 mg twice daily. Dosing must be adjusted in patients with renal impairment. • Recent trials do not support the use of estrogen to prevent or treat cognitive decline. • Evidence related to the role of vitamin E in preventing AD is mixed, and conclusions cannot be drawn at this time. 731

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• Because of a significant incidence of side effects and a lack of compelling evidence, Nonsteroidal antiinflammatory drugs are not recommended for treatment or prevention of AD. • There is interest in the use of lipid-lowering agents, especially the 3hydroxy-3-methylglutaryl coenzyme A–reductase inhibitors, to prevent AD. Pravastatin and lovastatin, but not simvastatin, were associated with a lower prevalence of AD. Further study is needed before these agents can be recommended for this use. • A metaanalysis indicated that EGb 761 (an extract of ginkgo biloba) may have some therapeutic effect at doses of 120 to 240 mg of the standard leaf extract twice daily. Because of limited efficacy data, the potential for adverse effects (e.g., nausea, vomiting, diarrhea, headache, dizziness, weakness, and hemorrhage), and the poor standardization of herbal products, it is recommended that ginkgo biloba be used only with caution. ✓ Ginkgo biloba should not be used in individuals taking anticoagulants or antiplatelet drugs, and should be use cautiously in those taking nonsteroidal antiinflammatory drugs. • Although initial studies suggest potential effectiveness of huperzine A, it has not been adequately evaluated for treatment of AD.

PHARMACOTHERAPY OF NONCOGNITIVE SYMPTOMS • Pharmacotherapy is aimed at treating psychotic symptoms, inappropriate or disruptive behavior, and depression. Medications and recommended doses for noncognitive symptoms are shown in Table 67-5. • General guidelines are as follows: (1) use reduced doses, (2) monitor closely, (3) titrate dosage slowly, (4) document carefully, and (5) periodically attempt to reduce medication in minimally symptomatic patients. • Psychotropic medications with anticholinergic effects should be avoided because they may worsen cognition. Cholinesterase Inhibitors and Memantine • Cholinesterase inhibitors and memantine are first-line therapy in early management of behavioral symptoms. Modest improvement may be achieved. Antipsychotics • Antipsychotic medications have traditionally been used to treat disruptive behaviors and psychosis in AD patients. • A metaanalysis showed that 17% to 18% of dementia patients showed a modest treatment response to atypical antipsychotics. Adverse events included somnolence, extrapyramidal symptoms, abnormal gait, worsening cognition, cerebrovascular events, and increased risk of death. • Typical antipsychotics may also be associated with a small increased risk of death, as well as more severe extrapyramidal effects and hypotension. Antidepressants • Depression and dementia have many symptoms in common, and the diagnosis of depression can be difficult, especially later in the course of AD. 732

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TABLE 67-5

Medications Used for Noncognitive Symptoms of Dementia

Drugs

Starting Dose (mg)

Maintenance Dose in Dementia (mg/day)

0.25 2.5 25 0.25 20

1–3 5–10 100–300 0.75–2 40–160

10 5 5 10 25 25 25

10–20 20–40 10–40 10–40 75–100 75–225 75–150

100 125

200–600 500–1,000

Antipsychotics Haloperidol Olanzapine Quetiapine Risperidone Ziprasidone Antidepressants Citalopram Escitalopram Fluoxetine Paroxetine Sertraline Venlafaxine Trazodone Anticonvulsants Carbamazepine Valproic acid

Target Symptoms Psychosis: hallucinations, delusions, suspiciousness Disruptive behaviors: agitation, aggression

Depression: poor appetite, insomnia, hopelessness, anhedonia, withdrawal, suicidal thoughts, agitation, anxiety

Agitation or aggression

Data from Lleó A, Greenberg SM, Growdon JH. Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med 2006;57:513–533; Benoit M, Arbus C, Blanchard F, et al. Professional consensus on the treatment of agitation, aggressive behavior, oppositional behavior and psychotic disturbances in dementia. J Nutr Health Aging 2006;10:410–415; and Grossberg GT, Desai AK. Management of Alzheimer’s disease. J Gerontol A Biol Sci Med Sci 2003;58A:331–353.

• Treatment with a selective serotonin reuptake inhibitor is usually initiated in depressed patients with AD. Paroxetine causes more anticholinergic side effects than the other selective serotonin reuptake inhibitors. Venlafaxine may also be used. • Although probably equally effective, the tricyclic antidepressants are usually avoided because of anticholinergic side effects. Miscellaneous Therapies • Carbamazepine, mean dose 300 mg/day, may improve psychosis and behavioral disturbance in AD patients. • Oxazepam and other benzodiazepines have been used to treat anxiety, agitation, and aggression, but they generally show inferior efficacy compared with antipsychotics. They can also worsen cognition, cause disinhibition, and increase the risk of falls.

EVALUATION OF THERAPEUTIC OUTCOMES • Baseline assessment should define therapeutic goals and document cognitive status, physical status, functional performance, mood, thought processes, and behavior. Both the patient and caregiver should be interviewed. • Because target symptoms of psychiatric disorders may respond differently in demented patients, a detailed list of symptoms to be treated should be documented to aid in monitoring. 733

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• Objective assessments, such as the MMSE for cognition and the Functional Activities Questionnaire for activities of daily living, should be used to quantify changes in symptoms and functioning. • The patient should be observed carefully for potential side effects of drug therapy. The specific side effects to be monitored and the method and frequency of monitoring should be documented. • Assessments for drug effectiveness, side effects, compliance, need for dosage adjustment, or change in treatment should occur at least monthly. • A treatment period of 6 months to 1 year may be required to determine whether therapy is beneficial.

See Chap. 67, Alzheimer’s Disease, authored by Patricia W. Slattum, Russell H. Swerdlow, and Angela Massey Hill, for a more detailed discussion of this topic.

734

CHAP TER

68

Anxiety Disorders

DEFINITION • Anxiety disorders include a constellation of disorders in which anxiety and associated symptoms are irrational or experienced at a level of severity that impairs functioning. The characteristic features are anxiety and avoidance.

PATHOPHYSIOLOGY • Noradrenergic model. This model suggests that the autonomic nervous system of anxious patients is hypersensitive and overreacts to various stimuli. The locus ceruleus may have a role in regulating anxiety, as it activates norepinephrine release and stimulates the sympathetic and parasympathetic nervous systems. Chronic noradrenergic overactivity down regulates α2-adrenoreceptors in patients with generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD). Patients with social anxiety disorder (SAD) appear to have a hyperresponsive adrenocortical response to psychological stress. • γ-Aminobutyric acid (GABA) receptor model. GABA is the major inhibitory neurotransmitter in the CNS. Many antianxiety drugs target the GABAA receptor. Benzodiazepines (BZs) enhance the inhibitory effects of GABA, which has a strong regulatory or inhibitory effect on serotonin (5-HT), norepinephrine, and dopamine systems. Anxiety symptoms may be linked to underactivity of GABA systems or downregulated central BZ receptors. In patients with GAD, BZ binding in the left temporal lobe is reduced. Abnormal sensitivity to antagonism of the BZ binding site and decreased binding was demonstrated in panic disorder. Growth hormone response to baclofen in patients with generalized SAD suggests an abnormality of central GABAB receptor function. Abnormalities of GABA inhibition may lead to increased response to stress in PTSD patients. • 5-HT model. GAD symptoms may reflect excessive 5-HT transmission or overactivity of the stimulatory 5-HT pathways. Patients with SAD have greater prolactin response to buspirone challenge, indicating an enhanced central serotonergic response. The role of 5-HT in panic disorder is unclear, but it may have a role in development of anticipatory anxiety. Preliminary data suggest that the 5-HT and 5-HT2 antagonist metachlorophenylpiperazine causes increased anxiety in PTSD patients. • Patients with PTSD have a hypersecretion of corticotropin-releasing factor but demonstrate subnormal levels of cortisol at the time of trauma and chronically. Dysregulation of the hypothalamic-pituitary-adrenal axis may be a risk factor for eventual development of PTSD. • Functional neuroimaging studies suggest that frontal and occipital brain areas are integral to the anxiety response. Patients with panic disorder may have abnormal activation of the parahippocampal region and prefrontal cortex at rest. Panic anxiety is associated with activation of brain stem and basal ganglia regions. GAD patients have an abnormal increase in cortical 735

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Psychiatric Disorders

activity and a decrease in basal ganglia activity. In patients with SAD, there may be abnormalities in the amygdala, hippocampus, and various cortical regions. Lower hippocampal volumes in patients with PTSD may be a precursor for subsequent development of PTSD.

CLINICAL PRESENTATION GENERALIZED ANXIETY DISORDER • The clinical presentation of GAD is shown in Table 68-1. The diagnostic criteria require persistent symptoms most days for at least 6 months. The anxiety or worry must be about a number of matters and is accompanied by at least three psychological or physiologic symptoms. The illness has a gradual onset at an average age of 21 years. The course of illness is chronic, with multiple spontaneous exacerbations and remissions. There is a high percentage of relapse and a low rate of recovery.

PANIC DISORDER • Symptoms usually begin as a series of unexpected panic attacks. These are followed by at least 1 month of persistent concern about having another panic attack. • Symptoms of a panic attack are shown in Table 68-2. During an attack, there must be at least four physical symptoms in addition to psychological symptoms. Symptoms reach a peak within 10 minutes and usually last no more than 20 or 30 minutes. • Many patients eventually develop agoraphobia, which is avoidance of specific situations (e.g., crowded places, bridges) where they fear a panic attack might occur. Patients may become homebound.

TABLE 68-1

Presentation of Generalized Anxiety Disorder

Psychological and cognitive symptoms • Excessive anxiety • Worries that are difficult to control • Feeling keyed up or on edge • Poor concentration or mind going blank Physical symptoms • Restlessness • Fatigue • Muscle tension • Sleep disturbance • Irritability Impairment • Social, occupational, or other important functional areas • Poor coping abilities Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000:429–484; and Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Society for Psychopharmacology. J Psychopharmacology 2005;19:567–596.

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Anxiety Disorders TABLE 68-2

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CHAPTER 68

Symptoms of a Panic Attack

Psychological symptoms • Depersonalization • Derealization • Fear of losing control • Fear of going crazy • Fear of dying Physical symptoms • Abdominal distress • Chest pain or discomfort • Chills • Dizziness or lightheadedness • Feeling of choking • Hot flushes • Palpitations • Nausea • Paresthesias • Shortness of breath • Sweating • Tachycardia • Trembling or shaking Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000:429–484; Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Society for Psychopharmacology. J Psychopharmacology 2005;19:567–596; and Katon WJ. Panic disorder. N Engl J Med 2006;354:2360–2367.

SOCIAL ANXIETY DISORDER • The essential feature of SAD is an intense, irrational, and persistent fear of being negatively evaluated in a social or performance situation. Exposure to the feared situation usually provokes a panic attack. Symptoms of SAD are shown in Table 68-3. The fear and avoidance of the situation must interfere with daily routine or social/occupational functioning. It is a chronic disorder with a mean age of onset in the teens. • In the generalized subtype, fear is of many social situations where embarrassment may occur. In the discrete or specific subtype, fear is limited to one or two situations (e.g., performing, public speaking).

POSTTRAUMATIC STRESS DISORDER • In PTSD, exposure to a traumatic event causes immediate intense fear, helplessness, or horror. • The clinical presentation of PTSD is shown in Table 68-4. Patients must have at least one reexperiencing symptom, three signs or symptoms of persistent avoidance of stimuli, and at least two symptoms of increased arousal. Symptoms from each category must be present longer than 1 month and cause significant distress or impairment. PTSD can occur at any age, and the course is variable. • One-third of patients with PTSD have a poor prognosis, and about 80% have a concurrent depression or anxiety disorder. Over half of men with 737

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TABLE 68-3

Psychiatric Disorders Presentation of Social Anxiety Disorder

Fears • Being scrutinized by others • Being embarrassed • Being humiliated Some feared situations • Addressing a group of people • Eating or writing in front of others • Interacting with authority figures • Speaking in public • Talking with strangers • Use of public toilets Physical symptoms • Blushing • “Butterflies in the stomach” • Diarrhea • Sweating • Tachycardia • Trembling Types • Generalized type: fear and avoidance extend to a wide range of social situations • Nongeneralized type: fear is limited to one or two situations Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000:429–484; Schneier FR. Social anxiety disorder. N Engl J Med 2006;355:1029–1036; and Ballenger JC, Davidson JRT, Lecrubier Y, et al. Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 1998;59(Suppl 17):54–60.

PTSD have comorbid alcohol abuse or dependence, and about 20% of patients attempt suicide.

DIAGNOSIS • Evaluation of the anxious patient requires a complete physical and mental status examination; appropriate laboratory tests; and a medical, psychiatric, and drug history. • Anxiety symptoms may be associated with medical illnesses (Table 68-5) or drug therapy (Table 68-6). About 50% of patients with GAD have irritable bowel syndrome. • Anxiety symptoms may be present in several major psychiatric illnesses (e.g., mood disorders, schizophrenia, organic mental syndromes, and substance withdrawal).

DESIRED OUTCOME • The desired outcomes of treatment of GAD are to reduce severity, duration, and frequency of the symptoms and to improve overall functioning. The long-term goal is minimal or no anxiety or depressive symptoms, no functional impairment, and improved quality of life. • The goals of therapy of panic disorder include a complete resolution of panic attacks, marked reduction in anticipatory anxiety and phobic fears, 738

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Presentation of Posttraumatic Stress Disorder

Reexperiencing symptoms • Recurrent, intrusive distressing memories of the trauma • Recurrent, disturbing dreams of the event • Feeling that the traumatic event is recurring (e.g., dissociative flashbacks) • Physiologic reaction to reminders of the trauma Avoidance symptoms • Avoidance of conversations about the trauma • Avoidance of thoughts or feelings about the trauma • Avoidance of activities that are reminders of the event • Avoidance of people or places that arouse recollections of the trauma • Inability to recall an important aspect of the trauma • Anhedonia • Estrangement from others • Restricted affect • Sense of a foreshortened future (e.g., does not expect to have a career, marriage) Hyperarousal symptoms • Decreased concentration • Easily startled • Hypervigilance • Insomnia • Irritability or angry outbursts Subtypes • Acute: duration of symptoms is less than 3 months • Chronic: symptoms last for longer than 3 months • With delayed onset: onset of symptoms is at least 6 months posttrauma Screening questions • Have you ever experienced a significant trauma in your life? • Did this experience have a lasting negative impact or change your life? Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC: American Psychiatric Association, 2000:429–484; and Ballenger JC, Davidson JRT, Lecrubier Y, et al. Consensus statement update on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 2004;65(Suppl 1):55–62.

TABLE 68-5

Common Medical Illnesses Associated with Anxiety Symptoms

Cardiovascular Angina, arrhythmias, congestive heart failure, ischemic heart disease, myocardial infarction Endocrine and metabolic Cushing’s disease, hyperparathyroidism, hyperthyroidism, hypothyroidism, hypoglycemia, hyponatremia, hyperkalemia, pheochromocytoma, vitamin B12 or folate deficiencies Neurologic Dementia, migraine, Parkinson’s disease, seizures, stroke, neoplasms, poor pain control Respiratory system Asthma, chronic obstructive pulmonary disease, pulmonary embolism, pneumonia Others Anemias, systemic lupus erythematosus, vestibular dysfunction Data from Roy-Byrne PR, Wagner A. Primary care perspectives on generalized anxiety disorder. J Clin Psychiatry 2004;(65 Suppl 13):20–26; and Chen J, Reich L, Chung H. Anxiety disorders. West J Med 2002;176:249–253.

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TABLE 68-6

Psychiatric Disorders Drugs Associated with Anxiety Symptoms

Anticonvulsants: carbamazepine Antidepressants: selective serotonin reuptake inhibitors, tricyclic antidepressants Antihypertensives: felodipine Antibiotics: quinolones, isoniazid Bronchodilators: albuterol, theophylline Corticosteroids: prednisone Dopa agonists: levodopa Herbals: ma huang, ginseng, ephedra Nonsteroidal antiinflammatory drugs: ibuprofen Stimulants: amphetamines, methylphenidate, caffeine, cocaine Sympathomimetics: pseudoephedrine Thyroid hormones: levothyroxine Toxicity: anticholinergics, antihistamines, digoxin Withdrawal: alcohol, sedatives Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000:429–484; and Chen J, Reich L, Chung H. Anxiety disorders. West J Med 2002;176:249–253.

elimination of phobic avoidance, and resumption of normal activities. After treatment, 40% to 50% of patients continue to have occasional panic attacks and phobic avoidance. • The goals of treatment of SAD are to reduce the physiologic symptoms and phobic avoidance, increase participation in desired social activities, and improve quality of life. • The goals of therapy of PTSD are to decrease core symptoms, disability, and comorbidity and improve quality of life and resilience to stress.

TREATMENT GENERALIZED ANXIETY DISORDER • For patients with GAD, nonpharmacologic modalities include short-term counseling, stress management, cognitive therapy, meditation, supportive therapy, and exercise. GAD patients should be educated to avoid caffeine, stimulants, excessive alcohol, and diet pills. Cognitive behavioral therapy (CBT) is the most effective psychological therapy for GAD patients, and most patients with GAD should have psychological therapy, alone or in combination with antianxiety drugs. • An algorithm for the pharmacologic management of GAD is shown in Fig. 68-1. • Drug choices for anxiety disorders are shown in Table 68-7, and non-BZ antianxiety agents for GAD are shown in Table 68-8. • Kava kava is not recommended as an anxiolytic because of reports of lack of efficacy and hepatotoxicity. • Hydroxyzine was effective in 88% of patients for a duration of 3 months. • Pregabalin produced anxiolytic effects similar to lorazepam, alprazolam, and venlafaxine in acute trials. Sedation and dizziness were the most common adverse effects, and the dose should be tapered over 1 week upon discontinuation. 740

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GAD BZ for 2–4 weeks (A) Adequate Response?

Yes

Acute relief needed

No Venlafaxine (A) or SSRI (A)

Yes

Adequate Response? No Switch to venlafaxine (A) or an SSRI (A)

Continue therapy 6–12 months

Yes

Adequate Response? No Switch to another anxiolytic 1. SSRI (A) 2. imipramine (A) 3. buspirone (A) 4. hydroxyzine (A) 5. pregabalin (A) 6. duloxetine (B)

Yes

Adequate Response? No Add a BZ for somatic symptoms for 2–4 weeks (D)

FIGURE 68-1. Algorithm for the pharmacotherapy of generalized anxiety disorder (GAD). Strength of recommendations: A = directly based on category I evidence (i.e., metaanalysis of randomized clinical trials [RCT] or at least one RCT); B = directly based on category II evidence (i.e., at least one controlled study without randomization or one other type of quasi-experimental study); D = directly based on category IV evidence (i.e., expert committee reports or opinions and/or clinical experience of respected authorities). (BZ, benzodiazepine; SSRI, selective serotonin reuptake inhibitor.) (Data from Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Society for Psychopharmacology. J Psychopharmacology 2005;19:567–596; and National Institute for Clinical Excellence. The Management of Panic Disorder and Generalized Anxiety Disorder in Primary Care and Secondary Care: Clinical Guideline 22. London: National Collaborating Centre for Mental Health, December 2004.)

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TABLE 68-7

Psychiatric Disorders Drug Choices for Anxiety Disorders

Anxiety Disorder

First-Line Drugs

Second-Line Drugs

Alternatives

Generalized anxiety

Duloxetine Escitalopram Paroxetine Venlafaxine XR SSRIs Venlafaxine XR

Benzodiazepines Buspirone Imipramine Sertraline Alprazolam Clomipramine Clonazepam Imipramine Citalopram Clonazepam

Hydroxyzine Pregabalin

Panic disorder

Social anxiety disorder

Escitalopram Fluvoxamine Paroxetine Sertraline Venlafaxine XR

Phenelzine

Buspirone Gabapentin Mirtazapine Phenelzine Pregabalin

SSRI, selective serotonin reuptake inhibitor; XR, extended-release. Data from Schneier FR. N Engl J Med 2006;355:1029–1036; Baldwin DS, Anderson IM, Nutt DJ, et al. J Psychopharmacology 2005;19:567–596; Ballenger JC, Davidson JRT, Lecrubier Y, et al. J Clin Psychiatry 1998;59(Suppl 17):54–60; Bandelow B, Zohar J, Hollander E, et al. World J Biol Psychiatry 2002;3:171–199; and Work Group on Panic Disorder. Am J Psychiatry 1998;155(Suppl 5):1–34.

• The FDA has established a link between antidepressant use and suicidality (suicidal thinking and behaviors) in children, adolescents, and young adults 18 to 24 years old. All antidepressants carry a black box warning advising caution in the use of all antidepressants in this population, and the FDA also recommends specific monitoring parameters. The clinician TABLE 68-8 Generic Name Antidepressants Duloxetine Escitalopramb Imipraminec Paroxetineb,c Venlafaxineb Azapirones Buspirone b,c Diphenylmethane Hydroxyzine b,c,e Anticonvulsant Pregabalin

Nonbenzodiazepine Antianxiety Agents for Generalized Anxiety Disorder Trade Name

Starting Dose

Dosage Range (mg/day)a

Cymbalta Lexapro Tofranil Paxil Effexor XR

30 or 60 mg per day 10 mg per day 50 mg per day 20 mg per day 37.5 or 75 mg per day

60–120 10–20 75–200 20–50 75–225d

BuSpar

7.5 mg twice per day

15–60d

Vistaril, Atarax

25 or 50 mg four times daily

200–400

Lyrica

50 mg three times daily

150–600

XR, extended-release. aElderly patients are usually treated with approximately one-half of the dose listed. bFDA approved for generalized anxiety disorder. cAvailable generically. dNo dosage adjustment is required in elderly patients. eFDA approved for anxiety and tension in children in divided daily doses of 50–100 mg. Data from Bandelow B, Zohar J, Hollander E, et al. World J Biol Psychiatry 2002;3:171–199; Duloxetine [package insert]. Indianapolis, IN: Eli Lily and Company, May 2007; Lexapro [package insert]. St. Louis, MO: Forest Pharmaceuticals, Inc., September 2006; Paxil [package insert]. Research Triangle Park, NC: GlaxoSmithKline, July 2006; Effexor XR [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc., August 2006; Vistaril [package insert]. New York: Pfizer Labs, April 2004; and Kavoussi R. Eur Neuropsychopharmacol 2006;16:S128–S133.

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should consult the FDA-approved labeling or the FDA website for additional information (see Chap. 70). Antidepressants • Antidepressants are efficacious for acute and long-term management of GAD. They are considered the treatment of choice for long-term management of chronic anxiety, especially in the presence of depressive symptoms. Antianxiety response requires 2 to 4 weeks. • Venlafaxine extended release, duloxetine, paroxetine, and escitalopram are FDA approved for treatment of GAD. Sertraline is also effective. Acute response and remission rates are approximately 65% and 30%, respectively. Imipramine may be used when patients fail to respond to selective serotonin reuptake inhibitors (SSRIs). In one trial, diazepam, trazodone, and imipramine had greater anxiolytic activity than placebo. • Common side effects of the SSRIs are somnolence, nausea, ejaculation disorders, decreased libido, dry mouth, insomnia, and fatigue. Tricyclic antidepressants (TCAs) commonly cause sedation, orthostatic hypotension, anticholinergic effects, and weight gain. TCAs are very toxic on overdose. Evaluation of Therapeutic Outcomes • Initially, anxious patients should be monitored once to twice weekly for reduction in anxiety symptoms, improvement in functioning, and side effects. The Visual Analog Scale may assist in the evaluation of drug response. Benzodiazepine Therapy • The BZs are the most frequently prescribed drugs for the treatment of acute anxiety (Table 68-9). All BZs are equally effective anxiolytics, and most of the improvement occurs in the first 2 weeks of therapy. They are considered to be more effective for somatic and autonomic symptoms of GAD, while antidepressants are considered more effective for the psychic symptoms (e.g., apprehension and worry). TABLE 68-9

Benzodiazepine Antianxiety Agents

Generic Name

Brand Name

Alprazolamb

Niravam,c Xanax, Xanax XR Librium Klonopin Klonopin Wafersc Tranxene Valium Ativan Serax

Chlordiazepoxideb Clonazepamb Clorazepateb Diazepamb Lorazepamb Oxazepamb

Approved Dosage Range (mg/day)a

Approximate Equivalent Dose (mg)

0.75–4 1–10d 25–100 1–4d

0.5

7.5–60 2–40 0.5–10 30–120

7.5 5 1 15

10 0.25

XR, extended-release. aElderly patients are usually treated with approximately one-half of the dose listed. bAvailable generically. cOrally disintegrating formulation. dPanic disorder dose. Equivalent doses from Chouinard G. Issues in the clinical use of benzodiazepines: Potency, withdrawal and rebound. J Clin Psychiatry 2004;65(Suppl 5):7–12.

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• It is theorized that BZs ameliorate anxiety through potentiation of GABA activity. • The dose must be individualized. Some patients require longer treatment. • The elderly have an enhanced sensitivity to BZs and may experience falls when on BZ therapy. Pharmacokinetics • BZ pharmacokinetic properties are shown in Table 68-10. • Diazepam and clorazepate have high lipophilicity and are rapidly absorbed and distributed into the CNS. They have a shorter duration of effect after a single dose than would be predicted on the basis of half-life, as they are rapidly distributed to the periphery. • Lorazepam and oxazepam are less lipophilic and have a slower onset but a longer duration of action. They are not recommended for immediate relief of anxiety. • IM diazepam and chlordiazepoxide should be avoided because of variability in rate and extent of absorption. IM lorazepam provides rapid and complete absorption. • Clorazepate, a prodrug, is converted to desmethyldiazepam in the stomach through a pH-dependent process that may be impaired by concurrent antacid use. Several other BZs are also converted to desmethyldiazepam, which has a long half-life and can accumulate, especially in the elderly and those with impaired oxidation. • Intermediate- or short-acting BZs are preferred for chronic use in the elderly and those with liver disorders because of minimal accumulation and achievement of steady state within 1 to 3 days. Adverse Events • The most common side effect of BZs is CNS depression. Tolerance usually develops to this effect. Other side effects are disorientation, psychomotor impairment, confusion, aggression, excitement, and anterograde amnesia. TABLE 68-10 Pharmacokinetics of Benzodiazepine Antianxiety Agents

Generic Name

Time to Peak Plasma Level (hours)

Elimination Half-Life, Parent (hours)

Metabolic Pathway

Alprazolam Chlordiazepoxide

1–2 1–4

12–15 5–30

Oxidation N-Dealkylation Oxidation

Clonazepam Clorazepate Diazepam

1–4 1–2 0.5–2

30–40 Prodrug 20–80

Nitroreduction Oxidation Oxidation

Lorazepam Oxazepam

2–4 2–4

10–20 5–20

Conjugation Conjugation

a

Clinically Significant Metabolites

Protein Binding (%)

— Desmethylchlordiazepoxide Demoxepam DMDZa — DMDZ DMDZ Oxazepam — —

80 96 — — 85 97 98 85 97

Desmethyldiazepam (DMDZ) half-life 50–100 hours. Data from Bailey L, Ward M, Musa M. Clinical pharmacokinetics of benzodiazepines. J Clin Pharmacol 1994;34:804–811; and Benzodiazepines. Facts and Comparisons 4.0 Online. Wolters Kluwer Health, Inc. 2005, http://online.factsandcomparisons.com.

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Abuse, Dependence, Withdrawal, and Tolerance • Those with a history of drug abuse are at the greatest risk for becoming BZ abusers. • BZ dependence is defined by the appearance of a predictable withdrawal syndrome (i.e., anxiety, insomnia, agitation, muscle tension, irritability, nausea, malaise, diaphoresis, nightmares, depression, hyperreflexia, tinnitus, delusions, hallucinations, and seizures) upon abrupt discontinuation. Benzodiazepine Discontinuation • After BZs are abruptly discontinued, three events can occur: ✓ Rebound symptoms are an immediate, but transient, return of original symptoms with an increased intensity compared with baseline. ✓ Recurrence or relapse is the return of original symptoms at the same intensity as before treatment. ✓ Withdrawal is the emergence of new symptoms and a worsening of preexisting symptoms. • The onset of withdrawal symptoms is within 24 to 48 hours after discontinuation of short elimination half-life BZs and 3 to 8 days after discontinuation of long elimination half-life drugs. • Discontinuation strategies include the following: ✓ A 25% per week reduction in dosage until 50% of the dose is reached, then dosage reduction by one-eighth every 4 to 7 days. If therapy exceeds 8 weeks, a taper over 2 to 3 weeks is recommended, but if duration of treatment is 6 months, a taper over 4 to 8 weeks should ensue. Longer durations of treatment may require a 2- to 4-month taper. ✓ A BZ with a long elimination half-life (t1/2) (e.g., diazepam, clonazepam) may be substituted for a drug with a short t1/2 (e.g., lorazepam, oxazepam, alprazolam). The substituted drug should be given for several weeks before gradual tapering begins. ✓ Adjunctive use of imipramine, valproic acid, or buspirone can help to reduce withdrawal symptoms during the BZ taper. Drug Interactions • Drug interactions with the BZs are generally pharmacodynamic or pharmacokinetic (Table 68-11). The combination of BZs with alcohol or other CNS depressants may be fatal. • Alprazolam dose should be reduced by 50% if nefazodone (Serzone) or fluvoxamine is added. Dosing and Administration • Initial doses should be low, and dosage adjustments can be made weekly (see Table 68-9). • Treatment of acute anxiety generally should not exceed 4 weeks. BZs can be given as needed, and if several acute courses are necessary, a BZ-free period of 2 to 4 weeks should be implemented between courses. Persistent symptoms should be managed with antidepressants. • BZs with a long t1/2 may be dosed once daily at bedtime and may provide nighttime hypnotic and anxiolytic effects the next day. 745

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TABLE 68-11 Pharmacokinetic Drug Interactions with the Benzodiazepines Drug

Effect

Carbamazepine Ciprofloxacin Erythromycin Fluoxetine Fluvoxamine Isoniazid Ketoconazole Nefazodone Omeprazole Oral contraceptives

Decreased Cl of alprazolam Decreased Cl of diazepam and increased t1/2 Decreased Cl of alprazolam Decreased Cl of diazepam Decreased Cl of alprazolam and diazepam and prolonged t1/2 Decreased Cl of diazepam and increased t1/2 Decreased Cl and Vd of chlordiazepoxide; increased AUC of alprazolam Decreased Cl of alprazolam, AUC doubled, and t1/2 prolonged Decreased Cl of diazepam and prolonged t1/2 Decreased Cl and increased t1/2 of diazepam and chlordiazepoxide; decreased t1/2 of lorazepam and oxazepam Decreased Cl of alprazolam Increased Cl of clonazepam and reduced t1/2 Decreased Cl of alprazolam and prolonged t1/2 Decreased Cl of diazepam and prolonged t1/2 Increased metabolism of diazepam Decreased AUC of alprazolam Decreased Cl of lorazepam

Paroxetine Phenytoin Propoxyphene Propranolol Rifampin St. John’s wort Valproate

AUC, area under the plasma concentration curve; BZ, benzodiazepine; Cl, clearance; t1/2, elimination half-life; Vd, volume of distribution. Data from Benzodiazepines. Facts and Comparisons 4.0 Online. Wolters Kluwer Health, Inc. 2005, http://online.factsandcomparisons.com; and Madabushi R, Frank B, Drewelow B, et al. Hyperforin in St. John’s wort drug interactions. Eur J Clin Pharmacol 2006;62:225–233.

• In the elderly, doses should be low, and short-elimination half-life agents prescribed. Buspirone Therapy • Buspirone is a 5-HT1A partial agonist that lacks anticonvulsant, muscle relaxant, sedative-hypnotic, motor impairment, and dependence-producing properties. • It is considered a second-line agent for GAD because of inconsistent reports of efficacy, delayed onset of effect, and lack of efficacy for comorbid depressive and anxiety disorders (e.g., panic disorder or SAD). It is the agent of choice in patients who fail other anxiolytic therapies or in patients with a history of alcohol or substance abuse. It is not useful for situations requiring rapid antianxiety effects or as-needed therapy. • It has a mean t1/2 of 2.5 hours, and it is dosed two to three times daily. • Side effects include dizziness, nausea, and headaches. Drug Interactions • Buspirone may increase haloperidol levels and elevate blood pressure in patients taking a monoamine oxidase inhibitor (MAOI). • Verapamil, itraconazole, and fluvoxamine can increase buspirone levels, and rifampin reduces buspirone blood levels by 10-fold. Dosing and Administration • Buspirone doses can be titrated in increments of 5 mg/day every 2 or 3 days as needed. 746

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TABLE 68-12 Drugs Used in the Treatment of Panic Disorder Class/Generic Name Selective serotonin reuptake inhibitors Citalopramb Escitalopram Fluoxetineb Fluvoxamineb Paroxetineb Sertralineb Serotonin norepinephrine reuptake inhibitors Venlafaxine XR Benzodiazepines Alprazolamb Clonazepamb Diazepamb Lorazepamb Tricyclic antidepressant Imipramineb Monoamine oxidase inhibitor Phenelzine

Brand Name

Starting Dose

Antipanic Dosagea Range (mg)

Celexa Lexapro Prozac Luvox Paxil Paxil CR Zoloft

10 mg per day 5 mg per day 5 mg per day 25 mg per day 10 mg per day 12.5 mg per day 25 mg per day

20–60 10–20 10–30 100–300 20–60c 25–75c 50–200c

Effexor XR

37.5 mg per day

75–225c

Xanax Xanax XR Klonopin Valium Ativan

0.25 mg three times a day 0.5–1 mg per day 0.25 mg once or twice per day 2–5 mg three times a day 0.5–1 mg three times a day

4–10c 1–10c 1–4c 5–20 2–8

Tofranil

10 mg per day

75–250

Nardil

15 mg per day

45–90

CR, controlled-release; XR, extended-release. aDosage used in clinical trials but not FDA approved. bAvailable generically. cDosage is FDA approved. Data from Katon WJ. Panic disorder. N Engl J Med 2006;354:2360–2367; Bandelow B, Zohar J, Hollander E, et al. Guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. World J Biol Psychiatry 2002;3:171– 199; Work Group on Panic Disorder. Practice guideline for the treatment of patients with panic disorder. Am J Psychiatry 1998;155(Suppl 5):1–34; and Effexor XR [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc., August 2006.

• The onset of anxiolytic effects requires 2 weeks or more; maximum benefit may require 4 to 6 weeks. • When switching from a BZ to buspirone, the BZ should be tapered slowly.

PANIC DISORDER General Therapeutic Principles • Antipanic drugs are shown in Table 68-12. An algorithm for drug therapy of panic disorder is shown in Fig. 68-2. • A metaanalysis showed that SSRIs, TCAs, and CBT are similarly effective. Alprazolam, clonazepam, sertraline, paroxetine, and venlafaxine are FDA approved for this indication. • SSRIs are first-line agents, but BZs are the most commonly used drugs for panic disorder. • Most patients without agoraphobia improve with pharmacotherapy alone, but if agoraphobia is present, CBT typically is initiated concurrently. • Patients treated with CBT are less likely to relapse than those treated with imipramine alone. For patients who cannot or will not take medications, 747

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BZ (A)

Yes

Adequate Response?

Severe urgency? No

SSRI (A) or venlafaxine (A) Yes

Adequate Response? No

Switch to another SSRI or venlafaxine (C) Continue therapy for 6 months (A)

Yes

Adequate Response? No Switch to another antidepressant (C) 1. another SSRI 2. venlafaxine 3. imipramine

Yes

Adequate Response? No Add BZ or pindolol to antidepressant (D)

Yes

Adequate Response?

FIGURE 68-2. Algorithm for the pharmacotherapy of panic disorder. Strength of recommendations: A = directly based on category I evidence (i.e., metaanalysis of randomized clinical trials [RCT] or at least one RCT); B = directly based on category II evidence (i.e., at least one controlled study without randomization or one other type of quasi-experimental study); C = directly based on category III evidence (i.e., nonexperimental descriptive studies); D = directly based on category IV evidence (i.e., expert committee reports or opinions and/or clinical experience of respected authorities). (BZ, benzodiazepine; SSRI, selective serotonin reuptake inhibitor.) (Data from Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Society for Psychopharmacology. J Psychopharmacology 2005;19:567–596; and National Institute for Clinical Excellence. The Management of Panic Disorder and Generalized Anxiety Disorder in Primary Care and Secondary Care: Clinical Guideline 22. London: National Collaborating Centre for Mental Health, December 2004.)

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CBT alone is indicated, as it is associated with improvement in 80% to 90% of patients short-term and 75% of patients at 6-month follow-up. • Patients must be educated to avoid caffeine, drugs of abuse, and stimulants. • Antidepressants, especially the SSRIs, are preferred in elderly patients and youth. The BZs are second line in these patients because of potential problems with disinhibition. Antidepressants • Stimulatory side effects (e.g., anxiety, insomnia, jitteriness, irritability) can occur in TCA- and SSRI-treated patients. This may affect compliance and hinder dose increases. Low initial doses and gradual dose titration may eliminate these effects (see Table 68-12). • Imipramine blocks panic attacks within 4 weeks, but maximal improvement, including reduced anticipatory anxiety and antiphobic response, requires 8 to 12 weeks. • About 25% of panic patients discontinue TCAs because of side effects. • All SSRIs eliminate panic attacks in 60% to 80% of patients. The antipanic effect requires 4 weeks, and some patients do not respond until 8 to 12 weeks. • Low initial doses of SSRIs and gradual titration to the antipanic dose are required to avoid stimulatory side effects. • MAOIs are reserved for the most difficult or refractory panic disorder patients. Side effects and dietary and drug restrictions affect patient acceptance (see Chap. 70 for food and drug restrictions). Fluoxetine must be stopped 5 weeks before phenelzine (or another MAOI) is started. Other antidepressants should be stopped 2 weeks before phenelzine is started. • Approximately 54% to 60% of patients became panic-free on venlafaxineextended release 75 mg or 150 mg. Benzodiazepines • BZs are second-line agents except when rapid response is essential. They should not be used as monotherapy in panic disorder patients with a history of depression or alcohol or drug abuse. BZs are often used concomitantly with antidepressants in the first weeks to offset the delay in onset of antipanic effects. • About 60% to 80% of panic patients respond to BZs, but relapse rates of 50% or higher are common despite slow drug tapering. • Alprazolam and clonazepam are the most frequently used of the BZs and are well accepted by patients. Therapeutic response typically occurs in 1 to 2 weeks. With alprazolam, the duration of action may be as little as 4 to 6 hours with breakthrough symptoms between dosing. The use of extendedrelease alprazolam or clonazepam avoids this problem. Dosing and Administration • The starting dose of clonazepam is 0.25 mg twice daily, with a dose increase to 1 mg by the third day. Increases by 0.25 to 0.5 mg every 3 days to 4 mg/day can be made if needed. • The starting dose of alprazolam is 0.25 to 0.5 mg three times daily (or 0.5 mg once daily of alprazolam extended release), slowly increasing over several weeks to an ideal dose. Most patients require 3 to 6 mg/day. 749

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• Usually patients are treated for 12 to 24 months before discontinuation (over 4 to 6 months) is attempted. Many patients require long-term therapy. Successful maintenance with single weekly doses of fluoxetine has been described. Evaluation of Therapeutic Outcomes • Patients with panic disorder should be seen every 2 weeks during the first few weeks to adjust medication doses based on symptom improvement and to monitor side effects. Once stabilized, they can be seen every 2 months. The Hamilton Rating Scale for Anxiety (score less than or equal to 7 to 10) can be used to measure anxiety, and the Sheehan Disability Scale (with a goal of less than or equal to 1 on each item) can be used to measure for disability. During drug discontinuation, the frequency of appointments should be increased.

SOCIAL ANXIETY DISORDER • SAD patients often respond more slowly and less completely than patients with other anxiety disorders. • After improvement, at least 1 year of maintenance treatment is recommended to maintain improvement and decrease the rate of relapse. Longterm treatment may be needed for patients with unresolved symptoms, comorbidity, an early onset of disease, or a prior history of relapse. • CBT (exposure therapy, cognitive restructuring, relaxation training, and social skills training) and pharmacotherapy are considered equally effective in SAD, but CBT can lead to a greater likelihood of maintaining response after treatment termination. Even after response, most patients continue to experience more than minimal residual symptoms. • CBT and social skills training are effective in children with SAD. Evidence supports the efficacy of SSRIs and serotonin norepinephrine reuptake inhibitors in children 6 to 17 years of age. Individuals up to 24 years of age should be closely monitored for increased risk of suicidality. • Drugs used in treatment of SAD are shown in Table 68-13, and an algorithm for treatment of SAD is shown in Fig. 68-3. • Response rates of SSRIs in SAD ranged from 50% to 80% after 8 to 12 weeks of treatment. Paroxetine, sertraline, and venlafaxine extended release are approved for treatment of generalized SAD and are first-line agents. • With SSRI treatment, the onset of effect is delayed 4 to 8 weeks, and maximum benefit is often not observed until 12 weeks or longer. • The TCAs are not effective for SAD. • Limited data suggest that citalopram is also effective for SAD, but that fluoxetine is not effective. • SSRIs are initiated at doses similar to those used for depression (see Table 68-13). If there is comorbid panic disorder, the SSRI dose should be started at one-fourth to one-half the usual starting dose of antidepressants. The dose should be tapered slowly during discontinuation to decrease the risk of relapse. • Some patients unresponsive to SSRIs have improved with venlafaxine extended release. Response has been reported by week 3. 750

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TABLE 68-13 Drugs Used in the Treatment of Generalized Social Anxiety Disorder Class/Generic Name Selective serotonin reuptake inhibitors Citalopramb Escitalopram Fluvoxamineb Paroxetineb Paroxetine CR Sertralineb Serotonin-norepinephrine reuptake inhibitor Venlafaxine XR Benzodiazepine Clonazepamb,d Monoamine oxidase inhibitor Phenelzine Alternate agents Buspironeb,d Gabapentinb Mirtazapinea,b Pregabalin

Brand Name

Starting Dose

Dosage Rangea (mg/day)

Celexa Lexapro Luvox Paxil Paxil CR Zoloft

20 mg per day 5 mg per day 50 mg per day 10 mg per day 12.5 mg per day 25–50 mg per day

20–40 10–20 150–300 10–60c 12.5–37.5c 50–200c

Effexor XR

75 mg per day

75–225c

Klonopin

0.25 mg per day

1–4

Nardil

15 mg at bedtime

60–90

BuSpar Neurontin Remeron Lyrica

10 mg twice per day 100 mg three times a day 15 mg at bedtime 100 mg three times a day

45–60 900–3,600 30 600

CR, controlled-release; XR, extended-release. a Dosage used in clinical trials but not FDA approved. b Available generically. c Dosage is FDA approved. d Used as augmenting agent. Data from Schneier FR. N Engl J Med 2006;355:1029–1036; Ballenger JC, Davidson JRT, Lecrubier Y, et al. J Clin Psychiatry 1998;59(Suppl 17):54–60; Paxil [package insert]. Research Triangle Park, NC: GlaxoSmithKline, July 2006; Effexor XR [package insert]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc., August 2006; and Blanco C, Muhammad SR, Schneier FR, et al. Int J Neuropsychopharmacol 2003;6:427–442.

• BZs should be reserved for patients at low risk of substance abuse, those who require rapid relief, or those who have not responded to other therapies. • Clonazepam is the most extensively studied BZ for treatment of generalized SAD. It improved fear and phobic avoidance, interpersonal sensitivity, fears of negative evaluation, and disability measures. Adverse effects include sexual dysfunction, unsteadiness, dizziness, and poor concentration. Clonazepam should be tapered at a rate not to exceed 0.25 mg every 2 weeks. • Gabapentin was effective for SAD, and onset of effect was 2 to 4 weeks. • β-Blockers blunt the peripheral autonomic symptoms of arousal (e.g., rapid heart rate, sweating, blushing, and tremor) and are often used to decrease anxiety in performance-related situations. For specific SAD, 10 to 80 mg of propranolol or 25 to 100 mg of atenolol can be taken 1 hour before the performance. A test dose should be taken at home on a day before the performance to be sure adverse effects will not be problematic. • Incomplete response to a first-line agent may benefit from augmentation with buspirone or clonazepam. 751

Generalized Social Anxiety Disorder

SSRI or venlafaxine XR (A) for 12 weeks (A)

Response: continue for 12 months (A)

No response: switch to another SSRI or venlafaxine XR (C)

Partial response: consider augmentation with buspirone (C) or clonazepam (D)

Inadequate response: switch to phenelzine (A)

Nonresponse: consider gabapentin or pregabalin (A)

Response: continue for 12 months (A)

FIGURE 68-3. Algorithm for the pharmacotherapy of generalized social anxiety disorder. Strength of recommendations: A = directly based on category I evidence (i.e., metaanalysis of randomized clinical trials [RCT] or at least one RCT); B = directly based on category II evidence (i.e., at least one controlled study without randomization or one other type of quasi-experimental study); C = directly based on category III evidence (i.e., nonexperimental descriptive studies); D = directly based on category IV evidence (i.e., expert committee reports or opinions and/or clinical experience of respected authorities). (SSRI, selective serotonin reuptake inhibitor; XR, extendedrelease.) (Data from Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Society for Psychopharmacology. J Psychopharmacology 2005;19:567–596.)

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• Phenelzine, an MAOI, is effective, but is reserved for treatment-resistant patients because of dietary restrictions, potential drug interactions, and adverse effects. • Patients with SAD should be monitored for symptom response, adverse effects, and overall functionality and quality of life. Patients should be seen weekly during dosage titration and monthly once stabilized. Patients should be asked to keep a diary to record symptoms and their severity. The clinicianrelated Liebowitz Social Anxiety Scale and the patient-rated Social Phobia Inventory can be used to monitor severity of symptoms and symptom change.

POSTTRAUMATIC STRESS DISORDER • Immediately after the trauma, patients should receive treatment individualized to their presenting symptoms (e.g., non-BZ hypnotic, short courses of CBT). Brief courses of CBT in close proximity to the trauma resulted in lower rates of PTSD. • If symptoms (e.g., hyperarousal, avoidance, dissociation, insomnia, depression) persist for 3 to 4 weeks and there is social or occupational impairment, patients should receive pharmacotherapy or psychotherapy, or both. • Psychotherapies for PTSD include anxiety management (e.g., stress-inoculation training, relaxation training, biofeedback, distraction techniques), CBT, group therapy, hypnosis, psychodynamic therapies, and psychoeducation. Psychotherapy may be used in patients with mild symptoms, those who prefer not to use medications, or in conjunction with drugs in those with severe symptoms to improve response. • Table 68-14 shows antidepressants used in the treatment of PTSD, and Fig. 68-4 shows an algorithm for the pharmacotherapy of PTSD. TABLE 68-14 Antidepressants Used in the Treatment of Posttraumatic Stress Disorder Class/Generic Name Selective serotonin reuptake inhibitors Citalopramc Escitalopram Fluoxetinec Fluvoxaminec Paroxetinec Sertralinec Other agents Amitriptylinec Imipraminec Mirtazapinec Phenelzine Venlafaxine extended-release

Starting Dose

Dosage Rangea (mg/day)

20 mg per day 10 mg per day 10–20 mg per day 50 mg per day 10–20 mg per day 25–50 mg per day

20–60 10–20 10–80 100–250 20–50b 50–200b

25–50 mg per day 25–50 mg per day 15 mg at bedtime 15 mg every night 37.5 mg per day

50–300 50–300 15–45 15–90 37.5–225

a

Dosage used in clinical trials but not FDA approved. is FDA approved. generically. Data from Ballenger JC, Davidson JRT, Lecrubier Y, et al. J Clin Psychiatry 2004;65(Suppl 1):55–62; Baldwin DS, Anderson IM, Nutt DJ, et al. J Psychopharmacol 2005;19:567–596; Bandelow B, Zohar J, Hollander E, et al. World J Biol Psychiatry 2002;3:171–199; Paxil [package insert]. Research Triangle Park, NC: GlaxoSmithKline, July 2006; Zoloft [package insert]. New York: Pfizer, September 2006; and Schoenfeld FB, Marmar CR, Neylan TC. Psychiatr Serv 2004;55:519–531.

bDoasge

cAvailable

753

SECTION 13

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Psychiatric Disorders

PTSD

SSRI (A)

No response: change to another SSRI or venlafaxine extended-release (A)

No response: change to TCA or mirtazapine (A)

Response: continue for 12 months (D)

Response: continue for 12 months (D)

FIGURE 68-4. Algorithm for the pharmacotherapy of posttraumatic stress disorder (PTSD). Strength of recommendations: A = directly based on category I evidence (i.e., metaanalysis of randomized clinical trials [RCT] or at least one RCT); D = directly based on category IV evidence (i.e., expert committee reports or opinions and/or clinical experience of respect authorities). (SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.) (Data from Ballenger JC, Davidson JRT, Lecrubier Y, et al. Consensus statement update on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 2004;65(Suppl 1):55–62; Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Association for Pharmacology. J Psychopharmacol 2005;19:567–596; and Bandelow B, Zohar J, Hollander E, et al. Guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders. World J Biol Psychiatry 2002;3:171–199.)

• The SSRIs are first-line pharmacotherapy for PTSD. Venlafaxine, the TCAs, and MAOIs may also be effective, but they have less favorable sideeffect profiles. • Sertraline and paroxetine are approved for acute treatment of PTSD, and sertraline is approved for long-term management of PTSD. • Antiadrenergics and atypical antipsychotics can be used as augmenting agents. • The SSRIs are believed to be more effective for numbing symptoms than other drugs. About 60% of sertraline-treated patients showed improvement in arousal and avoidance/numbing symptoms, but not reexperiencing symptoms. Similar numbers of patients have been shown to improve on paroxetine. Fluoxetine was effective in a placebo-controlled trial, and fluvoxamine was effective in an open trial. • Amitriptyline and imipramine, and the MAOI phenelzine, can be considered second- or third-line drugs for PTSD after SSRIs have failed. Mirtazapine and venlafaxine may also be effective. 754

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• If there is no improvement in the acute stress response 3 to 4 weeks post trauma, SSRIs should be started in a low dose with slow titration upward toward antidepressant doses. Eight to 12 weeks is an adequate duration of treatment to determine response. • Responders to drug therapy should continue treatment for at least 12 months. When discontinued, drug therapy should be tapered slowly over a period of 1 month or more to reduce the likelihood of relapse. • Antiadrenergic drugs (prazosin) can be useful in some patients with PTSD, and antipsychotics (risperidone, quetiapine, and olanzapine) may be used as augmenting agents in partial responders. • Patients should be seen weekly for the first month, then biweekly through the second month. During months 3 to 6, patients can be seen monthly, then every 1 to 2 months from months 6 to 12. Responders after 1 year of pharmacotherapy can be seen every 3 months. Patients should be monitored for symptom response, side effects, and treatment adherence. • Remission can be monitored with the Treatment Outcome PTSD Scale (score less than or equal to 5) and the Sheehan Disability Scale (score less than or equal to 1 on each item).

See Chap. 73, Anxiety Disorders I, authored by Cynthia K. Kirkwood and Sarah T. Melton, and Chap. 74, Anxiety Disorders II, authored by Cynthia K. Kirkwood, Eugene H. Makela, and Barbara G. Wells, for a more detailed discussion of this topic.

755

69

CHAP TER

Bipolar Disorder

DEFINITION • Bipolar disorder, previously known as manic-depressive illness, is a cyclical, lifelong disorder with recurrent extreme fluctuations in mood, energy, and behavior. Diagnosis requires the occurrence, during the course of the illness, of a manic, hypomanic, or mixed episode (not caused by any other medical condition, substance, or psychiatric disorder).

ETIOLOGY AND PATHOPHYSIOLOGY • Medical conditions, medications, and somatic treatments that may induce mania are shown in Table 69-1. • See Chap. 70 for medical conditions, substance use disorders, and medications associated with depressive symptoms. • Etiology and pathophysiology of bipolar disorder are shown in Table 69-2.

CLINICAL PRESENTATION AND DIAGNOSIS • The Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, classifies bipolar disorders as (1) bipolar I, (2) bipolar II, (3) cyclothymic disorder, and (4) bipolar disorder not otherwise specified. Table 69-3 defines mood disorders by type of episode. Table 69-4 describes the evaluation and diagnostic criteria for mood disorders.

MAJOR DEPRESSIVE EPISODE • In bipolar depression, patients often have mood lability, hypersomnia, low energy, psychomotor retardation, cognitive impairments, anhedonia, decreased sexual activity, slowed speech, carbohydrate craving, and weight gain. • Delusions, hallucinations, and suicide attempts are more common in bipolar depression than in unipolar depression.

MANIC EPISODE • Acute mania usually begins abruptly, and symptoms increase over several days. The severe stages may include bizarre behavior, hallucinations, and paranoid or grandiose delusions. There is marked impairment in functioning or the need for hospitalization. • Manic episodes may be precipitated by stressors, sleep deprivation, antidepressants, CNS stimulants, or bright light.

HYPOMANIC EPISODE • There is no marked impairment in social or occupational functioning, no delusions, and no hallucinations. 756

Bipolar Disorder TABLE 69-1

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CHAPTER 69

Secondary Causes of Mania

Medical conditions that induce mania • CNS disorders (brain tumor, strokes, head injuries, subdural hematoma, multiple sclerosis, systemic lupus erythematosus, temporal lobe seizures, Huntington’s disease) • Infections (encephalitis, neurosyphilis, sepsis, human immunodeficiency virus) • Electrolyte or metabolic abnormalities (calcium or sodium fluctuations, hyper- or hypoglycemia) • Endocrine or hormonal dysregulation (Addison’s disease, Cushing’s disease, hyper- or hypothyroidism, menstrual-related or pregnancy-related or perimenopausal mood disorders) Medications or drugs that induce mania • Alcohol intoxication • Drug withdrawal states (alcohol, α2-adrenergic agonists, antidepressants, barbiturates, benzodiazepines, opiates) • Antidepressants (MAOIs, TCAs, 5-HT and/or NE and/or DA reuptake inhibitors, 5-HT antagonists) • DA-augmenting agents (CNS stimulants: amphetamines, cocaine, sympathomimetics; DA agonists, releasers, and reuptake inhibitors) • Hallucinogens (LSD, PCP) • Marijuana intoxication precipitates psychosis, paranoid thoughts, anxiety, and restlessness • NE-augmenting agents (α2-adrenergic antagonists, β-agonists, NE reuptake inhibitors) • Steroids (anabolic, adrenocorticotropic hormone, corticosteroids) • Thyroid preparations • Xanthines (caffeine, theophylline) • Nonprescription weight loss agents and decongestants (ephedra, pseudoephedrine) • Herbal products (St. John’s wort) Somatic therapies that induce mania • Bright light therapy • Sleep deprivation DA, dopamine; 5-HT, serotonin; LSD, lysergic acid diethylamide; MAOI, monoamine oxidase inhibitor; NE, norepinephrine; PCP, phencyclidine; TCA, tricyclic antidepressant. Data from Torrey EF, Knable MB. New York: Basic Books, 2002; American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Washington, DC: American Psychiatric Association, 2000:382–401; American Psychiatric Association. Am J Psychiatry 2002;159:1–50; and Goodnick PJ, ed. Washington, DC: American Psychiatric Press, 1998.

• During a hypomanic episode, some patients may be more productive and creative than usual, but 5% to 15% of patients may rapidly switch to a manic episode.

MIXED EPISODE • Mixed episodes occur in up to 40% of all episodes, are often difficult to diagnose and treat, and are more common in younger and older patients and females. • Patients with mixed states often have comorbid alcohol and substance abuse, severe anxiety symptoms, a higher suicide rate, and a poorer prognosis.

COURSE OF ILLNESS • The average age of onset of a first manic episode is 21 years. More than 80% of bipolar patients have more than four episodes during their lifetime. Usually there is normal functioning between episodes. • Rapid cyclers (10% to 20% of bipolar patients) have four or more episodes per year (major depressive, manic, mixed, or hypomanic). Rapid-cycling 757

SECTION 13 TABLE 69-2

|

Psychiatric Disorders Etiologic and Pathophysiologic Theories of Bipolar Disorder

Genetic factors 80–90% of patients with bipolar disorder have a biologic relative with a mood disorder (e.g., bipolar disorder, major depression, cyclothymia, or dysthymia). First-degree relatives of bipolar patients have a 15–35% lifetime risk of developing any mood disorder and a 5–10% lifetime risk for developing bipolar disorder. The concordance rate of mood disorders is 60–80% for monozygotic twins and 14–20% for dizygotic twins. Linkage studies suggest that certain loci on genes and the X chromosome may contribute to genetic susceptibility of bipolar disorder. Nongenetic factors Perinatal insult Head trauma Environmental factors Desynchronization of circadian or seasonal rhythms cause diurnal variations in mood and sleep patterns and can result in seasonal recurrences of mood episodes. Changes in the sleep-wake cycle or light-dark cycle can precipitate episodes of mania or depression. Bright light therapy can be used for the treatment of winter depression and can precipitate hypomania, mania, or mixed episodes. Psychosocial or physical stressors Stressful life events often precede mood episodes and can increase recurrence rates and prolong time to recovery from mood episodes. Nutritional factors Deficiency of essential amino acid precursors in the diet can cause a dysregulation of neurotransmitter activity (e.g., L-tryptophan deficiency causes a decrease in 5-HT and melatonin synthesis and activity). Deficiency in essential fatty acids (e.g., omega-3 fatty acids) can cause a dysregulation of neurotransmitter activity. Neurotransmitter/neuroendocrine/hormonal theories Dysregulation between excitatory and inhibitory neurotransmitter systems; excitatory: NE, DA, glutamate, and aspartate; inhibitory: 5-HT and GABA. Monoamine hypothesis An excess of catecholamines (primarily NE and DA) causes mania. Agents that decrease catecholamines are used for the treatment of mania (e.g., DA antagonists and α2adrenergic agonists). Deficit of neurotransmitters (primarily NE, DA, and/or 5-HT) causes depression. Agents that increase neurotransmitter activity are used for the treatment of depression (e.g., 5-HT and NE/ DA reuptake inhibitors and MAOIs). Dysregulation of amino acid neurotransmitters Deficiency of GABA or excessive glutamate activity causes dysregulation of neurotransmitters (e.g., increased DA and NE activity). Agents that increase GABA activity or decrease glutamate activity are used for the treatment of mania and for mood stabilization (e.g., benzodiazepines, lamotrigine, lithium, or valproic acid). Cholinergic hypothesis Deficiency of acetylcholine causes an imbalance in cholinergic-adrenergic activity and can increase the risk of manic episodes. Agents that increase acetylcholine activity can decrease manic symptoms (e.g., use of cholinesterase inhibitors or augmentation of muscarinic cholinergic activity). Increased central acetylcholine levels can increase the risk of depressive episodes. Agents that decrease acetylcholine activity can alleviate depressive symptoms (i.e., anticholinergic agents). Secondary messenger system dysregulation Abnormal G protein functioning dysregulates adenylate cyclase activity, phosphoinositide responses, sodium/potassium/calcium channel exchange, and activity of phospholipases. Abnormal cyclic adenosine monophosphate and phosphoinositide secondary messenger system activity. Abnormal protein kinase C activity and signaling pathways. (continued)

758

Bipolar Disorder TABLE 69-2

|

CHAPTER 69

Etiologic and Pathophysiologic Theories of Bipolar Disorder (Continued)

Hypothalamic-pituitary-thyroid axis dysregulation Hyperthyroidism can precipitate manic-like symptoms. Hypothyroidism can precipitate a depression and be a risk factor for rapid cycling; thyroid supplementation can be used for refractory rapid cycling and augmentation of antidepressants in unipolar depression. Positive antithyroid antibody titers reported in patients with bipolar disorder. Hormonal changes during the female life cycle can cause dysregulation of neurotransmitters (e.g., premenstrual, postpartum, and perimenopause). Membrane and cation theories Abnormal neuronal calcium and sodium activity and homeostasis cause neurotransmitter dysregulation. Hypocalcemia has been associated with causing anxiety, mood irritability, mania, psychosis, and delirium. Hypercalcemia has been associated with causing depression, stupor, and coma. Extracellular and intracellular calcium concentrations may affect the synthesis and release of NE, DA, and 5-HT, as well as the excitability of neuronal firing. Sensitization and kindling theories Recurrences of mood episodes causes behavioral sensitivity and electrophysiologic kindling (similar to the amygdala-kindling models for seizures in animals) and can result in rapid or continuous mood cycling. DA, dopamine; GABA, γ-aminobutyric acid; 5-HT, serotonin; MAOI, monoamine oxidase inhibitor; NE, norepinephrine. Data from Torrey EF, Knable MB. New York: Basic Books, 2002; Goldberg JF, Harrow M, eds. Washington, DC: American Psychiatric Press, 1999; Kelso JR. J Affect Disord 2003;73:183–197; Manji HK, Bowden CL, Belmaker RH, eds. Washington, DC: American Psychiatric Press, 2000; Lenox RH, Gould TD, Manji HK. Am J Med Genet 2002;114:391–406; Baron M. Mol Psychiatry 2002;7:342– 358; Bezchlibnyk Y, Young LT. Can J Psychiatry 2002;47:135–148; Goodnick PJ, ed. Washington, DC: American Psychiatric Press, 1998; Soares JC. Mol Psychiatry 2002;7(Suppl 1):S64–S70; Manji HK, Moore GJ, Chen G. Br J Psychiatry Suppl 2001;41:S107–S119; Gould TD, Manji HK. J Psychosom Res 2002;53:687–697; Sobczak S, Honig A, van Duinen MA, Riedel WJ. Bipolar Disord 2002;4:347– 356; Freeman MP, Wosnitzer Smith K, Freeman SA, et al. J Clin Psychiatry 2002;63:284–287; Ketter TA, Wang PW. J Clin Psychiatry 2003;64(Suppl 3):15–20; White HS. J Clin Psychiatry 2003;64(Suppl 8):5–8.; Rasgon N, Bauer M, Glenn T, et al. Bipolar Disord 2003;5:48–52; and Mahmood T, Silverstone T. J Affect Disord 2001;66:1–11.

TABLE 69-3

Mood Disorders Defined by Episodes

Disorder Subtype

Episode(s)a

Major depressive disorder, single episode Major depressive disorder, recurrent Bipolar disorder, type Ib Bipolar disorder, type IIc Dysthymic disorder Cyclothymic disorder d

Major depressive episode

Bipolar disorder not otherwise specified

Two or more major depressive episodes Manic episode ± major depressive or mixed episode Major depressive episode + hypomanic episode Chronic subsyndromal depressive episodes Chronic fluctuations between subsyndromal depressive and hypomanic episodes (2 years for adults and 1 year for children and adolescents) Mood states do not meet criteria for any specific bipolar disorder

a

The length and severity of a mood episode and the interval between episodes vary from patient to patient. Manic episodes are usually briefer and end more abruptly than major depressive episodes. The average length of untreated manic episodes ranges from 4 to 13 months. Episodes can occur regularly (at the same time or season of the year) and often cluster at 12-month intervals. Women have more depressive episodes than manic episodes, whereas men have a more even distribution of episodes. b For bipolar I disorder, 90% of individuals who experience a manic episode later have multiple recurrent major depressive, manic, hypomanic, or mixed episodes alternating with a normal mood state. c Approximately 5–15% of patients with bipolar II disorder will develop a manic episode over a 5-year period. If a manic or mixed episode develops in a patient with bipolar II disorder, the diagnosis is changed to bipolar I disorder. d Patients with cyclothymic disorder have a 15–50% risk of later developing a bipolar I or II disorder. Data from American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Association, 2000:382–401; Goldberg JF, Harrow M, eds. Bipolar Disorders: Clinical Course and Outcome. Washington, DC: American Psychiatric Press, 1999; and Goodnick PJ, ed. Mania: Clinical and Research Perspectives. Washington, DC: American Psychiatric Press, 1998.

759

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TABLE 69-4

Psychiatric Disorders Evaluation and Diagnostic Criteria of Mood Episodes

Diagnostic workup depends on clinical presentation and findings

• • • • • •

• •

Diagnosis Episode Major depressive

Impairment of Functioning or Need for Hospitalizationa Yes

Manic

Yes

Hypomanic

No

760

Mental status examination Psychiatric, medical, and medication history Physical and neurologic examination Basic laboratory tests: complete blood count, blood chemistry screen, thyroid function, urinalysis, urine drug screen Psychological testing Brain imaging: magnetic resonance imaging and functional scan; alternative: computed tomography scan, positron emission tomography scan Lumbar puncture Electroencephalogram

DSM-IV-TR Criteriab >2-Week period of either depressed mood or loss of interest or pleasure in normal activities, associated with at least five of the following symptoms: • Depressed, sad mood (adults); can be irritable mood in children • Decreased interest and pleasure in normal activities • Decreased appetite, weight loss • Insomnia or hypersomnia • Psychomotor retardation or agitation • Decreased energy or fatigue • Feelings of guilt or worthlessness • Impaired concentration and decision making • Suicidal thoughts or attempts >1-Week period of abnormal and persistent elevated mood (expansive or irritable), associated with at least three of the following symptoms (four if the mood is only irritable): • Inflated self-esteem (grandiosity) • Decreased need for sleep • Increased talking (pressure of speech) • Racing thoughts (flight of ideas) • Distractible (poor attention) • Increased activity (either socially, at work, or sexually) or increased motor activity or agitation • Excessive involvement in activities that are pleasurable but have a high risk for serious consequences (buying sprees, sexual indiscretions, poor judgment in business ventures) At least 4 days of abnormal and persistent elevated mood (expansive or irritable); associated with at least three of the following symptoms (four if the mood is only irritable): • Inflated self-esteem (grandiosity) • Decreased need for sleep • Increased talking (pressure of speech) • Racing thoughts (flight of ideas) • Increased activity (either socially, at work, or sexually) or increased motor activity or agitation • Excessive involvement in activities that are pleasurable but have a high risk for serious consequences (buying sprees, sexual indiscretions, poor judgment in business ventures) (continued)

Bipolar Disorder TABLE 69-4 Mixed

Yes

Rapid cycling

Yes

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CHAPTER 69

Evaluation and Diagnostic Criteria of Mood Episodes (Continued) Criteria for both a major depressive episode and manic episode (except for duration) occur nearly every day for at least a 1-week period >Four major depressive or manic episodes (manic, mixed, or hypomanic) in 12 months

DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. a Impairment in social or occupational functioning; need for hospitalization because of potential self-harm, harm to others, or psychotic symptoms. b The disorder is not caused by a medical condition (e.g., hypothyroidism) or substance-induced disorder (e.g., antidepressant treatment, medications, electroconvulsive therapy). Data from Torrey EF, Knable MB. Surviving Manic Depression: A Manual on Bipolar Disorder for Patients, Families, and Providers. New York: Basic Books, 2002; American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Association, 2000:382–401; and American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002;159:1–50.

• •

•

• •

and mixed states are associated with a poorer prognosis and nonresponse to antimanic agents. Risk factors for rapid cycling include biologic rhythm dysregulation, antidepressant or stimulant use, hypothyroidism, and premenstrual and postpartum states. Women are more likely to have mixed states, depressive episodes, and rapid cycling than men. Suicide attempts occur in up to 50% of patients with bipolar disorder, and approximately 10% to 19% of individuals with bipolar I disorder commit suicide. Bipolar II patients may be more likely than bipolar I patients to attempt suicide. Bipolar patients with substance abuse disorders are more likely to have an earlier onset of illness, mixed states, higher relapse rates, poorer response to treatment, higher suicide risk, and more hospitalizations. Approximately 10% to 15% of adolescents with recurrent major depressive episodes subsequently have an episode of mania or hypomania. Episodes may become longer in duration and more frequent with aging.

DESIRED OUTCOME • The goals of treatment are shown in Table 69-5.

TREATMENT GENERAL APPROACH • The general approach to treatment is shown in Table 69-5.

NONPHARMACOLOGIC THERAPY • Psychoeducation for the patient and family includes: ✓ Early signs and symptoms of mania and depression and how to chart mood changes ✓ Importance of compliance with therapy 761

SECTION 13 TABLE 69-5

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Psychiatric Disorders General Principles for the Management of Bipolar Disorder

Goals of treatment • Eliminate mood episode with complete remission of symptoms (i.e., acute treatment) • Prevent recurrences or relapses of mood episodes (i.e., continuation phase treatment) • Return to complete psychosocial functioning • Maximize adherence with therapy • Minimize adverse effects • Use medications with the best tolerability and fewest drug interactions • Treat comorbid substance use and abuse • Eliminate alcohol, marijuana, cocaine, amphetamines, and hallucinogens • Minimize nicotine use and stop caffeine intake at least 8 hours prior to bedtime • Avoidance of stressors or substances that precipitate an acute episode Monitor for • Mood episodes: document symptoms on a daily mood chart (document life stressors, type of episode, length of episode, and treatment outcome); monthly and yearly life charts are valuable for documenting patterns of mood cycles • Medication adherence (missing doses of medications is a primary reason for nonresponse and recurrence of episodes) • Adverse effects, especially sedation and weight gain (manage rapidly and vigorously to avoid noncompliance) • Suicidal ideation or attempts (suicide completion rates with bipolar I disorder are 10–15%; suicide attempts are primarily associated with depressive episodes, mixed episodes with severe depression or presence of psychosis) Frequency of visits • Severely ill patients should be seen more often (i.e., weekly) compared with less ill patients who are symptomatic (i.e., every 2 weeks) • When starting new medications or switching therapies, frequent monitoring is recommended (e.g., every 2 weeks) to assess adherence, efficacy, dosing, and adverse effects • When a patient is stabilized on medication, less frequent monitoring is possible during the continuation phase (e.g., every month for the first 3 months, then every 2–3 months) • Patients should be encouraged to call their clinician if any problems or adverse events occur or if mood episodes occur between scheduled appointments; rapidly identifying and correcting potential problems or making dosage adjustments is essential in achieving mood stabilization Data from Torrey EF, Knable MB. New York: Basic Books, 2002; American Psychiatric Association. Am J Psychiatry 2002;159:1–50; Goodnick PJ, ed. Washington, DC: American Psychiatric Press, 1998; and Suppes T, Dennehy EB, Swann AC, et al. J Clin Psychiatry 2002;63:288–299.

✓

Psychosocial or physical stressors that may precipitate an episode and strategies for coping with stressful life events ✓ Limiting substances and drugs that can trigger mood episodes ✓ Development of a crisis intervention plan • Other nonpharmacologic approaches include: ✓ Psychotherapy (e.g., individual, group, and family), interpersonal therapy, and/or cognitive behavioral therapy ✓ Stress reduction techniques, relaxation therapy, massage, yoga, etc. ✓ Sleep (regular bedtime and awake schedule; avoid alcohol or caffeine intake prior to bedtime) ✓ Nutrition (regular intake of protein-rich foods or drinks and essential fatty acids; supplemental vitamins and minerals) ✓ Exercise (regular aerobic and weight training at least three times a week) ✓ The use of electroconvulsive therapy for severe mania or mixed episodes, psychotic depression, or rapid cycling is still considered the best 762

Bipolar Disorder

|

CHAPTER 69

acute treatment approach for those patients who do not respond to firstline mood stabilizers, such as lithium and valproate

PHARMACOLOGIC THERAPY • An example treatment algorithm for the acute treatment of mood episodes in patients with bipolar I disorder is shown in Table 69-6. Treatments of First Choice • Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. • Lithium is the drug of choice for bipolar disorder with euphoric mania, whereas valproate has better efficacy for mixed states, irritable/dysphoric mania, and rapid cycling compared with lithium. • Combination therapies (e.g., lithium plus valproate or carbamazepine; lithium or valproate plus an atypical antipsychotic) may provide better acute response and prevention of relapse and recurrence than monotherapy in some bipolar patients, especially those with mixed states or rapid cycling. • Useful guidelines include the following: Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision) published by the American Psychiatric Association; Texas Medication Algorithm Project developed by the Texas Department of Mental Health and Mental Retardation; World Federation of Societies of Biological Psychiatry guideline; Practice Parameters for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder developed by the American Academy of Child and Adolescent Psychiatry; and the Treatment Guidelines for Children and Adolescents with Bipolar Disorder: Child Psychiatric Workgroup on Bipolar Disorder. • Lithium was the first established mood stabilizer and is still considered a first-line agent for acute mania and maintenance treatment of both bipolar I and II disorders. It is the only bipolar medication approved for adults and children 12 years and older. Long-term use of lithium reduces suicide risk. Patients with rapid cycling or mixed states may not respond as well to lithium monotherapy as to some anticonvulsants. • Divalproex sodium (sodium valproate) is now the most prescribed mood stabilizer in the United States. It is FDA approved only for the treatment of acute manic or mixed episodes, but it is often used as maintenance monotherapy for bipolar disorder. • Carbamazepine is also commonly used for acute and maintenance therapy, but it is not FDA approved for bipolar disorder. Some data support the efficacy of oxcarbazepine, but it is also not FDA approved for bipolar disorder in the United States. • Lamotrigine is approved for the maintenance treatment of bipolar I disorder. It has been used as monotherapy or add-on therapy for refractory bipolar depression. 763

TABLE 69-6

Algorithm and Guidelines for the Acute Treatment of Mood Episodes in Patients with Bipolar I Disorder

Acute Manic or Mixed Episode General guidelines Assess for secondary causes of mania or mixed states (e.g., alcohol or drug use) Taper off antidepressants, stimulants, and caffeine if possible Treat substance abuse Encourage good nutrition (with regular protein and essential fatty acid intake), exercise, adequate sleep, stress reduction, and psychosocial therapy Optimize the dose of mood stabilizing medication(s) before adding on benzodiazepines; if psychotic features are present, add on antipsychotic; ECT used for severe or treatment-resistant manic/mixed episodes or psychotic features Hypomania Mania First, optimize current mood stabilizer or initiate moodFirst, two or three drug combinations: lithiuma or stabilizing medication: lithium,a valproate,a or carbavalproatea plus a benzodiazepine (lorazepam or mazepine.a Consider adding a benzodiazepine clonazepam) for short-term adjunctive treatment of agitation or insomnia; lorazepam is recommended (lorazepam or clonazepam) for short-term adjuncfor catatonia. If psychosis is present, initiate atypical tive treatment of agitation or insomnia if needed antipsychotic in combination with above. Alternative medication treatment options: carbama azepine ; if patient does not respond or tolerate, Alternative medication treatment options: carbamconsider atypical antipsychotic (e.g., olanzapine, azepinea; if patient does not respond or tolerate, quetiapine, risperidone) or oxcarbazepine. consider oxcarbazepine.

Acute Depressive Episode General guidelines Assess for secondary causes of depression (e.g., alcohol or drug use) Taper off antipsychotics, benzodiazepines, or sedative-hypnotic agents if possible Treat substance abuse Encourage good nutrition (with regular protein and essential fatty acid intake), exercise, adequate sleep, stress reduction, and psychosocial therapy Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g., bupropion or an SSRI); if psychotic features are present, add on an antipsychotic; ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia Mild to Moderate Depressive Episode Severe Depressive Episode First, initiate and/or optimize mood-stabilizing medicaFirst, two or three drug combinations: lithiuma tion: lithiuma or lamotrigine.b or lamotrigineb plus an antidepressantc; lithium plus lamotrigine. If psychosis is present, Alternative anticonvulsants: valproate,a carbamazeinitiate atypical antipsychotic in combination pine,a or oxcarbazepine. with above. Alternative anticonvulsants: valproate,a carbamazepine,a or oxcarbazepine. Second, if response is inadequate, consider adding an atypical antipsychotic (quetiapine).

Second, if response is inadequate, consider a twodrug combination: • Lithiuma plus an anticonvulsant or an atypical antipsychotic • Anticonvulsant plus an anticonvulsant or atypical antipsychotic

Second, if response is inadequate, consider a threedrug combination: • Lithiuma plus an anticonvulsant plus an atypical antipsychotic • Anticonvulsant plus an anticonvulsant plus an atypical antipsychotic Third, if response is inadequate, consider ECT for mania with psychosis or catatonia d; or add clozapine for treatment-refractory illness

Third, if response is inadequate, consider a three-drug combination: • Lamotrigineb plus an anticonvulsant plus an antidepressant • Lamotrigineb plus lithiuma plus an antidepressant Fourth, if response is inadequate, consider ECT for treatment-refractory illness and depression with psychosis or catatoniad

ECT, electroconvulsive therapy; MAOI, monoamine oxidase inhibitor; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. aUse standard therapeutic serum concentration ranges if clinically indicated; if partial response or breakthrough episode, adjust dose to achieve higher serum concentrations without causing intolerable adverse effects; valproate is preferred over lithium for mixed episodes and rapid cycling; lithium and/or lamotrigine is preferred over valproate for bipolar depression. bLamotrigine is not approved for the acute treatment of depression, and the dose must be started low and slowly titrated up to decrease adverse effects if used for maintenance therapy of bipolar I disorder. A drug interaction and a severe dermatologic rash can occur when lamotrigine is combined with valproate (i.e., lamotrigine doses must be halved from standard dosing titration). cAntidepressant monotherapy is not recommended for bipolar depression. Bupropion, SSRIs, (e.g., citalopram, escitalopram, or sertraline), and SNRIs (e.g., venlafaxine) have shown good efficacy and fewer adverse effects in the treatment of unipolar depression; MAOIs and TCAs have more adverse effects (e.g., weight gain) and can have a higher risk of causing antidepressant-induced mania; fluoxetine, fluvoxamine, nefazodone, and paroxetine inhibit liver metabolism and should be used with caution in patients on concomitant medications that require cytochrome P450 clearance; paroxetine and venlafaxine have a higher risk for causing a discontinuation syndrome. dECT is used for severe mania or depression during pregnancy and for mixed episodes; prior to treatment, anticonvulsants, lithium, and benzodiazepines should be tapered off to maximize therapy and minimize adverse effects. Data from American Psychiatric Association. Am J Psychiatry 2002;159:1–50; Suppes T, Dennehy EB, Swann AC, et al. J Clin Psychiatry 2002;63:288–299; Sachs GS. J Clin Psychiatry 2003;64(Suppl 80):35–40; Keck PE Jr., McElroy SL. J Affect Disord 2003;73:163– 169; and Kusmakar V. J Clin Psychiatry 2002;63(Suppl 10):23–28.

SECTION 13

|

Psychiatric Disorders

• Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are effective as monotherapy or as add-on therapy to lithium or valproate for acute mania. Prophylactic use of antipsychotics can be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed in view of long-term side effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). Alternative Treatments • High-potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to or in combination with antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or in those who cannot take mood stabilizers. Lorazepam IM may be used for acute agitation. A relative contraindication for long-term benzodiazepines is a history of drug or alcohol abuse or dependency. • Antidepressants are routinely added for the treatment of acute depression, but tricyclic antidepressants are associated with an increased risk of inducing mania in bipolar I disorder and possibly cause rapid cycling. Some guidelines recommend avoiding antidepressants in the treatment of bipolar depression or limiting their use to brief intervals, but evidence suggests that coadministration of therapeutic doses of mood stabilizers can reduce the risk of antidepressant-induced switching. Generally the antidepressant should be withdrawn 2 to 6 months after remission and the patients maintained on a mood stabilizer. Long-term antidepressants are required in some patients. • Nimodipine may be more effective than verapamil for rapid-cycling bipolar disorder because of its anticonvulsant properties, high lipid solubility, and good penetration into the brain. Special Populations • Approximately 20% to 50% of women with bipolar disorder relapse postpartum; prophylaxis with mood stabilizers (e.g., lithium or valproate) is recommended immediately postpartum to decrease the risk of relapse. • Current estimates of the rate of occurrence of Epstein anomaly in infants exposed to lithium during the first trimester is between 1:1,000 and 1:2,000. • When lithium is to be used during pregnancy, it should be used at the lowest effective dose in order to avoid “floppy” infant syndrome, hypothyroidism, and nontoxic goiter in the infant. • Serum concentrations in the nursing infant are 10% to 50% of the mother’s serum concentration, thus breast-feeding is usually discouraged for women taking lithium. • When valproate is taken during the first trimester, the risk of neural tube defect is 5% to 9%. For carbamazepine, the risk is estimated to be 0.5% to 1%. • Administration of folic acid can reduce the risk of neural tube defects. • Women taking valproate may breast-feed, but mother and infant should have identical laboratory monitoring. Drug Class Information • Product information, dosing and administration, clinical use, and proposed mechanisms of action for agents used for bipolar disorder are shown in Table 69-7. 766

TABLE 69-7

Product Formulations, Dosage and Administration, Clinical Use, and Proposed Mechanism of Action of Agents Used in the Treatment of Bipolar Disorder

Generic Name

Trade Name

Formulations

Lithium salts: FDA approved for bipolar disorder Lithium Eskalith Capsule: 300 mg carbonate Eskalith CR Extended-release tablet: 450 mg Lithobid Extended-release tablet: 300 mg Generic Tablet: 300 mg (scored) Capsule: 150, 300, 600 mg Lithium citrate Cibalith-S 8 mEq/5 mL

Anticonvulsants: FDA approved for bipolar disorder Divalproex sodium Depakote Enteric-coated, delayedrelease tablet: 125, 250, 500 mg Sprinkle capsule: 125 mg Depakote ER Enteric-coated, extended release tablet: 250, 500 mg

Dosage and Administration

Clinical Use

Proposed Mechanism of Action

900–2,400 mg/day in 2–4 divided doses, preferably with meals. There is wide variation in the dosage needed to achieve therapeutic response and trough serum lithium concentration (i.e., 0.6–1.2 mEq/L for maintenance therapy and 1.0–1.2 mEq/L for acute mood episodes taken 8–12 hours after the last dose).

Use alone or in combination with other drugs (e.g., valproate, carbamazepine, antipsychotics) for the acute treatment of mania and for maintenance treatment.

Normalizes or inhibits secondary messenger systems (e.g., inhibits phosphoinositide and adenylate cyclase signaling; normalizes guanine nucleotide-binding protein [G protein] signal transduction system); Decreases 5-HT reuptake and increases postsynaptic 5-HT receptor sensitivity; Inhibits the synthesis of DA, decreases the number of β-adrenergic receptors and inhibits DA2 and β-adrenergic receptor supersensitivity; Enhances GABAergic activity and normalizes GABA levels; Reduces glutamatergic activity (e.g., increases glutamate uptake) with chronic therapy. Decreases Ca+ transport into cells, interferes with Ca+-Na+ active transport system, increases renal tubular reabsorption of Ca+ and increases serum Ca+ and parathyroid concentrations; Increases choline in red blood cells and potentiates the cholinergic secondary messenger system.

750–3,000 mg/day (20–60 mg/kg per day) given once daily or in divided doses for delayed-release divalproex or valproic acid. Extended-release divalproex can be given once daily at bedtime after stabilization. A loading dose of divalproex (20–30 mg/kg per day) can be given, then 20 mg/kg per day and titrated to a serum concentration of 50–125 mcg/ mL or clinical response.

Use alone or in combination with other drugs (e.g., lithium, carbamazepine, antipsychotics) for the acute treatment of mania and for maintenance treatment. Use caution when combining with lamotrigine because of potential drug interaction.

Increases GABA levels in plasma and CNS; inhibits GABA catabolism, increases synthesis, and release; can prevent GABA reuptake; enhances the action of GABA at the GABAA receptor; Normalizes Na+ and Ca+ channels; Reduces intracellular inositol and protein kinase C isozymes; Can modulate gene expression. Antikindling properties can decrease rapid cycling and mixed states.

(continued)

TABLE 69-7

Product Formulations, Dosage and Administration, Clinical Use, and Proposed Mechanism of Action of Agents Used in the Treatment of Bipolar Disorder (Continued)

Generic Name

Trade Name

Formulations

Dosage and Administration

Clinical Use

Proposed Mechanism of Action

Valproic acid Valproate sodium Lamotrigine

Depakene Depakene Lamictal

Capsule: 250 mg Syrup: 250 mg/5 mL Tablet: 25, 100, 150, 200 mg Chewable tablet: 2, 5, 25 mg

— — 50–400 mg/day in divided doses. Dosage should be slowly increased (e.g., 25 mg/day for 2 weeks, then 50 mg/day for weeks 3 and 4, then 50mg/day increments at weekly intervals up to 200 mg/day). When combined with valproate, initial and titration dosing should be decreased by 50% to minimize the risk of a serious rash.

— — Use alone or in combination with other drugs (e.g., lithium, carbamazepine) for long-term maintenance treatment for bipolar I disorder. Lamotrigine can have efficacy for prevention of bipolar depression.

— — Blocks voltage-sensitive Na+ and Ca+ channels; Modulates or decreases presynaptic aspartate and glutamate release; Antikindling properties may decrease rapid cycling and mixed states.

200–1,800 mg/day in 2–4 divided doses. Dosage should be slowly increased according to response and adverse effects (e.g., 100–200 mg twice daily and increase by 200 mg/day at weekly intervals). Dose can be increased rapidly for inpatients. Administer conventional tablets and suspension with meals. Extendedrelease tablets should be swallowed whole and not be broken or chewed. Carbatrol capsules can be opened and contents sprinkled over food.

Use alone or in combination with other medications (e.g., lithium, valproate, antipsychotics) for the acute and long-term maintenance treatment of mania or mixed episodes for bipolar I disorder. APA guidelines recommend reserving it for patients unable to tolerate or who have inadequate response to lithium or valproate.

Blocks voltage-sensitive Na+ channels; Stimulates the release of antidiuretic hormone and decreases Na+ serum concentrations; Blocks Ca+ influx through the NMDA glutamate receptor and decreases Ca+ serum concentrations; Modulates presynaptic aspartate and glutamate release; Antikindling properties may decrease rapid cycling and mixed states.

Anticonvulsants: Not FDA approved for bipolar disorder Carbamazepine Tegretol, Tablet: 200 mg Epitol Tegretol Chewable tablet: 100 mg Suspension: 100 mg/5 mL Tegretol-XR Extended-release tablet: 100, 200, 400 mg

Carbatrol

Extended-release capsule: 200, 300 mg

Equetro

Extended-release capsule: 100, 200, 300 mg

Oxcarbazepine

Trileptal

Tablet: 150, 300, 600 mg Suspension: 300 mg/5 mL

Clonazepam

Klonopin

Tablet: 0.5, 1, 2 mg

Lorazepam

Ativan

Tablet: 0.5, 1, 2 mg Oral solution: 2 mg/mL Injection: 2, 4 mg/mL

Atypical antipsychotics: FDA approved for bipolar disorder Aripiprazole Abilify Tablet: 5, 10, 15, 20, 30 mg Olanzapine Zyprexa Tablet: 2.5, 5, 7.5, 10, 15, 20 mg Zyprexa Zydis Tablet, orally disintegrating: 5, 10, 15, 20 mg Quetiapine Seroquel Tablet: 25, 50, 100, 200, 300, 400 mg Risperidone Risperdal Tablet: 0.25, 0.5, 1, 2, 3, 4 mg Oral solution: 1 mg/mL

300–1,200 mg/day in two divided doses. Dosage should be slowly adjusted up and down according to response and adverse effects (e.g., 150–300 mg twice daily and increase by 300–600 mg/day at weekly intervals). Dose can be increased rapidly for inpatients. 0.5–20 mg/day in divided doses or one dose at bedtime. Dosage should be slowly adjusted up and down according to response and adverse effects. 2–40 mg/day in divided doses or one dose at bedtime. Dosage should be slowly adjusted up and down according to response and adverse effects.

Can have fewer adverse effects and be better tolerated than carbamazepine

Oxcarbazepine and its monohydroxy metabolite increase K+ conductance; modulates the activity of high-voltage activated Ca+ channels; and blocks Na+ channels.

Use in combination with other drugs (e.g., antipsychotics, lithium, valproate) for the acute treatment of mania or mixed episodes. Use as a short-term adjunctive sedative-hypnotic agent.

Binds to the benzodiazepine site and augments the action of GABAA by increasing the frequency of Cl– channel opening, which causes hyperpolarization (a less excitable state) and inhibits neuronal firing.

10–30 mg/day once daily

Use in combination with lithium or valproate for the acute treatment of mania or mixed states (primarily with psychotic features) for bipolar I disorder. Only olanzapine is FDA approved at this time for maintenance treatment and only quetiapine for bipolar depression.

Antagonist of postsynaptic DA2 receptors; atypical agents also block 5HT2A receptors that increase the presynaptic release of DA, thus lowering the risk of extrapyramidal symptoms and prolactin release

5–20 mg/day once daily or in divided doses

50–800 mg/day in divided doses or once daily when stabilized 0.5–6 mg/day once daily or in divided doses

Receptor blockade varies by agent: DA4, 5-HT2A–2C, α1–2-adrenergic, muscarinic, and histamine1.

(continued)

TABLE 69-7

Product Formulations, Dosage and Administration, Clinical Use, and Proposed Mechanism of Action of Agents Used in the Treatment of Bipolar Disorder (Continued)

Generic Name

Trade Name

Formulations 0.5, 1, 2, 3, 4 mg

Ziprasidone

Risperdal M-Tab Geodon

Capsule: 20, 40, 60, 80 mg Calcium channel blockers: Not FDA approved for bipolar disorder Nimodipine Nimotop Capsule: 30 mg Verapamil Verelan Capsule: 120, 180, 240, 360 mg Calan, Isoptin Film-coated tablet: 40, 80, 120 mg Extended-release tablet: 120, 180, 240 mg

Dosage and Administration

Clinical Use

Proposed Mechanism of Action

40–160 mg/day in divided doses

—

—

30–120 mg/day 80–480 mg/day

Use as third-line agent for combination with other drugs (e.g., carbamazepine, valproate, antipsychotics).

Blocks Ca+ influx through L-type Ca+ channels Alters Ca+-Na+ exchange Decreases 5-HT, DA, and endorphin activity

APA, American Psychiatric Association; Ca+, calcium; Cl–, chloride; DA, dopamine; GABA, γ-aminobutyric acid; 5-HT, serotonin; K+, potassium; Na+, sodium; NMDA, N-methyl-D-aspartate; NE, norepinephrine. Compiled data from Torrey EF, Knable MB. New York: Basic Books, 2002; American Psychiatric Association. Am J Psychiatry 2002;159:1–50; Goldberg JF, Harrow M, eds. Washington, DC: American Psychiatric Press, 1999; Manji HK, Bowden CL, Belmaker RH, eds. Washington, DC: American Psychiatric Press, 2000; Baron M. Mol Psychiatry 2002;7:342–358; Goodnick PJ, ed. Washington, DC: American Psychiatric Press, 1998; Freeman MP, Wosnitzer Smith K, Freeman SA, et al. J Clin Psychiatry 2002;63:284–287; White HS. J Clin Psychiatry 2003;64(Suppl 8):5–8; and Calabrese JR, Shelton MD, Rapport DJ, et al. J Affect Disord 2001;67:241–255.

Bipolar Disorder

|

CHAPTER 69

• Guidelines for baseline and routine laboratory monitoring of mood stabilizers are shown in Table 69-8. • For more information on the side effects, pharmacokinetics, and drug interactions of specific agents, refer to Chap. 71 on Schizophrenia, Chap. 70 on Major Depressive Disorder, and Chap. 52 on Epilepsy. Antipsychotics • Both typical and atypical antipsychotics are effective in approximately 70% of patients with acute mania associated with agitation, aggression, and psychosis, and atypical antipsychotics are better tolerated. • Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are FDA approved for the treatment of acute manic episodes in bipolar I disorder. • Depot antipsychotics (e.g., haloperidol decanoate, fluphenazine decanoate, and risperidone long-acting injection) can be used for maintenance therapy of bipolar disorder with noncompliance or treatment resistance. • Lithium plus an antipsychotic and valproate plus an antipsychotic may be more effective than any of these agents alone. • Adjunctive atypical antipsychotics can be beneficial for breakthrough manic episodes or if there is incomplete response to lithium or valproate monotherapy. • Only olanzapine is FDA approved for maintenance treatment, and only quetiapine is FDA approved for bipolar depression. • Clozapine monotherapy has acute and long-term mood stabilizing effects in refractory bipolar disorder, including mixed mania and rapid cycling, but requires regular white blood cell monitoring for agranulocytosis. • Higher initial doses of antipsychotics (e.g., 20 mg/day of olanzapine) are required for acute mania, but once mania is controlled (usually 7 to 28 days), the antipsychotic can be gradually tapered and discontinued, and the patient maintained on the mood stabilizer alone. Carbamazepine • Carbamazepine is usually reserved for lithium-refractory patients, rapid cyclers, or mixed states. It has some acute antimanic effects, but its longterm effectiveness is unclear. • The combination of carbamazepine with lithium, valproate, and antipsychotics is often used for manic episodes in treatment-resistant patients. • Carbamazepine induces the metabolism of antidepressants, anticonvulsants, and antipsychotics, thus, dosage adjustments may be required. • Acute overdoses of carbamazepine are potentially lethal. • Women who receive carbamazepine require higher doses of oral contraceptives or alternative contraceptive methods. • Certain medications (e.g., cimetidine, diltiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefazodone, propoxyphene, and verapamil) added to carbamazepine therapy may cause carbamazepine toxicity. • Doses can be started at 400 mg to 600 mg/day in divided doses, and increased by 200 mg/day every 2 to 4 days up to 10 to 15 mg/kg/day. Outpatients should be titrated upward more slowly to avoid side effects. Many patients are able to tolerate once daily dosing once their mood episode has stabilized. 771

Guidelines for Baseline and Routine Laboratory Tests and Monitoring for Agents Used in the Treatment of Bipolar Disorder

TABLE 69-8

Baseline: Physical Examination & General Chemistry a

Atypical antipsychotics i Carbamazepine j Lamotrigine k Lithiuml Oxcarbazepinem Valproate n a

Baseline X X X X X X

Hematologic Testsb Baseline

6–12 months

Liver Function Testsd

Metabolic Testsc Baseline X

6–12 months X

X

X

X

X

X

X

X

X

X

X

Baseline

X

6–12 months

X

Renal Function Testse Baseline

X

X

Baseline

6–12 months

X X

Screen for drug abuse and serum pregnancy. b Complete blood cell count (CBC) with differential and platelets. c Fasting glucose, serum lipids, weight. d Lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase.

6–12 months

Thyroid Function Testsf

X

X

X

Serum Electrolytesg Baseline

6–12 months

X

X

X X

X X

Dermatologic h Baseline

3–6 months

X X X

X X X

X

X

e Serum

creatinine, blood urea nitrogen, urinalysis, urine osmolality, specific gravity. total thyroxine, thyroxine uptake, and thyroid-stimulating hormone. sodium. h Rashes, hair thinning, alopecia. i Atypical antipsychotics: Monitor for increased appetite with weight gain (primarily in patients with initial low or normal body mass index); monitor closely if rapid or significant weight gain occurs during early therapy; cases of hyperlipidemia and diabetes reported. j Carbamazepine: Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug; discontinue if platelets are 200% of normal.

963

APPENDICES TABLE A4-4

An Approach to Determining a Drug-Monitoring Plan to Detect Hepatotoxicity

The patient is to be started on a drug that may cause a hepatotoxic reaction ↓ Is the patient pregnant? Is the patient older than age 60 years? Is the patient exposed to an environmental hepatotoxin at work or at home? Is the patient drinking more than one alcoholic beverage per day or bingeing on weekends? Is the patient using any injected recreational drug? Is the patient using herbal remedies or tisanes that are associated with hepatic damage? Is the patient’s diet deficient in magnesium, vitamin E, vitamin C, or α- or β-carotenes? Is the patient’s diet excessive in vitamin A, iron, or selenium? Does the patient have hypertriglyceridemia or type 2 diabetes mellitus? Does the patient have juvenile arthritis or systemic lupus erythematosus? Is the patient HIV-positive, have AIDS, or on reverse transcriptase inhibitors? Does the patient have chronic or chronic remitting viral hepatitis (hepatitis B or C)? ↓ Draw a baseline set of blood samples for liver enzymes, bilirubin, albumin, and transferrin before beginning the drug ↓ Does the patient have more than two risk factors? Is the drug identified as one that may cause a predictable hepatotoxic reaction? a ↓Yes ↓No Redraw liver enzymes every 60–90 days depending Redraw liver enzymes if other signs or symptoms on the drug, for the first year manifest If no toxicity is manifested during the first year of therapy, then redraw liver enzymes every 6–12 months; assess liver for cirrhosis every 1–2 years by ultrasound and every 4–6 years by CT or MRI scan; biopsy as directed by other findings AIDS, acquired immune deficiency syndrome; CT, computer tomography; HIV, human immunodeficiency virus; MRI, magnetic resonance imaging. aA drug can become a predictable risk if it is administered concurrently with another drug or food that is known to induce or inhibit its metabolism.

See Chapter 40, Drug-Induced Liver Disease, authored by William R. Kirchain and Rondall E. Allen, for a more detailed discussion of this topic.

964

APPENDIX CHAP TER

5

TABLE A5-1

Drug-Induced Pulmonary Disorders

Drugs That Induce Apnea Relative Frequency of Reactions

CNS depression Narcotic analgesics Barbiturates Benzodiazepines Other sedatives and hypnotics Tricyclic antidepressants Phenothiazines Ketamine Promazine Anesthetics Antihistamines Alcohol Fenfluramine L-Dopa Oxygen Respiratory muscle dysfunction Aminoglycoside antibiotics Polymyxin antibiotics Neuromuscular blockers Quinine Digitalis Myopathy Corticosteroids Diuretics Aminocaproic acid Clofibrate

F F F I R R R R R R I R R R I I I R R F I R R

F, frequent; I, infrequent; R, rare.

TABLE A5-2

Drugs That Induce Bronchospasm Relative Frequency of Reactions

Anaphylaxis (IgE-mediated) Penicillins Sulfonamides Serum Cephalosporins Bromelin Cimetidine Papain Pancreatic extract Psyllium Subtilase Tetracyclines Allergen extracts L-Asparaginase Pyrazolone analgesics

F F F F R R F I I I I I F I (continued)

965

APPENDICES TABLE A5-2

Drugs That Induce Bronchospasm (Continued)

Direct airway irritation Acetate Bisulfite Cromolyn Smoke N-acetylcysteine Inhaled steroids Precipitating IgG antibodies β-Methyldopa Carbamazepine Spiramycin Cyclooxygenase inhibition Aspirin/nonsteroidal antiinflammatory drugs Phenylbutazone Acetaminophen Anaphylactoid mast-cell degranulation Narcotic analgesics Ethylenediamine Iodinated-radiocontrast media Platinum Local anesthetics Steroidal anesthetics Iron–dextran complex Pancuronium bromide Benzalkonium chloride Pharmacologic effects α-Adrenergic receptor blockers Cholinergic stimulants Anticholinesterases β-Adrenergic agonists Ethylenediamine tetraacetic acid Unknown mechanisms Angiotensin-converting enzyme inhibitors Anticholinergics Hydrocortisone Isoproterenol Monosodium glutamate Piperazine Tartrazine Sulfinpyrazone Zinostatin Losartan F, frequent; I, infrequent; Ig, immunoglobulin; R, rare.

966

R F R F F I R R R F I R I R F R I I I R I I–F I R R R I R R R I R R R R R

Drug-Induced Pulmonary Disorders TABLE A5-3

aA

|

App. 5

Tolerance of Antiinflammatory and Analgesic Drugs in Aspirin-Induced Asthma

Cross-Reactive Drugs

Drugs with No Cross-Reactivity

Diclofenac Diflunisal Fenoprofen Flufenamic acid Flurbiprofen Hydrocortisone hemisuccinate Ibuprofen Indomethacin Ketoprofen Mefenamic acid Naproxen Noramidopyrine Oxyphenbutazone Phenylbutazone Piroxicam Sulindac Sulfinpyrazone Tartrazine Tolmetin

Acetaminophena Benzydamine Chloroquine Choline salicylate Corticosteroids Dextropropoxyphene Phenacetina Salicylamide Sodium salicylate

very small percentage (5%) of aspirin-sensitive patients react to acetaminophen and phenacetin.

967

APPENDICES TABLE A5-4

Drugs That Induce Pulmonary Edema Relative Frequency of Reactions

Cardiogenic pulmonary edema Excessive IV fluids Blood and plasma transfusions Corticosteroids Phenylbutazone Sodium diatrizoate Hypertonic intrathecal saline β2-Adrenergic agonists Noncardiogenic pulmonary edema Heroin Methadone Morphine Oxygen Propoxyphene Ethchlorvynol Chlordiazepoxide Salicylate Hydrochlorothiazide Triamterene + hydrochlorothiazide Leukoagglutinin reactions Iron–dextran complex Methotrexate Cytosine arabinoside Nitrofurantoin Dextran 40 Fluorescein Amitriptyline Colchicine Nitrogen mustard Epinephrine Metaraminol Bleomycin Iodide Cyclophosphamide VM-26 F, frequent; I, infrequent; R, rare.

968

F F F R R R I F I I I R R R R R R R R R R R R R R R R R R R R R R

Drug-Induced Pulmonary Disorders TABLE A5-5

|

App. 5

Drugs That Induce Pulmonary Infiltrates with Eosinophilia (Loeffler’s Syndrome) Relative Frequency of Reactions

Drug

F F I I I I R R R R

Nitrofurantoin para-Aminosalicylic acid Sulfonamides Penicillins Methotrexate Imipramine Chlorpropamide Carbamazepine Phenytoin Mephenesin

Drug

Relative Frequency of Reactions

Tetracycline Procarbazine Cromolyn Niridazole Gold salts Chlorpromazine Naproxen Sulindac Ibuprofen

R R R R R R R R R

F, frequent; I, infrequent; R, rare.

TABLE A5-6

Drugs That Induce Pneumonitis and/or Fibrosis

Drug Oxygen Radiation Bleomycin Busulfan Carmustine Hexamethonium Paraquat Amiodarone Mecamylamine Pentolinium Cyclophosphamide Practolol Methotrexate Mitomycin Nitrofurantoin Methysergide Sirolimus Azathioprine, 6-mercaptopurine

Relative Frequency of Reactions F F F F F F F F I I I I I I I I I R

Drug Chlorambucil Melphalan Lomustine and semustine Zinostatin Procarbazine Teniposide Sulfasalazine Phenytoin Gold salts Pindolol Imipramine Penicillamine Phenylbutazone Chlorphentermine Fenfluramine Leflunomide Mefloquine Pergolide

Relative Frequency of Reactions R R R R R R R R R R R R R R R R R R

F, frequent; I, infrequent; R, rare.

969

APPENDICES TABLE A5-7

Possible Causes of Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (fibrosing alveolitis) Pneumoconiosis (asbestosis, silicosis, coal dust, talc berylliosis) Hypersensitivity pneumonitis (molds, bacteria, animal proteins, toluene diisocyanate, epoxy resins) Smoking Sarcoidosis Tuberculosis Lipoid pneumonia Systemic lupus erythematosus Rheumatoid arthritis Systemic sclerosis Polymyositis/dermatomyositis Sjögren’s syndrome Polyarteritis nodosa Wegener’s granuloma Byssinosis (cotton workers) Siderosis (arc welders’ lung) Radiation Oxygen Chemicals (thioureas, trialkylphosphorothioates, furans) Drugs (see Tables A5-5, A5-6, and A5-8)

TABLE A5-8

Drugs That May Induce Pleural Effusions and Fibrosis Relative Frequency of Reactions

Idiopathic Methysergide Practolol Pindolol Methotrexate Nitrofurantoin Drug-induced lupus syndrome Procainamide Hydralazine Isoniazid Phenytoin Mephenytoin Griseofulvin Trimethadione Sulfonamides Phenylbutazone Streptomycin Ethosuximide Tetracycline Pseudolymphoma syndrome Cyclosporine Phenytoin

F F R R R F F R R R R R R R R R R R R

F, frequent; I, infrequent; R, rare.

See Chapter 31, Drug-Induced Pulmonary Diseases, authored by Hengameh H. Raissy, Michelle Harkins, and Patricia L. Marshik, for a more detailed discussion of this topic. 970

APPENDIX APPENDIX

6

TABLE A6-1

Drug-Induced Kidney Disease

Drug-Induced Renal Structural–Functional Alterations

Tubular epithelial cell damage Acute tubular necrosis • Adefovir, cidofovir, tenofovir • Aminoglycoside antibiotics • Amphotericin B • Cisplatin, carboplatin • Cyclosporine, tacrolimus • Foscarnet Hemodynamically mediated kidney injury • Angiotensin-converting enzyme inhibitors • Angiotensin II receptor blockers Obstructive nephropathy Intratubular obstruction • Acyclovir • Foscarnet • Indinavir • Methotrexate • Sulfonamides Glomerular disease • Gold • Lithium

• Pentamidine • Radiographic contrast media • Zoledronate Osmotic nephrosis • Dextran • Intravenous immunoglobulin • Mannitol • Cyclosporine, tacrolimus • Nonsteroidal antiinflammatory drugs • OKT3 Nephrolithiasis • Indinavir • Sulfonamides • Triamterene

• Nonsteroidal antiinflammatory drugs, cyclooxygenase-2 inhibitors • Pamidronate

Tubulointerstitial disease Nephrocalcinosis Acute allergic interstitial nephritis • Ciprofloxacin • Oral sodium phosphate solution • Loop diuretics Papillary necrosis • Nonsteroidal antiinflammatory drugs, cyclo• Nonsteroidal antiinflammatory drugs, combined pheoxygenase-2 inhibitors nacetin, aspirin, and caffeine analgesics • Penicillins • Proton pump inhibitors Chronic interstitial nephritis • Cyclosporine • Lithium • Aristolochic acid Renal vasculitis, thrombosis, and cholesterol emboli • Mitomycin C Vasculitis and thrombosis • Hydralazine • Methamphetamines • Propylthiouracil • Cyclosporine, tacrolimus • Allopurinol Cholesterol emboli • Penicillamine • Warfarin • Gemcitabine • Thrombolytic agents

971

APPENDICES TABLE A6-2

Potential Risk Factors for Aminoglycoside Nephrotoxicity

A. Related to aminoglycoside dosing: Large total cumulative dose Prolonged therapy Trough concentration exceeding 2 mg/L Recent previous aminoglycoside therapy B. Related to synergistic nephrotoxicity. Aminoglycosides in combination with: Amphotericin B Cyclosporine Diuretics Vancomycin C. Related to predisposing conditions in the patient: Dehydration Gram-negative bacteremia Hypoalbuminemia Increased age Liver disease Obstructive jaundice Preexisting kidney disease Poor nutrition Potassium or magnesium deficiencies Shock

TABLE A6-3

Recommended Interventions for Prevention of Contrast Nephrotoxicity

Intervention

Recommendation

Recommendation Gradea

Contrast

Medications

• • • •

A-1 A-2 A-2 A-2

Normal (0.9%) saline

• •

Sodium bicarbonate 154 mEq/L

•

N-acetylcysteine

•

a

Minimize contrast volume/dose Use noniodinated contrast studies Use low- or isoosmolar contrast agents Avoid concurrent use of potentially nephrotoxic drugs (e.g., nonsteroidal antiinflammatory drugs, aminoglycosides) Initiate infusion at least 3 hours prior to contrast exposure and continue 8–24 hours postexposure Infuse at 1 mL/kg/hour up to 150 mL/hour, adjusting postexposure as clinically indicated Initiate infusion at 3 mL/kg/hour, beginning 1 hour prior to contrast exposure, then continue at 1 mL/kg/ hour for 6 hours postexposure Administer 600 mg orally, every 12 hours × 4 doses beginning prior to contrast exposure (i.e., one dose prior to exposure and 3 doses postexposure)

A-1

B-2

B-1

Strength of recommendations: A, B, C, good, moderate, and poor evidence to support recommendation, respectively. Quality of evidence: 1, Evidence from more than one properly randomized, controlled trial. 2, Evidence from more than one well-designed clinical trial with randomization, from cohort or case-controlled analytic studies or multiple time series; or dramatic results from uncontrolled experiments. 3, Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert communities. Derived from data in Barrett BJ, Parfrey PS. N Engl J Med 2006;354:379–386; Rudnick MR, Kesselheim A, Goldfarb S. Cleve Clin J Med 2006;73:75–77; Bagshaw SM, McAlister FA, Manns BJ, Ghali WA. Arch Intern Med 2006;166:161–166; and Schweiger MJ, Chambers CE, Davidson CJ, et al. Catheter Cardiovasc Interv 2006;69:135–140.

972

Drug-Induced Kidney Disease TABLE A6-4

|

App. 6

Drugs Associated with Allergic Interstitial Nephritis

Antimicrobials Acyclovir Aminoglycosides Amphotericin B β-Lactams Erythromycin Ethambutol Diuretics Acetazolamide Amiloride Chlorthalidone Neuropsychiatric Carbamazepine Lithium Phenobarbital Nonsteroidal antiinflammatory drugs Aspirin Cyclooxygenase-2 inhibitors Diclofenac Diflunisal Ibuprofen Indomethacin Miscellaneous Acetaminophen Allopurinol Aspirin Azathioprine Captopril Cimetidine Clofibrate Cyclosporine Glyburide Gold Interferon-alfa

Indinavir Rifampin Sulfonamides Tetracyclines Trimethoprim–sulfamethoxazole Vancomycin Loop diuretics Triamterene Thiazide diuretics Phenytoin Valproic acid

Ketoprofen Naproxen Phenylbutazone Piroxicam Zomepirac

Lansoprazole Methyldopa Omeprazole p-Aminosalicylic acid Phenylpropanolamine Propylthiouracil Radiographic contrast media Ranitidine Sulfinpyrazone Warfarin

See Chapter 49, Drug-Induced Kidney Disease, authored by Thomas D. Nolin and Jonathan Himmelfarb, for a more detailed discussion of this topic.

973

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CHAP TER

Index

Note: Page numbers followed by f refer to figures, those followed by t refer to tables. A Abacavir in HIV infection, 440t, 441, 442t Abatacept in rheumatoid arthritis, 35t, 36t, 40 Abciximab in acute coronary syndromes, 51 Abdominal infections, 456–464 sepsis in, 491t Abdominal pain in pancreatitis acute, 305–306, 307–308 chronic, 309–310, 311, 312 in peptic ulcer disease, 315 Abscess, intraabdominal, 456–464 antibiotics in, 461t–462t Absorption of drugs kidney disorders affecting, 875 reduced, failure of antimicrobial therapy in, 385 Abstinence method of contraception, 322 Acamprosate in alcohol dependence, 835 Acarbose in diabetes mellitus, 217t, 220 Acebutolol in hypertension, 117t, 121 Acetaminophen in bronchitis, acute, 466 in migraine headache, 603t, 605 in osteoarthritis, 12, 14t, 17 in otitis media, 479 in pain management, 616, 619t, 620t in pancreatitis, chronic, 310, 311 in pharyngitis, 482 in rituximab therapy for lymphoma, 710 in tension-type headache, 612 Acetate in parenteral nutrition solutions, 673, 674 Acetazolamide in glaucoma, 721, 723t in sleep apnea, 819 Acetic acids in osteoarthritis, 14t in pressure ulcers, 519 Acetohexamide in diabetes mellitus, 216t Acetylsalicylic acid. See Aspirin Acid-base disorders, 839–848 acidosis in. See Acidosis alkalosis in. See Alkalosis in cardiac arrest, 81 definition of, 839 diagnosis of, 839, 842t

goals of treatment in, 840 mixed type, 847–848 in shock, 143, 144 Acid secretion, gastric in peptic ulcer disease, 314 reflux of, 263–272 Acidemia, metabolic, 840, 842 Acidosis metabolic, 839, 840–844 in cardiac arrest, 81 diabetic ketoacidosis, 211, 840 etiologies of, 842t in kidney disorders, 842t, 870–873 in mixed acid–base disorders, 847–848 in shock, 143 in status epilepticus, 642 respiratory, 839, 845–847 chronic, 847 in chronic obstructive pulmonary disease, 923 in mixed acid–base disorders, 847–848 in status epilepticus, 642 Acinetobacter infections, 381t Acitretin in psoriasis, 193, 194, 195 Acne vulgaris, 179–185 clinical presentation in, 179 conglobate, 180 definition of, 179 diagnosis of, 180 evaluation of therapeutic outcomes in, 185 general approach to treatment in, 180 goals of therapy in, 180 nodulocystic, 180, 184 nonpharmacologic therapy in, 180 papulopustular, 180 pathophysiology in, 179 systemic pharmacotherapy in, 184–185 topical pharmacotherapy in, 180–184 treatment algorithm on, 181f ACTH. See Adrenocorticotropic hormone Acute coronary syndromes, 43–59, 130. See also Myocardial ischemia and infarction Acute Physiology and Chronic Health Evaluation II (APACHE II) score in sepsis and septic shock, 490t, 492

975

INDEX Acyclovir dose adjustment in kidney disease, 877t in herpes simplex virus infections, 503, 505t in HIV infection, 446t in pregnancy, 504 in meningitis, 395t in varicella-zoster virus infection and HIV infection, 446t Adalimumab adverse effects of, 36t, 40, 192, 292 in inflammatory bowel disease, 286–287, 290f, 291, 292 in psoriasis, 192 in rheumatoid arthritis, 33, 35t, 36t, 39–40 Adapalene in acne vulgaris, 182–183 Addiction, 823, 835 Addison’s disease, 203, 207–209 Adefovir in hepatitis B, 277, 278f, 279f Adenocarcinoma of prostate, 713 Adenoma of adrenal gland, Cushing’s syndrome in, 203, 205t of pituitary, hyperthyroidism in, 229 of thyroid, 228, 230 Adenosine in paroxysmal supraventricular tachycardia, 69 Adipose tissue, 663 Adrenal gland disorders, 203–209 crisis in, 209 Cushing’s syndrome in, 203–207 primary insufficiency, Addison’s disease in, 203, 207–209 secondary insufficiency, 203, 207, 209 α-Adrenergic agonists in urinary incontinence, 947t, 948 α2-Adrenergic agonists in glaucoma, 722t, 724 in hypertension, 114, 117t, 122–123 β2-Adrenergic agonists in asthma, 909, 913, 913t, 920 in acute severe exacerbation, 914t in combination therapy, 919 in chronic obstructive pulmonary disease, 924, 926 in acute exacerbation, 929 α-Adrenergic antagonists in hypertension, 114, 117t, 122 in prostate hyperplasia, benign, 933–934 β-Adrenergic blockers adverse effects of, 53, 121 for antipsychotic drug side effects, 807t

976

in arrhythmias, 64, 64t in atrial fibrillation and flutter, 65, 66 in bradyarrhythmias, 72–73 in paroxysmal supraventricular tachycardia, 69 in premature ventricular complexes, 71 in glaucoma, 721, 722t, 724 in heart failure, 85, 87–88, 96 and hypertension, 124 in hypertension, 114, 117t, 121 in diabetes mellitus, 226 indications for, 124, 125, 126, 127 in hyperthyroidism, 232 interaction with other drugs, 793t, 794t in migraine prophylaxis, 608t, 610 in myocardial ischemia and infarction, 134–135, 136, 137 adverse effects of, 53 and hypertension, 124 non–ST-segment elevation, 54, 56 in secondary prevention, 57, 58 ST-segment elevation, 48, 53 and stable exertional angina, 139 therapeutic outcome in, 142 in social anxiety disorders, 751 in variceal hemorrhage, 243, 245t, 246 Adrenocorticotropic hormone in adrenal insufficiency, 208 in Cushing’s syndrome, 203, 206–207 ectopic production of, 203, 205t, 206 in gout, 6 Adrenolytic agents in Cushing’s syndrome, 206 Adriamycin. See Doxorubicin Adsorbents in diarrhea, 258, 262t African Americans, hypertension therapy in, 127 Agoraphobia, 736, 747 Agranulocytosis, drug-induced, 812, 958t Akathisia from antipsychotic drugs, 808 Alanine transaminase levels in liver disorders, 241, 963t Albumin administration in hypovolemic shock, 146, 149, 150 serum levels in nutritional assessment, 650t, 654 Albuterol in asthma, 913, 913t, 914t in bronchitis, chronic, 469 in chronic obstructive pulmonary disease, 469, 924, 926 in hyperkalemia, 893, 894t

INDEX Alclometasone dipropionate in psoriasis, 189t Alcohol use and alcoholism, 823–824 acetaminophen hepatotoxicity in, 12 blood levels of alcohol in, 823, 824, 824t dependence in, 835 drug interactions in, 791t, 792t intoxication in, 823, 830t pancreatitis in, 305, 309, 310 pneumonia in, 474t in posttraumatic stress disorder, 738 withdrawal symptoms in, 824, 832, 833t–834t Aldosterone antagonists in acute coronary syndromes, 58 in heart failure, 85, 88–89 in hypertension, 116t, 118 Aldosteronism, hypertension in, 111, 112 Alefacept in psoriasis, 192 Alendronate in osteoporosis, 23, 26t, 30 Alfuzosin in benign prostatic hyperplasia, 933t Alginic acid and antacids in gastroesophageal reflux disease, 266 Aliskiren in hypertension, 117t, 122 Alkaline phosphatase levels in liver disorders, 241, 963t Alkalosis metabolic, 839, 844–845, 846f in mixed acid–base disorders, 847–848 respiratory, 839, 845 in mixed acid–base disorders, 847–848 in shock, 144 Allergic reactions in Aspergillus infection, 422–424 asthma in, 906, 909 drug-induced, 951t–954t from allopurinol, 7 anaphylaxis in, 951t, 953t from antipsychotic drugs, 812 classification of, 951t desensitization in, 953t–954t interstitial nephritis in, 973t to penicillin, 951t, 952t photoallergic reactions in, 196 skin reactions in, 952t rhinitis in, 897–905 in pregnancy, 358 Allopurinol in gout, 7 Almotriptan in migraine headache, 604t, 606, 607t Alosetron interaction with other drugs, 793t

Alprazolam abuse of, 824, 825 dependence on, 826t in generalized anxiety disorder, 740, 743t, 744t, 745 interaction with other drugs, 793t in nausea and vomiting, 299t in panic disorder, 747, 747t, 749 withdrawal from, 825 Alprostadil in erectile dysfunction, 938t, 939, 942–943 Alteplase in acute coronary syndromes, 50, 52 in ischemic stroke, 159t, 159–160, 161t inclusion and exclusion criteria for, 160t in venous thromboembolism, 175 Aluminum acetate in contact dermatitis, 199 Aluminum carbonate in chronic kidney disease, 872t Aluminum hydroxide in chronic kidney disease, 872t Alzheimer’s disease, 727–734 clinical presentation of, 728, 729t definition of, 727 diagnosis of, 728–729 evaluation of therapeutic outcomes in, 733–734 goals of therapy in, 729 nonpharmacologic therapy in, 729–730 pathophysiology in, 727 pharmacotherapy in, 730–733 for cognitive symptoms, 730t, 730–732, 731t for noncognitive symptoms, 732–733, 733t stages of, 728, 728t Amantadine for antipsychotic drug side effects, 807t, 808, 810 in influenza, 453, 455, 466 in Parkinson’s disease, 630, 631–632, 632t Amcinonide in psoriasis, 189t Amenorrhea in menopause, 342 in premature ovarian failure, 351–352 American Academy of Pediatrics recommendations on rehydration therapy, 426 American Association of Clinical Endocrinologists on diabetes mellitus therapy goals, 212t

977

INDEX American College of Cardiology angina pectoris treatment recommendations, 137, 138t heart failure staging system, 83, 84f American College of Endocrinology on diabetes mellitus therapy goals, 212t American College of Gastroenterology variceal hemorrhage treatment recommendations, 245 American Diabetes Association on goals of therapy in diabetes mellitus, 212t, 225 American Heart Association angina pectoris treatment recommendations, 137, 138t cardiopulmonary resuscitation guidelines, 75, 76t heart failure staging system, 83, 84f stroke therapy guidelines, 159, 160 American Rheumatism Association classification criteria on rheumatoid arthritis, 32, 32t American Society of Anesthesiologists assessment score, 522, 523t American Stroke Association guidelines on stroke therapy, 159, 160 Amikacin dose adjustment in kidney disease, 542t, 877t in meningitis, 397 in tuberculosis, 539t, 542t in urinary tract infections, 547t Amiloride in diabetes insipidus, 884t in hypertension, 116t in renal failure, acute, 855 Amino acids in parenteral nutrition, 670–672, 673, 674 in adult regimen, 675f osmolarity of, 673t γ-Aminobutyric acid receptors in anxiety disorders, 735 Aminoglutethimide in breast cancer, 685 in Cushing’s syndrome, 205t, 206 in prostate cancer, 718 Aminoglycoside antibiotics in cellulitis, 515t, 516t, 517 in combination therapy, 384 in endocarditis, 407, 410 interaction with other drugs, 383t nephrotoxicity of, 972t in urinary tract infections, 547t, 551, 552 Aminophylline in asthma, 916

978

in chronic obstructive pulmonary disease, 927 5-Aminosalicylic acid. See Mesalamine p-Aminosalicylic acid in tuberculosis, 539t, 542t Amiodarone in arrhythmias, 64, 64t, 79 in atrial fibrillation and flutter, 65, 67, 69 in cardiopulmonary resuscitation, 76t, 79 intravenous dosage of, 66t side effects of, 67t in ventricular tachycardia, 71 Amitriptyline in depression, 782t, 784t, 790t in insomnia, 816 in migraine prophylaxis, 608t, 610 in posttraumatic stress disorder, 753t, 754 Amlodipine in hypertension, 116t, 120 in ischemic heart disease, 137, 139 Ammonia blood levels in hepatic encephalopathy, 240, 248 Amobarbital dependence, 826t Amoxapine in depression, 785 Amoxicillin in bronchitis, chronic, 470t in chlamydial infections, 503t in pregnancy, 357, 494, 503t in endocarditis prophylaxis, 411t in otitis media, 479, 480t in peptic ulcer disease, 316, 318, 318t in pharyngitis, 482t in pneumonia, 475t in sinusitis, 485t, 486 skin reactions from, 952t in surgical site infections, 526t in urinary tract infections, 548t, 549t, 551 in pregnancy, 553 Amoxicillin-clavulanate in bite wounds, 513t, 520, 521 in cellulitis, 516t in chronic obstructive pulmonary disease, 470t, 930 in diabetic foot infections, 512t, 517 in otitis media, 479, 480t in pharyngitis, 483t in pneumonia, 475t, 476t in sinusitis, 485t in urinary tract infections, 547t, 548t, 549t in pregnancy, 553 Amphetamines interaction with other drugs, 792t

INDEX in narcolepsy, 821, 821t in obesity, 667 Amphotericin B in blastomycosis, 416, 417t in candidiasis, 422, 423t–424t in coccidioidomycosis, 418 in HIV infection, 445t in cryptococcosis, 419, 420t–421t in histoplasmosis, 413t, 414t, 415 in HIV infection, 445t interaction with other drugs, 383t in meningitis, 392t, 395t, 398 in HIV infection, 445t nephrotoxicity of, 854 Ampicillin in bronchitis, chronic, 470t in endocarditis, 407, 408t, 411t in meningitis, 392t, 395t, 396 in pneumonia, 475t skin reactions from, 952t in streptococcal group B infection in pregnancy, 361 in surgical site infections, 526t in urinary tract infections, 547t, 551 Ampicillin-sulbactam in bite wounds, 520, 521 in intraabdominal infections, 460t, 462t in pneumonia, 475t in urinary tract infections, 547t Amprenavir in HIV infection, 442t Amylase replacement therapy in pancreatitis, 311, 312t serum levels in pancreatitis, 306, 310 Anabolic therapy in osteoporosis, 29 Anakinra in rheumatoid arthritis, 36t, 40 Analgesia in labor and delivery, 361 regional, local anesthetics in, 627, 627t Analgesics, 616–628 dosage of, 619t–622t in migraine headache, 603t, 605 in tension-type headache, 612 Anaphylaxis in allergic drug reactions, 951t, 953t shock in, 143 treatment of, 953t Anastrozole in breast cancer, 685, 686, 686t Androgens and antiandrogens in prostate cancer, 714, 716 in combined hormonal blockade, 716–717 in salvage therapy, 718

in breast cancer, 686t interaction with other drugs, 792t in menopause therapy, 346, 346t Anemia, 363–370 aplastic, drug-induced, 958t in children, 364, 366, 369 in chronic disease, 363, 366 evaluation of therapeutic outcomes in, 369–370 of kidney, 865–868, 866f, 867f treatment of, 367–369 classification of, 363, 364t in critical illness, 363, 366, 369 diagnosis of, 365t, 365–366 drug-induced, 363, 958t–960t in elderly, 363, 366 folate deficiency, 363, 365 diagnosis of, 366 evaluation of therapeutic outcomes in, 369 treatment of, 367, 369 hemolytic, 364 diagnosis of, 366 drugs associated with, 959t, 960t treatment of, 369 in inflammatory bowel disease, 292 iron deficiency. See Iron, deficiency of macrocytic, 363, 366 megaloblastic, 369 drugs associated with, 960t microcytic, 363 pernicious, 363, 367 of prematurity, 369 sickle cell, 371–376 vitamin B12 deficiency, 363, 365 diagnosis of, 366 evaluation of therapeutic outcomes in, 369 treatment of, 367, 369 Anesthetics, local, 627, 627t Angel dust (phencyclidine), 829, 830t, 831 Angina, 130–142 clinical presentation in, 44, 131–132 drug therapy in, 134–142 exertional, 134 treatment of, 137–139, 138t goals of therapy in, 133 risk factor modification in, 134 stable, 43 treatment of, 137–139, 138t, 140f–141f unstable, 43, 132, 133 variant, 54, 132 Prinzmetal’s, 54, 132 treatment of, 139–142

979

INDEX Angioedema, from ACE inhibitors in hypertension, 119 Angiography in ischemic heart disease, 133 in venous thromboembolism, 165 Angioplasty in acute coronary syndromes, 48 Angiotensin-converting enzyme inhibitors in acute coronary syndromes, 48 and hypertension, 124 in secondary prevention, 57, 58 in heart failure, 84–85, 86t, 86–87, 88 and hypertension, 124 in hypertension, 113, 114, 116t, 118–119 adverse effects of, 119 contraindication in pregnancy, 119 in diabetes mellitus, 226 indications for, 124, 125, 126, 127 in ischemic stroke, 159t, 160 Angiotensin receptor blockers in acute coronary syndromes, 58 and hypertension, 124 in heart failure, 84–85, 88 and hypertension, 124 in hypertension, 113–114, 116t, 119–120 in diabetes mellitus, 226 indications for, 124, 125, 126, 127 Animal bite wounds, 510t, 511t, 519–520 antibiotics in, 511t, 513t, 520 Animal dander, allergic rhinitis from, 897 Anion gap in metabolic acidosis, 840 Antacids in gastroesophageal reflux disease, 265, 267t in nausea and vomiting, 298t, 300 in pancreatitis, chronic, 312 Anthralin in psoriasis, 191, 194 Anthropometric measurements in nutritional assessment, 648, 649t, 654 Antiandrogens in prostate cancer, 714, 716 in combined hormonal blockade, 716–717 in salvage therapy, 718 Antianxiety agents, 740–755 Antiarrhythmic drugs, 63–73 in cardiopulmonary resuscitation, 79 classification of, 63–65, 64t intravenous dosage of, 66t side effects of, 67t Antibiotics, 377–387 in acne vulgaris systemic agents, 184–185 topical agents, 180, 181f, 183

980

anxiety symptoms from, 740t in bite wounds, 511t, 513t, 520–521 in bronchiolitis, 471 in bronchitis acute, 466 chronic, 469, 470t in cellulitis, 515t–516t, 517 in chlamydial infections, 382t, 497t, 502, 503t, 551 in chronic obstructive pulmonary disease, 469, 470t in acute exacerbation, 929–930 in combination therapy, 384 in diabetic foot infections, 511t, 512t, 517–518 in endocarditis, 401–411 evaluation of response to, 407, 410 prophylactic use of, 410t, 410–411, 411t failure of therapy with, 385–386 in gastrointestinal infections, 426–427, 429t in gonorrhea, 380t, 494, 496, 497t–498t interaction with other drugs, 379, 383t in intraabdominal infections, 460t, 460–464, 461t–462t evidence-based treatment principles on, 462, 463t in meningitis, 388, 389–398. See also Meningitis, antibiotics in minimum inhibitory concentration of, 379, 384 monitoring therapeutic response to, 384–386 nephrotoxicity of, 972t in otitis media, 479–480, 480t in pancreatitis, 308 in peptic ulcer disease, 316–318, 318t in peritonitis, spontaneous bacterial, 247 pharmacokinetics and pharmacodynamics of, 379, 384 in pneumonia, 474t–476t, 477 in pressure ulcers, 519 in prostatitis, 549t, 555 pseudomembranous colitis from, 430 resistance to, 385–386 selection of, 377–387 drug factors in, 379, 384, 385 host factors in, 379, 385 pathogen factors in, 378, 385–386 systematic approach to, 378t in sepsis, 490t, 490–491, 491t in sickle cell disease, 373, 375 in sinusitis, 485, 485t, 486

INDEX in skin and soft-tissue infections, 511t–513t in streptococcal group B infection in pregnancy, 361 in surgical site infections, 522–531 indications for, 523t scheduling of, 524, 524t selection of, 524–525 in syphilis, 382t, 500, 501t in urinary tract infections, 546–555 common agents in, 547t–548t dosage in outpatient therapy, 548t Anticholinergic effects of antidepressant drugs, 783t–784t, 785 of antihistamines, 900, 900t, 901 of antipsychotic drugs, 806t, 806–807 Anticholinergic medications in asthma, 914t, 917–918 in chronic obstructive pulmonary disease, 926 in combination with sympathomimetics, 926 interaction with other drugs, 792t in nausea and vomiting, 298t, 300 in Parkinson’s disease, 631, 632t in urinary incontinence, 947t Anticoagulants in acute coronary syndromes non–ST-segment elevation, 54, 56 in secondary prevention, 57–58 ST-segment elevation, 52 in atrial fibrillation and flutter, 66, 67, 69 in venous thromboembolism, 165–170, 171–175 evaluation of therapeutic outcomes in, 177 prophylactic use of, 176t Anticonvulsant drugs in Alzheimer’s disease, 733t anxiety symptoms from, 740t in bipolar disorder, 764t–765t, 767t–769t in epilepsy, 580–598 adverse effects of, 586–589, 587t–588t dosage and administration of, 589, 592t–593t efficacy of, 586 in females, 580, 583 interaction with other drugs, 580, 589, 590t–591t pharmacokinetics of, 583, 585t, 586 in pregnancy, 583 serum concentration of, 586 in status epilepticus, 639–646

in generalized anxiety disorder, 742t in lung cancer metastasis to brain, 703 in migraine prophylaxis, 610–611 Antidepressant drugs, 781–798 in Alzheimer’s disease, 732–733, 733t in bipolar disorder, 764t–765t, 766 in cataplexy, 822 in depression, 781–798 in children and adolescents, 792, 794 dosage of, 782t, 796 in elderly, 791–792, 796 interaction with foods, 787, 787t interaction with other drugs, 787, 788, 788t, 791, 791t–794t pharmacokinetics of, 787–788, 789t–790t relative potency of, 783t–784t therapeutic plasma concentration of, 782t, 788 in generalized anxiety disorder, 742t, 743 in insomnia, 816 in migraine prophylaxis, 608t, 610 in panic disorder, 747, 747t, 749 in posttraumatic stress disorder, 753t, 753–755 in pregnancy, 360, 794–795 side effects of, 783t–784t, 785–787 anxiety symptoms in, 740t suicidal behavior in, 742–743, 792, 794 in urinary incontinence, 947t Antidiuretic hormone secretion, 881 inappropriate, 881, 882 therapy in cardiopulmonary resuscitation, 76t, 77, 79, 80 in shock, 154 in variceal hemorrhage, 245 Antiemetic drugs, 296–304, 302t, 303t in children, 304 dosage of, 298t–299t in migraine headache, 602 in pregnancy, 304 Antiepileptic drugs, 580–598. See also Anticonvulsant drugs Antiestrogens in breast cancer, 684–685, 686, 686t Antifungal agents in aspergillosis, 422, 424, 425 in blastomycosis, 416, 417t in candidiasis, 422, 423t–424t in coccidioidomycosis, 418 in cryptococcosis, 419–421, 420t–421t

981

INDEX Antifungal agents (cont.) in histoplasmosis, 413t–414t, 415 in meningitis, 395t Antihistamines in allergic rhinitis, 900t, 900–902 dosage and administration of, 901t side effects of, 900t, 900–901, 902 in atopic dermatitis, 201 in nausea and vomiting, 298t, 300 Antihypertensive drugs, 113–129 anxiety symptoms from, 740t in chronic kidney disease, 860, 863f, 873 dosage and frequency of, 116t–117t in hypertensive urgencies and emergencies, 128, 129t indications for, 124–127 in pregnancy, 356, 359 selection of, 115f Antihyperuricemic drugs, 7–8 Antiinflammatory drugs, nonsteroidal in Alzheimer’s disease, 732 anxiety symptoms from, 740t in gout, 3–5, 4f, 5t in migraine headache, 603t, 605 in prophylaxis, 608t, 611 in osteoarthritis, 12, 15, 17 dosage and frequency of, 14t selection of, 12, 13f in pain management, 616, 620t, 628 in pancreatitis, chronic, 310 peptic ulcer disease from, 314, 315, 316 treatment of, 318–319 in rheumatoid arthritis, 34, 35t, 36t, 37t in tension-type headache, 612 Antiinflammatory response syndrome, compensatory, 488, 488t Antimotility agents in diarrhea, 258, 262t Antiplatelet therapy in ischemic stroke, 159t Antipsychotic drugs in alcohol withdrawal, 833t in Alzheimer’s disease, 732, 733t in bipolar disorder, 769t–770t, 771, 772t in schizophrenia, 800–813 adverse effects of, 806t, 806–813, 807t dosage of, 801, 803t in initial therapy, 803 interaction with other drugs, 813 in maintenance therapy, 804–805 pharmacokinetics of, 801, 804t in pregnancy, 813 in stabilization therapy, 804

982

Antiresorptive therapy in osteoporosis, 20–29 Antiretroviral therapy in HIV infection, 438–444, 439t–440t failure of, 443–444 interaction with other drugs, 441 and lymphoma, 711 outcome evaluation in, 443–444 pharmacologic characteristics of agents in, 442t–443t in postexposure prophylaxis, 441–443 in pregnancy, 359, 438, 441 Antirheumatic drugs, 33–38 dosage of, 35t–36t monitoring of, 35t–36t treatment algorithm on, 34f Antisecretory agents in diarrhea, 258, 262t Antispasmodic agents in urinary incontinence, 947t α1-Antitrypsin deficiency, 921, 922 Antituberculous drugs, 535–543 Antiviral agents in herpes simplex virus infections, 503, 505t in influenza, 455 in meningitis, 395t Anuria in acute renal failure, 849 Anxiety disorders, 735–755 clinical presentation in, 736–738 definition of, 735 diagnosis of, 738 drugs associated with symptoms of, 738, 740t generalized algorithm on pharmacotherapy in, 741f clinical presentation in, 736, 736t pathophysiology in, 735–736 treatment of, 738, 740–747 goals of therapy in, 738, 740 medical illnesses associated with symptoms of, 738, 739t panic disorder, 736, 747–750 pathophysiology in, 735–736 posttraumatic stress disorder, 737–738, 753–755 social anxiety disorder, 737, 750–753 treatment of, 740–755 Aortic balloon pump in heart failure, 95 APACHE II score in sepsis and septic shock, 490t, 492 Aplastic anemia, drug-induced, 958t Aplastic crisis in sickle cell disease, 372, 375 Apnea drug-induced, 965t

INDEX in sleep, 819, 820f, 822 central, 819 obstructive, 819, 822 Apomorphine in erectile dysfunction, 938t in Parkinson’s disease, 632t, 636 Appendectomy, surgical site infections in, 526t, 529 Appendicitis, 462t, 463t Apraclonidine in glaucoma, 722t, 724 Aprepitant in nausea and vomiting, 301, 302t Arformoterol in chronic obstructive pulmonary disease, 926 Argatroban in venous thromboembolism, 169, 171 Aripiprazole in alcohol withdrawal, 833t in bipolar disorder, 763, 766, 769t, 771 in schizophrenia, 800, 810 dosage of, 803t pharmacokinetics of, 804t side effects of, 806t, 810 Aromatase inhibitors in breast cancer, 685–686, 686t Arrhythmias, 60–73 atrial. See Atrial arrhythmias bradyarrhythmias, 61–62, 63, 72–73 cardiopulmonary arrest in, 74, 77–80 cardiopulmonary resuscitation in, 72 clinical presentation in, 62 definition of, 60 diagnosis of, 62–63 electrocardiography in, 62–63 in hyperkalemia, 893 in hypokalemia, 892 in hypomagnesemia, 895, 895t pathophysiology in, 60–62 tachycardia. See Tachycardia treatment of, 63–73 goals in, 63 outcome in, 73 ventricular. See Ventricular arrhythmias Arsenic exposure, 963t Arthritis degenerative, 9–17. See also Osteoarthritis gonococcal, 493 in gout, 2–8 treatment of, 3–8, 4f, 5t in inflammatory bowel disease, 282 psoriatic, 187 rheumatoid, 31–41. See also Rheumatoid arthritis in Yersinia infections, 433

Articaine with epinephrine in regional analgesia, 627t Ascites, 239 management of, 242–243, 246, 248t outcome assessment in, 248t Aspartate transaminase levels in liver disorders, 241, 963t Aspergilloma, 424–425 Aspergillosis, 422–425 allergic bronchopulmonary, 422–424 Aspiration pneumonia, 474t Aspirin in acute coronary syndromes adverse effects of, 51, 57 non–ST-segment elevation, 54, 56 in secondary prevention, 57 ST-segment elevation, 48, 50–51 asthma from, 967t in atrial fibrillation and flutter, 69 in bronchitis, acute, 466 in migraine headache, 603t, 605, 608t in osteoarthritis, 12, 14t in pain management, 616, 619t, 620t peptic ulcer disease from, 314, 316 in pregnancy, 356 in rheumatoid arthritis, 37t in stroke, ischemic, 159t, 160, 161t in tension-type headache, 612 Asplenia, vaccinations in, 556, 565t Asthma, 906–920 in allergic rhinitis, 898, 907 aspirin-induced, 967t clinical presentation of, 907–908 definition of, 906 diagnosis of, 908 evaluation of therapeutic outcomes in, 920 in exercise-induced bronchospasm, 908–909, 913 goals of therapy in, 908–909 home management of, 909, 912f hypertension management in, 127 nocturnal, 913 nonpharmacologic therapy in, 909 pathophysiology in, 906–907 pharmacotherapy in, 909–920 in acute severe exacerbation, 914t in pregnancy, 358, 909 treatment algorithms on, 910f–911f Asystole, 75, 77, 80 Atazanavir in HIV infection, 439t, 441, 442t Atenolol in acute coronary syndromes, 53 in hypertension, 117t, 121 in migraine prophylaxis, 608t, 610 in social anxiety disorders, 751

983

INDEX Atheromas, 99 Atherosclerosis of carotid artery, ischemic stroke in, 156 of coronary artery. See Coronary artery disease lipid levels in, 58–59, 98, 109. See also Lipid levels Atopic dermatitis, 196, 197 diagnosis of, 198 treatment of, 199–201, 200f Atorvastatin in hyperlipidemia, 104t, 105t, 106, 109 Atovaquone in Pneumocystis jiroveci pneumonia, 445t Atrial arrhythmias, 65–71 algorithm on treatment of, 68f clinical presentation in, 62 diagnosis of, 62 fibrillation. See Fibrillation, atrial flutter. See Flutter, atrial goals of treatment in, 63 intravenous drug dose in, 66t pathophysiology in, 60 tachycardia, automatic, 60, 71 thromboembolism risk in, 66, 69 Atrioventricular block, 62, 63, 73 Atropine in atrioventricular block, 73 in cardiopulmonary resuscitation, 76t, 77, 80 in diarrhea, 261 in erectile dysfunction, 942 Attapulgite in diarrhea, 262t Aura in migraine, 599 Auranofin in rheumatoid arthritis, 33, 35t, 38 Aurothioglucose in rheumatoid arthritis, 38 Auspitz sign in psoriasis, 186 Automated external defibrillator use in cardiopulmonary arrest, 75, 77 Autonomic nervous system, antipsychotic drugs affecting, 806–807 Azathioprine in inflammatory bowel disease, 286 adverse effects of, 292 in Crohn’s disease, 289, 290f, 291 in ulcerative colitis, 289 in rheumatoid arthritis, 33, 38–39 adverse effects of, 36t, 39 dosage and monitoring of, 35t Azelaic acid in acne vulgaris, 180, 181f, 183 Azelastine in allergic rhinitis, 900t, 901–902

984

Azithromycin in acne vulgaris, 184 in bronchitis acute, 466 chronic, 470t, 930 in chancroid, 507t in chlamydial infections, 502, 503t, 551 in pregnancy, 357, 494, 503t in chronic obstructive pulmonary disease, 470t, 930 in acute exacerbation, 930 in endocarditis prophylaxis, 411t in gastrointestinal infections, 429t, 431 in gonorrhea, 494 in otitis media, 480t in pneumonia, 475t in sinusitis, 485t in urinary tract infections, 547t, 548t Azotemia, prerenal, 849, 852t Aztreonam in intraabdominal infections, 460t, 461t in meningitis, 395t in urinary tract infections, 548t, 551 B B cells in rheumatoid arthritis, 31, 39 Back pain in osteoporosis-related spinal fractures, 18, 19 Bacteremia definition of, 488t in Salmonella infections, 431, 432 in HIV infection, 446t in Yersinia infections, 433 Bacterial infections acute exacerbation of COPD in, 929–930 antibiotics in. See Antibiotics bronchiolitis in, 470, 471 bronchitis in, 465, 466 diagnosis in, 377, 378 endocarditis in, 399–411 of gastrointestinal tract, 426–433 gonorrhea in, 493–496 in HIV infection and AIDS, 446t meningitis in, 387–398 otitis media in, 478–480 peritonitis in, 456–464 spontaneous, 243, 247, 248t pharyngitis in, 481–484 pneumonia in, 471–477 prostatitis in, 554–555 sepsis in, 487, 488, 490–491, 491t sexually transmitted, 494t sinusitis in, 484–486

INDEX of skin and soft tissues, 509–521 of surgical wounds, 522–531 of urinary tract, 544–554 in pregnancy, 356–357, 361, 553 Bacteriuria asymptomatic, 551 in catheterization, 553–554 diagnostic criteria in, 545–546, 546t in pregnancy, 356–357, 361, 553 Bacteroides infections antibiotics in, 381t peritonitis in, 457, 458t Balance disorders, nausea and vomiting in, 303–304 Balloon pump, intraaortic, in heart failure, 95 Balneotherapy in psoriasis, 187 Balsalazide in inflammatory bowel disease, 287t Band ligation, endoscopic, in variceal hemorrhage, 243, 245, 245t, 246 Barbiturates dependence on, 826t withdrawal symptoms from, 826t, 831t Barium studies in gastroesophageal reflux disease, 264 Barrett’s esophagus, 263, 264, 269 Barrier methods of contraception, 322, 324t–325t with spermicide, 326 Basic life support in cardiopulmonary arrest, 75–77 Beclomethasone dipropionate in allergic rhinitis, 903t in asthma, 915t in psoriasis, 189t Benazepril in hypertension, 116t Benserazide, 632 Benzodiazepines abuse of, 824–825 in anxiety disorders, 745 in alcohol withdrawal, 832, 834t for antipsychotic drug side effects, 807, 807t in anxiety disorders, 735, 743t, 743–746 abuse and dependence on, 745 adverse effects of, 744 discontinuation of therapy, 745 dosage of, 743t, 745–746 interaction with other drugs, 745, 746t in panic disorder, 747t, 749 pharmacokinetics of, 744, 744t in social anxiety disorder, 751, 751t

in bipolar disorder, 766 dependence on, 745, 825, 826t in insomnia, 817–818, 818t intoxication from, 825, 830t in nausea and vomiting, 299t in status epilepticus, 642, 644 withdrawal from, 745, 825, 826t, 831t, 832 Benzoyl peroxide in acne vulgaris, 180–182 Benztropine for antipsychotic drug side effects, 807, 807t, 808 in Parkinson’s disease, 632t Bepridil interaction with other drugs, 792t Beta blockers. See β-Adrenergic blockers Betamethasone in adrenal insufficiency, 208t in preterm delivery, 360 in psoriasis, 189t Betaxolol in glaucoma, 722t in hypertension, 117t, 121 Bethanechol in gastroesophageal reflux disease, 271 in urinary incontinence, 947t Bevacizumab in breast cancer, 687 in colorectal cancer, 692–693 metastatic, 694, 695t, 698 side effects of, 698 in lung cancer, 702 Bicalutamide in prostate cancer, 716, 717t in prostate hyperplasia, benign, 933, 933t Bicarbonate serum levels, 839, 840t in metabolic acidosis, 840, 842 in chronic kidney disease, 870, 873 in metabolic alkalosis, 844 Bicarbonate therapy in cardiopulmonary arrest, 81 in gastroesophageal reflux disease, 270 in hyperkalemia, 893, 894t in metabolic acidosis, 842, 843t, 844 in chronic kidney disease, 870 in ventricular proarrhythmias, 72 Bichloracetic acid in genital papillomavirus warts, 507t Biguanides in diabetes mellitus, 217t, 218 Bile acid resins in hyperlipidemia, 103–105, 108 in combination therapy, 108 monitoring of, 110 Biliary tract surgical infections, 525, 526t

985

INDEX Bimatoprost in glaucoma, 721, 723t Bioelectrical impedance analysis, 648 Biologic agents in breast cancer, 682, 687 in lymphoma, non-Hodgkin’s, 709–710 in rheumatoid arthritis, 33, 39–40 Biopsy in breast cancer, 681 in lung cancer, 699 Biperiden for antipsychotic drug side effects, 807t, 808 Bipolar disorder, 756–777 clinical presentation and diagnosis of, 756, 759t–761t course of illness in, 757, 761 definition of, 756 etiology and pathophysiology in, 756, 757t, 758t–759t evaluation of therapeutic outcomes in, 777 general principles in management of, 762t goals of treatment in, 761, 762t mixed episodes in, 757, 761t, 764t–765t nonpharmacologic therapy in, 761–763 pharmacologic therapy in, 763–777 monitoring of, 772t–773t, 777 in pregnancy, 766, 776 rapid cycling, 757, 761, 761t Bisacodyl in constipation, 252, 253t Bismuth subsalicylate in diarrhea, 258, 262t in peptic ulcer disease, 317, 318, 318t Bisoprolol in heart failure, 87 in hypertension, 117t, 121 Bisphosphonates in osteoporosis, 23–25, 26t–27t, 30 Bite wounds, 519–521 animal, 510t, 511t, 519–520 antibiotics in, 511t, 513t, 520 human, 510t, 511t, 513t, 520–521 Bitolterol in chronic obstructive pulmonary disease, 924 Bivalirudin in acute coronary syndromes, 54, 56 in venous thromboembolism, 169, 171 Blackhead (open comedo), 179 Bladder cystitis of, 544, 549t, 550–551 overactivity of, urinary incontinence in, 944 differential diagnosis of, 945t

986

pharmacologic therapy in, 947t, 948–949 underactivity of, urinary incontinence in, 944, 945 diagnosis of, 946 pharmacologic therapy in, 947t Blastomycosis, 416, 417t Bleeding disorders in heparin therapy, 168, 170 in uremia, 874 in warfarin therapy, 172, 174f Bleomycin in Hodgkin’s lymphoma, 705t, 707t Blood pressure in diabetes mellitus, 120, 125, 225–226 diastolic, 111, 112t goals for, 113 in heart failure, 96, 97 in hypertension, 111–129. See also Hypertension in hypotension. See Hypotension monitoring of, 128–129 in shock, 143, 144, 155 in stroke, 158 systolic, 111, 112t Body mass index, 648, 649t in obesity, 664, 664t Bone mineral density in osteoporosis, 18, 19 and bisphosphonate therapy, 23 and estrogen therapy, 28 glucocorticoid-induced, 30 monitoring of, 30 and teriparatide therapy, 29 and testosterone therapy, 29 treatment algorithm on, 21f–22f Borrelia burgdorferi infections, 382t Bouchard’s nodes, 10 Bradyarrhythmias clinical presentation in, 62 diagnosis of, 63 pathophysiology in, 61–62 treatment in, 72–73 Bradykinesia in Parkinson’s disease, 629 Breast cancer, 679–688 clinical presentation in, 679 diagnosis of, 679–680 early stage, 680 treatment in, 681–685, 688 epidemiology of, 679 goals of therapy in, 681 locally advanced (stage III), 680 treatment in, 685, 688 in menopause hormone therapy, 342, 350 metastatic, 679, 680, 685–688

INDEX in oral contraceptive use, 334 pathologic evaluation in, 680 prevention of, 688 prognostic factors in, 680 staging of, 680 Breast-feeding contraception in, 338 drug use in, 361–362 in schizophrenia therapy, 813 Breathing disorders in sleep, 819, 820f Bretylium in arrhythmias, 64 Brimonidine in glaucoma, 721, 722t, 723t Brinzolamide in glaucoma, 723t Bromocriptine in neuroleptic malignant syndrome, 810 in Parkinson’s disease, 632t, 635 in withdrawal symptoms, 831t Brompheniramine maleate in allergic rhinitis, 900t Bronchiolitis, 470–471, 471t Bronchitis, 465–469 acute, 465–466 chronic, 467–469, 921–930 acute exacerbation of, 923, 928–930 classification of, 467, 468t clinical presentation in, 467, 469t pneumonia in, 474t Bronchodilator drugs anxiety symptoms from, 740t in chronic obstructive pulmonary disease, 924, 926 in acute exacerbation, 929 Bronchospasm drug-induced, 965t–966t exercise-induced, 908–909, 913 Brudzinski’s sign, 388 Budesonide in asthma, 915t, 919 in chronic obstructive pulmonary disease, 928 in Crohn’s disease, 290f in rhinitis, allergic, 903t Buffer systems in acid–base balance, 839 Bumetanide in heart failure, 85, 86t, 91 in hypertension, 116t in renal failure, acute, 855 Bupivacaine in regional analgesia, 627t Buprenorphine in opiate withdrawal, 831t, 832 in pain management, 622t, 624t Bupropion in depression, 785 and cytochrome P450 activity, 795t dosage of, 782t, 796

in elderly, 792 interaction with other drugs, 794t pharmacokinetics of, 789t refractory, 795 relative potency of, 783t side effects of, 783t, 786 in smoking cessation, 835, 836, 837t, 838 Burns, infections in, 510t Buspirone in generalized anxiety disorder, 742t, 745, 746–747 interaction with other drugs, 746 in social anxiety disorder, 751t Butalbital in migraine headache, 603t, 605 Butorphanol in migraine headache, 604t, 607 in pain management, 622t, 624t Butyrate in sickle cell disease, 373 Butyrophenones in nausea and vomiting, 299t C C-reactive protein in pancreatitis, 307 Caffeine interaction with other drugs, 794t in migraine headache, 603t, 605 in osteoporosis, 20 in panic disorder, avoidance of, 749 Calcipotriene in psoriasis, 190, 194 Calcipotriol in psoriasis, 193 Calcitonin in hypercalcemia, 885, 887t in osteoporosis, 27t, 28 Calcitriol in kidney disease, chronic, 870, 873t in osteoporosis, 26t Calcium in osteoporosis, intake of, 20, 26t, 30 food sources of, 20, 24t preparations available, 25t recommended daily, 23t treatment algorithm on, 21f–22f in parenteral nutrition solutions, 673, 673t, 674 in pregnancy, 356 serum levels of, 885–888 in hypercalcemia, 885, 886f, 887t, 888 in hyperphosphatemia, 890 in hypocalcemia, 888, 889f, 890 in kidney disease, chronic, 868, 870t therapy with in hyperkalemia, 893, 894t in hypermagnesemia, 896

987

INDEX Calcium acetate in chronic kidney disease, 871t Calcium carbonate in kidney disease, chronic, 871t, 872t in osteoporosis, 20, 25t Calcium channel blockers in acute coronary syndromes, 53–54, 56, 58 in arrhythmias, 65, 69 in bipolar disorder, 770t in hemorrhagic stroke, 161 in hypertension, 114, 116t–117t, 120–121 indications for, 125, 126, 127 in ischemic heart disease, 136–137 and stable exertional angina, 139 therapeutic outcome in, 142 and variant angina, 141–142 in migraine prophylaxis, 611 Calcium chloride in hypocalcemia, 888 Calcium citrate in osteoporosis, 20, 25t Calcium gluconate in hypocalcemia, 888 in parenteral nutrition solutions, 673t Calculi gallstone pancreatitis in, 305, 309 urinary, uric acid in, 2, 6 Calicivirus gastroenteritis, 434 Caloric intake, 651–653 in enteral nutrition, 658, 659t in kidney disease, chronic, 874 in obesity, 663 in parenteral nutrition, 672, 675f Calorimetry, indirect, 651, 653 Campylobacter infections, 433 antibiotics in, 429t, 433, 446t in HIV infection, 446t Cancer, 679–718. See also specific anatomic sites of breast, 679–688 colorectal, 689–698 hypercalcemia in, 885, 888 of lung, 699–703 nausea and vomiting in, 294, 297t in chemotherapy, 294, 296t pain management in, 628 treatment algorithm on, 618f of prostate, 713–718 Candesartan in acute coronary syndromes, 58 in heart failure, 88 in hypertension, 116t Candida infections, 421–422, 423t–424t hepatosplenic, 424t in HIV infection and AIDS, 445t intraabdominal, 463t, 464

988

sepsis in, 487 urinary, 424t, 545 Cannabinoids in nausea and vomiting, 299t, 301 Capecitabine in breast cancer, 684t, 687 in colorectal cancer, 692, 693 in adjuvant regimens, 694t metastatic, 696t Capreomycin in tuberculosis, 539t, 542t Capsaicin in osteoarthritis, 14t, 15 Captopril in acute coronary syndromes, 58 in heart failure, 86t in hypertension, 116t, 119, 128 Carbachol in glaucoma, 721, 722t Carbamazepine in Alzheimer’s disease, 733, 733t in bipolar disorder, 763, 766, 771, 774 dosage and administration of, 768t, 771 guidelines on, 764t monitoring of, 772t, 774 in diabetes insipidus, 884t interaction with other drugs in anxiety disorders, 746t in bipolar disorder, 771 in depression, 791t, 793t, 794t in seizures, 589, 590t–591t, 591 in schizophrenia, treatment-resistant, 806 in seizures, 586, 589–591 adverse effects of, 587t, 588, 589, 591 dosage and serum levels of, 593t indications for, 581t, 582t, 589 pharmacokinetics of, 585t, 589 Carbidopa in Parkinson’s disease, 632t, 632–634 adverse effects of, 633t, 633–634 Carbinoxamine maleate in allergic rhinitis, 900t Carbohydrates in oral rehydration solutions, 261t, 428t Carbon dioxide in arterial blood, 840t in chronic obstructive pulmonary disease, 923 in metabolic alkalosis, 844 in respiratory acidosis, 845, 847 in respiratory alkalosis, 845 in venous blood, 840t Carbon tetrachloride exposure, 963t Carboplatin in lung cancer, 700, 701t, 703 in lymphoma, 711

INDEX Carbuncles, 511t, 512t Carcinoembryonic antigen in colorectal cancer, 690, 698 Carcinoma adrenal, Cushing’s syndrome in, 203, 205t colorectal, 690. See also Colorectal cancer of lung, 699. See also Lung cancer Cardiac index in heart failure, 97 normal values for, 145t in shock, 144, 145, 155 Cardiac output in heart failure, 91 normal values for, 145t in shock, 144, 155 Cardiopulmonary arrest, 74–81 acidosis in, 81 advanced life support in, 77 basic life support in, 75–77 chain of survival in, 75 clinical presentation in, 74 definition of, 74 diagnosis of, 75 pathophysiology in, 74 treatment in, 75–81 algorithm on, 78f Cardiopulmonary resuscitation, 72 by bystander, 75, 76t chest compressions in, 74, 75–77, 81 evaluation of outcome in, 81 evidence-based guidelines on, 75, 76t mechanism of blood flow in, 74 return of spontaneous circulation in, 75 Cardiovascular disorders, 43–177 acute coronary syndromes, 43–59 from antipsychotic drugs, 810–811 anxiety symptoms in, 739t arrhythmias, 60–73 cardiopulmonary arrest in, 74–81 endocarditis, 399–411 heart failure, 82–97 in hyperkalemia, 893 hyperlipidemia, 98–110 in hypermagnesemia, 896 hypertension, 111–129 in hypokalemia, 892 in hypomagnesemia, 895, 895t ischemic heart disease, 130–142 shock, 143–155 stroke, 156–162 surgical site infections in, 527t, 530 venous thromboembolism, 163–177

Cardioversion in arrhythmias, 65 with implantable cardioverterdefibrillator, 63, 72 in supraventricular tachycardia, 69 in ventricular tachycardia, 71 Carnitine deficiency, 651 Carotid artery atherosclerosis, ischemic stroke in, 156 Carotid sinus hypersensitivity, 72 Carteolol in glaucoma, 722t in hypertension, 117t, 121 Carvedilol in heart failure, 87 in hypertension, 117t Caspofungin in aspergillosis, 425 Castor oil in constipation, 252, 255 Cat bites, 520 Cataplexy, 821, 821t, 822 Catechol-O-methyltransferase inhibitors in Parkinson’s disease, 630, 632t, 634–635 Cathartics, saline, in constipation, 252, 254–255 Catheter-related infections candidiasis in, 421 sepsis in, 491t of urinary tract, 553–554 CD4+ T cells in HIV infection, 435, 436t, 437, 438 in evaluation of treatment outcome, 443 Cefaclor in cellulitis, 515t in sinusitis, 485t in urinary tract infections, 547t Cefadroxil in impetigo, 512t in urinary tract infections, 547t Cefazolin in cellulitis, 514 in endocarditis, 406t, 411t in intraabdominal infections, 460t, 461t in peritonitis, dialysis-associated, 462 in surgical site infections, 524, 525, 529, 530, 531 in prophylaxis, 526t–528t Cefdinir in otitis media, 479, 480t in sinusitis, 485t Cefepime in intraabdominal infections, 460t, 461t in meningitis, 395t, 397 in peritonitis, dialysis-associated, 462 in pneumonia, 475t

989

INDEX Cefixime in gonorrhea, 497t in sinusitis, 485t in urinary tract infections, 547t Cefotaxime in gonorrhea, 497t in intraabdominal infections, 461t in meningitis, 395t, 397 Haemophilus influenzae, 396 Neisseria meningitidis, 392 in peritonitis, spontaneous bacterial, 247 Cefotetan in pelvic inflammatory disease, 462t in surgical site infections, 524, 526t, 527t, 529, 530 Cefoxitin in bite wounds, 520, 521 in cellulitis, 516t in gonorrhea, 497t in pelvic inflammatory disease, 462t in surgical site infections, 524, 526t, 529 Cefpodoxime in otitis media, 479, 480t in sinusitis, 485t in urinary tract infections, 547t Cefprozil in otitis media, 479, 480t in sinusitis, 485t Ceftazidime dose adjustment in kidney disease, 877t, 879t in intraabdominal infections, 460t, 461t in meningitis, 395t, 397 in pneumonia, 475t in urinary tract infections, 551 Ceftizoxime in cellulitis, 516t in gonorrhea, 497t in meningitis, meningococcal, 392 Ceftriaxone in cellulitis, 514 in chancroid, 507t in endocarditis, 401, 402t, 403, 404t, 405t in prophylaxis, 411t in gastrointestinal infections, 432 in gonorrhea, 494, 497t, 498t in pregnancy, 357 in meningitis, 395t, 397 Haemophilus influenzae, 396 meningococcal, 392 pneumococcal, 396 in otitis media, 479, 480t in pneumonia, 475t

990

in sickle cell disease, 375 in sinusitis, 485t in surgical site infections, 526t in syphilis, 501t Cefuroxime in bite wounds, 513t in cellulitis, 515t dose adjustment in kidney disease, 879t in meningitis, meningococcal, 392 in otitis media, 479, 480t in sinusitis, 485t in surgical site infections, 527t in urinary tract infections, 547t Cefzil in urinary tract infections, 547t Celecoxib in colorectal cancer prevention, 689 in osteoarthritis, 12, 14t in pain management, 619t in rheumatoid arthritis, 37t Cellulitis, 511t, 514–517 in animal bites, 519 initial treatment regimens in, 515t–516t Centers for Disease Control and Prevention HIV infection classification system, 435, 436t Centers for Medicare and Medicaid Services guidelines for monitoring medications, 957t Central nervous system drugs affecting antipsychotic, 807–810 as depressants, 823–825 as stimulants, 825–827 infections of, 387–398 antibiotic selection in, 379, 385 in coccidioidomycosis, 418 cryptococcal, 398, 419, 420t, 421t in syphilis, 499 pain transmission in, 614 Central venous pressure normal values for, 145t in shock, 144, 155 Cephalexin in bronchitis, chronic, 470t in endocarditis prophylaxis, 411t in furuncles and carbuncles, 512t in impetigo, 512t in pharyngitis, 481, 481t in urinary tract infections, 547t in pregnancy, 553 Cephalosporins in acute exacerbation of COPD, 930 in endocarditis, 403, 406t in prophylaxis, 411t

INDEX in gastrointestinal infections, 432, 433 in gonorrhea, 494 interaction with other drugs, 383t in intraabdominal infections, 460t, 461t, 462t in meningitis, 397 skin reactions from, 952t in urinary tract infections, 547t, 549t, 551 Cephalothin in intraabdominal infections, 461t in meningitis, 392t Cerebrospinal fluid in meningitis, 387, 388t, 388–389 antibiotic penetration of, 390, 391t in fungal infections, 388t, 419 shunt procedures, prevention of infections in, 528t Cerebrovascular disorders, 156–162 diagnosis of, 157–158 goals of therapy in, 158 hemorrhagic, 156–157 clinical presentation in, 157 general approach to treatment in, 158 monitoring in, 161t nonpharmacologic therapy in, 158–159 pathophysiology in, 156–157 pharmacologic therapy in, 161–162 in hyperlipidemia, 159t, 160–161 in hypertension, 125–126, 159t, 160 ischemic, 156 clinical presentation in, 157 general approach to treatment in, 158 monitoring in, 161t nonpharmacologic therapy in, 158 pathophysiology in, 156 pharmacologic therapy in, 159t, 159–161 transient attacks, 156 in postmenopausal hormone therapy, 350 risk factors in, 156 Cervical cap, contraceptive, 322, 325t Cervical ripening in labor and delivery, 361 Cervicitis, 495t Cesarean section, surgical site infections in, 527t, 529 Cetirizine in allergic rhinitis, 900t, 901t Cetuximab in colorectal cancer, 693, 696t, 698 Chancroid, 507t Chemoreceptor trigger zone in nausea and vomiting, 294

Chemotherapy in breast cancer early stage, 681–682, 683t–684t locally advanced, 685 metastatic, 687 outcome evaluation in, 688 in colorectal cancer, 692–698, 695t–697t in adjuvant regimens, 693, 694t metastatic, 691, 693–694, 695t–697t, 698 in rectal cancer, 691, 693 in lung cancer common regimens in, 701t–702t non-small cell, 700–702 outcome evaluation in, 703 small cell, 703 in lymphoma Hodgkin’s, 706, 705t, 707t–708t non-Hodgkin’s, 708–711 nausea and vomiting in prevention of, 301, 302t risk of, 294, 296t treatment of, 296, 297, 303 in prostate cancer, 718 Chest compressions in cardiopulmonary resuscitation, 74, 75–77, 81 Chest pain in acute coronary syndromes, 44 in ischemic heart disease, 131–132 Child-Pugh classification of liver disease, 242, 243t Children anemia in, 364, 366, 369 antidepressant drug use and suicidal behavior in, 742–743 asthma in, 910f, 915t, 917t, 918, 920 body mass index in, 649t bronchiolitis in, 470 bronchitis in, acute, 466 cardiopulmonary arrest in, 74, 78 cellulitis in, 515t–516t chlamydial infections in, 500, 502, 503t constipation in, 254 dehydration in, 427t depression in, 792, 794 dermatitis in, atopic, 198 diabetes mellitus in, 223f diarrhea in, 258, 426, 434 fluid requirements in, 653 gastrointestinal infections in, 426, 434 gonorrhea in, 496, 497t, 498t growth velocity in, 650t histoplasmosis in, 412, 414t HIV infection and AIDS in, 435–437

991

INDEX Children (cont.) antiretroviral therapy in, 438 classification of, 435, 436t hypertension in, 126 hypothyroidism in, 234 impetigo in, 510 influenza in, 450, 454t, 455 prevention of, 451, 452t, 557t–560t, 571 meningitis in, 388 antibiotics in, 390t, 395t dexamethasone in, 390–391 Haemophilus influenzae, 396 meningococcal, 391, 392 pneumococcal, 395 tuberculous, 397, 398 nausea and vomiting in, 304 nutrition in assessment of, 648, 649t, 650t calcium in, 23t energy requirements in, 651, 652t enteral, 660 parenteral, 669, 672, 674, 676 protein in, 652t, 653 vitamin D in, 23t otitis media in, 478–480 pain management in, 616 pharyngitis in, 482t, 483t, 483–484 pneumonia in, 472, 475t rheumatoid arthritis in, 37t rhinitis in, allergic, 898, 901t, 904 seizures in, 578, 581t–582t in status epilepticus, 637, 641t, 643, 645t sickle cell disease in, 371, 373 sinusitis in, 485t social anxiety disorder in, 750 tuberculosis in, 532, 538t–540t, 541 vaccination schedule for, 556, 557t–563t weight and height measurements in, 648, 650t Chlamydial infections antibiotics in, 382t, 497t, 502, 503t, 551 clinical presentation of, 500, 502t with gonorrhea, 494, 497t in pregnancy, 357, 494, 497t, 503t sexually transmitted, 495t, 500–502 Chloral hydrate dependence, 826t Chlorambucil in lymphoma, 709 Chloramphenicol in gastrointestinal infections, 429t, 433 interaction with other drugs, 383t in meningitis, 392, 392t, 395t Chlordiazepoxide abuse of, 825

992

in alcohol withdrawal, 834t in generalized anxiety disorder, 743t, 744, 744t Chloroprocaine in regional analgesia, 627t Chlorpheniramine maleate in allergic rhinitis, 900t, 901t Chlorpromazine in nausea and vomiting, 298t in schizophrenia, 801 dosage of, 803t pharmacokinetics of, 804t side effects of, 806t, 809, 811, 812, 813 in stabilization therapy, 804 Chlorpropamide in diabetes insipidus, 884t in diabetes mellitus, 216t Chlorthalidone in hypertension, 116t, 118 Cholangiopancreatography, endoscopic retrograde, in pancreatitis, 309, 310 Cholangitis, 462t Cholecalciferol in osteoporosis, 25t, 26t Cholecystectomy, surgical infections in, 525, 526t Cholecystitis, acute, 462t Cholera, 427–428 Cholesterol levels, 98–110 classification of, 101t in coronary artery disease, 58–59, 98, 99 and diabetes mellitus, 225 risk categories in, 101–102, 102t in diabetes mellitus and coronary artery disease, 225 and metformin therapy, 218 measurement of, 99–100, 101, 101t risk categories and therapy goals, 101t, 101–102, 102t Cholestyramine in hyperlipidemia, 103–105, 104t, 105t Choline magnesium salicylate in osteoarthritis, 14t Choline salicylate in osteoarthritis, 14t Cholinergic agonists in glaucoma, 722t Cholinesterase inhibitors in Alzheimer’s disease for cognitive symptoms, 730t, 730–731, 731t for noncognitive symptoms, 732 in glaucoma, 723t Cholinomimetics in urinary incontinence, 947t Chondrocytes in osteoarthritis, 9

INDEX Chondroitin sulfate in osteoarthritis, 14t, 15–16 Chronic obstructive pulmonary disease, 467–469, 921–930 acute exacerbation of, 923, 928–930 classification of, 467, 468t clinical presentation in, 467, 469t, 922 definition of, 921 diagnosis of, 922–923 etiologies of, 921 evaluation of therapeutic outcomes in, 930 goals of therapy in, 467, 923, 928 hypertension management in, 127 nonpharmacologic therapy in, 924, 928–929 pathophysiology in, 467, 921–922 pharmacologic therapy in, 469, 924–928 in acute exacerbation, 929–930 stepwise approach to, 924, 925f pneumonia in, 474t respiratory failure in, 923 Chylomicrons, 98, 99, 108 Cilastatin and imipenem. See Imipenemcilastatin Cimetidine in gastroesophageal reflux disease, 267t, 268t, 269 interaction with other drugs, 771, 791t in nausea and vomiting, 298t, 300 in peptic ulcer disease, 319t Cinacalcet in chronic kidney disease, 870 Ciprofloxacin in bronchitis, chronic, 470t in cellulitis, 516t in chancroid, 507t dose adjustment in kidney disease, 877t in gastrointestinal infections, 429t, 431, 432 in HIV infection, 446t in gonorrhea, 497t in inflammatory bowel disease, 286 interaction with other drugs, 383t, 746t in intraabdominal infections, 460t, 461t, 462t in meningitis, 395t in pancreatitis, acute, 308 in pneumonia, 475t in prostatitis, 555 in sepsis, 491t in surgical site infections, 525, 530 in urinary tract infections, 547t, 548t, 550

Circulatory support, mechanical, in heart failure, 95–96 Cirrhosis, 239–249 clinical presentation in, 240–242, 241t etiology of, 239, 240t in hepatitis B, 275, 277, 279f liver function tests in, 241–242, 242f outcome assessment in, 248t, 249 peritonitis in, 461t Cisapride in gastroesophageal reflux disease, 270 Cisplatin in lung cancer, 700, 701t–702t, 703 in lymphoma, 711 Citalopram in Alzheimer’s disease, 733t in depression and cytochrome P450 activity, 795t dosage of, 782t interaction with other drugs, 793t pharmacokinetics of, 788, 789t refractory, 796 relative potency of, 783t side effects of, 783t in panic disorder, 747t in posttraumatic stress disorder, 753t in social anxiety disorder, 750, 751t Citric acid in metabolic acidosis, 843t Cladribine in lymphoma, 709 Clarithromycin in bronchitis, chronic, 470t, 930 in chronic obstructive pulmonary disease, 470t, 930 in acute exacerbation, 930 in gastrointestinal infections, 429t in Mycobacterium avium infection with HIV infection, 446t in otitis media, 480t in peptic ulcer disease, 316, 318, 318t in pneumonia, 475t in sinusitis, 485t Clavulanate and amoxicillin. See Amoxicillin-clavulanate and ticarcillin in urinary tract infections, 547t, 551 Clemastine fumarate in allergic rhinitis, 900t, 901t Climatotherapy in psoriasis, 187 Clindamycin in acne vulgaris, 183, 185 in bite wounds, 513t, 521 in cellulitis, 514, 516t in diabetic foot infections, 518 in endocarditis prophylaxis, 411t in erysipelas, 512t

993

INDEX Clindamycin (cont.) in furuncles and carbuncles, 512t in impetigo, 510, 512t in intraabdominal infections, 461t, 462t in lymphangitis, 512t in otitis media, 480t in pharyngitis, 483t in sinusitis, 485t in streptococcal group B infection in pregnancy, 361 in surgical site infections, 527t in vaginosis in pregnancy, 358 Clobetasol in psoriasis, 189t Clocortolone pivalate in psoriasis, 189t Clofibrate in diabetes insipidus, 884t in hyperlipidemia, 104t, 107 Clomipramine in cataplexy, 822 in depression, 782t, 784t, 790t Clonazepam abuse of, 824 in alcohol withdrawal, 834t in bipolar disorder, 764t, 766, 769t in generalized anxiety disorder, 743t, 744t, 745 in panic disorder, 747, 747t, 749 in seizures, 592t in social anxiety disorder, 751, 751t Clonidine in alcohol withdrawal, 833t in hypertension, 117t, 122, 128 in hyperthyroidism, 232 interaction with other drugs, 792t in menopause, 349t in opiate withdrawal, 831t, 835 in smoking cessation, 836, 837t, 838 Clopidogrel in acute coronary syndromes, 51, 54–56, 57 in ischemic stroke, 159t, 160, 161t Clorazepate abuse of, 825 dependence on, 826t in generalized anxiety disorder, 743t, 744, 744t in seizures, 592t Clostridium difficile infections, 430 in antibiotic therapy, 430 antibiotics in, 381t, 429t, 430 Clostridium perfringens infections, 380t Clozapine in bipolar disorder, 771 interaction with other drugs, 793t in schizophrenia, 800 dosage of, 803t

994

and lactation, 813 in maintenance therapy, 804 pharmacokinetics of, 801, 804t side effects of, 806t, 808, 809, 810, 811, 812 treatment-resistant, 805, 806 Coagulation cascade of events in, 163, 164f disorders of in cirrhosis, 239, 240, 248t in shock, 144, 155 venous thromboembolism in, 163 disseminated intravascular, in sepsis, 488 Coal tar preparations in atopic dermatitis, 201 in psoriasis, 191 Cobalamin in vitamin B12 deficiency, 367 Cocaine, 825, 827 acute coronary syndrome from, 54 intoxication from, 827, 830t, 831 withdrawal symptoms from, 827, 831t Coccidioidomycosis, 417–418 in HIV infection, 445t Codeine acetaminophen with in osteoarthritis, 14t in pancreatitis, chronic, 311 in bronchitis, acute, 466 in pain management, 620t, 623t in sickle cell crisis, 375 Cognitive-behavioral therapy in generalized anxiety disorder, 740 in panic disorder, 747, 749 in posttraumatic stress disorder, 753 in social anxiety disorder, 750 Cognitive function in Alzheimer’s disease evaluation of treatment outcomes in, 734 stages of decline in, 728, 728t treatment of symptoms in, 730t, 730–732, 731t in elderly, drugs affecting, 956t in schizophrenia, 800 antipsychotic drugs affecting, 809 Colchicine in gout, 4f, 5–6, 7 Colesevelam in hyperlipidemia, 103–105, 104t, 105t Colestipol in hyperlipidemia, 103–105, 104t, 105t Colistin in meningitis, 395t Colitis pseudomembranous, 430 ulcerative, 282–293. See also Ulcerative colitis

INDEX Colloid solutions in hypovolemic shock, 146, 149–150 in pancreatitis, 307 Colonoscopy in colorectal cancer, 689, 690 Colorectal cancer, 689–698 chemotherapy in, 691, 692–698, 695t–697t in adjuvant regimens, 693, 694t in metastasis, 691, 693–694, 695t–697t, 698 in rectal cancer, 691, 693 clinical manifestations of, 689 diagnosis of, 690 evaluation of therapeutic outcomes in, 698 goals of treatment in, 690 metastatic. See Metastasis, of colorectal cancer pathophysiology in, 689 prevention of, 689 radiation therapy in, 691, 693 screening for, 689 staging of, 690 surgery in, 691 Colorectal surgery in cancer, 691 surgical site infections in, 525, 526t, 529 Coma medically induced, in refractory status epilepticus, 644 myxedema, 235, 237 Comedolytic agents in acne vulgaris, 182, 183 Comedones, 180 closed (whitehead), 179 open (blackhead), 179 Compliance with drug therapy in glaucoma, 725 in tuberculosis, 535, 541 Computed tomography in lung cancer, 699 in pancreatitis, 307, 310 in stroke, 157, 159 Condoms female, 322, 324t male, 322, 324t Conduction abnormalities from antidepressant drugs, 783t–784t Congenital syphilis, 501t Conjunctivitis in allergic rhinitis, 897, 902 chlamydial, 503t gonococcal, 498t Constipation, 250–255 clinical presentation of, 250–251, 251t

diseases associated with, 250 drug-induced, 250, 251t, 252 in pain management, 626, 628 in pregnancy, 354 Contact dermatitis, 196, 199 from antipsychotic drugs, 813 Contraceptives, 321–340 in emergency, 334, 337–338 failure of, 321 intrauterine device, 339 long-acting injectable and implantable, 338–339 nonhormonal, 322–326, 324t–325t oral, 326–338 in acne vulgaris, 185 adverse effects of, 330, 330t, 336, 336t composition of, 327t–329t discontinuation of, 337 extended-cycle, 334 initiation of, 335 interaction with other drugs, 336–337, 337t, 580, 746t, 771, 776, 791t missed dose, 335, 335t precautions in use of, 330, 331t–332t in seizures, 580, 586 selection of, 335–336 transdermal, 338 in vaginal ring, 338 Contrast agents, nephrotoxicity of, 853, 972t Convulsions, definition of, 577 COPD. See Chronic obstructive pulmonary disease Copper, occupational exposure to, 963t Coronary artery anatomy of, 131f angiography in ischemic heart disease, 133 angioplasty in acute coronary syndromes, 48 atherosclerosis of. See Coronary artery disease bypass surgery in acute coronary syndromes, 48, 56 spasm of, 132, 139–142 Coronary artery disease acute coronary syndromes in, 43–59 in diabetes mellitus, 100, 109, 225–226 diagnosis of, 132–133 heart failure in, 82 hypertension management in, 125 ischemic heart disease in, 130–142

995

INDEX Coronary artery disease (cont.) lipid levels in, 99, 109, 110 agents lowering, 58–59, 109 in diabetes mellitus, 100, 109, 225 goals for, 58–59 in pathophysiology, 98 risk categories in, 101–102, 102t in menopause, 349–350 pathophysiology in, 43–44, 98, 130–131 Corticosteroid therapy in adrenal insufficiency, 208t, 208–209 adrenal insufficiency from, 207, 209 anxiety symptoms in, 740t in aspergillosis, 424, 425 in asthma, 913–916 in acute severe exacerbation, 914t in combination therapy, 919 inhaled preparations in, 915t, 915–916 systemic preparations in, 916, 916t in chronic obstructive pulmonary disease, 928 in acute exacerbation, 929 in cutaneous drug reactions, 201 in dermatitis, 199, 200–201 in glaucoma, 724 in gout, 4f, 5 in hypercalcemia, 887t in inflammatory bowel disease, 286 adverse effects of, 292 in Crohn’s disease, 289, 290f, 291 and pregnancy, 292 and toxic megacolon, 291 in ulcerative colitis, 287, 288, 288f, 289 in maculopapular reactions, druginduced, 201 in migraine headache, 607 in myxedema coma, 237 in nausea and vomiting, 300 in osteoarthritis, 16 osteoporosis in, 18, 23, 30 in preterm delivery, 360–361 in psoriasis, 188, 189t–190t in rheumatoid arthritis, 34, 36t, 40–41 in rhinitis, allergic, 903, 903t in septic shock, 154–155 in thyroid storm, 233, 233t, 234 in tuberculous meningitis, 398 Cortisol levels in adrenal insufficiency, 208 in Cushing’s syndrome, 203–207 measurement of, 204, 207 Cortisone in adrenal insufficiency, 208, 208t

996

Cosyntropin-stimulation test in adrenal insufficiency, 208 Craniotomy, surgical site infections in, 528t Creatinine clearance rate and drug dose adjustment in kidney disease, 875, 876–877, 877t serum levels in acute renal failure, 849 Creatinine kinase-MB in acute coronary syndromes, 44, 46f, 47 in ischemic heart disease, 133 Crisis adrenal, 209 hypertensive, 111 in monoamine oxidase inhibitor therapy, 786–787 in sickle cell disease, 372, 375 Crohn’s disease, 282–293 clinical presentation in, 285, 285t compared to ulcerative colitis, 282, 283t drug therapy in, 286, 287, 289–291 evaluation of therapeutic outcomes in, 293 pathophysiology in, 284 surgery in, 286 Crohn’s Disease Activity Index, 293 Cromolyn sodium in allergic rhinitis, 904 in asthma, 918 Cryoprecipitate in hypovolemic shock, 150 Cryotherapy in genital papillomavirus warts, 507t Cryptococcal infections, 419–421 in HIV infection and AIDS, 419, 421, 421t meningitis in, 398, 419, 421, 445t prevention of, 448t meningitis in, 398, 419, 420t, 421t in HIV infection and AIDS, 398, 419, 421, 445t Crystalloid solutions in hypovolemic shock, 146, 149 Cushing’s disease, 203, 206 Cushing’s syndrome, 203–207 hypertension in, 111, 112 nonpharmacologic therapy in, 204, 205t pharmacotherapy in, 204–207, 205t Cyanocobalamin skin reactions from, 952t in vitamin B12 deficiency, 367 Cyclizine in nausea and vomiting, 298t

INDEX Cyclooxygenase-2 inhibitors in gout, 5 in osteoarthritis, 12, 15 in pain management, 619t Cyclophosphamide in breast cancer, 682, 683t in lung cancer, small cell, 703 in lymphoma Hodgkin’s, 705t, 707t non-Hodgkin’s, 709, 710, 710t, 711 in rheumatoid arthritis, 34, 35t Cycloserine in tuberculosis, 539t, 541, 542t Cyclosporine in inflammatory bowel disease, 286 in Crohn’s disease, 290f, 291 in ulcerative colitis, 288, 288f interaction with other drugs, 665 in psoriasis, 193, 195 in rheumatoid arthritis, 33, 34, 36t, 39 Cyclothymic disorder, 759t Cyproheptadine in allergic rhinitis, 900t in Cushing’s syndrome, 205t, 206–207 Cystitis, 544, 549t, 550–551 Cytarabine in non-Hodgkin’s lymphoma, 711 Cytochrome P450 and antidepressant drugs, 791, 795t and antipsychotic drugs, 801 Cytomegalovirus infections in HIV infection, 446t, 448t D D-dimer test in venous thromboembolism, 165 Dacarbazine in Hodgkin’s lymphoma, 705t, 707t Dalteparin in acute coronary syndromes, 56 in venous thromboembolism, 169, 170, 176t Dantrolene in neuroleptic malignant syndrome, 810 Darbepoetin alfa in anemia of chronic kidney disease, 865 Darifenacin in urinary incontinence, 947t, 949 Darunavir in HIV infection and AIDS, 442t Date-rape drugs, 824, 825 De Quervain’s thyroiditis, 228 Decitabine in sickle cell disease, 373 Decongestants in rhinitis, allergic, 901t, 902t, 902–903 in sinusitis, 486 Decubitus ulcers, 510t, 518t, 518–519

Defibrillation with automated external defibrillator, 75, 77 in ventricular fibrillation and tachycardia, 77 Dehydration in diarrhea, 258, 426, 427t Delavirdine in HIV infection, 442t Delivery, 360–361 Delusions in schizophrenia, 799, 800 Dementia in Alzheimer’s disease, 727–734 in postmenopausal hormone therapy, 351 Dental procedures, endocarditis risk and prophylaxis in, 410t, 411, 411t Deoxycorticosterone trimethylacetate in adrenal insufficiency, 209 Dependence, 823, 835–838 on alcohol, 835 on benzodiazepines, 745, 825, 826t on nicotine, 835–838 Depression, 778–798 in Alzheimer’s disease, 732–733 in bipolar disorder, 756, 759t diagnostic criteria on, 760t treatment guidelines in, 764t–765t clinical presentation in, 778 definition of, 778 diagnostic criteria on, 779, 779t evaluation of therapeutic outcomes in, 796–798 goals of treatment in, 779 in isotretinoin therapy, 184 medical conditions and drugs associated with, 780t nonpharmacologic therapy in, 780–781 pathophysiology in, 778 pharmacologic therapy in, 781–798 in children and adolescents, 792, 794 dosage in, 782t, 796 drug interactions in, 787, 788, 788t, 791, 791t–794t in elderly, 791–792, 796 food interactions in, 787, 787t pharmacokinetics in, 787–788, 789t–790t in pregnancy, 794–795 relative potency of agents in, 783t–784t side effects of, 783t–784t, 785–787 postpartum, 362 in posttraumatic stress disorder, 737 in pregnancy, 360, 794–795 refractory or treatment-resistant, 795–796

997

INDEX Dermatitis, 196–202 atopic, 196, 197 diagnosis of, 198 treatment of, 199–201, 200f contact, 196, 199 from antipsychotic drugs, 813 diaper, 196, 197, 199 seborrheic, 197, 199 Dermatologic disorders, 179–202. See also Skin disorders Desensitization in drug allergy, 953t–954t in rhinitis, allergic, 904–905 Desipramine in depression in children, 794 dosage of, 782t in elderly, 792 pharmacokinetics of, 790t relative potency of, 784t side effects of, 784t in urinary incontinence, 947t Desirudin in venous thromboembolism, 171, 176t Desloratadine in allergic rhinitis, 900t Desmopressin in diabetes insipidus, 884, 884t Desogestrel in oral contraceptives, 327t, 328t Desonide in psoriasis, 189t Desoximetasone in psoriasis, 189t Desvenlafaxine in depression, 785 Dexamethasone in adrenal insufficiency, 208t in asthma, 916t in lung cancer metastasis to brain, 703 in lymphoma, non-Hodgkin’s, 711 in meningitis, 390–391 tuberculous, 398 in nausea and vomiting, 300, 302t, 303t in preterm delivery, 360 in psoriasis, 189t in thyroid storm, 233t Dexchlorpheniramine maleate in allergic rhinitis, 900t Dextran solutions in hypovolemic shock, 149, 150 Dextroamphetamine in narcolepsy, 821t Dextromethorphan in acute bronchitis, 466 Dextrose administration in hyperkalemia, 893, 894t in hypernatremia, 884 in hypoglycemia, 214

998

in parenteral nutrition, 672, 673, 673t, 674, 675f Diabetes insipidus central, 884, 884t hypernatremia in, 882, 884 nephrogenic, 884, 884t drug-induced, 775 Diabetes mellitus, 210–226 biguanides in, 218 clinical presentation in, 211 coronary artery disease in, 100, 109, 225–226 definition of, 210 diagnosis of, 211, 211t dipeptidyl peptidase-IV inhibitors in, 220 evaluation of therapeutic outcomes in, 226 foot problems in, 225, 510t, 511t, 512t, 517–518 general approach to treatment, 212 gestational, 210, 211, 355 α-glucosidase inhibitors in, 219–220 goals of therapy in, 212, 212t, 223f honeymoon phase in, 210 hypertension in, 120, 125, 225–226 insulin therapy in, 213–214. See also Insulin, therapy in diabetes mellitus ketoacidosis in, 840 kidney disorders in, 120, 225, 853 hyperglycemia control in, 860 progression-modifying therapies in, 860, 861f lipid levels in, 99, 100, 109, 110 and coronary artery disease, 100, 109, 225 in metformin therapy, 218 monitoring of, 110, 226 in niacin therapy, 106, 109 neuropathy in, 224–225 and foot infections, 517 nonpharmacologic therapy in, 212 nutrition in, 212, 220–222 enteral nutrition formulations in, 659t in obesity, 224, 668 oral contraceptive use in, 333, 339 in pancreatitis, 310 pathophysiology in, 210 peripheral vascular disease in, 225 and pregnancy, 210, 211, 355, 358–359 retinopathy in, 224 short-acting insulin secretagogues in, 215–218 sulfonylureas in, 215, 216t

INDEX thiazolidinediones (glitazones) in, 218–219 type 1, 220–222 clinical presentation in, 211 insulin therapy in, 214, 220–222 nutrition in, 212, 220–222 pathophysiology in, 210 type 2, 222–224 clinical presentation in, 211 complications in, 224, 225 diagnosis of, 211 insulin therapy in, 214, 222, 224 metformin in, 218, 224 monitoring of therapy in, 226 nutrition in, 212 pathophysiology in, 210 in schizophrenia, 810 vaccinations in, 556, 565t Dialysis in acute renal failure, 854 in chronic kidney disease, 870, 873, 873t drug dose adjustment in, 879t, 879–880 in hyperkalemia, 893, 894t in hypermagnesemia, 896 metabolic acidosis in, 873 peritonitis in, 461t, 462 vitamin D therapy in, 870, 873t Diaper dermatitis, 196, 197, 199 Diaphragm, contraceptive, 322, 324t Diarrhea, 256–262 acute, 258, 259f chronic, 258, 260f clinical presentation in, 256, 257t in diabetes mellitus, 225 drug-induced, 256, 257t in antibiotic therapy, 430 in colorectal cancer chemotherapy, 692 in enteral nutrition, 660–661 exudative, 256 infectious bacterial, 426–433 in travel, 258, 428, 429t viral, 434 in intestinal motility alterations, 256 osmotic, 256 rehydration therapy in, 426 indications for, 426, 427t oral solutions in, 258, 261t, 426, 428t secretory, 256 in travel, 258, 428, 429t treatment algorithms on, 259f–260f Diazepam abuse of, 824, 825

in alcohol withdrawal, 834t for antipsychotic drug side effects, 807, 807t, 808 dependence on, 826t in generalized anxiety disorder, 743, 743t, 745 pharmacokinetics of, 744, 744t in panic disorder, 747t in seizures, 592t in status epilepticus, 641t, 642 Dichloralphenazone in migraine headache, 603t, 605 2,4-Dichlorophenoxyacetic acid, occupational exposure to, 963t Diclofenac in migraine headache, 603t in osteoarthritis, 14t, 15 in pain management, 619t in rheumatoid arthritis, 37t Dicloxacillin in bite wounds, 513t, 520 in furuncles and carbuncles, 512t in impetigo, 510, 512t Didanosine in HIV infection and AIDS, 440t, 442t Dietary Approaches to Stop Hypertension, 113 Diethylpropion in obesity, 667, 667t Diethylstilbestrol in breast cancer, 686t Difenoxin in diarrhea, 262t Diflorasone diacetate in psoriasis, 189t Diflucortolone valerate in psoriasis, 189t Diflunisal in osteoarthritis, 14t in pain management, 619t in rheumatoid arthritis, 37t Digoxin in atrial fibrillation and flutter, 65 dose adjustment in kidney disease, 877t in heart failure, chronic, 85, 89–90 in supraventricular tachycardia, paroxysmal, 69 Dihydralazine hydrochloride, skin reactions from, 952t Dihydroergotamine in migraine headache, 603t, 606 Diltiazem in acute coronary syndromes, 54 in arrhythmias, 64t, 65, 66t in hypertension, 116t–117t, 120 in hyperthyroidism, 232 interaction with other drugs, 771, 791t, 793t in ischemic heart disease, 137, 139 and variant angina, 141, 142

999

INDEX Dimenhydrinate in nausea and vomiting, 298t Dimethylformamide, occupational exposure to, 963t Dipeptidyl peptidase-IV inhibitors in diabetes mellitus, 217t, 220 Diphenhydramine in antipsychotic drug side effects, 807, 807t, 808 in dermatitis, atopic, 201 in insomnia, 815 in nausea and vomiting, 298t in rhinitis, allergic, 900t, 901t in rituximab therapy for lymphoma, 710 Diphenoxylate in diarrhea, 262t Diphtheria toxoid, 569 in adults, 564t–566t, 569 in children, 557t–563t, 569 Dipivefrin in glaucoma, 721, 722t Dipyridamole in bradyarrhythmias, 73 in ischemic stroke, 159t, 160 Disopyramide in arrhythmias, 64t in bradyarrhythmias, 73 side effects of, 67t in tachycardia, paroxysmal supraventricular, 69 Disulfiram in alcohol dependence, 835 interaction with other drugs, 792t Diuretics in acute renal failure, 855, 855t in ascites, 246 in chronic kidney disease, 864–865 in edema, 885 in heart failure acute decompensated, 91–93 chronic, 85–86, 86t, 96 and hypertension, 124 in hypercalcemia, 885, 887t, 888 in hypernatremia, 884 in hypertension, 113, 114, 116t, 118 adverse effects of, 118 and heart failure, 124 indications for, 124, 125, 126, 127 in hyponatremia, 882 in ischemic stroke, 159t in osteoporosis, 29 Divalproex in bipolar disorder, 763, 767t, 777 in migraine prophylaxis, 608t, 610–611 in schizophrenia, 806 in seizures, 598 Dobutamine in heart failure, 93

1000

in sepsis, 492, 492t in shock, 151, 153t, 153–154 septic, 492, 492t Docetaxel in breast cancer, 682, 684t in lung cancer, 700, 701t, 702 in prostate cancer, 718 Docosahexaenoic acid in hyperlipidemia, 107 and coronary artery disease, 59 Docusate in constipation, 252, 253t, 254 Dofetilide in arrhythmias, 64t in atrial fibrillation and flutter, 67, 69 side effects of, 67t Dog bites, 519–520 Dolasetron in nausea and vomiting, 301, 302t, 303, 303t Donepezil in Alzheimer’s disease, 730, 730t, 731t Dopamine in atrioventricular block, 73 in depression pathophysiology, 778 in heart failure, 94 in Parkinson’s disease pathophysiology, 629 in sepsis, 492, 492t in shock, 151, 153t septic, 492, 492t Dopamine agonists in Parkinson’s disease, 632t, 635–636 Doppler studies in stroke, 157, 158 Dorzolamide in glaucoma, 723t Doxazosin in hypertension, 117t, 122 in prostate hyperplasia, benign, 933, 933t Doxepin in atopic dermatitis, 201 in depression, 782t, 784t, 790t in insomnia, 816 in migraine prophylaxis, 608t, 610 in urinary incontinence, 947t Doxercalciferol in chronic kidney disease, 870, 873t Doxorubicin in breast cancer, 682, 683t, 684t in lung cancer, small cell, 703 in lymphoma Hodgkin’s, 705t, 707t non-Hodgkin’s, 710, 710t, 711 Doxycycline in acne vulgaris, 185 in bite wounds, 513t, 520 in bronchitis, chronic, 470t, 930 in chlamydial infections, 503, 503t, 551

INDEX in chronic obstructive pulmonary disease, 470t, 930 in acute exacerbation, 930 in gastrointestinal infections, 428, 429t, 430 in gonorrhea, 494 in lymphogranuloma venereum, 507t in pelvic inflammatory disease, 462t in sinusitis, 485t in surgical site infections, 529 in syphilis, 501t in urinary tract infections, 547t, 548t Doxylamine in insomnia, 815 Dronabinol in nausea and vomiting, 299t, 301 Droperidol in nausea and vomiting, 299t, 303t Drospirenone in oral contraceptives, 327t Drotrecogin alfa in pancreatitis, 307 in sepsis and septic shock, 490t, 492 Dual-energy x-ray absorptiometry (DXA) scans in osteoporosis, 19, 30 Duke criteria in endocarditis, modified, 401 Duloxetine in depression, 785 interaction with other drugs, 793t pharmacokinetics of, 789t relative potency of, 783t side effects of, 783t, 786 in generalized anxiety disorder, 742t, 743 in urinary incontinence, 947t, 948 Duodenum, peptic ulcer disease of, 314–320 Dust mites, allergic rhinitis from, 897, 898–899 Dutasteride in benign prostatic hyperplasia, 933t, 934 DXA scans in osteoporosis, 19, 30 Dydrogesterone in menopause therapy, 345t Dysentery, bacillary, 430–431 Dyskinesia, tardive, from antipsychotic drugs, 808–809 Dyslipidemia, 98–110. See also Hyperlipidemia Dysthymic disorder, 759t, 778 Dystonia from antipsychotic drugs, 807 E Ear infections, otitis media in, 478–480 Echocardiography in heart failure, 83 in ischemic heart disease, 133

Echothiophate in glaucoma, 723t Eclampsia, 355 Ecstasy (3,4-methylenedioxy-methamphetamine), 828 Edema, 884–885 pitting, 884 pulmonary, 885 drug-induced, 968t Efalizumab in psoriasis, 192 Efavirenz in HIV infection, 439t, 441, 442t Effusions, pleural, drug-induced, 970t Eicosapentaenoic acid in hyperlipidemia, 107 and coronary artery disease, 59 Elderly, 955t–957t anemia in, 363, 366 bipolar disorder in, 776, 777 cognitive disorders from drug therapy in, 956t depression in, 791–792, 796 diabetes mellitus in, 215, 216t hypertension in, 126 influenza vaccination in, 451–452 monitoring of drug therapy in, 957t pain management in, 616 pharmacokinetics in, 956t physiologic changes in aging, 955t pneumonia in, 474t sleep physiology in, 814 status epilepticus in, 637, 643 tuberculosis in, 532, 533 urinary tract infections in, 545, 551 Electrocardiography in acute coronary syndromes, 43, 44, 45f antipsychotic drugs affecting, 811 in cardiopulmonary arrest, 75 in diagnosis of arrhythmias, 62–63 in ischemic heart disease, 133, 142 in monitoring of supraventricular tachycardia therapy, 69 Electroconvulsive therapy in bipolar disorder, 762–763, 765t in depression, 780–781 refractory, 796 Electroencephalography in seizures, 578 in status epilepticus, 639, 646 Electrolyte balance, 881–896 in acute kidney failure, 856 in chronic kidney disease, 864–865 Elemental enteral nutrition formulations, 658, 659t Eletriptan in migraine headache, 604t, 606, 607t

1001

INDEX Embolism ischemic stroke in, 156 pulmonary, 163 cardiopulmonary arrest in, 74, 80 clinical presentation in, 165 thrombolytic agents in, 175 Emergency contraceptives, 334, 337–338 Emesis. See Nausea and vomiting Emollient laxatives in constipation, 253t, 254 Emollient moisturizers in psoriasis, 187 Emphysema, 921–930 Emtricitabine in HIV infection and AIDS, 440t, 441, 442t Enalapril in acute coronary syndromes, 58 in heart failure, 86t in hypertension, 116t, 119 Encephalitis, in toxoplasmosis and HIV infection, 446t Encephalopathy, hepatic, 239, 240 management of, 243, 247t, 247–249 outcome assessment in, 248t precipitating factors in, 247, 247t Endarterectomy, carotid, in ischemic stroke, 158 Endocarditis, 399–411 antibiotics in, 401–411 evaluation of response to, 407, 410 prophylactic, 410t, 410–411, 411t clinical presentation in, 399–400, 400t in dental procedures, 410t, 411, 411t etiology of, 399, 400t surgery in, 401 Endocrine disorders, 203–237 adrenal, 203–209 from antipsychotic drugs, 810 anxiety symptoms in, 739t diabetes mellitus in, 210–226 thyroid, 227–237 Endoscopy in gastroesophageal reflux disease, 264 surgical site infections in, 526t in variceal hemorrhage, band ligation in, 243, 245, 245t, 246 Endotoxin, 487, 488 Enema preparations in constipation, 253, 255 Energy expenditure basal, 652t resting, 651, 653, 663 Energy requirements, 651–653 in chronic kidney disease, 874 Enfuvirtide in HIV infection and AIDS, 443t

1002

Enoxaparin in acute coronary syndromes, 48, 52, 54, 56 in venous thromboembolism, 169, 170, 176t Entacapone in Parkinson’s disease, 632t, 633, 634–635 Entecavir in hepatitis B, 277, 278f, 279f Enteral nutrition, 655–662 Enteric fever, 431, 432 Enterobacter infections, 381t, 467t Enterococcal infections antibiotics in, 380t, 384 endocarditis in, 399, 400t, 407, 409t peritonitis in, 457, 458t, 461t, 463t Enterocolitis in Salmonella infections, 431, 432 with HIV infection, 446t in Yersinia infections, 433 Enzyme supplements in pancreatitis, 311, 312t, 313 Eosinophilia and pulmonary infiltrates, drug-induced, 969t Ephedrine abuse, 827 Epididymitis, 495t, 544 Epilepsy, 577–598. See also Seizures Epinephrine in asthma, 914t in atrioventricular block, 73 in cardiopulmonary resuscitation, 76t, 77, 79, 80 in regional analgesia with articaine, 627t in sepsis, 492, 492t in shock, 151, 153t, 154 septic, 492, 492t in sickle cell disease, 375 in torsade de pointes, 72 Epirubicin in breast cancer, 682, 683t Eplerenone in acute coronary syndromes, 58, 124–125 in heart failure, 88–89 in hypertension, 118, 124–125 Epoetin alfa in anemia of chronic disease, 369, 865 Eprosartan in hypertension, 116t Eptifibatide in acute coronary syndromes, 51, 56 Erectile dysfunction, 936–943 clinical presentation in, 936 definition of, 936 in diabetes mellitus, 225 diagnosis of, 936 drug-induced, 936, 937t evaluation of therapeutic outcomes in, 943

INDEX goals of treatment in, 937 medical devices in, 939 pathophysiology in, 936 pharmacologic therapy in, 937, 938t, 939–943 psychogenic, 936 surgery in, 943 Ergocalciferol in osteoporosis, 25t, 26t Ergotamine tartrate in migraine headache, 603t, 605–606 Erlotinib in lung cancer, 702 Ertapenem in bite wounds, 521 in cellulitis, 516t in intraabdominal infections, 460t, 461t in urinary tract infections, 547t Erysipelas, 509, 510t, 511t, 512t Erythema multiforme, 197t Erythritol tetranitrate in angina pectoris, 136t Erythroblastosis fetalis, 575 Erythrocytes. See Red blood cells Erythromycin in acne vulgaris, 183, 184 in bite wounds, 513t, 520 in bronchitis, chronic, 470t in chancroid, 507t in chlamydial infections, 503t in pregnancy, 503t in erysipelas, 512t in gastrointestinal infections, 428, 429t, 433 interaction with other drugs, 746t, 771, 817 in lymphogranuloma venereum, 507t in ophthalmia neonatorum, 496, 498t, 502 in pharyngitis, 481, 481t in pneumonia, 475t skin reactions from, 952t in streptococcal group B infection in pregnancy, 361 in surgical site infections, 525, 526t Erythropoietin deficiency in chronic kidney disease, 865, 867f reference range for, 365t Escherichia coli infections, 428–430 antibiotics in, 381t, 429t bronchitis in, 467t enterotoxigenic, 428, 430 peritonitis in, 457, 458t prostatitis in, 549t, 554 sepsis in, 487 of urinary tract, 545, 549t

Escitalopram in Alzheimer’s disease, 733t in depression, 782t, 783t, 789t, 793t, 795t in generalized anxiety disorder, 742t, 743 in panic disorder, 747t in posttraumatic stress disorder, 753t in social anxiety disorder, 751t Esmolol in acute coronary syndromes, 53 in atrial arrhythmias, 65 in hypertensive emergency, 129t in thyroid storm, 234 Esomeprazole in gastroesophageal reflux disease, 268t, 270, 271 in peptic ulcer disease, 318t, 319t Esophagitis erosive, 263 in gastroesophageal reflux disease, 263, 264 Esophagus Barrett’s, 263, 264, 269 lower sphincter pressure foods and drugs affecting, 263, 264t in gastroesophageal reflux disease, 263, 265 Estazolam in insomnia, 817, 818, 818t Estolate in pharyngitis, 482t Estradiol in menopause therapy, 343, 343t, 344, 349 with progestogens, 345t Estramustine in prostate cancer, 718 Estrogen in acne vulgaris, 185 in Alzheimer’s disease, 731 in breast cancer and antiestrogen therapy, 684–685, 686, 686t metastatic, 686t in contraceptives, 326–338 adverse effects of, 330t preparations available, 327t–329t interaction with other drugs, 792t in menopause therapy, 342–344 adverse effects of, 344, 349–350, 351 alternatives to, 347–349, 349t benefits of, 347–349 dosage of, 344t monitoring in, 351 in osteoporosis, 28, 344t, 349 preparations available, 343t, 343–344

1003

INDEX Estrogen (cont.) with progestogen therapy, 345t, 345–346, 349–350, 351 topical, 349 in osteoporosis, 28, 344t, 349 in premature ovarian failure, 351–352 in urinary incontinence, 946, 947t Estrogen-receptor modulators, selective, in menopause therapy, 346–347 Eszopiclone in insomnia, 817, 818t Etanercept adverse effects of, 36t, 39, 192 in psoriasis, 192 in rheumatoid arthritis, 33, 35t, 36t, 39 Ethacrynic acid in acute renal failure, 855 Ethambutol in Mycobacterium avium infection with HIV infection, 446t in tuberculosis, 537t, 538t active, 535 adverse effects of, 543 dose adjustment in renal failure, 541, 542t and meningitis, 395t, 397 Ethinyl estradiol in breast cancer, 686t in menopause therapy, 343, 344t, 345t in oral contraceptives, 326–338 preparations available, 327t–329t Ethionamide in tuberculosis, 539t dose adjustment in renal failure, 542t and meningitis, 541 in pregnancy, 541 Ethosuximide in seizures, 586, 591 adverse effects of, 587t dosage and serum levels of, 592t indications for, 582t, 591 interaction with other drugs, 590t pharmacokinetics of, 585t, 591 Ethotoin in seizures, 592t Ethylsuccinate in pharyngitis, 482t Ethynodiol diacetate in oral contraceptives, 327t Etidronate in hypercalcemia, 887t Etodolac in gouty arthritis, 5t in osteoarthritis, 14t in pain management, 619t in rheumatoid arthritis, 37t Etomidate in Cushing’s syndrome, 206 Etonogestrel in subdermal contraceptive implant, 339 in vaginal ring, 338 Etoposide in lung cancer, 701t–702t, 703

1004

in lymphoma Hodgkin’s, 705t, 707t non-Hodgkin’s, 711 Exemestane in breast cancer, 685 Exenatide in diabetes mellitus, 213t, 214 Exercise programs in diabetes mellitus, 212 in exertional angina, 138 in hyperlipidemia, 102 in osteoarthritis, 11 in osteoporosis, 20 Exercise stress testing in ischemic heart disease, 133, 142 Extrapyramidal side effects of antipsychotic drugs, 807t, 807–810 Eye disorders, 719–725 from antipsychotic drugs, 811 in diabetic retinopathy, 224 in glaucoma, 719–725 in ophthalmia neonatorum, 496, 502 Eye movements in sleep, 814 Ezetimibe in hyperlipidemia, 104t, 107, 108 in combination therapy, 106, 107 dosage of, 105t F Factor VIII therapy in hypovolemic shock, 150 Famciclovir in herpes simplex virus infections, 503, 505t in HIV infection, 446t in varicella-zoster virus infections with HIV infection, 446t Famotidine in gastroesophageal reflux disease, 267t, 268t in nausea and vomiting, 298t, 300 in peptic ulcer disease, 319t Fasciitis, necrotizing, 510t, 511t Fat intake in hyperlipidemia, 102, 108, 109 in pancreatitis, chronic, 311 in parenteral nutrition, 672 Fatty acids, essential, deficiency of, 651 parenteral nutrition in, 672 Fears panic disorder in, 736, 738 social anxiety disorder in, 737 Fecal occult blood in colorectal cancer, 689 Feeding tubes, 655–662 drug delivery through, 661–662, 662t Felbamate in seizures, 586, 591 adverse effects of, 587t, 591

INDEX dosage and serum levels of, 593t interaction with other drugs, 589, 590t pharmacokinetics of, 585t Felodipine in hypertension, 116t, 120 Fenofibrate in hyperlipidemia, 104t, 105t, 107 Fenoldopam mesylate in hypertensive emergencies, 129t Fenoprofen in gouty arthritis, 5t in osteoarthritis, 14t in pain management, 619t in rheumatoid arthritis, 37t Fentanyl in pain management, 626 dosage of, 621t, 623t routes of administration, 623t, 625t, 626 in sickle cell crisis, 375 Ferritin levels in chronic kidney disease and anemia, 865 in iron deficiency anemia, 366 reference range for, 363 Ferrous fumarate in iron deficiency, 367t Ferrous gluconate in iron deficiency, 367t Ferrous sulfate in iron deficiency, 367t Fever, 377 drug-induced, 377 from antipsychotic drugs, 809 in infections, 377 Fexofenadine in allergic rhinitis, 900t, 901t Fiber, dietary in constipation, 252, 253 in enteral nutrition formulations, 658 in hyperlipidemia, 103 Fibrate therapy in hyperlipidemia, 107, 108 and coronary artery disease, 59 Fibrillation atrial, 60, 62, 65–69 algorithm on treatment of, 68f clinical presentation in, 62 diagnosis of, 62 goals of treatment in, 63 intravenous drug dose in, 66t pathophysiology in, 60 thromboembolism risk in, 66, 69 ventricular, 72, 77–80 cardiopulmonary arrest in, 74, 75, 77–80 cardiopulmonary resuscitation in, 72, 77 clinical presentation in, 62 intravenous drug dose in, 66t pathophysiology in, 61

Fibrinolytic therapy in acute coronary syndromes, 48–50, 54 in cardiopulmonary resuscitation, 76t, 80 in venous thromboembolism, 175 Fibrosis pleural, drug-induced, 970t pulmonary drug-induced, 969t etiologies of, 970t Finasteride in benign prostatic hyperplasia, 933t, 934 Fish oils in hyperlipidemia, 103, 107 and coronary artery disease, 59, 103, 109 Flecainide in arrhythmias, 64, 64t in atrial fibrillation and flutter, 67, 69 in paroxysmal supraventricular tachycardia, 69 side effects of, 67t Fluconazole in blastomycosis, 417t in candidiasis, 422, 423t–424t in HIV infection, 445t in coccidioidomycosis, 418 in HIV infection, 445t in cryptococcosis, 419, 420t–421t in HIV infection, 448t in histoplasmosis, 413t, 414t in meningitis, 395t in HIV infection, 445t Flucytosine in cryptococcosis, 419, 420t in HIV infection, 445t in meningitis, 395t, 398 in HIV infection, 445t Fludarabine in lymphoma, 709 Fludrocortisone in adrenal insufficiency, 208–209 in sepsis, 490t Fluid balance in chronic kidney disease, 864–865 in edema, 884–885 and sodium serum levels, 881–885 Fluid intake daily requirements for, 653 in enteral nutrition formulations, 659 restriction of in heart failure, 84 in hypotonic hyponatremia, 882 Fluid therapy in adrenal insufficiency, 209 in alcohol withdrawal, 833t in diarrhea, 426, 427t oral rehydration solutions in, 258, 261t, 426, 428t

1005

INDEX Fluid therapy (cont.) hypertonic solutions in, 881, 882t in hyponatremia, 882 hypotonic solutions in, 881, 882t in hypovolemic shock, 146–150, 155 isotonic solutions in, 881, 882t in pancreatitis, 307 Flumazenil in hepatic encephalopathy, 249 in substance intoxication, 830, 830t Flumethasone pivalate in psoriasis, 189t Flunisolide in allergic rhinitis, 903t in asthma, 915t Flunitrazepam abuse of, 824 dependence on, 826t Fluocinolone acetonide in psoriasis, 189t Fluocinonide in psoriasis, 189t Fluorine, occupational exposure to, 963t Fluoroquinolone antibiotics in bite wounds, 513t, 520, 521 in cellulitis, 516t in diabetic foot infections, 512t, 518 enteral feeding tube administration of, 662t in gonorrhea, 494 in urinary tract infections, 547t, 548t, 549t, 550 complicated, 551 in males, 552 Fluorouracil in breast cancer, 682, 683t in colorectal cancer, 692, 693 in adjuvant regimens, 693, 694t metastatic, 693, 694, 695t–696t, 698 in glaucoma, 721 Fluoxetine in Alzheimer’s disease, 733t in bradyarrhythmias, 73 in cataplexy, 821t, 822 in depression in children, 792 and cytochrome P450 activity, 795t dosage of, 782t interaction with other drugs, 788, 791, 793t pharmacokinetics of, 789t in pregnancy, 795 refractory, 796 relative potency of, 783t side effects of, 783t interaction with other drugs, 746t, 771 in depression, 788, 791, 793t in menopause, 349t in migraine prophylaxis, 608t, 610

1006

in panic disorder, 747t, 749, 750 in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 750 Fluoxymesterone in breast cancer, 686t in erectile dysfunction, 938t Fluphenazine in bipolar disorder, 771 in schizophrenia, 809 dosage of, 803t in maintenance therapy, 805 pharmacokinetics of, 804t side effects of, 806t, 807 Flurandrenolide in psoriasis, 189t Flurazepam in insomnia, 817, 818, 818t Flurbiprofen in osteoarthritis, 14t in rheumatoid arthritis, 37t Flutamide in prostate cancer, 716, 717, 717t in prostate hyperplasia, benign, 933, 933t Fluticasone in allergic rhinitis, 903t in asthma, 915t, 919 in chronic obstructive pulmonary disease, 928 in psoriasis, 189t Flutter, atrial, 60, 65–69 algorithm on treatment of, 68f clinical presentation in, 62 goals of treatment in, 63 Fluvastatin in hyperlipidemia, 104t, 106 Fluvoxamine in depression and cytochrome P450 activity, 795t dosage of, 782t interaction with other drugs, 793t–794t pharmacokinetics of, 789t refractory, 796 relative potency of, 783t side effects of, 783t interaction with other drugs, 746, 746t, 771, 817 in depression, 793t–794t in panic disorder, 747t in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 751t Folic acid deficiency of, 363 clinical presentation in, 365 diagnosis of, 366

INDEX evaluation of therapeutic outcomes in, 369 treatment of, 367, 369 in epilepsy and pregnancy, 359 in inflammatory bowel disease, 292 and pregnancy, 292 in preconception interventions, 354 reference range for serum levels, 365t in sickle cell disease, 373 Folinic acid in colorectal cancer, 694t Follicle-stimulating hormone in menopause, 341, 342 in menstrual cycle, 321, 326 in premature ovarian failure, 351 Folliculitis, 511t, 512t Fondaparinux in acute coronary syndromes, 54, 56 in venous thromboembolism, 170, 176, 176t Foot disorders in diabetes mellitus, 225, 510t, 511t, 512t, 517–518 in rheumatoid arthritis, 33 Formoterol in asthma, 913, 913t, 919 in chronic obstructive pulmonary disease, 926, 928 Fosamprenavir in HIV infection, 439t, 441, 442t Foscarnet in cytomegalovirus infections and HIV infection, 446t dose adjustment in kidney disease, 879t interaction with other drugs, 383t in meningitis, 395t Fosfomycin in urinary tract infections, 547t Fosinopril in heart failure, 86t in hypertension, 116t Fosphenytoin in status epilepticus, 641t, 643 Fractures in osteoporosis, 18–19 glucocorticoid-induced, 30 prevention of, 19, 23, 25, 28, 29 treatment algorithm on, 21f–22f in prostate cancer, 718 surgical site infections in, 528t, 531 Frovatriptan in migraine headache, 604t, 606, 607t Fulvestrant in breast cancer, 686, 686t Fungal infections, 412–425 aspergillosis, 422–425 blastomycosis, 416

candidiasis, 421–422 coccidioidomycosis, 417–418 cryptococcosis, 419–421 meningitis in, 398, 419, 420t, 421, 421t endocarditis in, 400t histoplasmosis, 412–415 in HIV infection and AIDS, 445t intraabdominal, 463t, 464 meningitis in, 398 cerebrospinal fluid values in, 388t, 419 cryptococcal, 398, 419, 420t, 421, 421t in HIV infection, 445t treatment of, 395t, 398, 419, 421 sexually transmitted, 494t Furazolidone in gastrointestinal infections, 428 Furosemide in ascites, 246 in heart failure, 85, 86t, 91 in hypercalcemia, 888 in hyperkalemia, 894t in hypernatremia, 884 in hypertension, 116t in hyponatremia, 882 in renal failure, acute, 855 Furuncles, 511t, 512t G Gabapentin in menopause, 349t in migraine prophylaxis, 608t in seizures, 594 adverse effects of, 587t, 588 dosage and serum levels of, 593t, 594 indications for, 581t, 582t, 594 interaction with other drugs, 589, 590t pharmacokinetics of, 585t, 594 in social anxiety disorder, 751, 751t Galantamine in Alzheimer’s disease, 730, 730t, 731, 731t Gallium nitrate in hypercalcemia, 887t Gallstone pancreatitis, 305, 309 Gamma-glutamyl transpeptidase levels in liver disorders, 241, 963t Ganciclovir, in cytomegalovirus infections and HIV infection, 446t, 448t Gardnerella vaginalis infections, 381t Gases arterial blood, 839, 840t analysis of, 841f

1007

INDEX Gases (cont.) in asthma, 908 in chronic obstructive pulmonary disease, 923, 929 normal values for, 840t mixed venous blood, 840t Gastritis in Helicobacter pylori infections, 314 Gastroenteritis, 426–434 bacterial, 426–433 viral, 434 Gastroesophageal reflux disease, 263–272 clinical presentation in, 263 definition of, 263 diagnosis of, 264–265 foods and drugs affecting, 263, 264t pathophysiology in, 263 in pregnancy, 354–355 treatment of, 265–272, 266f, 267t–268t combination therapy in, 271 long-term, 271 nonpharmacologic, 265, 269t outcome evaluation in, 271–272 Gastrointestinal disorders, 239–320 cirrhosis and portal hypertension, 239–249 constipation, 250–255 in diabetes mellitus, 225 diarrhea, 256–262 in enteral nutrition, 660–661 gastroesophageal reflux disease, 263–272 hepatitis, 273–281 in infections, 426–434 bacterial, 426–433 in HIV infection, 446t viral, 434 inflammatory bowel disease, 282–293 nausea and vomiting, 294–304 pancreatitis, 305–313 peptic ulcer disease, 314–320 in pregnancy, 354–355 surgical infections in, 525, 526t, 529 Gastroparesis in diabetes mellitus, 225 Gastrostomy for enteral nutrition, 656, 657t Gatifloxacin in gonorrhea, 497t in pneumonia, 475t in tuberculosis, 540t Gemcitabine in breast cancer, 684t, 687 in lung cancer, 700, 701t, 703 Gemfibrozil in hyperlipidemia, 104t, 105t, 107, 108, 109 Gemifloxacin in acute exacerbation of COPD, 930

1008

Genetic factors in bipolar disorder, 758t in breast cancer, 679, 680 in colorectal cancer, 689 in obesity, 663 in psoriasis, 186 in sickle cell disease, 371 Gentamicin dose adjustment in kidney disease, 877t, 879t in endocarditis enterococcal, 407, 408t staphylococcal, 406t, 408t streptococcal, 401, 402t, 404t, 405t in meningitis, 392t, 395t, 397 in peritonitis, dialysis-associated, 462 in pneumonia, 475t in sepsis, 491t in urinary tract infections, 547t Geriatrics, 955t–957t. See also Elderly Ghon complex, 532 Ginkgo biloba in Alzheimer’s disease, 732 Glaucoma, 719–725 closed-angle clinical presentation in, 720 diagnosis of, 721 drug-induced, 720t pathophysiology in, 719 treatment of, 721, 724 definition of, 719 drug-induced, 719, 720t, 811 normal tension, 720 open-angle clinical presentation in, 720 diagnosis of, 720 drug-induced, 720t pathophysiology in, 719 secondary, 719 treatment of, 721, 722t–723t Glimepiride in diabetes mellitus, 216t Glipizide in diabetes mellitus, 216t, 217t Glitazones in diabetes mellitus, 218–219 Glomerular filtration rate in acute renal failure, 849, 850f in chronic kidney disease, 858 Glucagon administration in hypoglycemia, 214 Glucocorticoid-receptor blocking agents in Cushing’s syndrome, 207 Glucosamine sulfate in osteoarthritis, 14t, 15–16 Glucose administration in hypoglycemia, 214 blood levels in diabetes mellitus, 210–226 and chronic kidney disease, 860

INDEX diagnostic criteria on, 211, 211t in fasting, 210, 211, 211t gestational, 355 in goals of therapy, 212, 212t, 223f and insulin therapy, 220, 221f in cerebrospinal fluid in meningitis, 388t, 388–389 tolerance, 210, 211 α-Glucosidase inhibitors in diabetes mellitus, 217t Glyburide in diabetes mellitus, 216t, 217t in pregnancy, 355, 358 Glycerin in constipation, 253, 255 in glaucoma, 724 Glycerol in parenteral nutrition, 672 Glycoprotein IIb/IIIa receptor inhibitors in acute coronary syndromes, 51–52, 56 Goiter, multinodular, 228, 230 Gold preparations in rheumatoid arthritis, 33, 35t, 36t, 38 Gonorrhea, 493–496 antibiotics in, 380t, 494, 496, 497t–498t with chlamydial infection, 494, 497t clinical presentation in, 493, 495t, 496t disseminated disease, 493, 497t in pregnancy, 357, 494, 496, 497t Goserelin in breast cancer, 685, 686t, 687 in prostate cancer, 716, 717t in prostate hyperplasia, benign, 933 Gout, 1–8 antiinflammatory drugs in, nonsteroidal, 3–5, 5t arthritis in, 2–8 treatment of, 3–8, 4f, 5t clinical presentation in, 2–3 colchicine in, 4f, 5–6, 7 corticosteroid therapy in, 4f, 5 definition of, 1 diagnosis of, 3 evaluation of therapeutic outcomes in, 8 lithiasis in, 2, 6 nonpharmacologic therapy in, 3 pathophysiology in, 1–2 prophylactic therapy in, 6–8 treatment algorithm on, 4f uric acid-lowering therapy in, 7–8 Granisetron in nausea and vomiting, 301, 302t, 303, 303t Granulocyte colony-stimulating factor in Hodgkin’s lymphoma, 708t in neutropenia and HIV infection, 448t

Granulocyte-macrophage colony-stimulating factor in neutropenia and HIV infection, 448t Graves’ disease, 228 diagnosis of, 229 treatment of, 232, 233 Growth velocity in infants and children, 650t Guanabenz in hypertension, 122 Guanadrel in hypertension, 124 interaction with other drugs, 792t Guanethidine in hypertension, 124 interaction with other drugs, 792t Guanfacine in hypertension, 122 Guanine metabolism, 1 Gynecology. See Obstetrics and gynecology H Haemophilus ducreyi infections, 507t Haemophilus influenzae infections acute exacerbation of COPD in, 930 antibiotics in, 381t bronchitis in, chronic, 467, 469 meningitis in, 387, 396 in children, 391 diagnosis of, 388, 389 treatment of, 390t, 394t, 396 otitis media in, 478, 479 pneumonia in, 474t, 475t sinusitis in, 484 vaccination against, 396, 570, 570t in children, 557t–558t, 561t–563t, 570 Halcinonide in psoriasis, 189t Hallucinations in schizophrenia, 799, 800 Hallucinogens, 829, 830t, 831 Hallucinosis, drug-induced, in Parkinson’s disease, 635, 636t Halobetasol propionate in psoriasis, 190t Haloperidol in alcohol withdrawal, 833t in Alzheimer’s disease, 733t in bipolar disorder, 771 interaction with other drugs, 746, 791t, 793t, 794t in nausea and vomiting, 299t in schizophrenia, 803, 805, 809 dosage of, 803t pharmacokinetics of, 804t in pregnancy, 813 side effects of, 806t, 807 in substance intoxication, 830t Haloperidol decanoate in schizophrenia, 804t, 805

1009

INDEX Hand osteoarthritis of, 10, 11, 17 rheumatoid arthritis of, 32, 32t, 33 Harris-Benedict equation, 651, 652t Hashimoto’s thyroiditis, 234 Hashish, 828 Hay fever, 897 Head and neck surgery, surgical site infections in, 527t, 528t, 530 Headache, 599–613 evaluation of therapeutic outcomes in, 613 in medication overuse, 605 migraine, 599–611. See also Migraine headache in pregnancy, 356 tension-type, 612 Heart block, 62, 63, 73 Heartburn in gastroesophageal reflux disease, 263, 266, 271 Heart failure, 82–97 acute decompensated, 90–96 algorithm on treatment of, 92f cardiac output in, 91 evaluation of therapeutic outcomes in, 96–97 fluid overload in, 91 general approach to treatment in, 90–91 pharmacologic therapy in, 91–95 chronic, 84–90 evaluation of therapeutic outcomes in, 96 general approach to treatment in, 84–85 pharmacologic therapy in, 84–90 clinical presentation in, 82–83 definition of, 82 diagnosis of, 83 in diastolic dysfunction, 82 drug-induced, 82 evaluation of therapeutic outcomes in, 96–97 goals of therapy in, 83 hemodynamic monitoring in, 91 and hypertension, 82, 124 mechanical circulatory support in, 95–96 pathophysiology in, 82 staging and classification of, 83, 84f surgical therapy in, 96 in systolic dysfunction, 82 Heart surgery in heart failure, 96 surgical site infections in, 527t, 530 Heberden’s nodes, 10

1010

Height and weight measurements in nutritional assessment, 648, 649t, 650t Helicobacter pylori infections, peptic ulcer disease in, 314, 315 diagnosis of, 315–316 treatment of, 316–318, 318t Hematocrit, reference range for, 365t Hematologic disorders, 363–376 anemia, 363–370 drug-induced, 958t–961t from antipsychotic drugs, 812 sickle cell disease, 371–376 Hematoma, subdural, 156 Hemodialysis in acute renal failure, 854 drug dosage adjustment in, 879–880 in hyperkalemia, 894t in hypermagnesemia, 896 Hemodynamic monitoring normal values in, 145t in shock, 144–146, 155 Hemoglobin concentration of in chronic kidney disease and anemia, 865 in iron deficiency anemia, 367, 368t reference range for, 365t fetal, 371, 373 in sickle cell disease, 371 Hemoglobin A1C in diabetes mellitus, 212, 212t, 215 and metformin therapy, 218 monitoring of, 226 in type 2 disease, 223f, 224 Hemoglobin C, 371, 372t Hemoglobin S, 371 Hemolytic anemia, 364, 366, 369 drugs associated with, 959t, 960t Hemorrhage cerebral, 156–157. See also Cerebrovascular disorders, hemorrhagic gastrointestinal, in peptic ulcer disease, 315 in heparin therapy, 168, 170 in uremia, 874 variceal, in cirrhosis and portal hypertension, 239, 242 management of, 243–246, 244f, 245t, 248t outcome assessment in, 248t in warfarin therapy, 172, 174f Hemorrhoids in pregnancy, 355 Heparin in acute coronary syndromes, 48, 52, 54, 56

INDEX in atrial fibrillation and flutter, 66 in stroke, 161, 161t in venous thromboembolism, 165–170 adverse effects of, 168–169 contraindications to, 167 dosage of, 167, 168t in pregnancy, 356 in prevention, 176, 176t warfarin therapy with, 171 Hepatitis drug-induced, from antipsychotic drugs, 812 viral, 273–281 Hepatitis A, 273–275 clinical presentation in, 274t vaccination, 273, 274t in adults, 564t–567t in children, 557t–563t in HIV infection, 447t Hepatitis B, 275–278 clinical presentation in, 276t serologic tests in, 275, 276t treatment algorithms on, 278f, 279f vaccination, 275, 277t in adults, 564t–568t in children, 557t–563t in HIV infection, 447t Hepatitis C, 278–281 interferon therapy in, 280t, 281, 281t response-optimized therapy in, 280f, 281 screening recommendations, 278, 279t Hepatopulmonary syndrome, 248t Hepatorenal syndrome, 243, 248t Hepatotoxins, 962t–964t acetaminophen as, 12 antipsychotic drugs as, 812 antituberculous drugs as, 542 diagnostic scale on, 962t leflunomide as, 38 methotrexate as, 37 monitoring for, 964t occupational exposure to, 963t Herbal products anxiety symptoms from, 740t in depression, 785 drug interactions with, 746t, 785 in insomnia, 817 in obesity, 667, 667t in prostate hyperplasia, benign, 934–935 Heroin, 825 withdrawal from, 832 Herpes simplex virus infections, 502–504 clinical presentation in, 503, 504t

genital, 502–504 in HIV infection, 446t in pregnancy, 357, 504 sexually transmitted, 495t Herpes zoster vaccination, 564t–568t, 574 Hetastarch in hypovolemic shock, 146, 149–150 Hip fractures of, surgical site infections in, 528t, 531 osteoarthritis of, 10, 11, 17 osteoporosis of, 19, 23, 28 calcitonin in, 28 raloxifene in, 25 Histamine2-receptor antagonists in gastroesophageal reflux disease, 265, 266, 267t, 268t, 269 in maintenance therapy, 271 in nausea and vomiting, 298t, 300 in pancreatitis, 312 in peptic ulcer disease, 318, 318t, 319t Histoplasmosis, 412–415 in HIV infection and AIDS, 414t, 415, 445t, 448t respiratory disorders in, 412, 413t sarcoid-like disease in, 413t, 415 HIV infection and AIDS, 435–449 antiretroviral therapy in, 438–444. See also Antiretroviral therapy in HIV infection blastomycosis in, 416 classification systems on, 435, 436t clinical presentation in, 435–437, 437t cryptococcal infections in, 419, 421, 421t meningitis in, 398, 419, 421, 445t prevention of, 448t diagnosis of, 437 histoplasmosis in, 414t, 415, 445t, 448t in human bite wounds, 521 lymphoma in, 711 opportunistic infections in, 444, 445t–448t, 449 Pneumocystis jiroveci pneumonia in, 444, 445t, 447t, 449 postexposure prophylaxis in, 441–443 in pregnancy, 359, 438, 441 tuberculosis in, 532, 533, 536 diagnosis of, 534t latent, 536t prophylaxis of, 447t vaccinations in, 565t, 569, 573 HMG-CoA reductase inhibitor therapy. See Statin therapy Hodgkin’s lymphoma, 704–706

1011

INDEX Homan’s sign in venous thromboembolism, 164 Hormones in contraceptives, 326–339 in menstrual cycle, 321–322, 323f in prostate cancer, 715f, 715–716 replacement therapy in women, 341–352 postmenopausal, 341–351 premenopausal, 351–352 Hot flushes in menopause, 341, 342 alternatives to estrogen therapy in, 347–349, 349t Human bite wounds, 510t, 511t, 513t, 520–521 Humidification of inspired air in chronic bronchitis, 468 Hyaluronan in osteoarthritis, 16 Hyaluronic acid in osteoarthritis, 16 Hydralazine in heart failure, 85, 90 in hypertension, 117t, 123 in emergencies, 129t in pregnancy, 126 in sickle cell disease, 375 Hydrochlorothiazide in diabetes insipidus, 884t in heart failure, 85, 93 in hypertension, 116t, 118 Hydrocodone in pain management, 621t, 623t in sickle cell crisis, 375 Hydrocortisone in adrenal insufficiency, 208, 208t, 209 in asthma, 916t in inflammatory bowel disease, 288f, 290f and toxic megacolon, 291 in myxedema coma, 237 in psoriasis, 188, 190t in sepsis, 490t in thyroid storm, 233t Hydrogen peroxide in pressure ulcers, 519 Hydromorphone in migraine headache, 607 in pain management, 620t, 623t, 625t in pancreatitis, acute, 307–308 in sickle cell crisis, 375 Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor therapy. See Statin therapy γ-Hydroxybutyrate abuse of, 825 in cataplexy, 822 Hydroxychloroquine in rheumatoid arthritis, 33, 34, 38

1012

adverse effects of, 36t, 38 dosage and monitoring of, 35t Hydroxyurea in psoriasis, 194 in sickle cell disease, 373, 374f Hydroxyzine in atopic dermatitis, 201 in generalized anxiety disorder, 740, 742t in nausea and vomiting, 298t Hylan polymers in osteoarthritis, 16 Hyperalimentation, 669. See also Nutrition, parenteral Hypercalcemia, 885, 886f, 887t, 888 of malignancy, 885, 888 pharmacotherapy in, 885, 886t, 887t, 888 Hypercapnia in COPD, 923, 929 Hypercholesterolemia, familial, 99, 108 Hypercoagulable states, venous thromboembolism in, 163 Hypercortisolism, 203–207 Hyperemesis gravidarum, 355 Hyperglycemia in diabetes mellitus, 210–226 and chronic kidney disease, 860 in parenteral nutrition, 676, 676t Hyperkalemia, 893 in acute renal failure, 856 in chronic kidney disease, 865 pharmacotherapy in, 893, 894t treatment algorithm on, 894f Hyperlipidemia, 98–110 cerebrovascular disorders in, 159t, 160–161 clinical presentation in, 99 coronary artery disease in, 58–59, 98, 99, 100, 109, 110 in diabetes mellitus, 100, 109, 225 risk categories in, 101–102, 102t definition of, 98 in diabetes mellitus, 99, 100, 109, 110 and coronary artery disease, 100, 109, 225 metformin in, 218 monitoring of, 110, 226 niacin in, 106, 109 diagnosis of, 99–100 drug therapy in, 103–110 evaluation of therapeutic outcomes in, 110 general approach to treatment of, 100–102 goals of therapy in, 100 hypertension management in, 127

INDEX in kidney disease, chronic, 873–874 management of, 862, 864t, 874 nonpharmacologic therapy in, 102–103, 107 oral contraceptive use in, 333 pathophysiology in, 98–99 risk categories in, 101t, 101–102, 102t Hyperlipoproteinemia, 98–110 Hypermagnesemia, 895–896 drug-induced, 896 Hypernatremia, 882–884 in acute renal failure, 856 Hyperparathyroidism hypercalcemia in, 885 secondary, in chronic kidney disease, 868–870 Hyperphosphatemia, 890 in kidney disorders, 868, 870, 870t, 890 Hyperpigmentation, 198 in Addison’s disease, 207 azelaic acid in, 183 Hyperplasia of prostate, benign, 931–935 Hyperpyrexia from antipsychotic drugs, 809 Hypersensitivity allergic reactions in. See Allergic reactions delayed cutaneous, in nutritional assessment, 649–650 Hypertension, 111–129 in African Americans, 127 cerebrovascular disorders in, 125–126, 159t, 160 in children, 126 classification of, 112t clinical presentation in, 112 and coronary artery disease, 125 crisis in, 111 in monoamine oxidase inhibitor therapy, 786–787 in Cushing’s syndrome, 204 definition of, 111 in diabetes mellitus, 120, 125, 225–226 diagnosis of, 112–113 drug-induced, 111 in elderly, 126 emergency in, 111, 128, 129t goals of therapy in, 113 and heart failure, 82, 124 and hyperlipidemia, 127 isolated systolic, 111 and kidney disorders, 120, 125, 126 pharmacologic therapy in, 860–861, 864f, 873 nonpharmacologic therapy in, 113

ocular, 720 treatment of, 721 oral contraceptive use in, 333 pathophysiology in, 111–112 and peripheral arterial disease, 127 pharmacologic therapy in, 113–129 dosage and frequency of, 116t–117t evaluation of therapeutic outcomes in, 128–129 indications for, 124–127 in kidney disease, 860–861, 864f, 873 selection of drug in, 115f portal, 239–249 in hepatitis B, 275 management of, 243–246 postmyocardial infarction, 124–125 in pregnancy, 126–127, 355–356, 359 primary or essential, 111 and respiratory disorders, 127 secondary, 111 in children, 126 clinical presentation in, 112t diagnosis in, 112–113 stages of, 112t treatment algorithm on, 114f urgency in, 111, 128 Hyperthyroidism, 227–234 Hypertriglyceridemia, 108–109 clinical presentation in, 99 diagnosis of, 99–100, 101t drug therapy in, 104t, 109 nutrition in, 103, 107, 109 in parenteral nutrition, 676t pathophysiology in, 98 Hyperuricemia, 1–8 conditions associated with, 8 definition of, 1 drug-induced, 1–2, 3 evaluation of therapeutic outcomes in, 8 pathophysiology in, 1–2 pharmacologic therapy in, 7–8 prophylactic therapy in, 6 Hypervolemic hyponatremia, 881, 882 Hypnotic drugs dependence on, 826t in insomnia, 815–818, 818t Hypocalcemia, 888, 889f in hyperphosphatemia, 890 Hypoglycemia in insulin therapy for diabetes mellitus, 214, 222, 226 in parenteral nutrition, 676, 676t Hypoglycemic agents, oral, interaction with other drugs, 792t

1013

INDEX Hypokalemia, 891–893 drug-induced, 892, 892t Hypomagnesemia, 893–895, 895t drug-induced, 893 and hypocalcemia, 888 Hypomania in bipolar disorder, 756–757 diagnostic criteria on, 760t treatment guidelines in, 764t–765t Hyponatremia, 881–882, 883f Hypoparathyroidism, hypocalcemia in, 888 Hypophosphatemia, 890–891 Hypotension orthostatic from antidepressant drugs, 783t–784t, 785 from antipsychotic drugs, 810 in shock, 143, 144 Hypothermia from antipsychotic drugs, 809 as therapy in cardiopulmonary resuscitation, 76t, 78 Hypothyroidism, 227, 234–237 diagnosis of, 229t in hyperthyroidism therapy, 233 Hypovolemia hypernatremia in, 884 hyponatremia in, 881, 882 shock in, 143, 144 drug therapy in, 150–151 evaluation of therapeutic outcomes in, 155 fluid resuscitation in, 146–150 treatment algorithm on, 146, 147f–148f Hypoxanthine-guanine phosphoribosyl transferase deficiency, 1 Hypoxemia in COPD, 923, 928–929 Hysterectomy, surgical site infections in, 527t, 529–530 I Ibandronate in hypercalcemia, 887t in osteoporosis, 23, 24, 27t Ibuprofen in bronchitis, acute, 466 in gouty arthritis, 5t in migraine headache, 603t, 605 in osteoarthritis, 12, 14t in otitis media, 479 in pain management, 619t in rheumatoid arthritis, 37t in tension-type headache, 612 Ibutilide in arrhythmias, 64t in atrial fibrillation and flutter, 67

1014

intravenous dosage of, 66t side effects of, 67t Ifosfamide in lymphoma, 711 Imipenem in cellulitis, 516t in urinary tract infections, 551 Imipenem-cilastatin in intraabdominal infections, 460t, 461t, 462t in pancreatitis, acute, 308 in urinary tract infections, 547t Imipramine in cataplexy, 821t, 822 in depression, 782t, 784t, 790t in generalized anxiety disorder, 742t, 743, 745 in migraine prophylaxis, 608t, 610 in panic disorder, 747, 747t, 749 in posttraumatic stress disorder, 753t, 754 in urinary incontinence, 947t Imiquimod in genital papillomavirus warts, 507t Immune globulin, 574–575 in hepatitis A, 273, 275, 574t in hepatitis B, 275, 276–277, 574t indications for, 574, 574t Rho(D), 574–575 in tetanus, 569–570, 570t Immune response nutrition affecting, 649–650 in psoriasis, 186, 191–192, 193 in rheumatoid arthritis, 31 Immunizations, 556–575. See also Vaccinations Immunocompromised host blastomycosis in, 416, 417t cryptococcosis in, 419, 421, 421t histoplasmosis in, 412, 414t immune globulin in, 574, 574t vaccinations in, 556, 565t, 568t, 569 influenza, 571 pneumococcal, 573 Immunoglobulins IgE in allergic rhinitis, 897, 898 linear IgA disease, 197t Immunotherapy in allergic rhinitis, 904–905 Impetigo, 509–510, 510t, 511t, 512t Impotence, 936–943 Incontinence, urinary, 944–950 clinical presentation in, 944–945, 945t definition of, 944 diagnosis of, 945–946 drug-induced, 944, 945t

INDEX evaluation of therapeutic outcomes in, 950 goals of therapy in, 946 nonpharmacologic treatment of, 946 overflow, 944, 947t, 949 pathophysiology in, 944 pharmacologic treatment of, 946–949 stress, 944, 946–948, 947t urge, 944, 946, 948–949 Indapamide in hypertension, 116t Indinavir in HIV infection, 442t Indomethacin in diabetes insipidus, 884t in gout, 3, 5t in osteoarthritis, 14t in rheumatoid arthritis, 37t in tension-type headache, 612 Infalyte oral rehydration solution, 261t, 428t Infarction cerebral, 158 myocardial. See Myocardial ischemia and infarction Infections, 377–434. See also specific infections antibiotic selection in, 377–387 of central nervous system, 387–398 definition of, 488t diagnosis in, 377–378 drug-resistant, 385–386 endocarditis, 399–411 fungal, 412–425 gastrointestinal, 426–434 hepatitis, 273–281 HIV infection and AIDS, 435–449 influenza, 450–455 intraabdominal, 456–464 opportunistic, in HIV infection and AIDS, 444, 445t–448t, 449 pathogen identification in, 378 prostatitis in, 554–555 respiratory, 465–486 sepsis and septic shock in, 487–492 sexually transmitted, 493–508 in pregnancy, 357–358, 359 in sickle cell disease, prevention of, 373 of skin and soft tissues, 509–521 surgical site, 522–531 tuberculosis, 532–543 of urinary tract, 544–555 vaccines and toxoids in prevention of, 556–575 Infiltrates, pulmonary, drug-induced, 969t Inflammation in asthma, 906–907

in gouty arthritis, 2 in infections, 378 in osteoarthritis, 9, 10 in rheumatoid arthritis, 31 Inflammatory bowel disease, 282–293 arthritis in, 282 Crohn’s disease. See Crohn’s disease etiologies of, 282, 283t pregnancy in, 292 toxic megacolon in, 282, 286, 291 ulcerative colitis. See Ulcerative colitis Inflammatory response syndrome, systemic, 487, 488, 488t Infliximab in inflammatory bowel disease, 286, 289, 290f, 291, 292 in psoriasis, 191–192 in rheumatoid arthritis, 33, 35t, 36t, 39 Influenza, 450–455 acute bronchitis in, 465, 466 antiviral drugs in, 455 nonpharmacologic therapy in, 455 postexposure prophylaxis in, 453–454, 454t in pregnancy, 455 vaccination, 451–453, 452t, 453t, 571 in adults, 564t–567t, 571 after myocardial infarction, 57 in children, 451, 452t, 557t–560t, 571 in chronic obstructive pulmonary disease, 924 in HIV infection, 447t live-attenuated, 451, 452t, 452–453, 453t, 454 in pregnancy, 451, 454, 571 in recurrent otitis media, 480 trivalent, 451, 452, 452t, 453t, 454 Inhalant abuse, 829, 831 Inotropic agents in heart failure, 93–94 in shock, 150–151, 152f, 153t Insomnia, 814–818, 822 chronic, 814, 815 drug-induced, 816t etiologies of, 815, 816t nonpharmacologic therapy in, 815, 816t pharmacologic therapy in, 815–818, 818t transient, 814, 815 Insulin deficiency of, 210 in hyperkalemia, 893, 894t interaction with other drugs, 792t

1015

INDEX Insulin (cont.) resistance to, 210, 214, 224 therapy in diabetes mellitus, 213–214, 213t–214t, 220–222 adverse effects of, 214 glucose levels in, 220, 221f infusion pump delivery of, 222 monitoring of, 226 pharmacokinetics of, 214t in pregnancy, 355, 358 preparations available, 213t in type 2 disease, 214, 222, 224 Insulin secretagogues, short-acting, in diabetes mellitus, 215, 216t, 218, 224 Interferon therapy in hepatitis B, 277–278, 278f in hepatitis C, 280t, 281, 281t Interleukin-1 in osteoarthritis, 9, 10 in rheumatoid arthritis, 31, 40 Interleukin-6 in rheumatoid arthritis, 31 International normalized ratio, in warfarin therapy for venous thromboembolism, 172, 174f Intoxication in substance abuse, 823, 830t, 830–831 of alcohol, 823, 830t of benzodiazepines, 825, 830t of cocaine, 827, 830t, 831 of marijuana, 828, 830t of methamphetamine, 827 of opiates, 825, 830t, 831 of phencyclidine, 829, 830t, 831 Intraabdominal infections, 456–464 sepsis in, 491t Intraaortic balloon pump in heart failure, 95 Intracranial pressure increase in hemorrhagic stroke, 157, 158–159 Intraocular pressure increase in glaucoma, 719–725, 720 Intrauterine contraceptive device, 339 Iodide in hyperthyroidism, 232, 234 Iodine, radioactive therapy in hyperthyroidism, 233 uptake in hyperthyroidism, 229, 230 Iopodate, skin reactions from, 952t Ipratropium bromide in allergic rhinitis, 904 in asthma, 914t, 917–918 in chronic obstructive pulmonary disease, 926 Irbesartan in hypertension, 116t Iridectomy in glaucoma, 721

1016

Irinotecan in colorectal cancer, 692 metastatic, 693, 694, 695t–696t, 698 side effects of, 698 in lung cancer, 702t, 703 Ibritumomab tiuxetan in lymphoma radioimmunotherapy, 710 Iron deficiency of, 363, 364 in children, 364, 369 in chronic kidney disease, 865, 866f clinical presentation in, 365 diagnosis of, 366 evaluation of therapeutic outcomes in, 369 treatment of, 366–367, 367t, 368t serum levels of, 365t total binding capacity, 365t, 366 Ischemia cardiac, 43–59, 130–142. See also Myocardial ischemia and infarction cerebral, 156. See also Cerebrovascular disorders, ischemic Isometheptene in migraine headache, 603t, 605 Isoniazid interaction with other drugs, 383t, 746t, 771 in tuberculosis, 537t, 538t active, 535, 536 adverse effects of, 542 dose adjustment in renal failure, 541, 542t latent, 535, 536t and meningitis, 395t, 397, 398, 541 Isoproterenol in asthma, 913t in torsade de pointes, 72 Isosorbide dinitrate in angina pectoris, 135, 136, 136t, 139 in heart failure, 85, 90 Isosorbide mononitrate in angina pectoris, 135, 136t, 139 in variceal hemorrhage, 246 Isosporiasis in HIV infection, 446t Isotretinoin in acne vulgaris, 180, 181f, 184 Isradipine in hypertension, 116t Itraconazole in aspergillosis, 424 in blastomycosis, 416, 417t in candidiasis and HIV infection, 445t in coccidioidomycosis, 418 in histoplasmosis, 413t, 414t, 415 in HIV infection, 445t, 448t interaction with other drugs, 746, 771 Ixabepilone in breast cancer, 687

INDEX J Jarisch-Herxheimer reaction, 500 Jejunostomy for enteral nutrition, 656, 657t Joint disorders in gouty arthritis, 2–8 in osteoarthritis, 9–17 in rheumatoid arthritis, 31–41 surgical site infections in, 528t, 530–531 K Kanamycin in tuberculosis, 539t, 542t Kaolin-pectin in diarrhea, 258, 262t Kava kava, 740 Keratolytic agents in acne vulgaris, 182–183 in psoriasis, 187–188 Kernig’s sign, 388 Ketamine, 829 Ketoacidosis, diabetic, 211, 840 Ketoconazole in blastomycosis, 416, 417t in coccidioidomycosis, 418 in Cushing’s syndrome, 205t, 206 interaction with other drugs, 746t, 771, 817 in prostate cancer, 718 Ketoprofen in gouty arthritis, 5t in migraine prophylaxis, 608t in osteoarthritis, 14t in pain management, 619t in tension-type headache, 612 Ketorolac in migraine headache, 605 in osteoarthritis, 14t in pain management, 619t in tension-type headache, 612 Kidney disorders, 839–896 acid–base balance in, 839–848 in metabolic acidosis, 842t, 870–873 acute failure, 849–857 classification of, 849, 850f, 851t–852t clinical presentation in, 849 definition of, 849 diagnosis of, 849, 852t, 852–853 differential diagnosis in, 853t drug dosing guidelines in, 856 electrolyte management in, 856 etiologies of, 851t–852t goals of therapy in, 853 intrinsic, 849, 851t–852t monitoring in, 856t, 857

nonpharmacologic treatment in, 854 nutrition in, 856 pathophysiology in, 849 pharmacologic therapy in, 855 postrenal, 849, 852t prerenal, 849, 851t, 852t prevention of, 853–854 risk factors for, 853 urinalysis in, 852, 852t, 853t, 856t anemia in, 865–868, 866f, 867f chronic disease, 858–874 clinical presentation in, 858, 860 complications of, 862–874 definition of, 858 goals of therapy in, 860 nonpharmacologic therapy in, 860 pathophysiology in, 858, 859f pharmacologic therapy in, 860–862 progression of, 858, 859f, 861f, 862f stages of, 858 in diabetes mellitus, 120, 225, 853 hyperglycemia control in, 860 progression-modifying therapies in, 860, 861f drug dose adjustment in, 875–880 absorption and bioavailability of drugs affecting, 875 in continuous renal replacement therapy, 878 creatinine clearance rate affecting, 875, 876–877, 877t distribution of drugs affecting, 875 in hemodialysis, 879–880 metabolism and clearance of drugs affecting, 875–876, 876t in peritoneal dialysis, 879 stepwise approach to, 877t in tuberculosis, 541, 542t electrolyte balance in, 881–896 in acute failure, 856 in chronic disease, 864–865 end-stage disease, 858 fluid balance in, 864–865 hyperlipidemia in, 873–874 management of, 862, 864t, 874 hyperparathyroidism in, 868–870 hyperphosphatemia in, 868, 870, 870t, 890 and hypertension, 120, 125, 126, 873 pharmacologic therapy in, 860–861, 864f, 873 from nephrotoxins, 971t–973t aminoglycoside antibiotics as, 972t contrast agents as, 853, 972t structural-functional alterations in, 971t

1017

INDEX Kidney disorders (cont.) nutrition in in acute failure, 856 in chronic disease, 860, 862, 864, 874 enteral, 659t osteodystrophy in, 868, 869f, 870 pruritus in, 874 in shock, 144, 145 tuberculosis therapy in, 541, 542t uremia in bleeding in, 874 symptoms of, 858, 860 in uric acid nephropathy, 2, 7 vaccinations in, 556, 565t Klebsiella infections, 381t, 467t, 474t Knee osteoarthritis, 10, 11, 16, 17 Kwashiorkor, 647 Kyphosis in osteoporosis-related spinal fractures, 18, 19 L Labetalol in alcohol withdrawal, 833t in angina pectoris, 135 in hypertension, 117t in pregnancy, 126 in urgencies and emergencies, 128, 129t interaction with other drugs, 791t Labor and delivery, 360–361 analgesia in, 361 cervical ripening in, 361 induction of, 361 preterm, 360–361 Lactase in diarrhea, 262t Lactate dehydrogenase levels in liver disorders, 963t Lactate serum levels in heart failure, 97 Lactated Ringer’s solution in hypovolemic shock, 146, 149 Lactation contraception in, 338 drug use in, 361–362 in schizophrenia therapy, 813 Lactic acidosis, 840, 842t, 844 in shock, 143 Lactobacillus in diarrhea, 258, 262t Lactulose in constipation, 252, 253, 253t, 254 in hepatic encephalopathy, 248 Lamivudine in hepatitis B, 277, 278, 279f in HIV infection, 440t, 441, 442t Lamotrigine in bipolar disorder, 763, 768t, 774

1018

guidelines on, 764t–765t monitoring of, 772t in seizures, 586, 594 adverse effects of, 587t, 588, 594 dosage and serum levels of, 593t indications for, 581t, 582t, 583t, 594 interaction with other drugs, 590t pharmacokinetics of, 585t Lansoprazole enteral feeding tube administration of, 662t in gastroesophageal reflux disease, 268t, 270, 271 in peptic ulcer disease, 318t, 319t Lanthanum carbonate in chronic kidney disease, 868, 871t Laparoscopy, surgical site infections in, 531 Lapatinib in breast cancer, 687 Latanoprost in glaucoma, 721, 723t, 724 Laxatives abuse of constipation in, 250–251 diarrhea in, 256 in constipation therapy, 252, 253, 253t, 254 Lean body mass, 648, 649, 650t Leflunomide in rheumatoid arthritis, 33, 37–38 adverse effects of, 36t, 38 dosage and monitoring of, 35t Legionella infections antibiotics in, 381t pneumonia in, 471, 472, 473 Lepirudin in venous thromboembolism, 169, 170 Lesch-Nyhan syndrome, 1 Letrozole in breast cancer, 685, 686, 686t Leucovorin in colorectal cancer, 692, 693 metastatic, 693, 694, 695t–696t in toxoplasmic encephalitis and HIV infection, 446t Leukocytes. See White blood cells Leukotriene receptor antagonists in allergic rhinitis, 904 in asthma, 918–919 Leuprolide in breast cancer, 686t, 687 in prostate cancer, 716, 717t in prostate hyperplasia, benign, 933, 933t Levalbuterol in asthma, 914t in chronic obstructive pulmonary disease, 924

INDEX Levetiracetam in seizures, 594 adverse effects of, 587t, 594 dosage and serum levels of, 593t, 594 indications for, 581t, 582t, 583t, 594 interaction with other drugs, 589, 590t pharmacokinetics of, 585t, 594 in status epilepticus, 645t Levobunolol in glaucoma, 722t Levobupivacaine in regional analgesia, 627t Levocabastine in allergic rhinitis, 902 Levocetirizine in allergic rhinitis, 900t, 901t Levodopa anxiety symptoms from, 740t interaction with other drugs, 791t in Parkinson’s disease, 630, 632t, 632–634 adverse effects of, 633t, 633–634 end-of-dose wearing off in, 633, 633t Levofloxacin in bite wounds, 513t in bronchitis acute, 466 chronic, 470t, 930 in cellulitis, 516t in chlamydial infections, 503t in chronic obstructive pulmonary disease, 470t, 930 in acute exacerbation, 930 in diabetic foot infections, 512t in gonorrhea, 497t in pancreatitis, acute, 308 in pneumonia, 475t in prostatitis, 555 in sepsis, 491t in sinusitis, 485t in surgical site infections, 525 in tuberculosis, 540t, 542t in urinary tract infections, 547t, 548t, 550 Levonorgestrel in menopause therapy, 345t in oral contraceptives, 327t, 329t, 337 Levorphanol in pain management, 620t, 623t Levothyroxine in hyperthyroidism, 231 in hypothyroidism, 235–236, 236t and myxedema coma, 237 Lewy bodies in Parkinson’s disease, 629 Lidocaine in arrhythmias, 64, 72, 79 intravenous dosage, 66t

mechanism of action, 64t side effects of, 67t in cardiopulmonary resuscitation, 76t, 77, 79 in regional analgesia, 627t in status epilepticus, refractory, 645t, 646 Light therapy in depression, 781 Linear IgA disease, 197t Linezolid interaction with other drugs, 793t in meningitis, 395t Liothyronine in hypothyroidism, 236t, 237 and myxedema coma, 237 Liotrix in hypothyroidism, 236t, 237 Lipase replacement therapy in pancreatitis, 311, 312t serum levels in pancreatitis, 306, 310 Lipid emulsion in parenteral nutrition, 672, 673t Lipid levels, 98–110 antipsychotic drugs affecting, 811 in cerebrovascular disorders, 159t, 160–161 classification of, 101t in coronary artery disease, 99, 100, 109, 110 agents lowering, 58–59, 109 and diabetes mellitus, 100, 109, 225 goals for, 58–59 in pathophysiology, 98 risk categories in, 101–102, 102t in diabetes mellitus, 99, 100, 109, 110 and coronary artery disease, 100, 109, 225 and metformin therapy, 218 monitoring of, 226 and niacin therapy, 106, 109 in hypertension, 127 in kidney disease, 873–874 management of, 862, 864t, 874 measurement of, 99–100, 110 in oral contraceptive use, 333 risk categories and therapy goals, 101t, 101–102, 102t Lipoprotein lipase deficiency, familial, 99, 100 Lipoproteins, 98–110 high-density, 98, 99, 100 in coronary artery disease, 109 in diabetes mellitus, 109 drug therapy affecting, 104t, 106 measurement of, 101, 101t nutrition affecting, 103, 107

1019

INDEX Lipoproteins (cont.) in oral contraceptive use, 333 treatment of low levels, 109 intermediate density, 98 low-density, 98–110 in coronary artery disease, 58–59 in diabetes mellitus, 109 drug therapy affecting, 104t in ischemic stroke, 161 measurement of, 101, 101t nutrition affecting, 107 optimal levels, 101t, 102t in oral contraceptive use, 333 risk categories and therapy goals, 101–102, 102t very low density, 98, 100 drug therapy affecting, 104t, 106, 107 nutrition affecting, 107 Liquor carbonis detergens in atopic dermatitis, 201 Lisinopril in acute coronary syndromes, 58 in heart failure, 86t in hypertension, 116t, 119 Listeria monocytogenes meningitis, 387, 396–397 treatment of, 390, 390t, 393t, 396–397 Lithium in bipolar disorder, 763, 766, 771, 774–776 dosage of, 767t, 776 formulations of, 767t guidelines on, 764t–765t mechanism of action, 767t monitoring of, 772t, 776 in pregnancy, 766, 776 toxicity of, 775–776 in depression, refractory, 796 dose adjustment in kidney disease, 877t interaction with other drugs, 774–775, 792t in schizophrenia, treatment-resistant, 806 Liver disorders abscess, 462t Child-Pugh classification of, 242, 243t cirrhosis, 239–249 encephalopathy in, 239, 240 management of, 243, 247t, 247–249 outcome assessment in, 248t precipitating factors in, 247, 247t enteral nutrition formulations in, 659t enzyme elevation patterns in, 241, 963t hepatitis, 273–281

1020

from hepatotoxins, 962t–964t. See also Hepatotoxins in parenteral nutrition, 676t in shock, 144 vaccinations in, 556, 565t Loeffler’s syndrome, 969t Lomefloxacin in gonorrhea, 497t Loperamide in diarrhea, 258, 262t in colorectal cancer chemotherapy, 692 Lopinavir in HIV infection, 439t, 441, 442t Loratadine in allergic rhinitis, 900t, 901t Lorazepam abuse of, 824, 825 for antipsychotic drug side effects, 807, 807t in bipolar disorder, 764t, 766, 769t in generalized anxiety disorder, 740, 743t, 744, 744t in nausea and vomiting, 299t in panic disorder, 747t in schizophrenia, 803 in seizures, 592t in status epilepticus, 641t, 642 in substance intoxication, 830t withdrawal from, 825 in withdrawal symptoms, 831t, 832, 834t Losartan in hypertension, 116t Lovastatin in Alzheimer’s disease, 732 in hyperlipidemia, 104t, 105t, 106 Lovaza in hyperlipidemia, 107 Loxapine in schizophrenia, 803t LSD (lysergic acid diethylamide), 829 Lubiprostone in constipation, 255 Lugol’s solution in thyroid storm, 233t Lumpectomy in breast cancer, 681 Lung cancer, 699–703 clinical presentation in, 699 diagnosis of, 699–700 evaluation of therapeutic outcomes in, 703 non-small cell, 699, 700–702 paraneoplastic syndromes in, 699 pathophysiology in, 699 small cell, 699 staging classification of, 700 treatment of, 702–703 staging of, 700 Lung function tests in asthma, 908, 920 in chronic obstructive pulmonary disease, 922–923 Lupus erythematosus, oral contraceptive use in, 334

INDEX Lupus syndrome, drug-induced, 123, 970t Luteinizing hormone in menopause, 341 in menstrual cycle, 321, 326 Luteinizing hormone-releasing hormone agonists in breast cancer, 685, 686t in prostate cancer, 714, 716 in combined hormonal blockade, 716–717 in salvage therapy, 718 Lymph node involvement in breast cancer, 680 sentinel lymph node biopsy in, 681 in colorectal cancer, 690 in lung cancer, 700 in lymphomas, 704–712 Lymphangitis, 510t, 512t Lymphocyte count in nutritional assessment, 649–650 Lymphogranuloma venereum, 507t Lymphoma, 704–712 definition of, 704 evaluation of therapeutic outcomes in, 711–712 Hodgkin’s, 704–706 non-Hodgkin’s, 706–711 advanced diffuse large B-cell, 711 advanced follicular, 709–710 aggressive, 708, 710–711 early-stage diffuse large B-cell, 710 in HIV infection and AIDS, 711 indolent, 706, 708, 709–710 localized follicular, 709 salvage therapy in, 711 Lymphoproliferative disorders, hyperuricemia and gout in, 1–2, 7 Lysergic acid diethylamide (LSD), 829 M Macrolide antibiotic interaction with other drugs, 383t Macules, 196 Maculopapular eruptions, drug-induced, 197–198, 201 Magnesium in parenteral nutrition solutions, 673, 673t serum levels of, 893–896 and calcium serum levels, 888 in hypermagnesemia, 895–896 in hypomagnesemia, 888, 893–895, 895t therapy in chronic kidney disease, 872t in constipation, 253t, 255

in hypomagnesemia, 895, 895t in pain management, 619t in torsade de pointes, 72, 76t, 80 Malabsorption of drugs, 385 in pancreatitis, chronic, 309, 311 Malnutrition, protein-energy, 647 in chronic kidney disease, 874 Mania in bipolar disorder, 756 diagnostic criteria on, 760t treatment guidelines in, 764t–765t secondary causes of, 757t Manic-depressive illness, 756–777. See also Bipolar disorder Mannitol in glaucoma, 724 in renal failure, acute, 855 Mantoux text in tuberculosis, 533–534 Maprotiline in depression, 785 Marasmus, 647 Marijuana, 828, 830t Mastectomy in breast cancer, 681 Mastitis, 362 Matrix metalloproteinases in osteoarthritis, 9 MDA (3,4-methylenedioxy-amphetamine), 828 MDMA (3,4-methylenedioxy-methamphetamine), 828 Measles immune globulin in exposure to, 574t vaccination, 571 in adults, 564t–566t, 571 in children, 557t–563t, 571 Mechanical ventilation in chronic obstructive pulmonary disease, 929 respiratory alkalosis in, 845 Mechlorethamine in Hodgkin’s lymphoma, 707t Meclizine in nausea and vomiting, 298t Meclofenamate in osteoarthritis, 14t in pain management, 619t in rheumatoid arthritis, 37t Mediastinitis, fibrosing, in histoplasmosis, 413t Medroxyprogesterone in breast cancer, 686t in injectable contraceptives, 338–339, 340 in menopause therapy, 344, 345t, 346 Mefenamic acid in osteoarthritis, 14t in pain management, 619t

1021

INDEX Megacolon, toxic, 282, 286, 291 Megaloblastic anemia, 369 drugs associated with, 960t Megestrol acetate in breast cancer, 686t in menopause, 349t in prostate hyperplasia, benign, 933t Meglitinides in diabetes mellitus, 215–218 Meloxicam in osteoarthritis, 14t in rheumatoid arthritis, 37t Memantine in Alzheimer’s disease, 730t, 731, 732 Meningitis, 387–398 antibiotics in, 388, 389–398 cerebrospinal fluid penetration of, 390, 391t dosage by age groups, 395t in empirical therapy by age groups, 390t first choice and alternative choices, 393t–394t intraventricular and intrathecal dosage, 390, 392t selection of, 379 cerebrospinal fluid analysis in, 387, 388t, 388–389 in fungal infections, 388t, 419 clinical presentation in, 387–389, 388t fungal, 398 cerebrospinal fluid values in, 388t, 419 cryptococcal, 398, 419, 420t, 421, 421t, 445t in HIV infection, 398, 419, 421, 445t treatment of, 395t, 398, 419, 421 Haemophilus influenzae, 387, 396 in children, 391 diagnosis of, 388, 389 treatment of, 390t, 394t, 396 Listeria monocytogenes, 387, 396–397 treatment of, 390, 390t, 393t, 396–397 meningococcal, 387, 391–392 diagnosis of, 388, 389, 392 treatment of, 389, 390t, 392, 394t pathophysiology in, 387 pneumococcal, 387, 395–396 diagnosis of, 388, 389 treatment of, 389, 390t, 393t, 396 Pseudomonas aeruginosa, 394t, 397 tuberculous, 388t, 397–398, 533 diagnosis of, 389 treatment of, 395t, 397–398, 541 viral, 388t, 395t

1022

Meningococcal infections meningitis in, 387, 391–392 diagnosis of, 388, 389, 392 treatment of, 389, 390t, 392, 394t vaccination, 571–572 in adults, 564t–568t in children, 557t–560t, 571 Menopause coronary artery disease in, 349–350 hormone replacement therapy in, 341–351 osteoporosis in, 18, 19 bisphosphonates in, 23 calcitonin in, 28 estrogen in, 28, 344t, 349 evaluation of therapy in, 351 raloxifene in, 25, 28, 347 teriparatide in, 29 treatment algorithm on, 347, 348f Menstrual cycle, 321–322, 323f cessation of, 341 seizures in, 583 Meperidine in migraine headache, 607 in pain management, 621t, 623t, 626 in pancreatitis, 307 in sickle cell crisis, 375 Mephenytoin in seizures, 592t Mephobarbital in seizures, 592t Mepivacaine in regional analgesia, 627t Meprobamate dependence, 826t Mercaptopurine in inflammatory bowel disease, 286 adverse effects of, 292 in Crohn’s disease, 289, 290f, 291 Meropenem in cellulitis, 516t in intraabdominal infections, 460t, 461t, 462t in meningitis, 395t, 397 in urinary tract infections, 547t, 551 Mesalamine adverse effects of, 292 in Crohn’s disease, 289, 290f, 291 in ulcerative colitis, 287, 287t, 288f, 289 Mesna in lymphoma, 711 Mestranol in oral contraceptives, 326, 327t Metabolic rate, basal, 652t, 663 Metabolic syndrome, 102, 811 Metabolism of drugs, kidney disorders affecting, 875–876 Metaproterenol in asthma, 913t Metastasis of breast cancer, 679, 680, 685–688

INDEX of colorectal cancer chemotherapy in, 691, 693–694, 695t–697t, 698 clinical manifestations in, 689 goals of treatment in, 690 staging of, 690 surgery in, 691 of lung cancer, 700, 703 of prostate cancer, 713 Metformin in diabetes mellitus, 217t, 218, 224 Methadone interaction with other drugs, 793t in opiate withdrawal, 831t, 832 in pain management, 621t, 623t, 626, 628 in sickle cell crisis, 375 L-Methadyl acetate hydrochloride in opiate withdrawal, 832 Methamphetamine abuse of, 827 in narcolepsy, 821t Methazolamide in glaucoma, 723t Methicillin in meningitis, 392t staphylococcal infections resistant to, 407, 408t Methimazole in hyperthyroidism, 231, 233t Methotrexate in breast cancer, 682, 683t in inflammatory bowel disease, 286 in Crohn’s disease, 289, 290f, 291 in psoriasis, 193, 194, 195 in rheumatoid arthritis, 33, 34, 37 adverse effects of, 36t, 37 dosage and monitoring of, 35t infliximab therapy with, 39 Methoxsalen and ultraviolet light A in psoriasis, 193, 194 Methsuximide in seizures, 592t Methylcellulose in constipation, 253t Methyldopa in hypertension, 117t, 122–123 in pregnancy, 127 interaction with other drugs, 792t 3,4-Methylenedioxy-amphetamine (MDA), 828 3,4-Methylenedioxy-methamphetamine (MDMA), 828 Methylphenidate interaction with other drugs, 791t in narcolepsy, 821, 821t Methylprednisolone in adrenal insufficiency, 208t in asthma, 914t, 916t

in gout, 6 in lymphoma, 711 in osteoarthritis, 16 in psoriasis, 190t in rheumatoid arthritis, 41 in thyroid storm, 233t Methyltestosterone in menopause therapy, 346t in osteoporosis, 27t, 29 Methylxanthines in asthma, 916–917 in chronic obstructive pulmonary disease, 927–928 Methysergide in migraine prophylaxis, 608t, 611 Metipranolol in glaucoma, 722t Metoclopramide in gastroesophageal reflux disease, 271 in migraine headache, 602, 604t in nausea and vomiting, 299t, 300 Metolazone in heart failure, 85, 93 in hypertension, 116t in renal failure, acute, 855 Metoprolol in acute coronary syndromes, 53 for antipsychotic drug side effects, 808 in atrial fibrillation and flutter, 65 in bradyarrhythmias, 72 in heart failure, 87 in hypertension, 117t, 121 in migraine prophylaxis, 608t, 610 Metronidazole in bacterial vaginosis in pregnancy, 358 in bite wounds, 513t, 521 in cellulitis, 516t in diabetic foot infections, 512t, 518 in gastrointestinal infections, 429t, 430 in hepatic encephalopathy, 249 in inflammatory bowel disease, 286, 289 interaction with other drugs, 383t in intraabdominal infections, 460t, 461t, 462t in pancreatitis, acute, 308 in peptic ulcer disease, 316, 317, 318, 318t in surgical site infections, 527t, 529 in trichomoniasis, 505, 506t, 508 Metyrapone in Cushing’s syndrome, 205t, 206 Mexiletine in arrhythmias, 64, 64t, 67t Midazolam in status epilepticus, 641t, 642, 645t Midodrine in bradyarrhythmias, 72, 73

1023

INDEX Mifepristone in Cushing’s syndrome, 207 Miglitol in diabetes mellitus, 217t, 220 Migraine headache, 599–611 clinical presentation in, 599–600 definition of, 599 diagnosis of, 600–601 nonpharmacologic treatment of, 601–602 in oral contraceptive use, 334 pathophysiology in, 599 pharmacologic treatment of, 602–611 prophylactic, 608t, 608–611 in pregnancy, 356 treatment algorithms on, 602f in prophylactic management, 609f triggers of, 599, 601, 601t Milk of magnesia in chronic kidney disease, 872t in constipation, 253, 255 Million Women Study on postmenopausal hormone therapy, 350 Milrinone in heart failure, 93–94 Mineral oil in constipation, 253t, 254 Mini-Mental State Examination, in Alzheimer’s disease, 729, 730, 734 Minocycline in acne vulgaris, 185 in bronchitis, chronic, 470t in rheumatoid arthritis, 33 in urinary tract infections, 547t Minoxidil in hypertension, 117t, 123–124 Mirtazapine in depression, 785 and cytochrome P450 activity, 795t dosage of, 782t interaction with other drugs, 794t pharmacokinetics of, 788, 790t refractory, 796 relative potency of, 783t side effects of, 783t, 786 in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 751t Mithramycin in hypercalcemia, 887t Mitomycin C in glaucoma, 721 Mitotane in Cushing’s syndrome, 205t, 206 Mitoxantrone in non-Hodgkin’s lymphoma, 711 Modafinil in narcolepsy, 821, 821t in sleep apnea, 819 Moexipril in hypertension, 116t Molds, allergic rhinitis from, 897, 898 Molindone in schizophrenia, 803t, 809 Mometasone furoate in allergic rhinitis, 903t

1024

in asthma, 915t in psoriasis, 190t Monoamine oxidase inhibitors in depression, 782 dosage of, 782t interaction with other drugs, 791, 792t, 793t, 794t relative potency of, 784t side effects of, 784t, 786–787 interaction with foods, 786–787, 787t interaction with other drugs, 787, 788t in depression, 791, 792t, 793t, 794t in panic disorder, 747t, 749 in Parkinson’s disease, 630, 632t, 634 in posttraumatic stress disorder, 754 in social anxiety disorder, 751t, 753 Monoclonal antibodies in breast cancer, 682, 685, 687 in colorectal cancer, 692–693, 698 in lung cancer, 702 in lymphoma, 709–710 in psoriasis, 191–192 in rheumatoid arthritis, 40 Monosodium urate crystals in gout, 1, 3 Montelukast in allergic rhinitis, 904 in asthma, 918–919 Moraxella catarrhalis infections antibiotics in, 380t chronic obstructive pulmonary disease in, 467t acute exacerbation of, 930 otitis media in, 478, 479 Moricizine in arrhythmias, 64t, 67t Morphine in acute coronary syndromes, 48, 54 in pain management, 625–626 dosage of, 620t, 623t routes of administration, 623t, 625t in pancreatitis, acute, 307 in sickle cell crisis, 375 Motility disorders, intestinal diarrhea in, 256 gastroesophageal reflux disease in, 270–271 Moxifloxacin in bite wounds, 513t in bronchitis, chronic, 470t, 930 in chronic obstructive pulmonary disease, 470t, 930 in acute exacerbation, 930 in diabetic foot infections, 512t in meningitis, 395t in tuberculosis, 540t

INDEX Mucolytic agents in chronic bronchitis, 468–469 Multiple-organ dysfunction syndrome, 488t Mumps vaccination, 572 in adults, 564t–566t, 572 in children, 557t–563t, 572 Mupirocin ointment in impetigo, 510, 512t Mycobacterial infections in HIV infection and AIDS, 446t, 532 active tuberculosis in, 536 clinical presentation in, 533 diagnosis of, 534t latent tuberculosis in, 536t prophylaxis of, 447t meningitis in, 388t, 397–398, 533 diagnosis of, 389 treatment of, 395t, 397–398, 541 tuberculosis in, 532–543. See also Tuberculosis Mycophenolate mofetil in psoriasis, 193 Mycoplasma pneumoniae infections acute bronchitis in, 465, 466 antibiotics in, 382t, 466 pneumonia in, 471, 473, 474t, 475t Myeloproliferative disorders, hyperuricemia and gout in, 1–2, 7 Myocardial ischemia and infarction, 43–59, 130–142 acute coronary syndromes in, 43–59 biochemical markers in, 44, 46f, 47, 133 cardiopulmonary arrest in, 74, 80 clinical presentation in, 44, 131–132 cocaine-induced, 54 complications of, 44 definitions of, 43, 130 diagnosis of, 44–47, 45f, 132–133 drug therapy in, 48–56, 134–142 in secondary prevention, 57–59 electrocardiography in, 43, 44, 45f, 133, 142 evaluation of therapeutic outcomes in, 59, 142 general treatment measures in, 47–48 goals of therapy in, 47, 57, 133 heart failure in, 82 hypertension management in, 124–125 non–ST-segment elevation, 43, 45f treatment in, 47–48, 54–56, 55f nonpharmacologic therapy in, 48 in oral contraceptive use, 330, 333 pathophysiology in, 43–44, 130–131 Q waves in, 43

risk factors in, 45f, 47–48 modification of, 134 secondary prevention in, 57–59 silent, 131–132 ST-segment elevation, 43, 44, 45f treatment in, 47, 48–54, 49f ventricular remodeling in, 44 Myoclonic jerks, 579 Myxedema coma, 235, 237 N Nabilone in nausea and vomiting, 299t, 301 Nabumetone in osteoarthritis, 14t in rheumatoid arthritis, 37t Nadolol in hypertension, 117t, 121 in hyperthyroidism, 232 in migraine prophylaxis, 608t, 610 in schizophrenia, treatment-resistant, 806 in variceal hemorrhage, 243, 246 Nafarelin in benign prostatic hyperplasia, 933t Nafcillin in cellulitis, 514, 515t in endocarditis, 403, 406t, 408t in meningitis, 392t, 395t Nalbuphine in pain management, 622t, 624t Nalidixic acid in gastrointestinal infections, 429t Naloxone in opioid reversal, 622, 625, 626, 831 dosage of, 622t, 624t, 830t Naltrexone in alcohol dependence, 835 Nandrolone decanoate in menopause therapy, 346t Naphazoline hydrochloride in allergic rhinitis, 902t Naproxen in gout, 3, 5t in migraine headache, 603t, 605 in prophylaxis, 608t in osteoarthritis, 12, 14t in pain management, 619t in rheumatoid arthritis, 37t in tension-type headache, 612 Naratriptan in migraine headache, 604t, 606, 607t Narcolepsy, 821t, 821–822 Nasal decongestants in sinusitis, 486 Nasoduodenal intubation for enteral nutrition, 656, 657t

1025

INDEX Nasogastric intubation for enteral nutrition, 656, 657t Nasojejunal intubation for enteral nutrition, 656, 657t Nateglinide in diabetes mellitus, 216t, 218 National Asthma Education and Prevention Program, 906, 908, 909 National Cholesterol Education Program, 103, 160 Adult Treatment Panel III, 100, 225 National Kidney Foundation on blood pressure control in diabetes mellitus, 225 National Psoriasis Foundation Psoriasis Score, 195 Nausea and vomiting, 294–304 antiemetic drugs in, 296–304, 302t, 303t dosage of, 298t–299t in balance disorders, 303–304 in chemotherapy prevention of, 301, 302t risk of, 294, 296t treatment of, 296, 297, 303 in children, 304 clinical presentation in, 294, 297t with diarrhea, 258 etiologies of, 294, 295t, 296t, 297t in pancreatitis, 307, 310 in peptic ulcer disease, 315 postoperative, 300, 303, 303t in pregnancy, 304, 355 psychogenic, 295 in radiation therapy, 303 Necrolysis, topical epidermal, 197t Nedocromil sodium in asthma, 918 Nefazodone in depression, 785 and cytochrome P450 activity, 795t dosage of, 782t pharmacokinetics of, 789t relative potency of, 783t side effects of, 783t, 786 interaction with other drugs, 746t, 771, 817 Neisseria gonorrhoeae infections. See Gonorrhea Neisseria meningitides infections. See Meningococcal infections Nelfinavir in HIV infection, 442t Neomycin in hepatic encephalopathy, 249 in surgical site infections, 525, 526t Nephritis, allergic interstitial, drugs associated with, 973t

1026

Nephrolithiasis in gout, 2 Nephropathy in diabetes mellitus, 120, 225 uric acid, 2, 7 Nephrotoxins, 853–854, 971t–973t aminoglycoside antibiotics as, 972t contrast agents as, 853, 972t lithium as, 775 structural-functional alterations in, 971t Nesiritide in heart failure, 95 Netilmicin dose adjustment in kidney disease, 879t Neurofibrillary tangles in Alzheimer’s disease, 727 Neurokinin1 receptor antagonists in nausea and vomiting, 301 Neuroleptic malignant syndrome, 810 Neurologic disorders, 577–646 from antipsychotic drugs, 806–810 anxiety symptoms in, 739t in central nervous system infections, 387–398 in coccidioidomycosis, 418 cryptococcal, 398, 419, 420t, 421t in diabetes mellitus, 224–225 foot infections in, 517 epilepsy, 577–598 and status epilepticus, 637–646 headache in, 599–613 in hepatic encephalopathy, 240 in hypothyroidism, 235 Parkinson’s disease, 629–636 in stroke, 157, 162 surgical site infections in, 528t, 531 in syphilis, 499, 500, 501t Neuropathy diabetic, 224–225 foot infections in, 517 optic, in glaucoma, 719 pain in, 614–615 Neurosurgery, surgical site infections in, 528t, 531 Neurosyphilis, 499, 500, 501t Neutrophil count in infections, 377 in candidiasis, 422, 423t, 424t in HIV infection, 448t Nevirapine in HIV infection, 439t, 442t New York Heart Association classification of heart failure, 83 Niacin in hyperlipidemia, 104t, 106, 108, 109 in combination therapy, 108 and coronary artery disease, 59, 109 dosage of, 105t monitoring of, 110

INDEX Nicardipine in hypertension, 116t, 129t Nicotine, 827–828 dependence on, 835–838 replacement therapy in, 835, 836, 837t transdermal in smoking cessation, 836, 837t in ulcerative colitis, 287 Nifedipine in acute coronary syndromes, 54 in hypertension, 116t, 120 in ischemic heart disease, 137, 139, 141, 142 in preterm labor, 360 Nilutamide in prostate cancer, 716, 717, 717t Nimodipine in bipolar disorder, 766, 770t in hemorrhagic stroke, 161, 161t Nisoldipine in hypertension, 116t Nitrates in acute coronary syndromes, 52–53, 56, 58 in heart failure, 90 interaction with other drugs, 53, 940, 941 in ischemic heart disease, 135–136, 136t, 138 and variant angina, 139 Nitric oxide in osteoarthritis, 9, 10 Nitrofurantoin in urinary tract infections, 547t, 548t, 549t in pregnancy, 553 Nitroglycerin in acute coronary syndromes non–ST-segment elevation, 54, 56 in secondary prevention, 57, 58 ST-segment elevation, 48, 52–53 in angina pectoris, 135, 136, 136t, 138, 139 therapeutic outcome in, 142 variant, 139 in heart failure, 95 in hypertensive emergencies, 129t Nitroprusside in heart failure, 94–95 in hypertensive emergencies, 128, 129t Nizatidine in gastroesophageal reflux disease, 267t, 268t in nausea and vomiting, 298t, 300 in peptic ulcer disease, 319t Nociceptors in pain sensation, 614 Nodules rheumatoid, 32, 32t of thyroid, 228, 230

Norepinephrine activity in anxiety disorders, 735 in depression, 778 Norepinephrine therapy in cardiopulmonary resuscitation, 79 in sepsis, 492, 492t in shock, 151, 153, 153t septic, 492, 492t Norethindrone in menopause therapy, 345t in oral contraceptives, 327t, 328t, 329t Norethisterone acetate in menopause therapy, 344 Norethisterone in menopause therapy, 345t Norfloxacin in gastrointestinal infections, 429t, 431, 432 in gonorrhea, 497t interaction with other drugs, 383t in urinary tract infections, 547t, 548t, 550 Norfluoxetine in depression, 788 Norgestimate in oral contraceptives, 328t Norgestrel in menopause therapy, 345t in oral contraceptives, 327t, 329t Norovirus gastroenteritis, 434 Nortriptyline in cataplexy, 821t, 822 in depression dosage of, 782t in elderly, 792 pharmacokinetics of, 790t refractory, 796 relative potency of, 784t side effects of, 784t therapeutic plasma concentration of, 782t, 788 in insomnia, 816 in migraine prophylaxis, 608t, 610 in smoking cessation, 836, 837t, 838 in urinary incontinence, 947t Norwalk virus gastroenteritis, 434 Nosocomial infections pneumonia in, 473–474, 474t sepsis in, 491t of urinary tract, 545 5-Nucleotidase in liver disorders, 963t Nutrition, 647–678 in ascites, sodium intake in, 246 assessment of, 647–654 lean body mass in, 648, 649, 650t weight and height measurements in, 648, 649t, 650t in constipation, 250, 251, 252, 253

1027

INDEX Nutrition (cont.) in diabetes mellitus, 212, 220–222 in diarrhea, 258, 426 drug–nutrient interactions affecting, 654, 654t energy requirements in, 651–653 enteral, 655–662 access routes in, 656, 657t administration methods, 656–658 bolus, 656, 658 complications in, 660–661 continuous, 656, 660 contraindications to, 655 cyclic, 656 definition of, 655 drug administration in, 661–662, 662t formulations in, 658–659, 659t hydration formulations in, 659 indications for, 655 initiation and advancement of feedings in, 660 intermittent, 658, 660 monitoring of, 661t in gastroesophageal reflux disease, 263, 264t, 269t in gout and hyperuricemia, 1, 2, 3 in heart failure, fluid and sodium intake in, 84 in hepatic encephalopathy, 247t, 248 in hyperlipidemia, 102–103, 103t, 107, 108 and coronary artery disease, 59, 103, 109 evaluation of, 110 fish oils in, 59, 103, 107, 109 in hypertension, 111, 113 in inflammatory bowel disease, 286 in iron deficiency anemia, 366 in kidney disorders in acute failure, 856 in chronic disease, 860, 862, 864, 874 enteral nutrition formulas in, 659t in menopause, 342 and monoamine oxidase inhibitor interaction with foods, 786–787, 787t in nausea and vomiting, 295 in obesity, 663–668 in osteoarthritis, dietary supplements in, 14t, 15–16 in osteoporosis, 20, 23, 23t, 24t in pancreatitis, 307, 311 parenteral, 669–678 administration of, 674–676 adult regimen in, 674, 675f

1028

complications of, 676, 676t composition of formulations in, 669–672 cyclic, 676 definition of, 669 drug administration in, 674 indications for, 669, 670t, 671f monitoring of, 677f, 678 in peptic ulcer disease, 315, 316 Nystatin in candidiasis and HIV infection, 445t O Obesity, 663–668 in Cushing’s syndrome, 203 diabetes mellitus in, 224, 668 pharmacologic therapy in, 665–668 treatment algorithm on, 666f Obstetrics and gynecology, 321–362 contraception, 321–340 hormone therapy, 341–352 postmenopausal, 341–351 premenopausal, 351–352 pregnancy and postpartum issues, 353–362 surgical site infections in, 527t, 529–530 Occupational exposure to hepatotoxins, 963t Octreotide in diarrhea, 261, 262t in pancreatitis, acute, 308 in variceal hemorrhage, 244f, 245 Ofloxacin in chlamydial infections, 503t dose adjustment in kidney disease, 877t in gastrointestinal infections, 429t in gonorrhea, 497t in peritonitis, spontaneous bacterial, 247 Olanzapine in Alzheimer’s disease, 733t in bipolar disorder, 763, 764t, 766, 769t, 771 in depression, refractory, 796 in posttraumatic stress disorder, 755 in schizophrenia, 800, 801, 810 dosage of, 803t in initial therapy, 803 pharmacokinetics of, 804t side effects of, 806t, 809, 810, 812 treatment-resistant, 806 Oliguria in acute renal failure, 849 Olmesartan in hypertension, 116t Olopatadine in allergic rhinitis, 902

INDEX Olsalazine in inflammatory bowel disease, 287t, 292 Omalizumab in asthma, 919 Omega-3 fatty acids in hyperlipidemia, 107 and coronary artery disease, 59 marine-derived (fish oils), 59, 103, 107, 109 Omeprazole enteral feeding tube administration of, 662t in gastroesophageal reflux disease, 265, 267t, 268t, 270 in maintenance therapy, 271 interaction with other drugs, 746t in peptic ulcer disease, 318t, 319, 319t Oncologic disorders, 679–718. See also Cancer Ondansetron in nausea and vomiting, 301, 302t, 303, 303t Oophorectomy in breast cancer, 687 Ophthalmia neonatorum, 496, 498t, 502 Ophthalmic disorders, 719–725 from antipsychotic drugs, 811 in diabetic retinopathy, 224 in glaucoma, 719–725 in ophthalmia neonatorum, 496, 502 Opiates abuse of, 825 in diarrhea, 258, 262t intoxication from, 825, 830t, 831 withdrawal from, 825, 831t, 832, 835 Opioid analgesics, 616–627 abuse of, 825 adverse effects of, 625t dosage of, 620t–622t in migraine headache, 607 in osteoarthritis, 17 in pancreatitis, acute, 307–308 routes of administration, 622, 623t–624t intraspinal, 622, 625, 625t Opioids, endogenous, 614 Opportunistic infections in HIV infection and AIDS, 444, 445t–448t, 449 Optic neuropathy in glaucoma, 719 Oral rehydration solutions, 258, 261t, 426, 428t Orchiectomy in prostate cancer, 714, 715 in combined hormonal blockade, 717 in salvage therapy, 718 Orlistat in obesity, 665, 667t Orthopedic surgery, surgical site infections in, 528t, 530–531 Oseltamivir in influenza, 453, 454t, 455

Osmolality of enteral nutrition formulations, 658 of oral rehydration solutions, 261t, 428t of serum in hyponatremia, 881, 883f Osmolarity of parenteral nutrition solutions, 673, 673t Osteoarthritis, 9–17 clinical presentation of, 10 definition of, 9 diagnosis of, 10–11 erosive, 9 evaluation of therapeutic outcomes in, 17 localized, 9 nonpharmacologic therapy in, 11 pathophysiology in, 9–10 pharmacologic therapy in, 11–17 primary idiopathic, 9 secondary, 9 treatment algorithm on, 13f Osteodystrophy, renal, 868, 869f, 870 Osteomyelitis in diabetic foot infections, 517, 518 Osteopenia, 19, 30 Osteophytes in osteoarthritis, 10, 11 Osteoporosis, 18–30 clinical presentation in, 18–19 in Cushing’s syndrome, 204 definition of, 18 diagnosis of, 19 drug-induced, 18, 23, 30 drug therapy in, 20–29, 30 estrogen therapy in, 28, 344t, 349 goals of therapy in, 19 in menopause. See Menopause, osteoporosis in nonpharmacologic therapy in, 20 pathophysiology in, 18 prevention of, 20 treatment algorithm on, 21f–22f Otitis media, 478–480 antibiotics in, 479–480, 480t clinical presentation in, 478, 479t Ovary ablation therapy in breast cancer, 687 premature failure of, 351–352 Overflow urinary incontinence, 944, 947t, 949 Overnutrition, 647 Ovulation, 321–322 Oxacillin in cellulitis, 514, 515t in endocarditis, 403, 406t, 408t in meningitis, 395t

1029

INDEX Oxaliplatin in colorectal cancer, 692 in adjuvant regimens, 693, 694t metastatic, 693, 694, 695t–696t, 698 Oxaprozin in osteoarthritis, 14t in rheumatoid arthritis, 37t Oxazepam in Alzheimer’s disease, 733 in generalized anxiety disorder, 743t, 744, 744t, 745 withdrawal from, 825 Oxcarbazepine in bipolar disorder, 764t, 769t, 776 monitoring of, 772t interaction with other drugs, 590t, 595, 776 in seizures, 586, 594–595 adverse effects of, 587t, 588, 595 dosage and serum levels of, 593t, 595 indications for, 581t, 582t, 595 interaction with other drugs, 590t, 595 pharmacokinetics of, 585t, 594–595 Oxybutynin in urinary incontinence, 947t, 948–949 Oxycodone abuse of, 825 in migraine headache, 607 in osteoarthritis, 14t, 17 in pain management, 621t, 623t Oxygen in arterial blood, 840t in chronic obstructive pulmonary disease, 923, 928–929 in respiratory acidosis, 847 consumption of, 145, 145t delivery of, 145, 145t myocardial demand, 130, 131, 137 therapy with in acute coronary syndromes, 48, 54 in asthma, 909 in cardiopulmonary arrest, 77 in chronic obstructive pulmonary disease, 928–929 in respiratory acidosis, 847 in venous blood, 840t Oxymetazoline in rhinitis, allergic, 902t in sinusitis, 486 Oxymorphone in pain management, 620t, 623t Oxytocin in labor induction, 361 P Pacing, cardiac in atrioventricular block, 73

1030

in bradyarrhythmias, 72 in torsade de pointes, 72 Paclitaxel in breast cancer, 682, 683t, 684t in lung cancer, 700, 701t Pain, 614–628 abdominal. See Abdominal pain acute, 614, 615, 617f, 628 cancer-related, 618f, 628 in chest in acute coronary syndromes, 44 in ischemic heart disease, 131–132 chronic, 614, 615, 628 clinical presentation in, 615 definition of, 614 drug therapy in, 616–628 evaluation of therapeutic outcomes in, 628 functional, 614–615 goals of therapy in, 615 in gout, 3 in infections, 378 in labor and delivery, 361 in migraine headache, 599–600 analgesics in, 603t, 605 neuropathic, 614–615 nociceptive, 614 in osteoarthritis, 10, 11 drug therapy in, 11–17 in osteoporosis-related fractures, 18 in pancreatitis acute, 305–306, 307–308 chronic, 309–310, 311, 312 pathophysiology in, 614–615 patient description of, 615 in peptic ulcer disease, 315 in rheumatoid arthritis, 31, 41 in sickle cell crisis, 372, 375 in tension-type headache, 612 Palonosetron in nausea and vomiting, 301, 302t Paliperidone in schizophrenia, 803t, 804t Pamidronate in hypercalcemia, 887t in prostate cancer, 718 Pancreatic enzyme supplements in pancreatitis, 311, 312t, 313 Pancreatitis, 305–313 acute, 305–309 clinical presentation in, 305–306 diagnosis of, 306–307 drugs associated with, 305, 306t, 307 pathophysiology in, 305 pharmacologic treatment in, 307–308 treatment algorithm on, 308f

INDEX chronic, 309–313 clinical presentation in, 309–310 diagnosis of, 310 pathophysiology in, 309 pharmacologic treatment in, 310–312 treatment algorithm on, 311f definition of, 305 necrotizing, 307, 308 Panic disorder clinical presentation in, 736, 737t pathophysiology in, 735 treatment of, 738, 740, 747–750 algorithm on, 748f dosage in, 747t, 749–750 drug choices in, 742t, 747t outcome evaluation in, 750 Panitumumab in colorectal cancer, 693, 698 Pannus formation in rheumatoid arthritis, 31 Pantoprazole in gastroesophageal reflux disease, 268t, 270 in peptic ulcer disease, 318t, 319t Papaverine in erectile dysfunction, 938t, 942, 943 Papillomavirus infections, 495t, 507t vaccination, 570–571 in adults, 564t–566t in children, 559t–560t, 562t–563t Papules, 197 Paracentesis in ascites, 246 Paraneoplastic syndromes in lung cancer, 699 Parasitic infections, sexually transmitted, 494t Parathyroid disorders calcium serum levels in, 885, 888 in chronic kidney disease, 868–870 Parathyroid hormone in chronic kidney disease, 868–870, 873t Paratyphoid fever, 431, 432 Paregoric in diarrhea, 262t Parenteral nutrition, 669–678. See also Nutrition, parenteral Paricalcitol in chronic kidney disease, 870, 873t Parkinson’s disease, 629–636 clinical presentation in, 629, 630t definition of, 629 diagnosis of, 629–630 evaluation of therapeutic outcomes in, 636 goals of treatment in, 630 pathophysiology in, 629

pharmacologic therapy in, 630–636 treatment algorithm on, 631f Paroxetine in Alzheimer’s disease, 733, 733t in depression and cytochrome P450 activity, 795t dosage of, 782t interaction with other drugs, 791, 794t pharmacokinetics of, 789t refractory, 796 relative potency of, 783t side effects of, 783t in generalized anxiety disorder, 742t, 743 interaction with other drugs, 746t, 791, 794t in menopause, 349t in panic disorder, 747, 747t in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 750, 751t Pasteurella multocida infections, 381t Pedialyte oral rehydration solution, 261t, 428t Pelvic inflammatory disease, 462t in gonorrhea, 493 Pemetrexed in lung cancer, 702 Pemphigoid, bullous, 197t Pemphigus, drug-induced, 197t Penbutolol in hypertension, 117t, 121 Penicillamine in rheumatoid arthritis, 33, 35t, 36t, 39 Penicillin allergy to skin reactions in, 952t skin testing in, 952t in bite wounds, 513t, 520 in cellulitis, 514, 515t, 517 in endocarditis enterococcal, 407, 408t resistance to, 403, 404t streptococcal, 401, 402t, 403 in erysipelas, 509, 512t in impetigo, 510 interaction with other drugs, 383t in lymphangitis, 512t in meningitis, 392, 395t, 396 in pharyngitis, 481, 481t, 483t in sickle cell disease, prophylactic, 373 in streptococcal group B infection in pregnancy, 361 in syphilis, 500, 501t in urinary tract infections, 547t, 549t Pentaerythritol tetranitrate in angina pectoris, 136t

1031

INDEX Pentaerythritol trinitrate in angina pectoris, 139 Pentamidine in Pneumocystis jiroveci pneumonia, 445t Pentazocine in pain management, 621t, 624t, 626 Pentobarbital dependence on, 826t in status epilepticus, refractory, 644, 645t Peptic ulcer disease, 314–320 drug-induced, 314, 315, 316 treatment of, 318–319 in Helicobacter pylori infections, 314, 315 diagnosis of, 315–316 treatment of, 316–318, 318t perforated, peritonitis in, 461t stress-related, 314, 316 treatment algorithm on, 317f Peptide-based enteral nutrition formulations, 658, 659t Pericarditis in histoplasmosis, 413t Perimenopause, 341 Perindopril in heart failure, 86t in hypertension, 116t Peripheral arterial disease in diabetes mellitus, 225 hypertension management in, 127 Peritoneal dialysis in acute renal failure, 854 drug dosage adjustment in, 879 peritonitis in, 461t, 462 Peritonitis, bacterial, 456–464 clinical presentation in, 458, 459t microbiology in, 456–457, 458t primary, 456–457, 457t clinical presentation in, 458, 459t treatment of, 458–459, 461t secondary, 456, 457, 457t, 458t clinical presentation in, 458, 459t treatment of, 459–460, 461t spontaneous, 243, 247, 248t Perphenazine in schizophrenia, 801, 803t, 804t, 806t Pertussis vaccination, 572 in adults, 564t–566t, 572 in children, 557t–563t, 572 contraindications to, 572 Petrolatum in diaper dermatitis, 199 pH of arterial blood, 839, 840t in metabolic acidosis, 840, 842, 844 in metabolic alkalosis, 844 in respiratory acidosis, 845 in respiratory alkalosis, 845

1032

esophageal, in gastroesophageal reflux disease, 264–265 gastric intramucosal, 145t, 146 of venous blood, 840t Pharyngitis, 481–484 clinical presentation in, 481, 481t in sexually transmitted infections, 495t Phencyclidine, 829, 830t, 831 Phendimetrazine in obesity, 667t Phenelzine in depression, 782, 782t, 784t, 786 in migraine prophylaxis, 608t in panic disorder, 747t, 749 in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 751t, 753 Phenindamine tartrate in allergic rhinitis, 900t Phenobarbital in seizures, 586, 595 adverse effects of, 587t, 588, 595 dosage and serum levels of, 592t, 595 indications for, 581t, 582t, 595 interaction with other drugs, 589, 590t–591t, 595 pharmacokinetics of, 585t, 595 in status epilepticus, 641t, 642, 643–644 Phenothiazines interaction with other drugs, 791t in nausea and vomiting, 298t, 300 Phentermine in obesity, 665, 667t Phentolamine in erectile dysfunction, 938t, 942, 943 Phenylephrine in rhinitis, allergic, 901t, 902t, 903 in sepsis, 492t in shock, 151, 153t, 154 septic, 492t in sickle cell disease, 375 in sinusitis, 486 in urinary incontinence, 947t Phenytoin enteral feeding tube administration of, 662t interaction with other drugs in anxiety disorders, 746t in depression, 791t, 792t, 793t in seizures, 589, 590t–591t, 596 in seizures, 586, 595–596 adverse effects of, 587t, 588, 596 dosage and serum levels of, 592t, 596 indications for, 581t, 582t, 595 interaction with other drugs, 589, 590t–591t, 596

INDEX pharmacokinetics of, 585t, 596 in status epilepticus, 641t, 642–643 Pheochromocytoma, hypertension in, 111, 112 Phosphate-binding agents in chronic kidney disease, 868, 870, 871t–872t Phosphodiesterase inhibitors in erectile dysfunction, 939–941 cardiovascular risk factors in, 940, 941t interaction with nitrates, 53, 940, 941 pharmacodynamics and pharmacokinetics of, 939, 940t Phosphoribosyl pyrophosphate synthetase, 1 Phosphorus dietary, in chronic kidney disease, 868 in parenteral nutrition solutions, 673, 674 replacement therapy in hypophosphatemia, 891, 891t serum levels of, 890–891 in chronic kidney disease, 868, 870, 870t in hyperphosphatemia, 890 in hypophosphatemia, 890–891 Photoallergic reactions, drug-induced, 196 Photosensitivity reactions, drug-induced, 196, 201 from antipsychotic drugs, 813 Phototherapy and photochemotherapy in psoriasis, 193, 194–195 Phototoxicity, drug-induced, 196 Physical therapy in osteoarthritis, 11 Phytoestrogens in menopause, 342 Phytonadione in reversal of warfarin therapy, 172 Phytotherapy in benign prostatic hyperplasia, 934–935 Pilocarpine in glaucoma, 721, 722t, 724 Pimecrolimus in atopic dermatitis, 201 Pimozide in schizophrenia, 809 Pindolol in hypertension, 117t, 121 in schizophrenia, treatment-resistant, 806 Pioglitazone in diabetes mellitus, 217t, 218–219, 224 Piperacillin dose adjustment in kidney disease, 877t in meningitis, 395t, 397 in urinary tract infections, 547t, 551

Piperacillin-tazobactam in bite wounds, 520 in cellulitis, 516t in meningitis, 397 in pneumonia, 475t in urinary tract infections, 547t Pirbuterol in asthma, 913t, 914t in chronic obstructive pulmonary disease, 924 Piroxicam in gouty arthritis, 5t in osteoarthritis, 14t in rheumatoid arthritis, 37t Pituitary gland disorders Cushing’s syndrome in, 203, 205t hyperthyroidism in, 229 hypothyroidism in, 234, 235 Plaque, cutaneous, 197 in psoriasis, 186, 190, 192 Plasma, fresh frozen, in hypovolemic shock, 150 Platelet transfusion in hypovolemic shock, 150 Pleural effusions and fibrosis, druginduced, 970t Plummer’s disease, 228 Pneumococcal infections acute exacerbation of COPD in, 930 meningitis in, 387, 395–396 diagnosis of, 388, 389 treatment of, 389, 390t, 393t, 396 otitis media in, 478, 479, 480 pneumonia in, 471, 474t, 475t sinusitis in, 484, 485t vaccination against, 396, 572–573 in adults, 564t–567t, 572–573 in children, 557t–563t, 572–573 in chronic obstructive pulmonary disease, 924 in HIV infection, 447t in recurrent otitis media, 480 Pneumocystis jiroveci pneumonia in HIV infection, 444, 445t, 447t, 449 Pneumonia, 471–477 antibiotics in, 474t–476t, 477 aspiration, 474t clinical presentation in, 472t, 472–474 community-acquired, 471–472, 476t, 477 nosocomial, 473–474, 474t, 477 pathophysiology in, 471–472 Pneumocystis jiroveci, in HIV infection, 444, 445t, 447t, 449 viral, 472, 473 in children, 475t

1033

INDEX Pneumonitis, drug-induced, 969t Podofilox in genital papillomavirus warts, 507t Podophyllin in genital papillomavirus warts, 507t Poikilothermia from antipsychotic drugs, 809 Poliovirus vaccination, 573 in children, 557t, 559t–563t, 573 Poloxamer 188 in sickle cell crisis, 375 Polycarbophil in constipation, 253t in diarrhea, 262t Polyethylene glycol-electrolyte lavage solution in constipation, 252, 253t, 255 Polymerase chain reaction technique in meningitis, 389 Polymeric enteral nutrition formulations, 658, 659t Polyposis, familial adenomatous, 689 Polysomnography, 814 Portal hypertension, 239–249 Portosystemic shunts, transjugular intrahepatic, surgical site infections in, 526t Positive pressure ventilation, noninvasive, in COPD, 929 Positron emission tomography in lung cancer, 699 Postmenopausal period. See Menopause Postoperative nausea and vomiting, 300, 303, 303t Postpartum period, 361–362 contraception in, 338 depression in, 362 Postthrombotic syndrome, 164 Posttraumatic stress disorder clinical presentation in, 737–738, 739t pathophysiology in, 735, 736 treatment of, 740, 753t, 753–755 algorithm on, 754f Potassium dietary, in hyperkalemia, 893 in oral rehydration solutions, 261t, 428t in parenteral nutrition solutions, 673, 673t replacement therapy in hypokalemia, 892–893 serum levels of, 891–893 in acute renal failure, 856 in chronic kidney disease, 865 in diuretic therapy for hypertension, 116t, 118 in hyperkalemia. See Hyperkalemia in hypokalemia, 891–893

1034

Potassium chloride in hypokalemia, 892 Potassium citrate in metabolic acidosis, 843t Potassium iodide in hyperthyroidism, 231, 232, 233t Potassium phosphate in hypophosphatemia, 891t Potassium-sparing diuretics in hypertension, 116t, 118 Pramipexole in Parkinson’s disease, 632t, 635 Pramlintide in diabetes mellitus, 213t, 215 Pravastatin in Alzheimer’s disease, 732 in hyperlipidemia, 104t, 105t, 106 Prazosin in hypertension, 117t, 122 in posttraumatic stress disorder, 755 in prostate hyperplasia, benign, 933t Prealbumin serum levels in nutritional assessment, 650t Prednisolone in adrenal insufficiency, 208t in asthma, 914t Prednisone in adrenal insufficiency, 208, 208t in asthma, 914t, 916, 916t in chronic obstructive pulmonary disease, 929 in cutaneous drug reactions, 201 in gout, 6 in hyperthyroidism, 233t in inflammatory bowel disease, 286, 287, 288f in lymphoma Hodgkin’s, 705t, 707t, 708t non-Hodgkin’s, 710, 710t, 711 in meningitis, tuberculous, 398 osteoporosis from, 18, 30 in prostate cancer, 718 in rheumatoid arthritis, 40–41 Preeclampsia, 126, 355, 356 Pregabalin in generalized anxiety disorder, 740, 742t in seizures, 596 adverse effects of, 588t, 596 dosage and serum levels of, 593t indications for, 582t, 596 interaction with other drugs, 590t pharmacokinetics of, 585t in social anxiety disorder, 751t Pregnancy, 353–360 adverse fetal effects of drugs in, 353–354, 359, 360 of isotretinoin, 184

INDEX asthma in, 358, 909 bipolar disorder in, 766, 776 chlamydial infections in, 357, 494, 497t, 503t depression in, 360, 794–795 and diabetes mellitus, 210, 211, 355, 358–359 drug selection in, 353–354 and epilepsy, 358–359, 583 gastrointestinal disorders in, 354–355 gonorrhea in, 357, 494, 496, 497t headache in, 356 herpes simplex virus infections in, 357, 504 HIV infection and AIDS in, 359, 438, 441 hypertension in, 126–127, 355–356, 359 in inflammatory bowel disease, 292 influenza in, 455 prevention of, 451, 454, 571 labor and delivery in, 360–361 lithium therapy in, 766, 776 nausea and vomiting in, 304, 355 pharmacokinetics in, 353 preconception planning for, 354 5α-reductase precautions in, 934 rhinitis in, allergic, 358 sexually transmitted diseases in, 357–358, 359 skin disorders in, 358 trichomoniasis in, 506t, 508 tuberculosis in, 535, 541 urinary tract infections in, 356–357, 361, 553 empirical treatment of, 549t vaccinations in, 556, 565t influenza, 451, 454, 571 Prehypertension, 112t, 113 Premature complexes, ventricular, 61, 62, 71 Premature ovarian failure, 351–352 Prematurity, anemia in, 369 Pressure sores, 510t, 518t, 518–519 Preterm labor, 360–361 Priapism in sickle cell disease, 372, 375 Prilocaine in regional analgesia, 627t Primidone in seizures, 585t adverse effects of, 588t dosage and serum levels of, 592t interaction with other drugs, 589, 590t Prinzmetal’s variant angina, 54, 132 Proarrhythmias, ventricular, 61, 62, 72 Probenecid in gonorrhea, 497t in gout, 7–8

Procainamide in arrhythmias, 64t, 69, 71 intravenous dosage, 66t side effects of, 67t Procaine in regional analgesia, 627t Procarbazine in Hodgkin’s lymphoma, 705t, 707t Prochlorperazine in migraine headache, 602, 604t in nausea and vomiting, 299t Proctitis, 495t Progesterone in menopause therapy, 344, 345t Progestins in breast cancer, 686t, 687 in contraceptives, 326–339 adverse effects of, 330t injectable, 338–339 preparations available, 327t–329t Progestogen in menopause therapy, 342, 344–346, 347 in combination with estrogen, 345t, 345–346, 349–350, 351 dosage of, 345t in premature ovarian failure, 351, 352 Prolactin serum levels in seizures, 578 Promethazine in nausea and vomiting, 299t in rhinitis, allergic, 900t Promotility agents in gastroesophageal reflux disease, 270–271 Propafenone in arrhythmias, 64t in atrial fibrillation and flutter, 67, 69 side effects of, 67t Propionibacterium acnes, 179, 180, 182, 183, 184 Propionic acids in osteoarthritis, 14t Propofol in parenteral nutrition, 672 in status epilepticus, refractory, 645t, 646 Propoxyphene interaction with other drugs, 746t, 771, 791t in pain management, 621t, 624t Propranolol in acute coronary syndromes, 53 in angina pectoris, 135 for antipsychotic drug side effects, 807t, 808 in atrial fibrillation and flutter, 65 in hypertension, 117t, 121 in hyperthyroidism, 231, 232, 233t interaction with other drugs, 746t in migraine prophylaxis, 608t, 610

1035

INDEX Propranolol (cont.) in schizophrenia, treatment-resistant, 806 in social anxiety disorders, 751 in variceal hemorrhage, 243, 246 Propylthiouracil in hyperthyroidism, 231, 233t, 234 Prostaglandin analogues in glaucoma, 721, 723t Prostate benign hyperplasia of, 931–935 classification of severity, 932, 932t clinical presentation in, 931 definition of, 931 diagnosis of, 931–932 drug-induced, 931 evaluation of therapeutic outcomes in, 935 goals of treatment in, 932 pathophysiology in, 931 pharmacologic therapy in, 932–934 phytotherapy in, 934–935 surgery in, 934 urinary incontinence in, 944, 949 watchful waiting in, 932 cancer of, 713–718 clinical presentation in, 713 definition of, 713 observation or watchful waiting in, 714 pathophysiology in, 713 salvage therapy in, 717–718 screening for, 713 treatment of, 714–718 urinary incontinence in, 949 inflammation of, 544, 554–555 clinical presentation in, 554, 554t treatment of, 549t, 555 Prostate-specific antigen levels in prostate cancer, 713, 714 Prostatectomy in prostate cancer, 714–715, 717 in prostate hyperplasia, benign, 934 Prostatitis, 544, 554–555 clinical presentation in, 554, 554t treatment of, 549t, 555 Prosthesis heart valve, endocarditis in staphylococcal, 407, 408t streptococcal, 403, 405t joint, surgical site infections in, 528t, 530–531 penile, in erectile dysfunction, 943 Protamine sulfate, in bleeding complications of heparin therapy, 168, 170

1036

Protease inhibitors in HIV infection, 439t, 441, 442t–443t Protease replacement therapy in pancreatitis, 311, 312t Protein cerebrospinal fluid levels in meningitis, 388t, 388–389 dietary in children, 652t, 653 daily requirements for, 652t, 653 in hepatic encephalopathy, 247t, 248 in kidney disease, chronic, 860, 874 in enteral nutrition formulations, 658, 659t in parenteral nutrition solutions, 670–672, 675f serum levels in nutritional assessment, 650t Protein-energy malnutrition, 647 in chronic kidney disease, 874 Proteus mirabilis infections, 381t Prothrombin time in shock, 144, 155 Proton pump inhibitors in gastroesophageal reflux disease, 265, 267t, 268t, 269–270 in maintenance therapy, 271 in peptic ulcer disease, 316–318, 318t, 319, 319t Protozoal infections in HIV infection and AIDS, 446t sexually transmitted, 494t, 504–508 trichomoniasis in, 504–508 Protriptyline in cataplexy, 821t, 822 in migraine prophylaxis, 608t, 610 Providencia stuartii infections, 381t Pruritus in chronic kidney disease, 874 Pseudoephedrine abuse of, 827 in allergic rhinitis, 901t, 902–903 in urinary incontinence, 947t Pseudolymphoma syndrome, druginduced, 970t Pseudomonas aeruginosa infections antibiotics in, 381t–382t, 384, 394t bronchitis in, 467t of foot in diabetes mellitus, 517 meningitis in, 394t, 397 peritonitis in, 461t pneumonia in, 474t sepsis in, 487, 491 Pseudoparkinsonism from antipsychotic drugs, 808 Pseudoporphyria, 197t Psoriasis, 186–195 arthritis in, 187

INDEX clinical presentation in, 186–187 combinational, rotational, and sequential therapy in, 195 definition of, 186 diagnosis of, 187 evaluation of therapeutic outcomes in, 195 goals of therapy in, 187 nonpharmacologic therapy in, 187 pathophysiology in, 186 phototherapy and photochemotherapy in, 194–195 of scalp, 187 severity score in, 195 systemic pharmacotherapy in, 191–194 topical pharmacotherapy in, 187–191 Psychiatric disorders, 727–838 Alzheimer’s disease, 727–734 anxiety disorders, 735–755 bipolar disorder, 756–777 depressive disorders, 778–798 drug-induced from antipsychotic drugs, 811 in Parkinson’s disease, 635, 636t schizophrenia, 799–813 sleep disorders, 814–822 substance-related disorders, 823–838 Psychogenic conditions erectile dysfunction in, 936 vomiting in, 295 Psychosis, drug-induced, in Parkinson’s disease, 635, 636t Psychotherapy in depression, 780 in posttraumatic stress disorder, 753 Psyllium in constipation, 253t Pulmonary artery catheterization in shock, 144, 155 Pulmonary artery occlusive pressure normal values for, 145t in shock, 144, 155 Pulseless electrical activity, 75, 77, 80 Purines, dietary, 1, 2, 3 Pyelonephritis, 544, 551–552 antibiotic dosage in, 548t empirical treatment of, 549t Pyrazinamide in tuberculosis, 537t, 538t active, 535 dose adjustment in renal failure, 541, 542t and meningitis, 395t, 397, 398, 541 in pregnancy, 541 Pyridoxine in isoniazid therapy in latent tuberculosis, 535 in tuberculous meningitis, 397

in nausea and vomiting of pregnancy, 304 Pyrilamine in insomnia, 815 Pyrilamine maleate in allergic rhinitis, 900t Pyrimethamine in toxoplasmic encephalitis and HIV infection, 446t Pyrosis in gastroesophageal reflux disease, 263 Pyuria, 546 Q Q waves in acute coronary syndromes, 43 QRS complex in paroxysmal supraventricular tachycardia, 69 Quazepam in insomnia, 817, 818, 818t Quetiapine in alcohol withdrawal, 833t in Alzheimer’s disease, 733t in bipolar disorder, 763, 764t, 766, 769t, 771 in posttraumatic stress disorder, 755 in schizophrenia, 800, 810 dosage of, 803t pharmacokinetics of, 801, 804t side effects of, 806t, 808, 810, 811 Quinapril in heart failure, 86t in hypertension, 116t Quinidine in arrhythmias, 64, 64t in atrial fibrillation and flutter, 69 in atrial tachycardia, 71 in paroxysmal supraventricular tachycardia, 69 side effects of, 67t interaction with other drugs, 791t Quinolone antibiotics interaction with other drugs, 383t in urinary tract infections, 549t Quinupristin-dalfopristin in meningitis, 392t R Rabeprazole in gastroesophageal reflux disease, 268t, 270, 271 in peptic ulcer disease, 318t, 319t Rabies, 520 Radiation therapy in breast cancer, 681, 688 in colorectal cancer, 691, 693 in Cushing’s syndrome, 204, 205t in lung cancer, 700, 702, 703 in lymphoma Hodgkin’s, 706, 705t non-Hodgkin’s, 708–709, 710

1037

INDEX Radiation therapy (cont.) nausea and vomiting in, 303 in prostate cancer, 714–715, 717 Radiofrequency ablation procedures in supraventricular tachycardia, 69–71 Radiography in heart failure, 83 in osteoarthritis, 11, 17 in peptic ulcer disease, 316 in rheumatoid arthritis, 32t, 33, 41 in tuberculosis, 534, 534t Radioimmunotherapy in lymphoma, 709, 710 Radioiodine therapy in hyperthyroidism, 233 uptake in hyperthyroidism, 229, 230 Radionuclide scans in ischemic heart disease, 133 Raloxifene in breast cancer prevention, 688 in menopause, 347, 350 in osteoporosis, 25, 28, 347, 350 Ramelteon in insomnia, 817 interaction with other drugs, 793t Ramipril in acute coronary syndromes, 58 in heart failure, 86t in hypertension, 116t Ranitidine dose adjustment in kidney disease, 879t in gastroesophageal reflux disease, 267t, 268t in nausea and vomiting, 298t, 300 in peptic ulcer disease, 319t Ranolazine in ischemic heart disease, 137 Rasagiline in Parkinson’s disease, 632t, 634 Rectal cancer, 691, 693. See also Colorectal cancer Rectal examination, digital in prostate cancer, 713, 714 in prostate hyperplasia, benign, 932 Red blood cells count of, 365t sedimentation rate in osteoarthritis, 11 in sickle cell disease, 371 transfusion of in anemia of chronic disease, 369 in hypovolemic shock, 150 in sickle cell disease, 373 urinary, in acute renal failure, 852t, 853t

1038

5α-Reductase inhibitors precautions in pregnancy, 934 in prostate hyperplasia, benign, 934 Reed-Sternberg cells in Hodgkin’s lymphoma, 704 Reentry supraventricular tachycardia, paroxysmal, 60 Reflux, gastroesophageal, 263–272. See also Gastroesophageal reflux disease Rehydralyte oral rehydration solution, 261t, 428t Relactation, 362 Renin inhibitors in hypertension, 114, 117t, 122 Repaglinide in diabetes mellitus, 215, 216t Reserpine in hypertension, 117t, 123 Resistance to drugs, 385–386 in tuberculosis, 535, 536, 541 Resol oral rehydration solution, 261t Resorcinol in acne vulgaris, 183–184 Respiratory disorders, 897–930 allergic rhinitis, 897–905 anxiety symptoms in, 739t asthma, 906–920 chronic obstructive pulmonary disease, 921–930 drug-induced, 965t–970t hypertension management in, 127 in infections, 465–486 in aspergillosis, 422–424, 425 in blastomycosis, 416, 417t bronchiolitis, 470–471 bronchitis, 465–469 in coccidioidomycosis, 417–418 in histoplasmosis, 412, 413t influenza, 450–455 otitis media, 478–480 pharyngitis, 481–484 pneumonia, 471–477 sepsis in, 491t sinusitis, 484–486 in tuberculosis, 532–543 Respiratory failure in COPD, 923 Respiratory quotient, 653 Retching, 294 Reteplase in acute coronary syndromes, 50, 52 Reticulocyte count, reference range for, 365t Retinoids, topical in acne vulgaris, 180, 181f, 182–183 in psoriasis, 190, 194 Retinopathy, diabetic, 224

INDEX Reverse transcriptase inhibitors in HIV infection nonnucleoside, 439t, 441, 442t nucleoside, 440t, 441 Rheumatoid arthritis, 31–41 clinical presentation in, 31–32 definition of, 31 diagnosis of, 32t, 32–33 evaluation of therapeutic outcomes in, 41 extra-articular involvement in, 32 goals of treatment in, 33 nonpharmacologic therapy in, 33 pathophysiology in, 31 pharmacologic therapy in, 33–41 adverse effects of, 36t dosage in, 35t–36t monitoring of, 35t–36t, 41 treatment algorithm on, 34f Rheumatoid factor, 31, 32t, 33 Rhinitis allergic, 897–905 asthma in, 898, 907 avoidance of allergens in, 898–899 nonseasonal allergens in, 897, 903, 904 pharmacologic therapy in, 900–905 in pregnancy, 358 seasonal allergens in, 897, 899, 903, 904 treatment algorithm on, 899f medicamentosa, 902 and sinusitis, 484 Rhinosinusitis, 484 Ribavirin in bronchiolitis, 471 in hepatitis C, 280f, 281 Rifabutin in Mycobacterium avium infection and HIV infection, 446t in tuberculosis, 535, 538t Rifampin in endocarditis, 408t interaction with other drugs, 383t, 746, 746t in meningitis meningococcal, 392 tuberculous, 395t, 397, 398 in tuberculosis, 537t, 538t active, 535, 536 adverse effects of, 542–543 dose adjustment in renal failure, 541, 542t latent, 535, 536t and meningitis, 395t, 397, 398 and pregnancy, 541

Rifapentine in tuberculosis, 537t, 538t Rifaximin in gastrointestinal infections, 429t Rigidity, muscular, in Parkinson’s disease, 629 Rimantadine in influenza, 453, 455, 466 Ringer’s solution, lactated, in hypovolemic shock, 146, 149 Risedronate in osteoporosis, 23, 26t, 30 Risperidone in Alzheimer’s disease, 733t in bipolar disorder, 763, 764t, 766, 769t, 771 in depression, refractory, 796 interaction with other drugs, 793t, 794t in posttraumatic stress disorder, 755 in schizophrenia, 800 dosage of, 803t in maintenance therapy, 805 pharmacokinetics of, 801, 804t side effects of, 806t, 808, 809, 810, 811, 812 treatment-resistant, 806 Ritonavir in HIV infection, 439t, 441, 442t Rituximab in lymphoma, 709–710, 711 in rheumatoid arthritis, 35t, 36t, 40 Rivastigmine in Alzheimer’s disease, 730, 730t, 731, 731t Rizatriptan in migraine headache, 604t, 606, 607t Ropinirole in Parkinson’s disease, 632t, 636 Ropivacaine in regional analgesia, 627t Rosiglitazone in diabetes mellitus, 217t, 218–219, 224 Rosuvastatin in hyperlipidemia, 104t, 105t, 106, 109 Rotavirus infections, 434 vaccination in children, 557t–558t, 563t Rotigotine in Parkinson’s disease, 632t, 635 RU-486 in Cushing’s syndrome, 207 Rubella vaccination, 573 in adults, 564t–566t in children, 557t–563t S Saint Anthony’s fire, 509 Saint John’s wort in depression, 785 interaction with other drugs, 746t, 785

1039

INDEX Salicylates acetylated. See Aspirin in osteoarthritis, 14t, 15 in pain management, 619t in rheumatoid arthritis, 36t, 37t topical in acne vulgaris, 180, 181f, 183–184 in osteoarthritis, 15 in psoriasis, 187–188 Salicylism, 183–184 Saline cathartics in constipation, 252, 254–255 Salmeterol in asthma, 913, 913t, 919 in chronic obstructive pulmonary disease, 926, 928 Salmonella infections, 431–433 antibiotics in, 382t, 429t, 432, 446t chronic carrier state in, 431, 432 in HIV infection, 446t vaccination against, 433 Salpingitis, 495t Salsalate in osteoarthritis, 14t Samarium-153 lexidronam in prostate cancer, 718 Saquinavir in HIV infection, 439t, 443t Scalp psoriasis, 187 Schizophrenia, 799–813 antipsychotic drugs in, 800–813. See also Antipsychotic drugs, in schizophrenia clinical presentation in, 799 definition of, 799 diagnosis of, 800 evaluation of therapeutic outcomes in, 813 goals of treatment in, 800 pathophysiology in, 799 principles of treatment in, 800–801 treatment algorithm on, 802f treatment-resistant, 805–806 Sclerotherapy in variceal hemorrhage, 245, 246 Scopolamine in bradyarrhythmias, 73 in nausea and vomiting, 298t Screening for colorectal cancer, 689 for hepatitis C, 278, 279t nutritional, 647 for prostate cancer, 713 Seborrheic dermatitis, 197, 199 Sebum production in acne vulgaris, 179, 184 Secobarbital dependence, 826t

1040

Sedative effects of antihistamines, 900t, 900–901, 902 of antipsychotic drugs, 809 Sedative medications dependence on, 826t interaction with other drugs, 792t Seizures, 577–598 absence, 578, 586, 638t in alcohol withdrawal, 832 anticonvulsant drugs in, 580–598 atonic, 579 catamenial, 583 classification of, 578, 579t clinical presentation in, 577–579 complex partial, 577, 578, 586, 638t definition of, 577 diagnosis of, 579 drug-induced from antidepressant drugs, 783t–784t, 785 from antipsychotic drugs, 809 in females, 580, 583 focal, 577, 578 generalized, 577, 578 goals of treatment in, 579–580 in hypomagnesemia, 895, 895t in lung cancer metastasis to brain, 703 pathophysiology in, 577 and pregnancy, 359, 583 simple partial, 578, 638t in status epilepticus, 637–646 tonic-clonic, 577, 578, 579, 586, 638t, 639 treatment algorithm on, 584f Selegiline in cataplexy, 821t in depression, 782, 784t in Parkinson’s disease, 632t, 634 Senna in constipation, 252, 253t Sepsis, 487–492 antibiotics in, 490t, 490–491, 491t clinical presentation in, 489, 489t in community-acquired infections, 491t definition of, 487, 488t evidence-based treatment of, 489, 490t hemodynamic support in, 491–492, 492t in nosocomial infections, 491t pathophysiology in, 487–488 severe, 488t shock in, 143, 144, 488t drug therapy in, 151–155, 152f, 153t evidence-based treatment of, 489, 490t pathophysiology of, 488

INDEX Serotonin in anxiety disorders, 735 in depression, 778 in schizophrenia, 799 Serotonin-norepinephrine reuptake inhibitors in depression, 785 dosage of, 782t interaction with other drugs, 793t pharmacokinetics of, 789t relative potency of, 783t side effects of, 783t in social anxiety disorder, 751t in urinary incontinence, 948 Serotonin receptor agonists in migraine headache, 603t–604t, 606–607 Serotonin receptor antagonists in nausea and vomiting, 301, 302t, 303 Serotonin reuptake inhibitors, selective in depression, 781 in Alzheimer’s disease, 733 dosage of, 782t in elderly, 792 interaction with other drugs, 791, 791t, 793t–794t pharmacokinetics of, 788, 789t in pregnancy, 360, 795 relative potency of, 783t side effects of, 783t, 786 in generalized anxiety disorder, 743 interaction with other drugs, 607 in depression, 791, 791t, 793t–794t in migraine prophylaxis, 610 in panic disorder, 747, 747t, 749 in posttraumatic stress disorder, 753t, 754, 755 in schizophrenia, treatment-resistant, 806 in social anxiety disorder, 750, 751t Serotonin syndrome, 607, 791 Serratia marcescens infections, 382t Sertraline in Alzheimer’s disease, 733t in bradyarrhythmias, 73 in depression and cytochrome P450 activity, 795t dosage of, 782t interaction with other drugs, 794t pharmacokinetics of, 788, 789t relative potency of, 783t side effects of, 783t in generalized anxiety disorder, 743 in panic disorder, 747, 747t in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 750, 751t

Sevelamer carbonate in chronic kidney disease, 871t Sevelamer hydrochloride in chronic kidney disease, 868, 871t Sexually transmitted diseases, 493–508 chlamydial, 500–502 gonorrhea, 493–496 herpes simplex virus, 502–504 HIV infection, 435 pathogens associated with, 494t, 495t in pregnancy, 357–358, 359 syndromes in, 494t, 495t syphilis, 496–500 trichomoniasis, 504–508 web site resources on, 493 Shigella infections, 430–431 antibiotics in, 429t, 431, 446t in HIV infection, 446t Shock, 143–155 anaphylactic, 143 cardiogenic, 82, 143 clinical presentation in, 143–144 definition of, 143 diagnosis of, 144–146, 145t goals of therapy in, 146 hemodynamic monitoring in, 144–146, 155 hypovolemic, 143, 144 drug therapy in, 150–151 evaluation of therapeutic outcomes in, 155 fluid resuscitation in, 146–150 treatment algorithm on, 146, 147f–148f neurogenic, 143 pathophysiology in, 143 septic, 143, 144, 488t drug therapy in, 151–155, 152f, 153t evidence-based treatment of, 489, 490t pathophysiology in, 488 Shohl solution in metabolic acidosis, 843t in chronic kidney disease, 870 Shunt procedures cerebrospinal, surgical site infections in, 528t transjugular intrahepatic portosystemic, surgical site infections in, 526t Sibutramine interaction with other drugs, 793t, 794t in obesity, 665, 667t Sick sinus syndrome, 61–62

1041

INDEX Sickle cell disease, 371–376 acute chest syndrome in, 371–372, 375 clinical features in, 371, 372t crisis in, 372, 375 Sickle cell trait, 371, 372, 372t Sildenafil in erectile dysfunction, 938t, 939–941 pharmacodynamics and pharmacokinetics of, 939, 940t interaction with nitrate therapy, 53, 940 Silver sulfadiazine in pressure ulcers, 519 Simvastatin in hyperlipidemia, 104t, 105t, 106, 109 Sinus bradyarrhythmias, 61–62 Sinusitis, 484–486 clinical presentation in, 484, 484t treatment of, 484–486, 485t Sitagliptin in diabetes mellitus, 217t, 220 Skin disorders, 179–202 acne vulgaris, 179–185 dermatitis, 196–202 drug-induced, 196 from antipsychotic drugs, 812–813 clinical presentation in, 197t, 197–198 common agents causing, 952t in sun exposure, 196, 198 treatment of, 201 in infections, 509–521 antibiotics in, 511t–513t evidence-based treatment recommendations in, 511t primary, 509, 510t secondary, 509, 510t sepsis in, 491t in pregnancy, 358 psoriasis, 186–195 Skin test in penicillin allergy, 952t tuberculin, 533–534, 534t Sleep, 814–822 apnea in, 819, 820f, 822 central, 819 obstructive, 819, 822 classification of disorders in, 815t eye movements in, 814 and insomnia, 814–818, 822 and narcolepsy, 821–822 physiology of, 814 Smoking, 827–828 cessation of, 835–838, 924 chronic obstructive pulmonary disease in, 467, 468, 921, 922, 924 oral contraceptive use in, 330, 333 osteoporosis in, 20

1042

peptic ulcer disease in, 314, 316 in pregnancy, 354 Social anxiety disorder clinical presentation in, 737, 738t pathophysiology in, 735, 736 treatment of, 740, 750–753 algorithm on, 752f drug choices in, 742t Sodium dietary in ascites, 246 in heart failure, 84 in hypertension, 111, 113 in kidney disease, chronic, 864 fractional excretion of in acute renal failure, 852t, 853 in chronic kidney disease, 864 in oral rehydration solutions, 261t, 428t in parenteral nutrition solutions, 673, 673t serum levels of, 881–885 in acute renal failure, 856 in chronic kidney disease, 864–865 in edema, 884–885 in hypernatremia, 856, 882–884 in hyponatremia, 881–882, 883f urinary in acute renal failure, 852t in chronic kidney disease, 864–865 Sodium channel blockers, 63–64 Sodium citrate in metabolic acidosis, 843t Sodium hyaluronate in osteoarthritis, 16 Sodium hypochlorite in pressure ulcers, 519 Sodium oxybate in cataplexy, 822 in narcolepsy, 821t Sodium phosphates in constipation, 253t in hypophosphatemia, 891t Sodium polystyrene sulfonate in hyperkalemia, 893, 894t Soft-tissue infections, 509–521 antibiotics in, 511t–513t evidence-based treatment recommendations in, 511t sepsis in, 491t Solifenacin in urinary incontinence, 947t, 949 Somatostatin in variceal hemorrhage, 244f, 245 Sorbitol in constipation, 253t, 254 Sotalol in arrhythmias, 64t, 64–65, 69 side effects of, 67t

INDEX Spasm bronchial drug-induced, 965t–966t exercise-induced, 908–909, 913 vascular cerebral, 161 coronary, 132, 139–142 Spectinomycin in gonorrhea, 497t in pregnancy, 357, 494, 497t Spermicides, 322, 324t–325t, 326 Spinal osteoporosis, 23 bone mineral density measurements in, 19 calcitonin in, 28 fractures in, 18, 25, 28 raloxifene in, 25 teriparatide in, 29 Spinal surgery, surgical site infections in, 528t Spirometry in asthma, 908, 920 Spironolactone in acute coronary syndromes, 58 in ascites, 246 in heart failure, 88–89 in hypertension, 118 in renal failure, acute, 855 Spleen abscess of, 462t sequestration crisis in sickle cell disease, 372, 375 Sponge, contraceptive, 322, 325t with spermicide, 326 ST-segment in acute coronary syndromes, 43, 44, 45f in ischemic heart disease, 133 Staging of breast cancer, 680 of colorectal cancer, 690 of lung cancer, 700 Staphylococcal infections antibiotics in, 380t endocarditis in, 399, 400, 400t in drug abuse, 403, 407 methicillin-resistant, 407, 408t in prosthetic valve, 407, 408t treatment of, 403, 406t, 407 meningitis in, 393t peritonitis in, 457, 458t, 461t pneumonia in, 472, 474t, 475t of skin and soft tissues, 509, 510 cellulitis in, 514, 515t, 517 in diabetes mellitus, 517, 518 of surgical site, 523, 524, 527t, 528t of urinary tract, 545, 549t Statin therapy in Alzheimer’s disease, 732

in hyperlipidemia, 104t, 106, 108, 109 and chronic kidney disease, 874 in combination therapy, 106, 107, 108 and coronary artery disease, 59 in ischemic stroke, 159t, 160–161 Status epilepticus, 577, 637–646 classification of, 637, 638t clinical presentation in, 637–638 diagnosis of, 639 evaluation of therapeutic outcomes in, 646 goals of treatment in, 639 morbidity and mortality in, 637–638 pathophysiology of, 637 pharmacologic therapy in, 639–646 phases of, 637 refractory, 644–646 treatment algorithm on, 640f Status migrainosus, 607 Stavudine in HIV infection, 441, 442t Stearate in pharyngitis, 482t Steatorrhea in pancreatitis, 310, 311, 311f, 312 Stem cell transplantation in lymphoma Hodgkin’s, 706 non-Hodgkin’s, 710, 711 in sickle cell disease, 373 Stenotrophomonas maltophilia infections, 382t Stent placement in acute coronary syndromes, 48, 54, 57 in ischemic stroke, 158 Steroidogenic inhibitors in Cushing’s syndrome, 204–206 Stevens-Johnson’s syndrome, 197t Stomach, peptic ulcer disease of, 314–320 Stool occult blood in colorectal cancer, 689 Stool softeners in constipation, 253t Streptococcal infections antibiotics in, 380t bronchitis in, chronic, 467, 469 endocarditis in, 399, 400t penicillin-resistant, 403, 404t in prosthetic valve, 403, 405t treatment of, 401–403, 402t, 404t–405t group B, in pregnancy, 361 in HIV infection, prevention of, 447t meningitis in, 387, 395–396 diagnosis of, 388, 389 treatment of, 389, 390t, 393t, 396 otitis media in, 478, 479, 480 peritonitis in, 456–457, 458t, 461t

1043

INDEX Streptococcal infections (cont.) pharyngitis in, 481t, 481–484, 483t pneumococcal. See Pneumococcal infections pneumonia in, 471, 474t, 475t sinusitis in, 484, 485t of skin and soft tissues, 509, 510 cellulitis in, 514, 515t in diabetes mellitus, 517 of surgical site, 527t Streptokinase in acute coronary syndromes, 50, 52 in venous thromboembolism, 175 Streptomycin in tuberculosis, 539t, 543 dose adjustment in renal failure, 542t in pregnancy, 541 Stress adrenal crisis in, 209 peptic ulcer disease in, 314, 316 and posttraumatic stress disorder. See Posttraumatic stress disorder social anxiety disorder in, 735 Stress urinary incontinence, 944, 946–948, 947t Stroke, 156–162. See also Cerebrovascular disorders Strontium-89 in prostate cancer, 718 Study on the Efficacy of Nosocomial Infection Control, 522 Substance abuse, 823–838 addiction in, 823 of alcohol, 823–824. See also Alcohol use and alcoholism of benzodiazepines, 745, 825, 830t and bipolar disorder, 761 of central nervous system depressants, 823–825 of central nervous system stimulants, 825–827 dependence in, 823, 835–838 endocarditis in, staphylococcal, 403, 407 goals of treatment in, 829–830 of inhalants, 829 intoxication in. See Intoxication in substance abuse of ketamine, 829 of lysergic acid diethylamide, 829 of marijuana, 828, 830t of methamphetamine, 827 of methamphetamine analogs, 828 of nicotine, 827–828 of phencyclidine, 829, 830t, 831 in posttraumatic stress disorder, 738 tolerance in, 823 withdrawal symptoms in, 823, 831t, 831–835

1044

Substance P in nausea and vomiting, 301 Sucralfate in gastroesophageal reflux disease, 271 in peptic ulcer disease, 318, 319t Sufentanil in pain management, 625t Suicidal behavior antidepressant drugs associated with, 742–743, 792, 794 in bipolar disorder, 761 Sulbactam and ampicillin. See Ampicillin-sulbactam Sulfadiazine in toxoplasmic encephalitis and HIV infection, 446t Sulfasalazine in inflammatory bowel disease, 286 adverse effects of, 292 in Crohn’s disease, 289, 290f, 291 and pregnancy, 292 in ulcerative colitis, 287, 287t, 288f, 289 in psoriasis, 194 in rheumatoid arthritis, 33, 34, 38 adverse effects of, 36t, 38 dosage and monitoring of, 35t Sulfinpyrazone in gout, 7–8 Sulfonamides interaction with other drugs, 383t in urinary tract infections, 547t Sulfonylureas in diabetes mellitus, 215, 216t Sulfur in acne vulgaris, 183–184 Sulindac in gout, 3, 5t in rheumatoid arthritis, 37t Sumatriptan in migraine headache, 603t–604t, 606, 607t Sun exposure, drug-induced skin disorders in, 196, 198, 201 from antipsychotic drugs, 813 Supraventricular arrhythmias atrial. See Atrial arrhythmias clinical presentation in, 62 diagnosis of, 62 pathophysiology in, 60 tachycardia. See Tachycardia, supraventricular treatment in, 65–71 Surgery in acute coronary syndromes, 47, 48 antimicrobial prophylaxis in, 522–531 scheduling of, 524, 524t selection of agents in, 524–525 in breast cancer, 681, 685 in colorectal cancer, 691, 698 in constipation, 252 in Cushing’s syndrome, 204, 205t

INDEX in endocarditis, 401 in erectile dysfunction, 943 in gastroesophageal reflux disease, 265, 268t in genital papillomavirus warts, 507t in heart failure, 96 in hyperthyroidism, 230–231 in inflammatory bowel disease, 285, 286 in lung cancer, 700, 702 nausea and vomiting after, 300, 303, 303t in osteoarthritis, 11 in pancreatitis, 309, 312 in prostate cancer, 714–715, 717 in prostate hyperplasia, benign, 934 in rheumatoid arthritis, 33 in stroke, 158–159 in urinary incontinence, 946 in variceal hemorrhage, 246 in venous thromboembolism, 175 wound infections in, 522–531 risk for, 522, 523t Sympathetic inhibitors, postganglionic, in hypertension, 124 Sympathomimetic therapy anxiety symptoms in, 740t in cardiopulmonary arrest, 79 in chronic obstructive pulmonary disease, 924, 926 in combination with anticholinergics, 926 drug interactions in, 792t Syncope, vasovagal, 72–73 Synovial fluid analysis in osteoarthritis, 11 in rheumatoid arthritis, 33 Syphilis, 496–500 antibiotics in, 382t, 500, 501t clinical presentation in, 496, 499, 499t congenital, 501t latent, 499, 499t, 501t in pregnancy, 357 primary, 496, 499t, 501t secondary, 499, 499t, 501t tertiary, 499, 499t T T cells in psoriasis, 186, 187, 193 in rheumatoid arthritis, 31, 39 T-score in osteoporosis, 19, 21f–22f T-waves in acute coronary syndromes, 44, 45f Tachycardia in shock, 143, 144

supraventricular automatic atrial, 60, 71 clinical presentation in, 62 paroxysmal, 60, 69–71 pathophysiology in, 60 reentry, 60 treatment of, 69–71, 70f ventricular, 61, 62, 71–72, 77–80 cardiopulmonary arrest in, 74, 77–80 cardiopulmonary resuscitation in, 72, 77 clinical presentation in, 62 intravenous drug dose in, 66t pathophysiology in, 61 pulseless, 72, 74, 77–80 Tacrine in Alzheimer’s disease, 731 Tacrolimus in atopic dermatitis, 201 in psoriasis, 193 Tadalafil in erectile dysfunction, 938t, 939–941, 940t Tamoxifen in breast cancer, 684–685, 686, 686t in prevention, 688 in menopause, 347 Tamsulosin in benign prostatic hyperplasia, 933, 933t, 934 Tardive dyskinesia from antipsychotic drugs, 808–809 Tazarotene in acne vulgaris, 183 in psoriasis, 190 Tazobactam and piperacillin. See Piperacillin-tazobactam Telbivudine in hepatitis B, 277 Telithromycin in sinusitis, 485t Telmisartan in hypertension, 116t Temazepam in insomnia, 817, 818, 818t Tenecteplase in acute coronary syndromes, 50, 52 Tenofovir in HIV infection, 440t, 442t Tension-type headache, 612 Terazosin in hypertension, 117t, 122 in prostate hyperplasia, benign, 933, 933t Terbutaline in asthma, 913t, 914t in chronic obstructive pulmonary disease, 924 in preterm labor, 360 in sickle cell disease, 375 Teriparatide in osteoporosis, 27t, 29, 30 Testosterone in erectile dysfunction, 938t, 941–942

1045

INDEX Testosterone (cont.) in menopause therapy, 346, 346t in osteoporosis, 27t, 28–29, 30 in premature ovarian failure, 352 Tetanus prophylaxis, 569–570, 570t in adults, 564t–566t, 569 in bite wounds, 520 in children, 557t–563t, 569 Tetany in hypocalcemia, 888 Tetracaine in regional analgesia, 627t Tetracycline in acne vulgaris, 180, 185 in bite wounds, 520 in bronchitis, chronic, 470t enteral feeding tube administration of, 662t in gastrointestinal infections, 429t, 433 interaction with other drugs, 383t in ophthalmia neonatorum, 496, 498t, 502 in peptic ulcer disease, 317, 318, 318t in pneumonia, 475t in syphilis, 501t in urinary tract infections, 547t Tetrahydrozoline hydrochloride in allergic rhinitis, 902t Thalassemia, 372t Theophylline in asthma, 916–917, 917t in bradyarrhythmias, 73 in chronic obstructive pulmonary disease, 927–928 interaction with other drugs, 794t, 916 Thermoregulation, antipsychotic drugs affecting, 809 Thiamine in alcohol withdrawal, 833t in status epilepticus, 642 Thiazide diuretics in heart failure, 85 in hypertension, 118 in osteoporosis, 29 Thiazolidinediones in diabetes mellitus, 217t, 218–219 Thienopyridines in acute coronary syndromes, 51, 54–56, 57 Thiethylperazine in nausea and vomiting, 299t 6-Thioguanine in psoriasis, 194 Thiopental in refractory status epilepticus, 644 Thiopurine S-methyltransferase deficiency, inflammatory bowel disease therapy in, 289, 292 Thioridazine interaction with other drugs, 793t, 794t

1046

in schizophrenia, 809 dosage of, 803t side effects of, 806t, 811, 812 Thiothixene in schizophrenia, 803t, 806t Thoracic surgery, surgical site infections in, 527t, 530 Thrombectomy in venous thromboembolism, 175 Thrombin inhibitors, direct, in venous thromboembolism, 170–171 Thrombocytopenia in cirrhosis, 242 drugs associated with, 168, 961t heparin-induced, 168–169 Thromboembolism in atrial fibrillation, 66, 69 venous, 163–177 clinical presentation in, 164–165 consensus guidelines for treatment of, 167t definition of, 163 diagnosis of, 165 direct thrombin inhibitors in, 170–171 evaluation of therapeutic outcomes in, 177 fondaparinux in, 170 goals of therapy in, 165 heparin therapy in, 165–170 in oral contraceptive use, 333–334 pathophysiology in, 163–164 in postmenopausal hormone therapy, 350 postthrombotic syndrome in, 164 in pregnancy, 356 prevention of, 175–176, 176t risk classification in, 176t in stroke, 161, 161t thrombectomy in, 175 thrombolytic agents in, 175 treatment algorithm on, 166f warfarin therapy in, 171–175 Thrombolytic therapy in acute coronary syndromes, 48–50, 54 in cardiopulmonary resuscitation, 76t, 80 in venous thromboembolism, 175 Thromboplastin time, activated partial in acute coronary syndromes, 52, 56 in shock, 144, 155 in venous thromboembolism, 167–168, 175, 176 Thyroglobulin in hypothyroidism, 236, 236t

INDEX Thyroid disorders, 227–237 hyperthyroidism, 227–234 hypothyroidism, 227, 234–237 diagnosis of, 229t in hyperthyroidism therapy, 233 Thyroid hormones anxiety symptoms from therapy with, 740t in hyperthyroidism, 227–234, 229t in hypothyroidism, 229t, 234–237 preparations available, 236t, 236–237 interaction with other drugs, 792t physiology of, 227 Thyroid-stimulating hormone, 227 in hyperthyroidism, 229, 229t in hypothyroidism, 235, 237 Thyroid storm, 229, 233t, 233–234 Thyroidectomy in hyperthyroidism, 230–231 Thyroiditis De Quervain’s, 228 granulomatous, 228 Hashimoto’s, 234 hyperthyroidism in, 228–229 hypothyroidism in, 234 painless, 228, 229, 230 subacute, 228–229, 230 Thyrotoxicosis, 227–234 drug-induced, 228 factitia, 228, 230 Thyroxine, 227 in hyperthyroidism, 227, 229t, 229–230 in hypothyroidism, 235, 237 Tiagabine in seizures, 596–597 adverse effects of, 588t, 597 dosage and serum levels of, 593t indications for, 582t, 597 interaction with other drugs, 590t, 597 pharmacokinetics of, 585t Tibolone in menopause, 347, 349t Ticarcillin-clavulanate in urinary tract infections, 547t, 551 Ticlopidine in acute coronary syndromes, 51 Tigecycline in cellulitis, 516t Timolol in glaucoma, 721, 722t, 723t in hypertension, 117t in migraine prophylaxis, 608t, 610 Tinidazole in trichomoniasis, 505, 506t, 508 Tinzaparin in venous thromboembolism, 169, 170, 176t Tiotropium bromide in asthma, 917–918

in chronic obstructive pulmonary disease, 926 Tipranavir in HIV infection, 443t Tirofiban in acute coronary syndromes, 51, 56 Titanium dioxide in diaper dermatitis, 199 Tobramycin dose adjustment in kidney disease, 877t in meningitis, 392t, 395t, 397 in peritonitis, dialysis-associated, 462 in pneumonia, 475t in urinary tract infections, 547t Tocolytic therapy in preterm labor, 360 Tolazamide in diabetes mellitus, 216t Tolbutamide in diabetes mellitus, 216t Tolcapone in Parkinson’s disease, 632t, 634–635 Tolerance to drugs, 823 to benzodiazepines, 744, 745 to cocaine, 827 Tolfenamic acid in migraine headache, 605 Tolmetin in rheumatoid arthritis, 37t Tolterodine in urinary incontinence, 947t, 949 Toluene, occupational exposure to, 963t Tophi in gout, 1, 2 Topiramate in migraine prophylaxis, 608t, 610, 611 in seizures, 586, 597 adverse effects of, 588, 588t, 597 dosage and serum levels of, 593t, 597 indications for, 581t, 582t, 583t, 597 interaction with other drugs, 589, 590t pharmacokinetics of, 585t in status epilepticus, 645t Topotecan in lung cancer, 703 Toremifene in breast cancer, 686, 686t Torsade de pointes, 61, 63 magnesium therapy in, 72, 76t, 80 Torsemide in acute renal failure, 855 in heart failure, 85, 86t, 91 in hypertension, 116t Tositumomab in lymphoma, 710 Toxic epidermal necrolysis, 197t Toxoids definition of, 556 diphtheria, 569 in adults, 564t–566t, 569 in children, 557t–563t, 569

1047

INDEX Toxoids (cont.) recommended use of, 556 tetanus, 569 Toxoplasmosis in HIV infection, 446t, 447t Tramadol in osteoarthritis, 14t, 17 in pain management, 624t, 627 in pancreatitis, chronic, 311 Trandolapril in acute coronary syndromes, 58 in heart failure, 86t in hypertension, 116t Transdermal preparations contraceptive, 338 of fentanyl, 623t, 626 of nicotine in smoking cessation, 836, 837t in ulcerative colitis, 287 of nitroglycerin in angina pectoris, 135, 136, 136t, 139 Transferrin levels in chronic kidney disease and anemia, 865 in nutritional assessment, 650t Transfusions in anemia of chronic disease, 369 in hypovolemic shock, 146, 150 in sickle cell disease, 373, 375 Transplantation candidiasis in, 423t of heart, 96 stem cell in lymphoma, 706, 710, 711 in sickle cell disease, 373 Tranylcypromine in depression, 782, 782t, 784t, 786 Trastuzumab in breast cancer, 682, 685, 687 Trauma abdominal, acute contamination in, 462t, 463t bite wounds in. See Bite wounds burns in, 510t vascular, thromboembolism in, 163 Traveler’s diarrhea, 258, 428, 429t Travoprost in glaucoma, 721, 723t Trazodone in Alzheimer’s disease, 733t in depression, 785 dosage of, 782t pharmacokinetics of, 789t relative potency of, 783t side effects of, 783t, 786 in erectile dysfunction, 938t, 943 in generalized anxiety disorder, 743 in insomnia, 817

1048

Tremor in Parkinson’s disease, 629 Treponema pallidum infections, 382t, 495t, 496–500. See also Syphilis Tretinoin in acne vulgaris, 182 in Cushing’s syndrome, 207 Triamcinolone, in adrenal insufficiency, 208t Triamcinolone acetonide in allergic rhinitis, 903t in asthma, 915t in psoriasis, 190t in rheumatoid arthritis, 41 Triamcinolone hexacetonide in gout, 6 in osteoarthritis, 16 in rheumatoid arthritis, 41 Triamterene in hypertension, 116t in renal failure, acute, 855 Triazolam in insomnia, 817, 818, 818t Tricalcium phosphate, 25t Trichloroacetic acid in genital papillomavirus warts, 507t Trichloroethylene, occupational exposure to, 963t Trichomoniasis, 495t, 504–508 clinical presentation in, 505, 506t in pregnancy, 506t, 508 Trifluoperazine in schizophrenia, 803t, 809 Triglyceride levels, 98, 99, 108–109 in diabetes mellitus, 109 drug therapy affecting, 104t, 109 antipsychotic, 811 measurement of, 99–100, 101t nutrition affecting, 103, 107, 109 in parenteral nutrition, 676t treatment goals for, 102 Trihexyphenidyl for antipsychotic drug side effects, 807t, 808 in Parkinson’s disease, 632t Triiodothyronine, 227 in hyperthyroidism, 227, 229t, 229–230 in hypothyroidism, 235 Trimethobenzamide in nausea and vomiting, 298t Trimethoprim-sulfamethoxazole in acne vulgaris, 185 in bite wounds, 513t, 520, 521 in bronchitis, chronic, 470t in cellulitis, 517 in gastrointestinal infections, 428, 429t, 430, 431, 433 in isosporiasis and HIV infection, 446t

INDEX in meningitis, 395t, 397 in Pneumocystis jiroveci pneumonia, 444, 445t, 447t, 449 in prostatitis, 549t, 555 in sinusitis, 485t skin reactions from, 952t in surgical site infections, 528t in urinary tract infections, 547t, 548t, 549t, 550 complicated, 551 failure of, 548t in males, 552, 553 recurrent, 553 Tripelennamine hydrochloride in allergic rhinitis, 900t Triptorelin in breast cancer, 686t, 687 in prostate cancer, 717t Tromethamine in metabolic acidosis, 844 Tropisetron in nausea and vomiting, 303t Troponins in acute coronary syndromes, 44, 46f, 47 in ischemic heart disease, 133 Trospium chloride in urinary incontinence, 947t, 949 Tuberculin skin test, 533–534, 534t Tuberculosis, 532–543 clinical presentation in, 533, 533t diagnosis of, 533–534, 534t extrapulmonary, 541 goals of therapy in, 534 in HIV infection and AIDS, 532, 533, 536 diagnosis of, 534t latent disease in, 536t prophylaxis of, 447t latent, 535, 536t meningitis in, 397–398, 533 cerebrospinal fluid values in, 388t diagnosis of, 389 treatment of, 395t, 397–398, 541 miliary, 533 pathophysiology in, 532–533 pharmacologic therapy in, 535–543 in active disease, 535–541 adverse effects of, 542–543 compliance with, 535, 541 dose adjustment in renal failure, 541, 542t in latent infection, 535, 536t monitoring of, 541–543 resistance to, 535, 536, 541 in pregnancy, 535, 541 primary infection, 532 reactivation of, 533

Tumor necrosis factor, in rheumatoid arthritis, 31 biologic agents inhibiting, 33, 39–40 Tumor necrosis factor-α in osteoarthritis, 9, 10 in psoriasis, 186, 191, 192 in sepsis, 487 Typhoid fever, 431, 432 U Ulcerative colitis, 282–293 clinical presentation in, 284t, 284–285 compared to Crohn’s disease, 282, 283t drug therapy in, 286, 287–289, 288f evaluation of therapeutic outcomes in, 293 mild to moderate disease, 284–285, 287 pathophysiology in, 282–283 remission therapy in, 288–289 severe or intractable disease, 285, 288 surgery in, 286 Ulcers decubitus, 510t, 518t, 518–519 of foot, in diabetes mellitus, 225, 517–518 genital, 495t of stomach and duodenum in peptic ulcer disease, 314–320 Ultrasonography in pancreatitis, 307, 310 Ultraviolet light A in psoriasis, 193, 194–195 Ultraviolet light B in psoriasis, 193, 194, 195 Undernutrition, 647 Urea breath test in Helicobacter pylori infections, 315, 316 Ureaplasma urealyticum infections, 495t Uremia bleeding in, 874 symptoms in, 858, 860 Urethra infections of, 495t, 544, 548t overactivity of, urinary incontinence in, 944, 945, 946 underactivity of, urinary incontinence in, 944, 946–948 differential diagnosis of, 945t Urethral syndrome, acute, 548t Urethritis, 495t, 544 Urge urinary incontinence, 944, 946, 948–949 Uric acid elevated serum levels of, 1–8. See also Hyperuricemia

1049

INDEX Uric acid (cont.) in lithiasis, 2, 6 production of, 1–2, 7 urinary excretion of, 2, 6 drugs increasing, 7–8 Uricosuric drugs, 7–8 Urinalysis in acute renal failure, 852, 852t, 853t, 856t Urinary tract disorders, 931–950 calculi, 2, 6 drug-induced, from antipsychotic drugs, 812 erectile dysfunction, 936–943 incontinence, 944–950 in infections, 544–555 antibiotics in, 546–555, 547t–548t asymptomatic, 551 in candidiasis, 424t, 545 catheter-related, 553–554 clinical presentation in, 545t, 545–546, 546t complicated, 544, 545, 551–553 diagnostic criteria in, 545–546, 546t in females, 550f in males, 552f, 552–553 microbiology in, 545 nosocomial, 545 outpatient therapy in, 548t in pregnancy, 356–357, 361, 549t, 553 recurrent, 544, 548t, 553 sepsis in, 491t surgical site, 526t, 529 virulence factors in, 544–545 of kidneys. See Kidney disorders in prostate hyperplasia, benign, 931–935 Urine output in acute renal failure, 849, 850f Urokinase in venous thromboembolism, 175 V Vaccinations, 556–575 contraindications to, 569 Haemophilus influenzae, 396, 570, 570t in children, 557t–558t, 561t–563t, 570 hepatitis A, 273, 274t in adults, 564t–567t in children, 557t–563t in HIV infection, 447t hepatitis B, 275, 277t in adults, 564t–568t in children, 557t–563t in HIV infection, 447t herpes zoster, 564t–568t, 574

1050

in HIV infection and AIDS, 565t, 569, 573 influenza. See Influenza, vaccination measles, 571 in adults, 564t–566t, 571 in children, 557t–563t, 571 meningococcal, 571–572 in adults, 564t–568t in children, 557t–560t, 571 mumps, 572 in adults, 564t–566t, 572 in children, 557t–563t, 572 papillomavirus, 570–571 in adults, 564t–566t in children, 559t–560t, 562t–563t pertussis, 572 in adults, 564t–566t, 572 in children, 557t–563t, 572 pneumococcal. See Pneumococcal infections, vaccination against poliovirus, 573 in children, 557t, 559t–563t, 573 in pregnancy, 556, 565t influenza, 451, 454, 571 recommended schedules for, 556, 557t–568t rotavirus, 557t–558t, 563t rubella, 573 in adults, 564t–566t in children, 557t–563t Salmonella, 433 in sickle cell disease, 373 varicella, 574 in adults, 564t–567t, 574 in children, 557t–563t, 574 Vacuum erection devices, in erectile dysfunction, 939 Vaginal atrophy in menopause, 349 Vaginal ring, contraceptive, 338 Vaginitis, 495t Vaginosis, bacterial, in pregnancy, 357–358 Valacyclovir in herpes simplex virus infections, 503, 505t in HIV infection, 446t in varicella-zoster virus infection and HIV infection, 446t Valerian in insomnia, 817 Valganciclovir, in cytomegalovirus infection and HIV infection, 446t, 448t Valley fever, 418 Valproic acid in Alzheimer’s disease, 733t in bipolar disorder, 763, 766, 771, 776–777

INDEX dosage and administration of, 768t, 777 guidelines on, 764t monitoring of, 772t side effects of, 776–777 in generalized anxiety disorder, 745, 746t interaction with other drugs in anxiety disorders, 746t in bipolar disorder, 776 in seizures, 589, 590t, 598 in migraine prophylaxis, 608t, 610–611 in schizophrenia, treatment-resistant, 806 in seizures, 586, 597–598 adverse effects of, 588, 588t, 597 dosage and serum levels of, 593t, 598 indications for, 581t, 582t, 583t interaction with other drugs, 589, 590t, 598 pharmacokinetics of, 585t, 597 in status epilepticus, 645t, 646 Valsartan in acute coronary syndromes, 58 in heart failure, 88 in hypertension, 116t Vancomycin in cellulitis, 514 in diabetic foot infections, 518 dose adjustment in kidney disease, 877t, 879, 879t in endocarditis, 410 enterococcal, 407, 408t staphylococcal, 403, 406t, 407, 408t streptococcal, 402t, 403, 404t, 405t in gastrointestinal infections, 429t, 430 in intraabdominal infections, 461t, 462t in meningitis, 392t, 395t, 396 in peritonitis, dialysis-associated, 462 in sepsis, 491, 491t in streptococcal group B infection in pregnancy, 361 in surgical site infections, 524–525, 530, 531 Vardenafil in erectile dysfunction, 938t, 939–941, 940t interaction with nitrate therapy, 53, 940 Varenicline in smoking cessation, 836, 837t, 838

Variceal hemorrhage in cirrhosis and portal hypertension, 239, 242 management of, 243–246, 244f, 245t, 248t outcome assessment in, 248t Varicella immune globulin in exposure to, 574t vaccination, 574 in adults, 564t–567t, 574 in children, 557t–563t, 574 Varicella-zoster virus infections in HIV infection, 446t, 447t Vascular surgery, surgical site infections in, 527t, 530 Vasodilator drugs in heart failure, 94–95 in hypertension, 114, 117t, 123 Vasomotor symptoms in menopause, 341, 350–351 alternatives to estrogen therapy in, 347–349, 349t Vasooclusive crisis in sickle cell disease, 372, 375 Vasopressin secretion, 881 inappropriate, 881, 882 therapy in cardiopulmonary resuscitation, 76t, 77, 79, 80 in shock, 154 in variceal hemorrhage, 245 Vasopressor drugs in shock, 150–151, 152f, 153t Vasovagal syncope, 72–73 Vaughan Williams classification of antiarrhythmic drugs, 63 Venlafaxine in Alzheimer’s disease, 733, 733t in cataplexy, 822 in depression, 785 and cytochrome P450 activity, 795t in elderly, 792 interaction with other drugs, 793t monitoring of, 796 pharmacokinetics of, 789t refractory, 795 relative potency of, 783t side effects of, 783t, 786 in generalized anxiety disorder, 740, 742t, 743 in menopause, 347, 349t in panic disorder, 747, 747t, 749 in posttraumatic stress disorder, 753t, 754 in social anxiety disorder, 750, 751t

1051

INDEX Venous stasis, 163 Venous thromboembolism, 163–177. See also Thromboembolism, venous Ventilatory support in chronic obstructive pulmonary disease, 929 respiratory alkalosis in, 845 Ventricular arrhythmias, 71–72, 77–80 clinical presentation in, 62 diagnosis of, 62–63 fibrillation. See Fibrillation, ventricular intravenous drug dose in, 66t pathophysiology in, 61 premature complexes, 61, 62, 71 proarrhythmias, 61, 62, 72 tachycardia. See Tachycardia, ventricular Ventricular assist devices in heart failure, 96 Ventricular remodeling in myocardial infarction, 44 Verapamil in acute coronary syndromes, 54 in arrhythmias, 64t in atrial fibrillation and flutter, 65 in atrial tachycardia, 71 intravenous dosage in, 66t in bipolar disorder, 766, 770t in hypertension, 117t, 120 interaction with other drugs, 746, 771, 791t in ischemic heart disease, 137, 139, 141, 142 in migraine prophylaxis, 608t, 611 Vertebral osteoporosis. See Spinal osteoporosis Vibrio cholerae infections, 427–428, 429t Vildagliptin in diabetes mellitus, 220 Vinblastine in Hodgkin’s lymphoma, 705t, 707t Vincristine in lung cancer, 703 in lymphoma Hodgkin’s, 705t, 707t non-Hodgkin’s, 710, 710t, 711 Vinorelbine in breast cancer, 683t, 687 in lung cancer, 700, 701t, 703 Vinyl chloride, occupational exposure to, 963t Viral infections bronchiolitis in, 470–471 bronchitis in, 465, 466 gastroenteritis in, 434 hepatitis in, 273–281

1052

herpes simplex, 502–504 HIV infection and AIDS, 435–449 in HIV infection complications, 446t influenza, 450–455 meningitis in, 388t, 395t pharyngitis in, 481 pneumonia in, 472, 473 in children, 475t sexually transmitted, 494t Virchow’s triad, 163 Vitamin A in acne vulgaris, 182 Vitamin B2 in migraine prophylaxis, 608t Vitamin B6 in isoniazid therapy in latent tuberculosis, 535 in tuberculous meningitis, 397 in nausea and vomiting of pregnancy, 304 Vitamin B12 deficiency of, 363 clinical presentation in, 365 diagnosis of, 366 evaluation of therapeutic outcomes in, 369 treatment of, 367 reference range for serum levels, 365t supplemental, 367, 369 Vitamin D in hypocalcemia, 888 in kidney disease, chronic, 870, 873t in osteoporosis, 20, 23, 26t dietary sources of, 24t glucocorticoid-induced, 30 preparations available, 25t recommended daily intake, 23, 23t treatment algorithm on, 21f–22f in psoriasis, 188–190 Vitamin E in Alzheimer’s disease, 731 Vitamin K1 in epilepsy and pregnancy, 359 in warfarin therapy, 172 Vitamins in alcohol withdrawal, 833t drug affecting serum levels of, 654, 654t in parenteral nutrition solutions, 674 Vomiting, 294–304. See also Nausea and vomiting Voriconazole in aspergillosis, 425 in meningitis, 395t Vulvovaginitis, 495t W Waist circumference measurements in obesity, 664, 664t

INDEX Warfarin in acute coronary syndromes, 56, 57–58 in atrial fibrillation and flutter, 66, 67, 69 enteral feeding tube administration of, 662t interaction with other drugs, 794t in ischemic stroke, 159t, 160, 161t in venous thromboembolism, 171–175, 177 adverse effects of, 172, 356 contraindications to, 172, 175 duration of therapy, 172 initiation of therapy, 171–172, 173f interaction with other drugs and foods, 175 in prevention, 176t Warts, genital/anal, 495t, 507t Web site resources on sexually transmitted diseases, 493 Weight measurements and growth curve in children, 648, 650t ideal body weight in, 649t in nutritional assessment, 648, 649t, 650t, 654 White blood cells in cerebrospinal fluid in meningitis, 388t, 389 count of, in infections, 377, 384–385 urinary, in acute renal failure, 852t, 853t Whitehead (closed comedo), 179 Witch hazel in contact dermatitis, 199 Withdrawal symptoms, 823, 831t, 831–835 from alcohol, 824, 832, 833t–834t from barbiturates, 826t, 831t from benzodiazepines, 745, 825, 826t, 831t, 832 from cocaine, 827, 831t from γ-hydroxybutyrate, 825 from methamphetamine, 827 from nicotine, 828 from opiates, 825, 831t, 832, 835 Women’s Health Initiative study on menopause therapy, 342, 349, 350, 351 World Health Organization oral rehydration solution, 261t, 428t precautions in hormonal contraceptives, 330, 331t–332t

Wound infections in bites, 519–521 in burns, 510t of foot in diabetes mellitus, 517–518 in pressure sores, 518–519 of surgical site, 522–531 X Xanthine oxidase inhibitor in gout, 7 Xanthomas in hyperlipidemia, 99, 110 Xylometazoline hydrochloride in allergic rhinitis, 902t Y Yersinia infections, 429t, 433 Yohimbine in erectile dysfunction, 938t, 943 Z Zafirlukast in asthma, 918–919 Zalcitabine in HIV infection, 442t Zaleplon in insomnia, 817, 818t Zanamivir in influenza, 453, 454t, 455 Zidovudine in HIV infection, 440t, 441 pharmacology of, 442t in pregnancy, 359, 441 Zileuton in asthma, 919 Zinc oxide in diaper dermatitis, 199 Ziprasidone in Alzheimer’s disease, 733t in bipolar disorder, 763, 766, 770t, 771 in schizophrenia, 800, 810 dosage of, 803t in initial therapy, 803 pharmacokinetics of, 801, 804t side effects of, 806t, 810, 811 Zoledronate in hypercalcemia, 887t in osteoporosis, 23, 27t in prostate cancer, 718 Zolmitriptan in migraine headache, 604t, 606, 607t Zolpidem in insomnia, 817, 818t Zonisamide in seizures, 598 adverse effects of, 588t, 598 dosage and serum levels of, 593t, 598 indications for, 582t, 583t, 598 pharmacokinetics of, 585t, 598

1053