Contents
Contributors ix
Preface xv
Acknowledgments xvii
Section I
General Principles 1
1. Drug Discovery: From Medicinal Plants to Computer-Aided
Drug Design ........................................................................................... 3
Michael K. Gilson and Laurence L. Brunton
2. Pharmacokinetics: The Dynamics of Drug Absorption,
Distribution, Metabolism, and Elimination ..................................... 23
Iain L. O. Buxton
3. Pharmacodynamics: Molecular Mechanisms of Drug Action ....... 43
David R. Manning and Donald K. Blumenthal
4. Membrane Transporters and Drug Response .................................. 79
Kathleen M. Giacomini and Yuichi Sugiyama
5. Drug Metabolism ............................................................................... 101
Frank J. Gonzalez and Michael Coughtrie
6. The Gastrointestinal Microbiome and Drug Response ................ 119
Shirley M. Tsunoda, Pieter C. Dorrestein, and Rob Knight
7. Pharmacogenetics and Pharmacogenomics ................................... 131
Dan M. Roden and Sara L. Van Driest
8. Postmarketing Drug Safety ............................................................... 145
C. Michael Stein and Wayne A. Ray
9. Principles of Clinical Toxicology ..................................................... 155
Amberly R. Johnson and Kaitlyn M. Brown
Section II
Neuropharmacology 171
10. Neurotransmission: The Autonomic and Somatic Motor
Nervous Systems ................................................................................ 173
Rebecca Petre Sullivan, Steven R. Houser, and Walter J. Koch
11. Muscarinic Receptor Agonists and Antagonists ............................ 207
Joan Heller Brown, Katharina Brandl, and Jürgen Wess
12. Anticholinesterase Inhibitors and Reactivators ............................. 221
Palmer Taylor
13. Neuromuscular Junction and Autonomic Ganglia; Nicotine,
Muscle Relaxants, and Spasmolytics ............................................... 235
Ryan E. Hibbs and Alexander C. Zambon
14. Adrenergic Agonists and Antagonists ............................................. 251
Douglas G. Tilley, Steven R. Houser, and Walter J. Koch
15. 5-Hydroxytryptamine (Serotonin) and Dopamine ....................... 285
Charles D. Nichols, Susan G. Amara, and David R. Sibley
16. Neurotransmission in the Central Nervous System ...................... 305
R. Benjamin Free, Suzanne M. Underhill, Susan G. Amara,
and David R. Sibley
17. The Blood-Brain Barrier and Its Influence on Drug
Transport to the Brain ....................................................................... 327
Richard Daneman, Margareta Hammarlund-Udenaes,
and Eric V. Shusta
18. Drug Therapy of Depression and Anxiety Disorders.................... 343
James M. O’Donnell, Robert R. Bies, and Aislinn J. Williams
19. Pharmacotherapy of Psychosis and Mania ..................................... 357
Jonathan M. Meyer
20. Pharmacotherapy of the Epilepsies .................................................. 385
Cameron S. Metcalf, Misty D. Smith, and Karen S. Wilcox
21. Treatment of Central Nervous System
Degenerative Disorders ..................................................................... 413
Erik D. Roberson and Talene A. Yacoubian
22. Hypnotics and Sedatives.................................................................... 427
S. John Mihic and Jody Mayfield
23. Opioid Analgesics ............................................................................. 443
Emily M. Jutkiewicz and John R. Traynor
24. General Anesthetics and Therapeutic Gases .................................. 471
Jerry Ingrande, Matthew L. Pearn, and Hemal H. Patel
25. Local Anesthetics ............................................................................... 489
William A. Catterall and Kenneth Mackie
26. Cannabinoids ...................................................................................... 505
Matthew N. Hill and Kenneth Mackie
27. Ethanol................................................................................................. 519
Jody Mayfield and S. John Mihic
28. Drug Use Disorders and Addiction ................................................. 531
Christine Konradi and Yasmin L. Hurd
Section III
Modulation of Pulmonary, Renal,
and Cardiovascular 555
29. Drugs Affecting Renal Excretory Function .................................... 557
Edwin K. Jackson
30. Renin and Angiotensin...................................................................... 585
Krishna Sriram and Paul A. Insel
31. Treatment of Ischemic Heart Disease.............................................. 607
Thomas Eschenhagen
32. Treatment of Hypertension ............................................................... 625
Thomas Eschenhagen
33. Therapy of Heart Failure ................................................................... 647
Thomas Eschenhagen
34. Antiarrhythmic Drugs ....................................................................... 667
Bjorn C. Knollmann, Dan M. Roden, and Katherine T. Murray
35. Treatment of Pulmonary Arterial Hypertension ........................... 695
Dustin R. Fraidenburg, Ankit A. Desai, Ayako Makino,
and Jason X.-J. Yuan
36. Blood Coagulation and Anticoagulant, Fibrinolytic, and
Antiplatelet Drugs .............................................................................. 709
Jeffrey I. Weitz
37. Drug Therapy for Dyslipidemias ..................................................... 729
Natalia Ruiz-Negrón and Donald K. Blumenthal

viii Section IV
Inflammation, Immunomodulation,
and Hematopoiesis 747
38. Introduction to Immunity and Inflammation................................ 749
Michael David
39. Immunosuppressants, Immunomodulation, and Tolerance ........ 769
Carla V. Rothlin and J. Silvio Gutkind
40. Immune Globulins and Vaccines ..................................................... 793
Roberto Tinoco and James E. Crowe, Jr.
41. Lipid-Derived Autacoids: Eicosanoids and
Platelet-Activating Factor.................................................................. 815
Emanuela Ricciotti, Tilo Grosser, and Garret A. FitzGerald
42. Pharmacotherapy of Inflammation, Fever, Pain, and Gout.......... 829
Tilo Grosser, Emanuela Ricciotti, and Garret A. FitzGerald
43. Histamine, Bradykinin, and Their Antagonists ............................. 857
Bruce L. Zuraw and Sandra C. Christiansen
44. Pulmonary Pharmacology ................................................................ 875
Peter J. Barnes
45. Hematopoietic Agents: Growth Factors, Minerals,
and Vitamins ....................................................................................... 899
Michael Choi and Thomas J. Kipps
Section V
Endocrine Pharmacology 921
46. Introduction to Endocrinology:
The Hypothalamic-Pituitary Axis.................................................... 923
Dequina A. Nicholas and Mark A. Lawson
47. Thyroid and Antithyroid Drugs ....................................................... 941
Ronald J. Koenig and Gregory A. Brent
48. Estrogens, Progestins, and the Female Reproductive Tract.......... 959
Ellis R. Levin, Wendy S. Vitek, and Stephen R. Hammes
49. Androgens and the Male Reproductive Tract ................................ 991
Peter J. Snyder
50. Adrenocorticotropic Hormone, Adrenal Steroids,
and the Adrenal Cortex ................................................................... 1003
Christopher J. Hupfeld and Jorge Iñiguez-Lluhí
51. Endocrine Pancreas and Pharmacotherapy of
Diabetes Mellitus and Hypoglycemia ............................................ 1023
Alvin C. Powers and David D’Alessio
52. Agents Affecting Mineral Ion Homeostasis
and Bone Turnover .......................................................................... 1049
Thomas D. Nolin and Peter A. Friedman
Section VI
Gastrointestinal Pharmacology 1071
53. Pharmacotherapy for Gastric Acidity, Peptic Ulcers, and
Gastroesophageal Reflux Disease................................................... 1073
Keith A. Sharkey and Wallace K. MacNaughton
54. Gastrointestinal Motility and Water Flux, Emesis,
and Biliary and Pancreatic Disease ................................................ 1085
Keith A. Sharkey and Wallace K. MacNaughton
55. Pharmacotherapy of Inflammatory Bowel Disease ..................... 1111
Wallace K. MacNaughton and Keith A. Sharkey
Section VII
Chemotherapy of Infectious Diseases 1125
Section Editor: Conan MacDougall
56. General Principles of Antimicrobial Therapy .............................. 1127
Conan MacDougall
57. DNA Disruptors: Sulfonamides, Quinolones,
and Nitroimidazoles ....................................................................... 1137
Conan MacDougall
58. Cell Envelope Disruptors: β-Lactam, Glycopeptide, and
Lipopeptide Antibacterials.............................................................. 1147
Conan MacDougall
59. Miscellaneous Antibacterials: Aminoglycosides, Polymyxins,
Urinary Antiseptics, Bacteriophages ............................................. 1167
Conan MacDougall and Robert T. Schooley
60. Protein Synthesis Inhibitors ........................................................... 1179
Conan MacDougall
61. Antifungal Agents ............................................................................ 1193
P. David Rogers and Damian J. Krysan
62. Antiviral Agents (Nonretroviral) ................................................... 1211
Edward P. Acosta
63. Treatment of Viral Hepatitis (HBV/HCV) ................................... 1227
Jennifer J. Kiser
64. Antiretroviral Agents and Treatment of HIV Infection .............. 1245
Charles W. Flexner
65. Chemotherapy of Tuberculosis and Nontuberculous
Mycobacteria, Including Leprosy .................................................. 1267
Elisa H. Ignatius and Kelly E. Dooley
66. Chemotherapy of Malaria ............................................................... 1289
Abdoulaye A. Djimdé and Steve M. Taylor
67. Chemotherapy of Protozoal Infections: Amebiasis, Giardiasis,
Trichomoniasis, Trypanosomiasis, Leishmaniasis, and Other
Protozoal Infections ......................................................................... 1309
Dawn M. Wetzel and Margaret A. Phillips
68. Chemotherapy of Helminth Infections ......................................... 1325
Jennifer Keiser, James McCarthy, and Peter Hotez
Section VIII
Pharmacotherapy of Neoplastic Disease 1335
Section Editor: Anton Wellstein
69. General Principles in the Pharmacotherapy of Cancer............... 1337
Anton Wellstein
70. Cytotoxics and Antimetabolites ..................................................... 1343
Anton Wellstein and Edward A. Sausville
71. Protein Kinase Inhibitors and Pathway-Targeted
Small Molecules ............................................................................... 1381
Anton Wellstein and Giuseppe Giaccone
72. Antibodies, CAR T Cells, and Proteins to Treat Cancer ............. 1415
Anton Wellstein and Michael B. Atkins
73. Hormones, Hormone Receptor Antagonists, and
Related Agents in the Therapy of Cancer ..................................... 1435
Claudine Isaacs, Kerry L. Burnstein, and Anna T. Riegel
Section IX
Special Systems Pharmacology 1451
74. Ocular Pharmacology ...................................................................... 1453
Upneet K. Bains, Zeba A. Syed, Jeffrey D. Henderer,
and Christopher J. Rapuano
75. Dermatological Pharmacology....................................................... 1475
Matthew J. Sewell and Dean S. Morrell
76. Environmental Toxicology .............................................................. 1507
Allison K. Ehrlich
Appendices
I. Design and Optimization of Dosage Regimens:
Pharmacokinetic Data ..................................................................... 1533
Isabelle Ragueneau-Majlessi, Jingjing Yu, and Nina Isoherranen
II. Drug-Drug Interactions .................................................................. 1591
Isabelle Ragueneau-Majlessi, Jingjing Yu, and Nina Isoherranen
Index 159