Workbook and Casebook for Goodman and Gilman’s The Pharmacological Basis of Therapeutics

785 Pages·2015·63.12 MB·English

by  Douglas E. Rollins

WORKBOOK AND CASEBOOK
For Goodman and Gilman’s
T e Pharmacological Basis of T erapeutics
Rollins_FM_p00i-vi.indd 1 06/11/15 4:13 pm
NOTICE
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WORKBOOK AND CASEBOOK
For Goodman and Gilman’s
T e Pharmacological Basis of T erapeutics
EDITORS
Douglas E. Rollins, MD, PhD Donald K. Blumenthal, PhD
Professor Emeritus, Pharmacology & Toxicology Associate Professor of Pharmacology & Toxicology
University of Utah Associate Dean for Interprofessional Education &
Salt Lake City, Utah Assessment, College of Pharmacy
University of Utah
Salt Lake City, Utah
New York Chicago San Francisco Lisbon London Madrid Mexico City
Milan New Delhi San Juan Seoul Singapore Sydney oronto
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CONTENTS
Pre ace. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .vi 28 Estrogens, Progestins, Androgens,
and Contraception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
SECTION I 1 29 AC H, Adrenal Steroids, and
Pharmacology o the Adrenal Cortex . . . . . . . . . . . . . . 459
General Principles
30 Endocrine Pancreas and Pharmacotherapy
1 Pharmacodynamics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
o Diabetes Mellitus and Hypoglycemia . . . . . . . . . . . . 470
2 Pharmacokinetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
31 Drug T erapy o Mineral Ion Homeostasis
3 Clinical and Environmental oxicity. . . . . . . . . . . . . . . . 40
and Bone urnover Disorders . . . . . . . . . . . . . . . . . . . . 480
4 Special Populations (Children and Elderly) . . . . . . . . . . 67
SECTION VI 489
SECTION II 79
Drugs Af ecting Gastrointestinal Function
Neuropharmacology
32 Pharmacotherapy o Gastric Acidity, Peptic
5 Neurotransmission. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Ulcers, and Gastroesophageal Re ux Disease . . . . . . . 490
6 Cholinergic Pharmacology. . . . . . . . . . . . . . . . . . . . . . . . 95
33 Drugs Used or the reatment o Bowel Disorders. . . 497
7 Adrenergic, Dopaminergic, and
Serotonergic Pharmacology . . . . . . . . . . . . . . . . . . . . . . 118
SECTION VII 511
8 Psychopharmacology. . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
Chemotherapy o Microbial Diseases
9 Hypnotics, Sedatives, and Ethanol. . . . . . . . . . . . . . . . . 176
10 Opioid Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . 194 34 General Principles o Antimicrobial T erapy . . . . . . . 512
11 Anesthetic Agents and T erapeutic Gases . . . . . . . . . . 210 35 Chemotherapy o Malaria. . . . . . . . . . . . . . . . . . . . . . . . 520
12 Pharmacotherapy o the Epilepsies . . . . . . . . . . . . . . . . 225 36 Chemotherapy o Protozoal In ections: Amebiasis,
13 Drug T erapy o Neurodegenerative Diseases. . . . . . . 238 Giardiasis, richomoniasis, rypanosomiasis,
14 Drug Addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254 Leishmaniasis, and Other Protozoal In ections. . . . . . . 530
37 Chemotherapy o Helminth In ections. . . . . . . . . . . . . 536
SECTION III 267 38 Sul onamides, rimethoprim-Sul amethoxazole,
Quinolones, and Agents or Urinary
Modulation o Cardiovascular Function
ract In ections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
15 Drug T erapy o Hypertension, Edema, and
39 Penicillins, Cephalosporins, and
Disorders o Sodium and Water Balance . . . . . . . . . . . 268
Other β-Lactam Antibiotics . . . . . . . . . . . . . . . . . . . . . . 549
16 Drug T erapy o Myocardial Ischemia . . . . . . . . . . . . . 289
40 Aminoglycosides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
17 Pharmacotherapy o Heart Failure . . . . . . . . . . . . . . . . 301
41 Protein Synthesis Inhibitors and
18
Antiarrhythmic Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . 312
Miscellaneous Antibacterial Agents . . . . . . . . . . . . . . . 568
19 Drug T erapy o T romboembolic Disorders . . . . . . . 323
42 Chemotherapy o uberculosis, Mycobacterium
20 Drug T erapy o Dyslipidemias. . . . . . . . . . . . . . . . . . . 334
Avium Complex Disease, and Leprosy . . . . . . . . . . . . . 578
43 Anti ungal Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 588
SECTION IV 345
44 Antiviral Agents and reatment
o HIV In ection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 600
In ammation, Immunomodulation,
and Hematopoiesis
SECTION VIII 625
21 Histamine, Bradykinin, and T eir Antagonists. . . . . . 346
22 Prostaglandins, NSAIDs, and Chemotherapy o Neoplastic Diseases
Pharmacotherapy o Gout. . . . . . . . . . . . . . . . . . . . . . . . 356
45 Cancer Chemotherapy and Cytotoxic Agents . . . . . . . 626
23 Immunotherapeutic Agents . . . . . . . . . . . . . . . . . . . . . . 375
46 argeted Anticancer T erapies. . . . . . . . . . . . . . . . . . . . 661
24 Pulmonary Pharmacology . . . . . . . . . . . . . . . . . . . . . . . 389
25 Hematopoietic Agents. . . . . . . . . . . . . . . . . . . . . . . . . . . 405
SECTION IX 689
Special Systems Pharmacology
SECTION V 421
47 Ocular Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . 690
Hormones and Hormone Antagonists
48 Dermatological Pharmacology. . . . . . . . . . . . . . . . . . . . 707
26 Introduction to Endocrinology:
T e Hypothalamic-Pituitary Axis . . . . . . . . . . . . . . . . . 422
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 728
27 T yroid and Antithyroid Drugs. . . . . . . . . . . . . . . . . . . 431
v
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PREFACE
T is Workbook and Casebook derives rom the 12th edition • Mechanisms o Action (and, where appropriate, Mechanisms
o Goodman & Gilman’s T e Pharmacological Basis of T era- o Resistance) able
peutics. T e organization o the parent text has been retained
• Clinical Cases
and many o the tables and gures are the same. T e editors
• Key Concepts
have attempted to provide the most important concepts rom
• Summary Quiz
the 12th edition o G&G in a user- riendly ormat without the
elimination o salient pharmacological in ormation. It is our • Summary able o Drugs that includes Drug Class, Drug
intention that the Workbook and Casebook will complement Name, Clinical Uses, and Common and Unique Clinically
the parent text and the second edition o Goodman & Gilman’s Important oxicities
Manual of Pharmacology and T erapeutics and be use ul to
Additional Side Bars are included to highlight signi cant phar-
students and educators who might need a companion text in
macological in ormation. Narrative pharmacological in orma-
an advanced pharmacology course.
tion is provided in the orm o Clinical Cases to give a clinical
T e number o chapters in the Workbook and Casebook has been context or the therapeutic use o drugs and their adverse events.
reduced rom 67 to 48 by combining the substance o multiple We have omitted research data, chemical structures, re erences,
chapters rom the 12th edition into one Workbook and Casebook and the pharmacokinetic data o Appendix II, all o which can
chapter. For example, Chapter 9 Muscarinic Receptor Agonists be ound on the G&G Web site on AccessMedicine.com and
and Antagonists, Chapter 10 Anticholinesterase Agents, and AccessPharmacy.com, along with pharmacotherapeutic updates
Chapter 11 Agents Acting at the Neuromuscular Junction and and mechanistic animations.
Autonomic Ganglia in the 12th edition have been combined
We thank the contributors and editors o the 12th edition
into one Workbook chapter entitled Cholinergic Pharmacology.
o G&G, Christie Naglieri and James Shanahan o McGraw
An additional chapter, Chapter 4 Special Populations: Children
Hill, and the long line o contributors and editors who have
and the Elderly, has been added to the Workbook and Casebook
worked on Goodman & Gilman over 12 editions. It is an
based in part on content that is published in Updates in the
honor to ollow in the path o Louis Goodman and Al red
online version o Goodman & Gilman (Accessmedicine.com
Gilman, and it is a tribute to their writing and editing that
and Accesspharmacy.com).
their book is use ul and relevant 74 years af er the publication
Each Workbook and Casebook chapter begins with a statement o the rst edition.
o how it di ers rom the 12th edition so that the reader can
re er to the parent text to obtain additional in ormation i nec-
Douglas E. Rollins
essary. Workbook and Casebook chapters (except or chapters
Donald K. Blumenthal
on general principles) are ormatted as ollows:

• Learning Objectives
• Drugs Included in the Chapter
vi
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SECTION
I
General Principles
1. Pharmacodynamics 1
2. Pharmacokinetics 18
3. Clinical and Environmental oxicity 40
4. Special Populations (Children and Elderly) 67
1
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CHAPTER
1
Pharmacodynamics
T is chapter will be most use ul a er having a basic understanding o the material in
PHARMACODYNAMIC
Chapter 3, Pharmacodynamics: Molecular Mechanisms o Drug Action in Goodman
CONCEPTS AND
& Gilman’s T e Pharmacological Basis of T erapeutics, 12th Edition Additional in or-
NOMENCLATURE (key terms
mation related to this chapter is provided in Chapter 1, Drug Invention and the Phar-
are indicated in italics) maceutical Industry and Chapter 7, Pharmacogenetics T e drugs presented in this
chapter are used to illustrate general pharmacodynamic principles T e mechanisms
• Pharmacodynamics is the study o the bio-
o action and therapeutic uses o drugs described in this chapter are discussed in more
chemical and physiological e ects o drugs
detail in subsequent chapters Neither a Mechanisms o Action able nor a Clinical
and their mechanisms o action.
Summary able is included in this chapter because this in ormation is provided in
• Pharmacodynamics re ers to the e ects o
subsequent chapters
a drug on the body; in contrast, the e ects
o the body on the actions o a drug are In addition to the material presented here, Goodman & Gilman’s T e Pharmacological
pharmacokinetic processes (see Chapter 2). Basis of T erapeutics, 12th Edition contains:
• The term drug receptor or drug target • A description in Chapter 1 o the process o drug invention and FDA approval
denotes the cellular macromolecule or
• able 1-1, ypical Characteristics o the Various Phases o the Clinical rials
macromolecular complex with which the
Required or Marketing o New Drugs
drug interacts to elicit a cellular response.
• Figure 1-1, T e Phases, ime Lines, and Attrition T at Characterize the Invention o
• Drugs commonly alter the rate or magni-
New Drugs
tude o an intrinsic cellular response rather
• A comprehensive description in Chapter 3 o the various mechanisms o drug action,
than create new responses.
including cellular pathways activated by physiological receptors, structural and unc-
• Drug receptors are o ten located on the
tional amilies o physiological receptors, second messengers, ion channels, nuclear
sur ace o cells but may also be located in
receptors, and transcription actors
speci c intracellular compartments.
• Chapter 3 also describes mechanisms o receptor desensitization and regulation, and
• Many drugs also interact with acceptors
an example o pharmacodynamic interactions in a multicellular context
within the body; acceptors are entities
• Chapter 7 includes a number o examples o genetic polymorphisms that a ect drug
that do not directly cause any change in
pharmacodynamics, the impact o pharmacogenetics on drug development, and a
biochemical or physiological response.
discussion o pharmacogenetics in clinical practice
• Proteins orm the most important class o
drug receptors. Examples include: LEARNING OBJECTIVES
Physiological receptors or hormones,
(cid:0) Understand key concepts and terms related to pharmacodynamics, including
»
growth actors, transcription actors,
drug receptor agonism and antagonism
and neurotransmitters (see Table 1-1)
(cid:0) Know concepts and terms that are used to quanti y drug receptor interactions,
Enzymes o crucial metabolic or
» including a nity, e cacy, potency, K and K.
D i
regulatory pathways (eg, dihydro olate
(cid:0) Understand how drug pharmacodynamic in ormation is used to predict benef -
reductase, acetylcholinesterase, and
cial and toxic drug e ects
cyclic nucleotide phosphodiesterases)
(cid:0) Know the modern process o drug invention and FDA approval, and post-market
Proteins involved in transport processes
»
surveillance
(eg, Na+, K+-ATPase); secreted
glycoproteins (eg, Wnts) (cid:0) Know how genetic polymorphisms and other actors can a ect the pharma-
codynamic properties o drugs and lead to variability in individual patient
Structural proteins (eg, tubulin)
»
responses to drugs
• Speci c binding o drugs to other cellular
(cid:0) Know how pharmacodynamics is applied to populations o patients to estimate
constituents such as DNA is also exploited or
population therapeutic windows or drug dosing
therapeutic purposes (eg, many cancer che-
motherapeutic agents and antiviral drugs).
• Antibiotic and other anti-in ectives o ten
target enzymes and biochemical processes
that are unique to the pathogen, resulting
in cytotoxicity or inhibition o proli eration.
2
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Pharmacodynamics CHAPTER 1
TABLE 1-1 Physiological Receptors
EFFECTORS AND
STRUCTURAL FAMILY FUNCTIONAL FAMILY PHYSIOLOGICAL LIGANDS TRANSDUCERS EXAMPLE DRUGS
G Protein coupled β Adrenergic receptors NE, Epi, DA G; AC Dobutamine, propranolol
s
receptors (GPCRs)
Muscarinic cholinergic ACh G and G ; AC, Atropine, carbachol
i q
receptors ion channels, PLC
Eicosanoid receptors Prostaglandins, leukotrienes, G, G, and G proteins Misoprostol, montelukast
s i q
thromboxanes
Thrombin receptors (PAR) Receptor peptide G , GEFs Vorapaxar
12/13
Ion channels Ligand-gated ACh (M ), GABA, 5-HT Na+, Ca2+, K+, Cl– Nicotine, gabapentin
2
Voltage-gated None (activated by Na+, Ca2+, K+, other ions Lidocaine, verapamil
membrane depolarization)
Transmembrane Receptor tyrosine kinases Insulin, PDGF, EGF, VEGF, SH2 domain and PTB- Herceptin, imatinib
enzymes growth actors containing proteins
Membrane-bound GC Natriuretic peptides Cyclic GMP Neseritide
Tyrosine phosphatases
Transmembrane, Cytokine receptors Interleukins and other Jak/STAT, soluble Anakinra
non enzymes cytokines tyrosine kinases
Toll-like receptors B L(PinS, dbeavceteloripaml pernotd)ucκts MyD88, IARKs, NF-
Nuclear receptors Steroid receptors Estrogen, testosterone Co-activators Estrogens, androgens, Cortisol
Thyroid hormone receptors Thyroid hormone Thyroid hormone
, PPARa Eicoγnsanoids, atty acids P PARRXR Thiazolidinediones
Intracellular enzymes Soluble GC NO, Ca2+ Cyclic GMP Nitrovasodilators
AC, adenylyl cyclase; DA, dopamine; GC, guanylyl cyclase; GEF, guanine nucleotide exchange actor; LPS, lipopolysaccharide; NE, norepinephrine;
PAR, protease-activated receptor; PLC, phospholipase C; PPAR, peroxisome proli erator-activated receptor.
CASE 1-1
A man who su ers rom hay ever is at his local pharmacy looking or a nonprescrip- DRUG-RECEPTOR
tion drug that can provide relie o symptoms One o the allergy medicines he f nds on
INTERACTIONS (key terms
the shel says the active ingredient is an antihistamine, diphenhydramine
are indicated in italics)
a. What is an “active ingredient” in an allergy medication such as this?
• Many drugs act on physiological receptors
Pharmaceuticals contain 1 or more pharmacologically active ingredients, which are and are particularly selective because
termed active ingredients. T e quantities o each active ingredient in each dose (eg, physiological receptors have evolved to
tablet, capsule, or volume o a liquid medication) are indicated on the packaging. In recognize and respond to individual signal-
addition to active ingredients, most medications also contain other ingredients that are ing molecules with great selectivity.
pharmacologically inactive, but may improve the pharmacokinetics, appearance, taste,
• Drugs that bind to physiological receptors
shel -li e, or other properties that may enhance dosing and product e ectiveness.
and mimic the regulatory e ects o the
endogenous signaling compounds are
b. What kind o drug is an “antihistamine” and why is it so named?
termed agonists.
As the name indicates, an antihistamine is an agent that antagonizes the action
A drug that binds to the same
o the endogenous mediator histamine. Histamine is released by mast cells and is »
recognition site as the endogenous
involved in a variety o allergic and in ammatory responses (see Chapter 21). T is
agonist (the primary or orthosteric
man’s hay ever is caused by mast cell release o histamine and other substances that
site on the receptor) is said to be
result in his symptoms o sneezing, runny nose, itching o the nose and throat, and
a primary agonist.
itchy, watery eyes. An antihistamine such as diphenhydramine will bind to hista-
mine receptors on cells throughout the body and block the e ects o histamine. (continues)
(Continued)
3
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