Basic and Clinical Pharmacology

1217 Pages·2014·101.765 MB·English

by  Bertram Katzung, Anthony Trevor

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S C H E D U L E O F C O N T R O L L E D D R U G S
SCHEDULE I Depressants:
Schedule II barbiturates in mixtures with noncontrolled drugs or in
(All nonresearch use illegal under federal law.) suppository dosage form
Flunitrazepam (Rohypnol)
Barbiturates (butabarbital [Butisol], butalbital [Fiorinal])
Narcotics:
Ketamine (Ketalar)
Heroin and many nonmarketed synthetic narcotics
Cannabinoids:
Hallucinogens:
Dronabinol (Marinol)
LSD
Anabolic Steroids: Fluoxymesterone (Androxy), Methyltestosterone
MDA, STP, DMT, DET, mescaline, peyote, bufotenine, ibogaine, (Android, Testred, Methitest), Nandrolone decanoate (Deca-
psilocybin, phencyclidine (PCP; veterinary drug only) Durabolin) Non US, Nandrolone phenpropionate (Durabolin) Non
Marijuana US, Oxandrolone (Oxandrin), Oxymetholone (Androl-50), Stanozolol
Methaqualone (Winstrol), Testolactone (Teslac), Testosterone and its esters
SCHEDULE II SCHEDULE IV
(No telephone prescriptions, no refills.)2 (Prescription must be rewritten after 6 months or five refills; differs from
Opioids: Schedule III in penalties for illegal possession.)
Opium Opioids:
Opium alkaloids and derived phenanthrene alkaloids: codeine, Butorphanol (Stadol)
morphine (Avinza, Kadian, MSContin, Roxanol), hydrocodone and Difenoxin 1 mg + atropine 25 mcg (Motofen)
hydrocodone combinations (Zohydro ER, Hycodan, Vicodin,
Pentazocine (Talwin)
Lortab), hydromorphone (Dilaudid), oxymorphone (Exalgo),
Stimulants:
oxycodone (dihydroxycodeinone, a component of Oxycontin,
Armodafinil (Nuvigil)
Percodan, Percocet, Roxicodone, Tylox)
Diethylpropion (Tenuate) not in US
Designated synthetic drugs: meperidine (Demerol), methadone,
levorphanol (Levo-Dromoran), fentanyl (Duragesic, Actiq, Modafinil (Provigil)
Fentora), alfentanil (Alfenta), sufentanil (Sufenta), remifentanil Phentermine (Ionamin, Adipex-P)
(Ultiva), tapentadol (Nycynta) Depressants:
Stimulants: Benzodiazepines: Alprazolam (Xanax), Chlordiazepoxide (Librium),
Coca leaves and cocaine Clonazepam (Klonopin), Clorazepate (Tranxene), Diazepam
Amphetamines: Amphetamine complex (Biphetamine), (Valium), Estazolam (ProSom), Flurazepam (Dalmane), Halazepam
Amphetamine salts (Adderall), Dextroamphetamine (Dexedrine, (Paxipam), Lorazepam (Ativan), Midazolam (Versed), Oxazepam
Procentra), Lisdexamfetamine (Vyvanse), Methamphetamine (Serax), Prazepam (Centrax), Quazepam (Doral), Temazepam
(Desoxyn), Methylphenidate (Ritalin, Concerta, Methylin, (Restoril) Triazolam (Halcion)
Daytrana, Medadate), Above in mixtures with other controlled or Chloral hydrate (Somnote)
uncontrolled drugs Eszopiclone (Lunesta)
Cannabinoids: Lacosamide (Vimpat)
Nabilone (Cesamet) Meprobamate (Equanil, Miltown, etc)
Depressants:
Methobarbital (Mebaral)
Amobarbital (Amytal)
Methohexital (Brevital)
Pentobarbital (Nembutal)
Paraldehyde
Secobarbital (Seconal)
Phenobarbital
Zaleplon (Sonata)
SCHEDULE III
Zolpidem (Ambien)
(Prescription must be rewritten after 6 months or five refills.)
Opioids: SCHEDULE V
Buprenorphine (Buprenex, Subutex)
(As any other nonopioid prescription drug)
Mixture of above Buprenorphine and Naloxone (Suboxone)
Codeine: 200 mg/100 mL
The following opioids in combination with one or more active
Difenoxin preparations: 0.5 mg + 25 mcg atropine
non-opioid ingredients, provided the amount does not exceed that
shown: Dihydrocodeine preparations: 10 mg/100 mL
Codeine and dihydrocodeine: not to exceed 1800 mg/dL or 90 mg/ Diphenoxylate (not more than 2.5 mg and not less than 0.025 mg of
tablet or other dosage unit atropine per dosage unit, as in Lomotil)
Opium: 500 mg/dL or 25 mg/5 mL or other dosage unit (paregoric) Ethylmorphine preparations: 100 mg/100 mL
Stimulants: Opium preparations: 100 mg/100 mL
Benzphetamine (Didrex) Pregabalin (Lyrica)
Phendimetrazine (Bontril) Pyrovalerone (Centroton, Thymergix)
1See http://www.usdoj.gov/dea/pubs/scheduling.html for additional details.
2Emergency prescriptions may be telephoned if followed within 7 days by a valid written prescription annotated to indicate that it was previously placed by
telephone.
Katzung_insidecover.indd 1 25/10/14 5:06 PM
a LANGE medical book
Basic & Clinical
Pharmacology
G
Thirteenth Edition
R
V
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Edited by e
t
Bertram G. Katzung, MD, PhD
i
n
Professor Emeritus
Department of Cellular & Molecular PharmU acology
University of California, San Francisco

Associate Editor -

Anthony J. Trevor, 9PhD
9
Professor Emeritus
Department of Cellular r& Molecular Pharmacology
University of Californiia, San Francisco
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New York Chicago San Francisco Athens London Madrid
Mexico City Milan New Delhi Singapore Sydney Toronto
Katzung-FM_p001-012.indd 1 10/24/14 4:00 PM
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Contents
Preface vii
Authors ix
I 10. Adrenoceptor Antagonist Drugs
S E C T I O N
David robertson, MD, & italo Biaggioni, MD 152
Basic PrinciPles 1
III G
S E C T I O N
1. Introduction: The Nature of Drugs & Drug
CArDiovASCULARr-rENAL
Development & Regulation
DrUgS 169
Bertram G. Katzung, MD, PhD 1 V
11. Antihypertensive Agents
2. Drug Receptors & Pharmacodynamics d
neal l. Benowitz, MD 169
Mark von Zastrow, MD, PhD 20
e
3. Pharmacokinetics & Pharmacodynamics: 12. Vtasodilators & the Treatment
Rational Dosing & the Time Course iof Angina Pectoris
n
Bertram G. Katzung, MD, PhD 191
of Drug Action
nicholas H. G. Holford, MB, chB, FracP 41 U
13. Drugs Used in Heart Failure
4. Drug Biotransformation Bertram G. Katzung, MD, PhD 209
-
Maria almira correia, PhD 56
14. Agents Used in Cardiac Arrhythmias
9
Joseph r. Hume, PhD, & augustus O.
5. Pharmacogenomics
Grant, MD, PhD 224
Jennifer e. Hibma, PharmD, 9
& Kathleen M. Giacomini, PhD 74
r 15. Diuretic Agents
II hi ramin sam, MD, David Pearce, MD, &
S E C T I O N Harlan e. ives, MD, PhD 249
a
aUTOnOMic DrUGs 87
IV
t S E C T I O N
6. Introduction to Autonomic Pharmacology
DrUgS WiTH iMPorTANT ACTioNS
Bertram G. Katzung, MD, PhD 87
oN SMooTH MUSCLE 271
7. Cholinoceptor-Activating &
Cholinesterase-Inhibiting Drugs 16. Histamine, Serotonin, & the Ergot Alkaloids
achilles J. Pappano, PhD 105 Bertram G. Katzung, MD, PhD 271
8. Cholinoceptor-Blocking Drugs 17. Vasoactive Peptides
achilles J. Pappano, PhD 121 ian a. reid, PhD 294
9. Adrenoceptor Agonists & 18. The Eicosanoids: Prostaglandins,
Sympathomimetic Drugs Thromboxanes, Leukotrienes, & Related
italo Biaggioni, MD, & David robertson, MD 133 Compounds
emer M. smyth, PhD, & Garret a.
FitzGerald, MD 313
iii
Katzung-FM_p001-012.indd 3 10/24/14 4:00 PM
iivv CCooNNTTEENNTTSS
19. Nitric Oxide 32. Drugs of Abuse
samie r. Jaffrey, MD, PhD 329 christian lüscher, MD 552
20. Drugs Used in Asthma VI
S E C T I O N
Joshua M. Galanter, MD, & Homer a.
Boushey, MD 336
DrUgS USED To TrEAT DiSEASES oF
V THE BLooD, iNFLAMMATioN,
S E C T I O N
& goUT 567
DrUgS THAT ACT iN THE
33. Agents Used in Cytopenias; Hematopoietic
CENTrAL NErvoUS SYSTEM 355
Growth Factors
James l. Zehnder, MD 567
21. Introduction to the Pharmacology
of CNS Drugs
34. Drugs Used in Disorders of Coagulation
John a. Gray, MD, PhD, &
James l. Zehnder, MD 584
roger a. nicoll, MD 355
35. Agents Used in Dyslipidemia
22. Sedative-Hypnotic Drugs
Mary J. Malloy, MD, & John P. Kane, MD, PhD 602
anthony J. Trevor, PhD 369
36. Nonsteroidal Anti-Inflammatory Drugs,
23. The Alcohols
Disease-Modifying Antirheumatic Drugs,
susan B. Masters, PhD, &
Nonopioid Analgesics, & Drugs Used
anthony J. Trevor, PhD 384
in Gout
24. Antiseizure Drugs nabeel H. Borazan, MD, & Daniel e. Furst,
roger J. Porter, MD, & MD 618
Brian s. Meldrum, MB, PhD 396
VII
S E C T I O N
25. General Anesthetics
ENDoCriNE DrUgS 643
Helge eilers, MD, & spencer Yost, MD 421
26. Local Anesthetics 37. Hypothalamic & Pituitary Hormones
Kenneth Drasner, MD 440 roger K. long, MD, & Hakan cakmak, MD 643
27. Skeletal Muscle Relaxants 38. Thyroid & Antithyroid Drugs
Marieke Kruidering-Hall, PhD, & Betty J. Dong, PharmD, FasHP, FccP, & Francis s.
lundy campbell, MD 455 Greenspan, MD, FacP 663
28. Pharmacologic Management of Parkinsonism 39. Adrenocorticosteroids & Adrenocortical
& Other Movement Disorders Antagonists
Michael J. aminoff, MD, Dsc, FrcP 472 George P. chrousos, MD 680
29. Antipsychotic Agents & Lithium 40. The Gonadal Hormones & Inhibitors
charles DeBattista, MD 490 George P. chrousos, MD 696
30. Antidepressant Agents 41. Pancreatic Hormones & Antidiabetic Drugs
charles DeBattista, MD 510 Martha s. nolte Kennedy, MD,
& Umesh Masharani, MBBs, MrcP (UK) 723
31. Opioid Agonists & Antagonists
42. Agents That Affect Bone Mineral Homeostasis
Mark a. schumacher, PhD, MD, allan i.
Basbaum, PhD, & ramana K. naidu, MD 531 Daniel D. Bikle, MD, PhD 747
Katzung-FM_p001-012.indd 4 10/24/14 4:00 PM
CCooNNTTEENNTTSS vv
VIII 54. Cancer Chemotherapy
S E C T I O N
edward chu, MD, & alan c. sartorelli, PhD 918
CHEMoTHErAPEUTiC DrUgS 767
55. Immunopharmacology
43. Beta-Lactam & Other Cell Wall- & Douglas F. lake, PhD, &
Membrane-Active Antibiotics adrienne D. Briggs, MD 946
Daniel H. Deck, PharmD, &
IX
lisa G. Winston, MD 769 S E C T I O N
ToXiCoLogY 971
44. Tetracyclines, Macrolides, Clindamycin,
Chloramphenicol, Streptogramins,
56. Introduction to Toxicology: Occupational
& Oxazolidinones
& Environmental G
Daniel H. Deck, PharmD, &
Daniel T. Teitelbaum, MD 971
lisa G. Winston, MD 788
R
57. Heavy Metal Intoxication & Chelators
45. Aminoglycosides & Spectinomycin
Daniel H. Deck, PharmD, & Michael J. KosneVtt, MD, MPH 987
lisa G. Winston, MD 799
58. Managemdent of the Poisoned Patient
46. Sulfonamides, Trimethoprim, Kent r. Olson, MD 1001
e
& Quinolones
t X
Daniel H. Deck, PharmD, & S EiC T I O N
lisa G. Winston, MD 807 n
SPECiAL ToPiCS 1013
47. Antimycobacterial Drugs U
59. Special Aspects of Perinatal &
Daniel H. Deck, PharmD, &
lisa G. Winston, MD 815 Pediatric Pharmacology
-
Gideon Koren, MD 1013

48. Antifungal Agents
9
Don sheppard, MD, & 60. Special Aspects of Geriatric Pharmacology
Harry W. lampiris, MD 825 9 Bertram G. Katzung, MD, PhD 1024
r
49. Antiviral Agents 61. Dermatologic Pharmacology
i
sharon safrin, MD 835 h Dirk B. robertson, MD &
Howard i. Maibach, MD 1033
a
50. Miscellaneous Antimicrobial Agents;
Disinfectants, Atntiseptics, & Sterilants 62. Drugs Used in the Treatment of
Daniel H. Deck, PharmD, & Gastrointestinal Diseases
lisa G. Winston, MD 865 Kenneth r. McQuaid, MD 1052
51. Clinical Use of Antimicrobial Agents 63. Therapeutic & Toxic Potential of
Harry W. lampiris, MD, & Daniel s. Maddix, Over-the-Counter Agents
PharmD 873 robin l. corelli, PharmD 1084
52. Antiprotozoal Drugs 64. Dietary Supplements & Herbal Medications
Philip J. rosenthal, MD 886 cathi e. Dennehy, PharmD, &
candy Tsourounis, PharmD 1094
53. Clinical Pharmacology of the
Antihelminthic Drugs
Philip J. rosenthal, MD 908
Katzung-FM_p001-012.indd 5 10/24/14 4:00 PM
vi CoNTENTS
65. Rational Prescribing & Prescription Writing Appendix: Vaccines, Immune Globulins,
Paul W. lofholm, PharmD, & & Other Complex Biologic Products
Bertram G. Katzung, MD, PhD 1108 Harry W. lampiris, MD, &
Daniel s. Maddix, PharmD 1133
66. Important Drug Interactions &
Their Mechanisms
index 1141
John r. Horn, PharmD, FccP 1118
Katzung-FM_p001-012.indd 6 10/24/14 4:00 PM
Preface
The thirteenth edition of Basic & Clinical Pharmacology continues development and regulation material previously covered in
the important changes inaugurated in the eleventh edition, with Chapter 5 has been incorporated into Chapter 1.
extensive use of full-color illustrations and expanded coverage of • A generic name–trade name table appears at the conclusion of 
transporters, pharmacogenomics, and new drugs. Case studies most chapters, providing a rapid reference for these names.
accompany most chapters and answers to questions posed in the • Many revised illustrations in full Gcolor provide significantly 
case studies appear at the end of each chapter. As in prior editions, more information about drug mechanisms and effects and help
to clarify important concepts.
the book is designed to provide a comprehensive, authoritative,
R
• Major revisions of the chapters on sympathomimetic, diuretic, 
and readable pharmacology textbook for students in the health
antipsychotic, antidepressant, antidiabetic, anti-inflammatory,
sciences. Frequent revision is necessary to keep pace with the rapid
and antiviral drugs, pVrostaglandins, nitric oxide, hypothalamic
changes in pharmacology and therapeutics; the 2–3 year revision
and pituitary hormones, central nervous system neurotrans-
cycle of the printed text is among the shortest in the field and the
mitters, immundopharmacology, and toxicology.
availability of an online version provides even greater currency.
• Continued expansion of the coverage of general concepts relat-
The book also offers special features that make it a useful reference ing to neewly discovered receptors, receptor mechanisms, and
for house officers and practicing clinicians. drug transporters.
Information is organized according to the sequence used in • Desctriptions  of  important  new  drugs  released  through 
i
many pharmacology courses and in integrated curricula: basic prin- nAugust 2014.
ciples; autonomic drugs; cardiovascular-renal drugs; drugs with
An important related educational resource is Katzung & Trevor’s
important actions on smooth muscle; central nervous system drugs; U
Pharmacology: Examination & Board Review, tenth edition (Trevor
drugs used to treat inflammation, gout, and diseases of the blood;
AJ, Katzung BG, & Masters SB: McGraw-Hill, 2013). This book
endocrine drugs; chemotherapeutic drugs; toxicology; and sp ecial
provides a succinct review of pharmacology with approximately
topics. This sequence builds new information on a founda-tion of
one thousand sample examination questions and answers. It is
information already assimilated. For example, early pres entation of
9 especially helpful to students preparing for board-type examina-
autonomic nervous system pharmacology allows students to inte-
tions. A more highly condensed source of information suitable for
grate the physiology and neuroscience they have learned elsewhere
9 review purposes is USMLE Road Map: Pharmacology, second
with the pharmacology they are learning and prepares them to
edition (Katzung BG, Trevor AJ: McGraw-Hill, 2006).
understand the autonomic effects of other rdrugs. This is especially
This edition marks the 32th year of publication of Basic &
important for the cardiovascular and cientral nervous system drug
h Clinical Pharmacology. The widespread adoption of the first twelve
groups. However, chapters can be used equally well in courses and
editions indicates that this book fills an important need. We
curricula that present these topics in a different sequence.
a
believe that the thirteenth edition will satisfy this need even more
Within each chapter, emphasis is placed on discussion of drug
groups and prototypes rathter than offering repetitive detail about successfully. Spanish, Portuguese, Italian, French, Indonesian,
individual drugs. Selection of the subject matter and the order of Japanese, Korean, Turkish, and Ukrainian translations are avail-
its presentation are based on the accumulated experience of teach- able. Translations into other languages are under way; the pub-
ing this material to thousands of medical, pharmacy, dental, lisher may be contacted for further information.
podiatry, nursing, and other health science students. I wish to acknowledge the prior and continuing efforts of my
Major features that make this book particularly useful in inte- contributing authors and the major contributions of the staff at
grated curricula include sections that specifically address the clini- Lange Medical Publications, Appleton & Lange, and McGraw-Hill,
cal choice and use of drugs in patients and the monitoring of their and of our editors for this edition, Donna Frassetto and Rachel
effects—in other words, clinical pharmacology is an integral part of D’Annucci Henriquez. I also wish to thank Alice Camp and
this text. Lists of the trade and generic names of commercial Katharine Katzung for their expert proofreading contributions.
preparations available are provided at the end of each chapter for Suggestions and comments about Basic & Clinical Pharmacology
easy reference by the house officer or practitioner writing a chart are always welcome. They may be sent to me in care of the publisher.
order or prescription.
Bertram G. Katzung, MD, PhD
San Francisco
Significant revisions in this edition include:
December, 2011
• Addition of a chapter on pharmacogenomics, an area of 
increasing importance in all aspects of pharmacology. The drug
vii
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