Page 33 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 1 Introduction: The Nature of Drugs & Drug Development & Regulation 19

The New England Journal of Medicine, which publishes much origi- Boutron I et al: Reporting and interpretation of randomized controlled trials
nal drug-related clinical research as well as frequent reviews of top- with statistically nonsignificant results for primary outcomes. JAMA
2010;303:2058.
ics in pharmacology; The Medical Letter on Drugs and Therapeutics, Brown WA: The placebo effect. Sci Am 1998;1:91.
which publishes brief critical reviews of new and old therapies; and Cochrane Collaboration website. www.thecochranelibrary.com.
Prescriber’s Letter, a monthly comparison of new and older drug Downing NS et al: Regulatory review of novel therapeutics—Comparison of three
therapies with much useful advice. On the Internet/World Wide regulatory agencies. N Engl J Med 2012;366:2284.
Web, two sources can be particularly recommended: the Cochrane Drug Interactions: Analysis and Management (quarterly). Wolters Kluwer Publications.
Collaboration and the FDA site (see reference list below). Emanuel EJ, Menikoff J: Reforming the regulations governing research with
Other sources of information pertinent to the United States human subjects. N Engl J Med 2011;365:1145.
should be mentioned as well. The “package insert” is a summary FDA accelerated approval website. http://www.fda.gov/forpatients/approvals/fast/
ucm20041766.htm.
of information that the manufacturer is required to place in the FDA website. http://www.fda.gov.
prescription sales package; Physicians’ Desk Reference (PDR) is Gilchrist A: 10 best-selling brand-name drugs in 2015. http://www.pharmacy-
a compendium of package inserts published annually with supple- times.com/news/10-best-selling-brand-name-drugs-in-2015/.
ments twice a year. It is sold in bookstores and distributed to licensed Goldacre B: Bad Pharma. Faber & Faber, 2012.
physicians. The package insert consists of a brief description of Hennekens CMH, DeMets D: Statistical association and causation. Contributions
of different types of evidence. JAMA 2011;305:1134.
the pharmacology of the product. This brochure contains much Huang S-M, Temple R: Is this the drug or dose for you? Impact and consideration
practical information, but also lists every toxic effect ever reported, of ethnic factors in global drug development, regulatory review, and clinical
no matter how rare, thus shifting responsibility for adverse drug practice. Clin Pharmacol Ther 2008;84:287.
reactions from the manufacturer to the prescriber. Micromedex Kesselheim AS et al: Whistle-blowers experiences in fraud litigation against
pharmaceutical companies. N Engl J Med 2010;362:1832.
and Lexi-Comp are extensive subscription websites. They provide Koslowski S et al: Developing the nation’s biosimilar program. N Engl J Med
downloads for personal digital assistant devices, online drug dos- 2011;365:385.
age and interaction information, and toxicologic information. A Landry Y, Gies J-P: Drugs and their molecular targets: An updated overview. Fund
useful and objective quarterly handbook that presents information & Clin Pharmacol 2008;22:1.
on drug toxicity and interactions is Drug Interactions: Analysis and The Medical Letter on Drugs and Therapeutics. The Medical Letter, Inc.
Management. Finally, the FDA maintains an Internet website that Ng R: Drugs from Discovery to Approval. Wiley-Blackwell, 2008.
carries news regarding recent drug approvals, withdrawals, warn- Pharmaceutical Research and Manufacturers of America website. http://www.
phrma.org.
ings, etc. It can be accessed at http://www.fda.gov. The MedWatch Pharmacology: Examination & Board Review, 11th ed. McGraw-Hill Education, 2015.
drug safety program is a free e-mail notification service that pro- Prescriber’s Letter. Stockton, California: prescribersletter.com.
vides news of FDA drug warnings and withdrawals. Subscriptions Rockey SJ, Collins FS: Managing financial conflict of interest in biomedical
may be obtained at https://service.govdelivery.com/service/user. research. JAMA 2010;303:2400.
html?code=USFDA. Scheindlin S: Demystifying the new drug application. Mol Interventions
2004;4:188.
Sistare FD, DeGeorge JJ: Preclinical predictors of clinical safety: Opportunities for
REFERENCES improvement. Clin Pharmacol Ther 2007;82(2):210.
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Avorn J: Debate about funding comparative effectiveness research. N Engl J Med Top 200 Drugs of 2014. http://www.pharmacytimes.com/publications/issue/2015/
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C ASE STUD Y ANSWER

Aspirin overdose commonly causes a mixed respiratory is an important component of the management of aspirin
alkalosis and metabolic acidosis. Because aspirin is a weak overdose. It causes alkalosis, reducing entry into tissues, and
acid, serum acidosis favors entry of the drug into tissues increases the pH of the urine, enhancing renal clearance of
(increasing toxicity), and urinary acidosis favors reabsorp- the drug. See the discussion of the ionization of weak acids
tion of excreted drug back into the blood (prolonging the and weak bases in the text.
effects of the overdose). Sodium bicarbonate, a weak base,