TAILIEUCHUNG - Chapter 005. Principles of Clinical Pharmacology (Part 13)

Epidemiology Patients receive, on average, 10 different drugs during each hospitalization. The sicker the patient, the more drugs are given, and there is a corresponding increase in the likelihood of adverse drug reactions. When 15 drugs are given, the probability is 40%. Retrospective analyses of ambulatory patients have revealed adverse drug effects in 20%. Serious adverse reactions are also well recognized with "herbal" remedies and OTC compounds: examples include kava-associated hepatotoxicity, L-tryptophan-associated eosinophilia-myalgia, and phenylpropanolamine-associated stroke, each of which has caused fatalities. . | Chapter 005. Principles of Clinical Pharmacology Part 13 Epidemiology Patients receive on average 10 different drugs during each hospitalization. The sicker the patient the more drugs are given and there is a corresponding increase in the likelihood of adverse drug reactions. When 6 different drugs are given to hospitalized patients the probability of an adverse reaction is 5 but if 15 drugs are given the probability is 40 . Retrospective analyses of ambulatory patients have revealed adverse drug effects in 20 . Serious adverse reactions are also well recognized with herbal remedies and OTC compounds examples include kava-associated hepatotoxicity L-tryptophan-associated eosinophilia-myalgia and phenylpropanolamine-associated stroke each of which has caused fatalities. A small group of widely used drugs accounts for a disproportionate number of reactions. Aspirin and other NSAIDs analgesics digoxin anticoagulants diuretics antimicrobials glucocorticoids antineoplastics and hypoglycemic agents account for 90 of reactions although the drugs involved differ between ambulatory and hospitalized patients. Toxicity Unrelated to a Drug s Primary Pharmacologic Activity Cytotoxic Reactions Drugs or more commonly reactive metabolites generated by CYPs can covalently bind to tissue macromolecules such as proteins or DNA to cause tissue toxicity. Because of the reactive nature of these metabolites covalent binding often occurs close to the site of production typically the liver. The most common cause of drug-induced hepatotoxicity is acetaminophen overdosage. Normally reactive metabolites are detoxified by combining with hepatic glutathione. When glutathione becomes exhausted the metabolites bind instead to hepatic protein with resultant hepatocyte damage. The hepatic necrosis produced by the ingestion of acetaminophen can be prevented or attenuated by the administration of substances such as N-acetylcysteine that reduce the binding of electrophilic metabolites to hepatic .

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