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Section 4. Antimicrobial Agents and Related Therapy
DRUG INTERACTIONS
The use of multiple drugs for therapy of seriously ill patients ensures that drug-drug interactions are inevitable. Drug-drug interactions (see Table 4.1, p 743) can be considered as producing either changes in drug concentrations (pharmacokinetics) or changes in the drug effect/toxicity profile (pharmacodynamics). Pharmacokinetics refers to the ways the body manipulates a drug, including absorption, distribution, metabolism, and excretion. Pharmacokinetic interactions result from alterations in the absorption, distribution, metabolism, or elimination of a drug and thereby result in a change in concentration in the body. Pharmacodynamics refers to the biochemical and physiologic effects of the drug and its mechanism of action. Pharmacodynamic drug-drug interactions act on target tissues and fluids and may produce synergistic, additive, or antagonistic drug effects or toxicities. Many of the serious adverse interactions between drugs are attributable to moderate or potent inhibition (clarithromycin, ciprofloxacin, erythromycin, fluconazole, itraconazole, ketoconazole, norfloxacin, telithromycin, and voriconazole) or induction (rifabutin, rifampin) of cytochrome P450 (CYP), especially CYP3A, which is thought to be involved in metabolism of
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