Drug interactions: keeping it straight

Drug interactions are common causes of treatment failure and adverse reactions. Patients who have a number of chronic disorders, patients who take many medications or patients who have impaired renal function are at increased risk for these problems. Special attention must be given to drugs that require blood level monitoring, because these agents have a narrow margin of safety. Drug interactions are especially likely to occur with enzyme inhibitors such as erythromycin, cimetidine, ciprofloxacin and metronidazole. Mechanisms of drug interactions include problems with absorption secondary to binding by antacids or other cations, interference with the distribution of drugs secondary to the displacement of highly protein-bound drugs, differences in metabolism secondary to variability of the cytochrome P450 enzyme system, and interaction-related problems with drug excretion by renal tubules. Antagonistic and synergistic reactions also need to be considered. Finally, the time course in which a given drug interaction is likely to occur must be taken into account when deciding whether the interaction is responsible for an adverse effect or treatment failure.