Principles of Drug Interactions Drugdrug interactions represent a

Principles of Drug Interactions Drug-drug interactions represent a difficult dilemma for the clinician. On the one hand, there is evidence that drug interactions may lead to adverse outcomes in patients. It is also clear, however, that most patients receiving potentially interacting drugs do not show adverse consequences. One must be alert for those situations in which the patient is truly at risk, without over-reacting every time a patient receives a potentially interacting combination of drugs. Although it is impossible to remember all drug interactions, knowledge of the interactive properties of drugs can help one predict many drug interactions before they occur. 1

Absorption ¡ The GI absorption of drugs may be inhibited by: ¡ ¡ Drugs with large surface areas such as antacids Binding resins such as cholestyramine (Questran) Drugs which affect GI motility Drugs that alter GI p. H 2

Distribution ¡ Drugs may compete with each other for binding sites of plasma proteins or tissues. When this happens, the unbound or free serum concentration of one drug may increase. The free portion is the active portion so this may increase response. 3

Metabolism Drugs which are enzyme-inducers, reduce the other drug e. g. carbamazepine, phenytoin, rifampin ¡ Drugs which are enzyme-inhibitors, INCREASE levels of the other drug e. g. INH, ketoconazole, erythromycin ¡ 4

Renal Excretion ¡ Most renal excretion drug interactions involve reduced excretion of one by another, leading to increased levels and possible toxicity. 5

Assessment of Risk in Specific Patients ¡ There is a common misconception that once one is aware that a patient is receiving a potentially interacting drug combination, one only needs to take the appropriate precautions that will prevent the adverse effects of the interaction. Thus, avoiding adverse drug interactions often is perceived as a two step process: ¡ ¡ Identify those patients who are receiving potentially interacting drugs Take steps to prevent any adverse effects 6

¡ Although this two-step method may sound reasonable, it omits a critical step in the process of minimizing the adverse effect of a drug interaction. This missing step involves identifying those patients who are actually at significant risk and who would benefit from preventative measures. Failure to assess risk before taking action often results in the institution of unnecessary precautions that may not be in the best interest of patient. 7

¡ These unnecessary precautions may produce the following undesirable results: Discontinuation of one or more drugs that are important in the patient’s treatment ¡ An unnecessary increase or decrease in a drug dose resulting in an excessive or inadequate response to that drug. ¡ The inconvenience and expense of more frequent medical visits to monitor the potential interaction. ¡ The added expense of performing unnecessary drug serum concentration determinations and/or other clinical laboratory tests. ¡ 8

Decision Support Systems for Drug Interactions ¡ Such systems only support the decision-making process. The judgment of the clinician is still the most important factor minimizing the occurrence of adverse drug interactions. 9