A drug interaction has occurred when the administration of one drug alters the clinical effects of another. The result may be an increase or decrease in either the beneficial or harmful effects of the second agent. Although the number of potential interacting drug combinations is very large only a small number are relevant in clinical practice.
Harmful drug interactions are most likely to occur when the affected drug has a:
- Low therapeutic index meaning that only a small increase in plasma concentration may cause toxic effects
- Steep dose-response curve meaning that a small change in plasma concentration leads to a significant increase in pharmacodynamic effect (where a small increase in dose results in a large increase in plasma level)
- High first-pass metabolism because these are drugs that are extensively metabolised in the liver or gastrointestinal tract and are therefore sensitive to the effects of metabolic inhibition or induction
- Single mechanism of elimination (e.g. renal clearance, cytochrome metabolism) meaning that the interacting drug can cause a significant increase in plasma concentration.