Drug interactions • I. Pharmaceutical interactions (incompatibilities) • II. Pharmacological interactions • [A] Pharmacokinetic drug interactions: • Absorption: • Change in GI pH: Raising gastric pH by cimetidine can markedly reduce the absorption of ketoconazole. • Adsorption: Activated charcoal/many drugs. This is beneficial in management of toxicity.of overdosage. • Chelation: Metalic ions (Ca++, Al+++) found in dairy products and antacids and iron form complex with tetracyclins that is poorly absorbed. • Ddistribution: • Alteration of plasma protein binding • Phenylbutazone and aspirin displace warfarin → bleeding tendency • Sulphonamides displace bilirubin → Kernicterus in newborn • Phenylbutazone displace tolbutamide → risk of hypoglycemia • Metabolism: • Enzyme induction: • Phenobarbitone induces metabolism of almost all drug metabolism by CYP450 as well as its own metabolism (auto-induction). • Enzyme inhibition • Cimetidine inhibits metabolism of carbamazepine, leading to elevation of its blood level. • Grapefruit juice inhibits metabolism of CCBs. Thus, the juice increases the bioavailability Excretion: Probenecid inhibits active renal tubular secretion of many acidic drugs e.g. penicillin, leading to prolongation of its duration