PCL201H1 Lecture 20: Lecture 20 Enzyme Inhibition, Matching Substrates to Enzymes
Document Summary
Lecture 20 enzyme inhibition, matching substrates to enzymes. Pulling drug economic loss to pharma, risk for patients (toxicity), loss of developmental costs, lawsuits. Dangerous heart rhythm abnormalities when taken with erythromycin or ketoconazole. Many patients take multiple drugs at one time. Terfenadine (seldane, pro-drug) + cyp3a4 fexofenadine (allegra, active metabolite) Erythromycin or ketoconazole inhibits cyp3a4, leading to buildup, accumulation of parent compound, leads to long q-t interval, possible death. Many over-the-counter medications have agents that inhibit the metabolism of other drugs. Cimetidine (gaviscon) inhibits metabolism of other drugs by inhibiting cyp3a4. Metabolic bottleneck : too many compounds compete for same enzyme. Grapefruit: agent inhibits metabolism of other drugs via cyp3a4. Knowing which enzymes metabolize a particular drug is important for: basic scientists mechanism of metabolism, pharma drug development, regulatory agencies that license drug physicians, patients who wish to avoid drug-drug interactions. There are a wide variety of technologies that predict which enzymes are involved with the metabolism of drugs.
