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Lecture 20

Lecture 20 Enzyme Inhibition, Matching Substrates to Enzymes

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Department
Pharmacology
Course
PCL201H1
Professor
Worlsey
Semester
Winter

Description
Lecture 20 Enzyme Inhibition Matching Substrates to EnzymesPulling drugeconomic loss to pharma risk for patients toxicity loss of developmental costs lawsuitsCASE Seldane nonsedating antihistamine Dangerous heart rhythm abnormalities when taken with erythromycin or ketoconazoleMany patients take multiple drugs at one timeTerfenadine Seldane prodrugCYP3A4Fexofenadine Allegra active metaboliteAntihistamine benefitsErythromycin or ketoconazole inhibits CYP3A4 leading to buildup accumulation of parent compound leads to Long QT interval possible deathCYP3A4 metabolizes wide range of drugsSubstrates dont necessarily have similar structureDrugs affect the pharmacokinetics of each otherMany overthecounter medications have agents that inhibit the metabolism of other drugsEg Cimetidine Gaviscon inhibits metabolism of other drugs by inhibiting CYP3A4Metabolic bottleneck too many compounds compete for same enzyme Limited active sites competitive inhibitionGrapefruit agent inhibits metabolism of other drugs via CYP3A4Knowing which enzymes metabolize a pa
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