Enzyme Induction and Inhibition: Mechanisms, Examples & Clinical Significance

This presentation explains the crucial role of enzyme induction and inhibition in drug metabolism. It covers:
✔️ Mechanisms of enzyme regulation in the liver
✔️ Examples of enzyme inducers (Rifampin, Carbamazepine) and inhibitors (Ketoconazole, Grapefruit juice)
✔️ Clinical significance of drug interactions affecting efficacy and toxicity
✔️ Factors like genetics, age, diet, and disease influencing enzyme activity

Ideal for pharmacy, pharmacology, and medical students, this presentation helps in understanding drug metabolism and dosage adjustments for safe medication use.

1. Enzyme Induction and Enzyme Inhibition Understanding Their Role in Drug Metabolism

2. Introduction to Enzyme Regulation • Enzymes regulate drug metabolism, primarily in the liver. • Two key processes: - Enzyme Induction: Increases enzyme activity → Faster drug metabolism. - Enzyme Inhibition: Decreases enzyme activity → Slower drug metabolism.

3. Enzyme Induction – Definition & Mechanism • Definition: Increased synthesis of metabolic enzymes → Faster drug metabolism. • Mechanism: 1. Drug binds to nuclear receptors (PXR, CAR, AhR). 2. Activates gene transcription for CYP enzymes. 3. Increases enzyme synthesis → Faster clearance of drugs.

4. Examples of Enzyme Inducers • Rifampin → Reduces effectiveness of warfarin, oral contraceptives. • Carbamazepine → Increases metabolism of theophylline, phenytoin. • Phenobarbital → Affects steroids, antidepressants. • St. John’s Wort → Reduces cyclosporine, digoxin levels.

5. Examples of Enzyme Inducers Enzyme Inducer Affected Drugs Rifampin Warfarin , Oral contraceptives Carbamazepine Theophylline , Phenytoin Phenobarbital Steroids, Antidepressants St. John’s Wort Cyclosporine, Digoxin Clinical Impact : Leads to reduced drug effectiveness due to faster clearance . May require higher doses of the affected drug.

6. Enzyme Inhibition – Definition & Mechanism • Definition: Decreased enzyme activity → Slower drug metabolism. • Mechanism: 1. Drug binds to enzyme's active site → Competitive inhibition. 2. Non-competitive inhibition → Irreversible enzyme inactivation. 3. Leads to drug accumulation → Increased toxicity risk.

7. Examples of Enzyme Inhibitors • Ketoconazole → Inhibits warfarin, statins metabolism. • Erythromycin → Increases levels of theophylline, carbamazepine. • Cimetidine → Slows down metabolism of diazepam, metoprolol. • Grapefruit juice → Inhibits CYP3A4, affecting calcium channel blockers, statins.

8. Enzyme Inhibitor Affected Drugs Ketoconazole Warfarin , Statins Erythromycin Theophylline , Carbamazepine Cimetidine Diazepam, Metoprolol Grapefruit Juice Calcium channel blockers, Statins

9. Clinical Significance of Enzyme Induction & Inhibition • Enzyme induction can cause treatment failure (e.g., Rifampin reduces contraceptive efficacy). • Enzyme inhibition can cause toxicity (e.g., Ketoconazole increases warfarin toxicity). • Critical in drug-drug interactions (e.g., Antidepressants & CYP inhibitors).

10. Factors Affecting Enzyme Activity • Genetics: CYP450 polymorphisms affect drug metabolism rates. • Age & Sex: Neonates and elderly have lower enzyme activity. • Diet: Grapefruit juice inhibits CYP3A4, affecting drug metabolism. • Diseases: Liver diseases slow down enzyme function, leading to drug accumulation.

11. Summary & Conclusion • Enzyme induction accelerates drug metabolism → Reduced drug effectiveness. • Enzyme inhibition slows metabolism → Increased risk of drug toxicity. • Understanding these mechanisms helps in proper dose adjustments and avoiding drug interactions.

12. References • Goodman & Gilman’s Pharmacological Basis of Therapeutics. • Rang & Dale’s Pharmacology. • Research articles on enzyme induction & inhibition.

13. Thank you