Mechanism-based (suicide) inhibition of CYP enzymes is clinically important because it differs from competitive inhibition in that:

• A It requires higher plasma concentrations to achieve the same degree of inhibition, making dose-dependent interactions more predictable
• B It is reversible at therapeutic doses but irreversible at toxic concentrations, explaining why toxic overdoses cause prolonged drug interactions
• C The inhibited enzyme degrades the inhibitor drug, establishing an auto-limiting feedback mechanism
• D The drug is metabolized by the CYP enzyme to a reactive intermediate that irreversibly inactivates the enzyme's active site, so inhibition persists long after the drug is eliminated and requires new enzyme synthesis to recover ✓

Explanation

Mechanism-based inhibitors (also called 'suicide substrates' or 'time-dependent inhibitors') are drugs that act as substrates for a CYP enzyme. Upon oxidation by the enzyme, they generate reactive metabolites (reactive nitroso intermediates, epoxides, carbene complexes, or covalent adducts) that irreversibly bind and destroy the enzyme's active site heme or apoprotein. Recovery requires synthesis of new CYP enzyme (days to weeks). Clinical examples: erythromycin (CYP3A4), diltiazem (CYP3A4), verapamil (CYP3A4), fluoxetine (CYP2D6 — 4-week washout for MAOI switching), isoniazid (CYP2E1), ritonavir (strongest CYP3A4 mechanism-based inhibitor used as 'pharmacokinetic booster'). Drug interactions from these persist beyond clearance of the inhibitor drug.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.