Cytochrome P450 Enzyme Inhibitors

Classic mnemonic for major CYP450 enzyme inhibitors that elevate substrate drug levels and cause toxicities.

Inhibition of hepatic cytochrome P450 isoenzymes (CYP3A4, CYP2D6, CYP2C9) decreases clearance of co-administered drugs, sharply increasing their plasma concentrations and risk of adverse events.

Systematic Breakdown

Sodium Valproate

Inhibits CYP2C9 and epoxide hydrolase, elevating lamotrigine and carbamazepine levels.

Isoniazid (INH)

Inhibits CYP2E1 and CYP2C19, interacting significantly with phenytoin and carbamazepine.

Cimetidine

Potent non-specific inhibitor of multiple CYP isoforms (CYP1A2, 2C9, 2D6, 3A4); antiandrogenic side effects.

Ketoconazole (& other Azoles)

Fluconazole, Itraconazole, Voriconazole are potent inhibitors of CYP3A4 and CYP2C9.

Fluoxetine

Potent CYP2D6 inhibitor, blocking metabolism of codeine, tamoxifen, and beta-blockers.

Alcohol (Acute Intoxication)

Acute heavy binge drinking saturates and competitively inhibits CYP2E1.

Chloramphenicol

Inhibits hepatic microsomes; historically linked to gray baby syndrome.

Erythromycin (& Clarithromycin)

Macrolides (excluding azithromycin) strongly inhibit CYP3A4, dangerously elevating statin and theophylline levels.

Sulfonamides (Bactrim)

Inhibits CYP2C9, causing dangerous rises in Warfarin INR and sulfonylurea hypoglycemia.

Ciprofloxacin

Inhibits CYP1A2, leading to theophylline toxicity.

Omeprazole

Inhibits CYP2C19, reducing activation of the clopidogrel prodrug.

Metronidazole

Inhibits CYP2C9 (disulfiram-like reaction with ethanol, increases warfarin effect).

High-Yield Clinical Pearls & Exam Tips

Grapefruit Juice is another legendary CYP3A4 intestinal inhibitor that sharply boosts oral bioavailability of statins, CCBs, and immunosuppressants.
Inhibitors cause RAPID elevation of drug levels (within 24-48 hours), whereas enzyme inducers take 1-2 weeks to build new protein enzymes.

Related Pharmaceuticals

Cimetidine Ketoconazole Clarithromycin Fluconazole Ciprofloxacin

Related Clinical Conditions

Warfarin Overdose Statin-Induced Rhabdomyolysis Theophylline Toxicity

Authoritative Sources: Katzung Basic & Clinical Pharmacology 15e · FDA Drug Development and Drug Interactions