Cytochrome P450 Inhibitors and Inducers

Inhibitors increase drug levels (toxicity risk). Inducers decrease drug levels (therapeutic failure). CYP3A4 is most important.

Detailed Explanation

CYP450 Enzymes:

Main site: Liver (also intestine)

CYP3A4 metabolizes ~50% of drugs

CYP2D6, 2C9, 2C19 also important

CYP450 INHIBITORS (↑ drug levels):

"Inhibitors INCREASE substrate levels"

Common inhibitors (think: "SICKFACES.COM"):

Sodium valproate

Isoniazid

Cimetidine

Ketoconazole

Fluconazole

Acute alcohol

Ciprofloxacin

Erythromycin/Clarithromycin

Sulfonamides

Chloramphenicol

Omeprazole

Metronidazole

Grapefruit juice

Ritonavir

CYP450 INDUCERS (↓ drug levels):

"Inducers make more enzyme = drugs metabolized FASTER"

Common inducers (think: "GPS CRAP"):

Griseofulvin

Phenytoin

St. John's Wort

Carbamazepine

Rifampin (most potent!)

Chronic Alcohol

Phenobarbital

Clinical Correlation

Starting rifampin in a patient on warfarin will decrease warfarin levels → risk of clotting. Clarithromycin with statins increases statin levels → rhabdomyolysis risk.

Memory Trick

"Rifampin RAMPS up P450 (inducer). Ritonavir ROBS drug metabolism (inhibitor)."