Core24: Enzyme inhibitors

⬇️ High-yield / 要点：Enzyme inhibition decreases CYP activity → slower metabolism → co-administered drug levels rise → toxicity risk.

Definition / 定義

• Enzyme inhibition = reduced cytochrome P450 enzyme activity.
• Often occurs by competitive inhibition at CYP enzymes, including binding to P450 heme iron.
• Result:
  • Reduced metabolism of endogenous substrates or co-administered drugs.
  • Higher plasma concentrations.
  • Increased side effects/toxicity.

Important CYP inhibitors / 重要な阻害薬

CYP	Inhibitors
CYP1A2	Cimetidine, fluoroquinolones, grapefruit juice, macrolides, isoniazid, zileuton
CYP2C9	Amiodarone, chloramphenicol, cimetidine, isoniazid, metronidazole, SSRIs, zafirlukast
CYP2C19	Fluconazole, omeprazole, SSRIs
CYP2D6	Amiodarone, cimetidine, quinidine, SSRIs, bupropion
CYP3A4	Amiodarone, cimetidine, azole antifungals, clarithromycin, cyclosporine, verapamil/diltiazem, grapefruit juice, metronidazole, tacrolimus, fluoroquinolones, ritonavir, cobicistat

High-yield examples / 重要例

• Clarithromycin + colchicine
  • Clarithromycin inhibits CYP3A4.
  • Colchicine is a CYP3A4 substrate.
  • Result: serum colchicine increases → severe toxicity risk.
  • Avoid coadministration.
• Statin + clarithromycin
  • Many statins are CYP3A4 substrates.
  • Clarithromycin inhibits CYP3A4.
  • Result: statin-induced myopathy risk.

Remember / 覚え方

• Inhibitor = enzyme down
• Enzyme down = drug level up
• Toxicity risk is highest when the substrate has a narrow therapeutic index.
• Classic CYP3A4 inhibitors: clarithromycin, azoles, grapefruit, ritonavir/cobicistat, verapamil/diltiazem