🔑 Key Learning

  • The cytochrome P450 (CYP450) enzyme system is responsible for the metabolism of over 75% of drugs
  • CYP450 Inducers increase enzyme activity → faster drug metabolism → reduced drug effect
    • PCBRASS
  • CYP450 Inhibitors decrease enzyme activity → slower metabolism → increased drug effect
    • OAAKDEVICES
  • Important interactions include effects on warfarin, antiepileptics, and immunosuppressants. Common exam questions which suggest an interaction since commencing a new medication (e.g. warfarin out of range, AEDs no longer effective, pregnant despite oral contraception etc.)

⚙️ Cytochrome P450 Inducers

🔥 PCBRASS mnemonic:

  • Phenytoin
  • Carbamazepine
  • Barbiturates
  • Rifampicin
  • Alcohol (chronic use)
  • Sulfonylureas
  • Smoking
  • St John’s Wort

📈 Effect

  • ↑ Enzyme activity  →  increases metabolism  →  ↓ Drug concentration/effect 

📝 Clinical Example

  • Background of metallic heart valve on warfarin. Commenced on rifampicin for TB.
    • Result:  ↓ INR / subtherapeutic anticoagulation 
  • Patients on inducers may need higher doses of warfarin

🧊 Cytochrome P450 Inhibitors

❄️ OAAK DEVICES mnemonic:

  • Omeprazole
  • Amiodarone
  • Allopurinol
  • Ketoconazole
  • Disulfiram
  • Ethanol (acute use)
  • Valproate
  • Isoniazid
  • Ciprofloxacin
  • Erythromycin / Clarithromycin
  • Sulphonamides (e.g. sulfadiazine, sulfamethoxazole)

📉 Effect

  • ↓ Enzyme activity  →  reduces drug metabolism. →  ↑ Drug concentration/effect

📝 Clinical Example

  • Background of metallic heart valve on warfarin. Commenced on erythromycin for infection
    • ↑ INR → risk of bleeding
  • Patients on inhibitors may need lower doses of warfarin

📝 Exam Clues & Clinchers

  • INR drops after starting drug = suspect enzyme induction (PCBRASS)
  • INR rises after starting drug = suspect enzyme inhibition (OAAKDEVICES)