Lecture Notes: Understanding P450 Enzymes

Introduction to P450 Enzymes

• P450 Enzymes: Important for drug metabolism, high yield for USMLE and COMLEX exams.
• Focus: Understanding inducers and inhibitors of P450 enzymes, and specific subtypes.

P450 Inducers

• Inducers: Drugs that accelerate P450 enzyme activity, increasing drug metabolism.
• List of Inducers:
  • Carbamazepine
  • Rifampin
  • Alcohol
  • Phenytoin
  • Griseofulvin
  • Phenobarbital
  • Sulfonylureas
• Mechanism: Inducers speed up the enzyme's ability to metabolize other drugs, leading to decreased efficacy of the other drugs due to increased breakdown.
• Mnemonic: "CRAP GPS induces my rage"
  • Carbamazepine
  • Rifampin
  • Alcohol
  • Phenytoin
  • Griseofulvin
  • Phenobarbital
  • Sulfonylureas

P450 Inhibitors

• Inhibitors: Drugs that slow down P450 enzyme activity, decreasing drug metabolism.
• List of Inhibitors:
  • Valproic acid
  • Ketoconazole
  • Isoniazid
  • Sulfonamides
  • Chloramphenicol
  • Amiodarone
  • Erythromycin (except Azithromycin)
  • Quinidine
  • Grapefruit juice
• Mechanism: Inhibitors prevent the enzyme from metabolizing drugs, leading to increased drug levels and potential toxicity.

Mnemonic Strategy

• Inducers: Memorize the CRAP GPS mnemonic.
• Inhibitors: Use the process of elimination.

P450 Enzyme Subtypes

• Questions on USMLE and COMLEX may involve specific subtypes.
• Subtypes and Mnemonics:
  • CYP1A2: Metabolizes acetaminophen
    • Mnemonic: "1 A 2" - Acetaminophen is one word with two A's.
  • CYP2E1: Metabolizes ethanol
    • Mnemonic: "21 to drink" - rearrange to "2E1".
  • CYP2C9: Metabolizes warfarin
    • Mnemonic: Factors 2, 7, 9, 10, C, S - pick every other factor to form 2C9.
  • CYP2D6: Metabolizes cardiovascular drugs
    • Mnemonic: "2D echo" - echocardiogram relates to cardio drugs.
  • CYP3A4: Most common subtype, metabolizes a wide range of drugs.
    • Mnemonic: Default choice if not the other subtypes (handles ~60% of drugs).

Summary

• Inducers: Increase enzyme activity, leading to decreased drug effects.
• Inhibitors: Decrease enzyme activity, leading to potential drug toxicity.
• Mnemonics: Helpful to remember drugs related to each subtype and their effects on metabolism.
• Exam Strategy: Use mnemonics and process of elimination for determining drug effects on enzyme activity.