Core23: Enzyme inducers

⬆️ High-yield / 要点：Enzyme induction increases CYP/UGT enzyme synthesis → faster metabolism → many co-administered drugs become less effective.

Definition / 定義

• Enzyme induction = increased rate/extent of metabolism due to increased synthesis of enzymes.
• Mainly involves:
  • Hepatic cytochrome P450 enzymes.
  • Cofactor heme.
  • Some phase 2 enzymes, e.g. UDP-glucuronosyltransferase.
• Mechanism: cytoplasmic drug receptors activate genes for CYP isoforms.

Clinical effect / 臨床的意義

• Inducers increase metabolism of other drugs.
• Result:
  • Lower drug concentration.
  • Reduced efficacy.
  • Possible treatment failure.
• Induction is especially important for drugs with narrow therapeutic range or concentration-dependent efficacy.

Important CYP inducers / 重要な誘導薬

CYP	Inducers
CYP1A2	Carbamazepine, phenobarbital, rifampin, omeprazole
CYP2C9	Barbiturates, especially phenobarbital; phenytoin; rifampin
CYP2C19	Carbamazepine, phenobarbital, phenytoin, rifampin
CYP2D6	Dexamethasone, corticosterone
CYP3A4	Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin

Example / 例

• Metoprolol is a CYP2D6 substrate.
• Dexamethasone/corticosterone induce CYP2D6.
• Result: metoprolol concentration may become ineffective.

Remember / 覚え方

• Inducer = enzyme up
• Enzyme up = drug level down
• Classic strong inducers: rifampin, carbamazepine, phenytoin, phenobarbital/barbiturates