10.1 Pharmacogenomics
Pharmacogenomics studies how genetic variations affect drug response, enabling personalized medicine through tailored drug selection and dosing based on individual genetic profiles.
CYP450 Polymorphisms
CYP2D6
- • Substrates: Codeine, tamoxifen, metoprolol, tricyclics
- • Poor metabolizers: No codeine analgesia (not converted to morphine)
- • Ultra-rapid: Codeine toxicity, tamoxifen inefficacy
CYP2C19
- • Substrates: Clopidogrel, PPIs, SSRIs
- • Poor metabolizers: Clopidogrel ineffective (prodrug); ↑ PPI efficacy
- • Common in Asian populations
Clinical Applications
Warfarin Dosing
- • CYP2C9: Metabolism polymorphisms (↓ dose if slow metabolizer)
- • VKORC1: Target enzyme variations (↓ dose if sensitive variant)
- • FDA-approved pharmacogenetic dosing algorithms
Thiopurine Methyltransferase (TPMT)
- • Metabolizes azathioprine, 6-MP
- • Low activity: Severe myelosuppression
- • FDA recommends testing before starting
HLA-B*5701 & Abacavir
- • Positive: High risk of hypersensitivity reaction
- • Mandatory screening before abacavir (HIV therapy)
- • Prevents life-threatening reactions
G6PD Deficiency
- • Avoid: Primaquine, dapsone, nitrofurantoin, sulfonamides
- • Risk of hemolytic anemia
- • Common in Mediterranean, African, Asian populations