Preparatory Mindset

Study this chapter with focus on how genetic principles affect clinical practice.

Core Concepts

• Pharmacogenetics: Study of how genetic variation affects drug response (efficacy and toxicity)


• CYP2D6: Key cytochrome P450 enzyme in phase I metabolism of >70 drugs (including codeine, tamoxifen, antidepressants)


• Poor metabolizers (CYP2D6) : Reduced conversion of prodrugs to active form → reduced efficacy (e.g., codeine → less morphine)


• Ultrarapid metabolizers: Increased conversion → risk of toxicity (e.g., codeine → morphine overdose)


• CYP2C9 and VKORC1: Affect warfarin metabolism and sensitivity → require reduced dose in variant carriers


• TPMT: Thiopurine methyltransferase — deficiency → severe myelosuppression with azathioprine/6-MP


• G6PD deficiency: Hemolytic anemia triggered by certain drugs (sulfonamides, primaquine, aspirin)

High-Yield Points

• CYP2D6 poor metabolizers: less morphine from codeine (reduced analgesia)


• CYP2C9/VKORC1 variants: require LOWER warfarin dose


• TPMT deficiency: life-threatening myelosuppression with standard thiopurine doses

Topic Summary

Pharmacogenetics explains why the same drug dose affects patients differently based on their genetic makeup.