Paper I
2021 February (Supplementary) (2010 Scheme) · 40 marks · 120 min

Question

Pharmacogenetics

Q33 marksShort Notes

Answer

Pharmacogenetics is the study of genetically determined variations in individuals’ responses to drugs, including differences in drug metabolism, efficacy, and toxicity based on genetic polymorphisms.

Examples

  • Slow acetylators (NAT2 polymorphism) — increased risk of isoniazid-induced peripheral neuropathy/hepatotoxicity
  • G6PD deficiency — haemolysis with primaquine, sulfonamides, dapsone
  • Atypical pseudocholinesterase — prolonged apnoea with succinylcholine
  • CYP2C19 polymorphism — variable response to clopidogrel (poor metabolizers have reduced antiplatelet effect)
  • CYP2C9/VKORC1 polymorphisms — variable warfarin dose requirements

Clinical significance

  • Explains inter-individual variation in drug response/toxicity not accounted for by age, weight, or organ function
  • Basis for personalized/precision medicine — genetic testing can guide dose selection or drug choice for certain drugs (e.g., warfarin, clopidogrel)

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