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MM20: Pharmacogenetics 1 (Cytochrome P450 Family (functions (metabolism +…

- - - - using genetics
        
        not all genetic components clinically relevant
- - - - less WBCs -> infections
      - less RBCs -> anaemia
    - - oxidised metabolites via xanthine oxidase
      - 6-methyl mercaptopurine via thiopurinemethyl transferase
        
        TPMT genotype influences enzyme activity...
        
        l - less active (lower drug dose needed in homozygotes)
        
        h - more active (higher drug dose needed in homozygotes)
        
        heterozygote - moderate activity (middle drug dose needed)
        
        finding patients TPMT genotype decreases toxicity incidence - FDA recommended
  - - - too high: haemorrhage
      - too low: no therapeutic effect
      - complicated by diet, other diseases, drug interactions
    - - increased activity: must increase drug dose (explains 6% dosing variability)
    - - increased VKORC1 activity: increase drug dose (explains 25% dosing variability)
- - - - converts codeine to morphine
        
        increased CYP function: less therapeutic effect
        
        decreased CYP function: increased risk of intoxication