ADT Exam 3

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Author:
Rx2013
ID:
121281
Filename:
ADT Exam 3
Updated:
2011-12-06 14:46:39
Tags:
Pharmacogenetics Drug Response
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Description:
Pharmacogenetics of Drug Response
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  1. Clopidogrel
    • pro drug
    • activated by CYP2C19
    • 15% of dose is activated and binds P2RY12 receptor
  2. Poor CYP2C19 metabolizers
    • cannot convert clopidogrel into active drug
    • higher risk for stroke or clot
  3. Ultra Rapid CYP2C19 metabolizers
    higher risk of bleed
  4. Clopidogrel CYP2C19 metabolism found on what chromosome?
    10
  5. CYP2C19*2 genotype accounts for ___ % of the variation in clopidogrel response
    12%
  6. Genotype + Age + BMI + lipid levels account for ___ % of variation in response
    22%
  7. Frequency of CYP2C19*2 in european americans
    24%
  8. Frequency of CYP2C19*2 in mexican americans
    18%
  9. Frequency of CYP2C19*2 in african americans
    33%
  10. Frequency of CYP2C19*2 in asian americans
    51%
  11. transporter responsible for uptake of statin from the blood
    • OATP1B1 or SL01B1
    • liver specific transporter
    • uptake transporter
  12. location of OATP1B1 mutation
    chromosome 12
  13. 2 copies of *5 allele
    17 fold risk of myopathy
  14. *5 SLCO1B1 allele
    codes for amino acid change from valine to alanine which reduces transport activity
  15. odds ratio for myopathy with 2 *5 alleles vs 1
    17%
  16. blood levels of simvastatin vs simvastatin acid with *5 alleles
    AUC of simvastatin acid is much higher
  17. enantiomer of warfarin that is most potent
    • s-warfarin is 3-4x mor potent than r-warfarin
    • s-warfarin responsible for most anicoagulation activity
  18. biotransformation of warfarin
    • S-warfarin to S-7-hydroxy warfarin to terminate anticoagulant activity
    • catalyzed by CYP2C9
  19. CYP2C9 Alleles
    • *1 active
    • *2 reduced activity
    • *3-6 no activity
  20. CYP2C9 acounts for ___% of the interindividual variability in warfarin dosing.
    10-12%
  21. factors contributing to interindividual variability in warfarin dose
    • VKORC1 28%
    • CYP2C9*3 8%
    • CYP2C9*2 3.8%
    • Age 15.5%
  22. CYP2C9 is more important for ____ anti-coagulation control
    initial
  23. VKORC1 is more important for determining ____ anti-coagulation control
    maintenance

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