5

Question 1

Warfarin

Answer 1

Anticoagulant - blocks vitamin K epoxide reductase (VKORC1)
-Decreases Vitamin K and CF 1,7,9,10

R and S isomer, S is major!

Question 2

Genetic polymorphisms explain 30-40% of inter- individual variability in warfarin dose

Answer 2

-CYP 2C9 (TCI low lower up) *D W
-CYP 4F2 (3 T down) *CF D VK
-VKORC1 (HAP B AND A) *CF VK D

Question 3

CYP 2C9 (gene change, activity change, prevalence)

Answer 3

TAA and CAS after CAUC

Question 4

CYP 2C9 3/3

Answer 4

-Increase S warfarin

-Decrease formation of Vit K and CF 2,7,9,10

Increased toxicity and bleeding risk = decrease dose

*Same for 2/2 but to lesser extent

Question 5

CYP 2C9 PK (phenotype, CR)

Answer 5

Question 6

VKORC1 genes/haplos/act

Answer 6

-VKORC1 G: wild type = increase activity
-WT is Haplotype B (-1639)

-VKORC1 A: variant = decrease activity
-Variant is Haplotype A (-1639)

BAA and AAS

Question 7

VKORC1 PK (phenotype, CR)

Answer 7

Question 8

VKORC1 Population Prevalence

Answer 8

hap b : caucasians

hap a : asians

Question 9

CYP4F2

Answer 9

Question 10

CYP4F2 PK (phenotype, CR)

Answer 10

TT = 33

Question 11

Pharmacogenomic Impact of CYP2C9 and VKORC1

Answer 11

● Tests available for CYP2C9 and VKORC1
● Pharmacogenomic information is included on drug label
● Dosing algorithm established taking into account self-reported ancestry/genotype
● But should still take into consideration other factors

Question 12

Maintenance Dosing of Warfarin (know)

Answer 12

Typical starting dose is 5mg

So (with knowing functional effect)
-around 3-4 will be normal
-0.5-2 will be decreased
-and 5-7 will be increased

NOT AG (not tested)