Warfarin Overview and Challenges

Question 1

What are the available brands of warfarin?

Answer 1

-Coumadin
-Jantoven
-Generic warfarin

Question 2

What are the available strengths of warfarin?

Answer 2

1, 2, 2.5, 3, 4, 5, 6, 7.5, and 10

Question 3

What are some challenges regarding warfarin?

Answer 3

-Narrow therapeutic window
-Considerable inter-subject variability
-Drug and diet interactions
-Good PK/PD understanding by both patient/provider

Question 4

Where in the body does warfarin work?

Answer 4

The liver

Question 5

How does warfarin work?

Answer 5

Inhibits synthesis of vitamin K dependent clotting factors by inhibiting the enzymes responsible for cyclic conversion of vitamin K

Question 6

What are the vitamin K-dependent clotting factors?

Answer 6

-Factors II, VII, IX, X
-Proteins C and S are also vitamin K-dependent

Question 7

Which enzyme is responsible for producing the vitamin k-dependent factors?

Answer 7

Vit K-dependent carboxylase

Question 8

Which enzyme is responsible for converting oxidized vitamin K into reduced vitamin K and is also the enzyme inhibited by warfarin?

Answer 8

Vitamin K reductase (VKORC1)

Question 9

Why does warfarin have such a prolonged peak action?

Answer 9

-Warfarin only prevents the creation of new clotting factors but does not affect clotting factors that are already produced and circulating in the blood
-These clotting factors have a half life of anywhere between a few hours to a few days

Question 10

When is the peak effect of warfarin?

Answer 10

72-96 hours or 2-5 days

Question 11

Which enantiomer of warfarin is more potent?

Answer 11

The S enantiomer

Question 12

Which enzymes metabolize the S enantiomer of warfarin?

Answer 12

CYPs 2C9, 2C19, and 2C18

Question 13

Which enzymes metabolize the R enantiomer of warfarin?

Answer 13

CYPs 1A2 and 3A4