Warfarin in NVAF

Question 1

Warfarin mechanism of action

Answer 1

Inhibits vitamin K recycling by inhibiting vitamin K epoxide reductase > vitamin K reductase, preventing γ-carboxylation of clotting factors II, VII, IX, and X, leaving these factors unable to bind to phospholipid membranes and unable to take part in coagulation, Also inhibits carboxylation and activation of natural anticoagulants protein C and protein S

Question 2

Warfarin inhibited clotting factor half lives

Answer 2

Factor II = 72 hours, factor VII = 6 hours, factor IX =24 hours, factor X = 36 hour

Question 3

Warfarin INR adjusting

Answer 3

INR is out of the therapeutic range in the outpatient setting, increase or decrease the cumulative weekly dose by 5%–20%, depending on the INR; if the INR is greater than 4.5, consider holding one or two doses before resuming at the reduced dose.

Question 4

Warfarin Time in Therapeutic Range

Answer 4

well managed when the individual patient’s time in therapeutic range (TTR) is greater than 65%–70%.

Question 5

Reduced warfarin absorption drug interaction

Answer 5

cholestyramine, sucralfate

Question 6

Enzyme induction producing a reduced INR and warfarin effect

Answer 6

phenytoin, phenobarbital, carbamazepine, rifampin, St. John’s wort

Question 7

warfarin cytochrome interactions

Answer 7

S-warfarin: cytochrome P450 (CYP) 2C9 > CYP3A4
R-warfarin: CYP1A2 and CYP3A4 > CYP2C19

Question 8

Agents that affect warfarin clearance

Answer 8

amiodarone, propafenone, cimetidine

Question 9

Enzyme inhibition producing a reduced INR and warfarin effect

Answer 9

clarithromycin, azoles, protease inhibitors, diltiazem, dronedarone, erythromycin grapefruit juice, verapamil