Warfarin

Warfarin is a coumarin anticoagulant, first discovered in spoiled sweet clover silage after causing hemorrhagic disease in cattle.

Uses

 

Mechanism

 

Warfarin blocks the regeneration of vitamin K by blocking the liver enzyme epoxide reductase. Vitamin K is required for the carboxylation of several glutamate residues in prothrombin, factors VII, IX, and X, as well as anticoagulant proteins S and C. Accordingly, the presence of warfarin results in the incomplete, inactive clotting factors, reducing blood clotting capability.

 

Dose and Half Life

Treatment should be initiated with small daily doses of 5-10 mg. Initial adjustment of prothrombin time is about 1 week, and PTT should be increased to a level representing 25% of normal activity. If activity is less than 20% dosage should be reduced or omitted until it again rises.

Therapeutic range is now defined by international normalized ratio (INR), which is the PTT ratio of test/control using an international reference.

 

Warfarin binds to plasma albumin, leading to small space of distribution, long plasma half-life (36 hours), and lack of urinary excretion.

There is an 8-12 hour delay in the action of warfarin, as anticoagulation is dependent on the degradation rate of active clotting factors. Half-lives for factors VII, IX, X, and II are 6, 24, 40, and 60 hours, respectively.

 

 

Side Effects

short term

long term

Counter-Indications

 

Metabolism and Excretion

 

Dependency