Warik Mechanism of Action

Pharmacology: Warfarin is a coumarin anticoagulant which acts by inhibiting the synthesis of vitamin K-dependent clotting factors II (prothrombin), VII, IX, and X, and of the anticoagulant protein C and its cofactor protein S. Half-lives of these clotting factors are as follows: Factor II-60 hours, VII-4-6 hours, IX-24 hours, and X-48-72 hours. The half-lives of proteins C and S are approximately 8 hours and 30 hours, respectively. The resultant in vivo effect is a sequential depression of Factor VII, Protein C, Factor IX, Protein S, and Factor X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins which are essential for biological activity.
Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K₁ epoxide. The degree of depression is dependent upon the dosage administered and, in part, by the patient's VKORC1 genotype. Therapeutic doses of Warfarin decrease the total amount of the active form of each vitamin K dependent clotting factor made by the liver by approximately 30% to 50%.
Pharmacokinetics: Warfarin sodium is readily absorbed from the gastrointestinal tract. It can also be absorbed through the skin. It is extensively bound to plasma proteins and its plasma half-life is about 37 hours. It crosses the placenta but does not occur in significant quantities in breast milk. Warfarin is used as a racemic mixture; the S-isomer is reported to be more potent. The R- and S-isomers are both metabolized in the liver, the S-isomer more rapidly than the R-isomer; the stereo-isomers may also be affected differently by other drugs. Metabolites, with negligible or no anticoagulant activity, are excreted in the urine following reabsorption from the bile.