Orfarin Mechanism of Action

Pharmacotherapeutic Group: Oral anticoagulants. ATC Code: B01AA03.
Pharmacology: Pharmacodynamics: Warfarin or 4-hydroxycoumarin is an anticoagulant that prevents the vitamin K-dependent synthesis of clotting factors included anticoagulants factor protein C and protein S. Warfarin is racemic mixture. Of its isomers, S-warfarin is approximately 5 times as potent an anticoagulant as R-warfarin. The effect of warfarin is based on its ability to prevent the reduction and activity of vitamin K in the synthesis of coagulation factors II, VII, IX and X. In therapeutic doses, warfarin prevents the synthesis of vitamin K-dependent coagulation factors by 30 to 50% and reduces the biological activity of coagulation factors. It takes 72 to 96 hours for the full effect of warfarin to appear. During this time the coagulation factors already synthesised are eliminated.
Pharmacokinetics: The bioavailability of oral warfarin is over 95% and peak plasma concentration is achieved in 3 to 9 hours. Meals slow down but do not reduce the absorption. Warfarin binds strongly to serum albumin, the free fraction varies between 0.5 and 3%. The volume of distribution of warfain is approximately 0.14 L/kg. Warfarin crosses the placenta but is not excreted in the breast milk. Warfarin is metabolised in the liver catalysed by CYP2C9 (S-warfarin) and CYP1A2 and CYP3A (R-warfarin) into inactive metabolites which are principally excreted in the urine and to a lesser extent into the bile. Enterohepatic circulation does exist. The elimination half life of S-warfarin is 18 to 35 hours and that of R-warfarin 20 to 60 hours.
Toxicology: Preclinical Safety Data: Animal studies have shown warfarin to be teratogenic. In other respects, available preclinical safety data do not reveal further relevant information for humans.