Dicumarol or dicoumarol is a vitamin K antagonist derived from sweet-clover hay in the 1940s. It was discovered as the cause of a bleeding disease in cattle that ingested it, and was then used to treat blood clots. Dicumarol is the drug that warfarin was based on. The drug works as other vitamin K antagonists, by reducing the stores of reduced vitamin K, by inhibiting the vitamin K reductase complex, and preventing the recycling of the vitamin K within the cell. This in turn prevents coagulation factors VIII, IX, X as well as prothrombin, factor II, from activating, which in turn prevents fibrin clots from being formed and stabilized. Dicumarol is administered orally, and within 2 days, it is absorbed in the intestine and enters the liver. There, it inhibits the vitamin K epoxide reductase complex, preventing vitamin K1 2,3-epoxide from being recycled into reduced vitamin K. This leads to less reduced vitamin K to be present in order to react with the precursors of coagulation factors II, VII, IX and X through the vitamin K dependent gamma-carboxylase, and prevents those coagulation factors from being produced. Normally, coagulation factor IX is activated by factor XIa, which then, with the addition of coagulation factor VIII, forms the tenase complex that activates coagulation factor X. Activated coagulation factor Xa then joins with coagulation factor V to form the prothrombinase complex which forms thrombin from prothrombin. Thrombin is then necessary to convert fibrinogen to loose fibrin within the blood plasma, as well as converting coagulation factor XIII into its activated form. The fibrin then is able to polymerizes, and is stabilized into a water insoluble clot by coagulation factor XIIIa. The presence of dicumarol and the absence of reduced vitamin K prevents this coagulation cascade from occurring as much due to lack of substrates, and thus helps to prevent blood clotting.

Dicoumarol Action References