warfarin brands

Molecular formula: C19H16O4

Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase. The reduced form of vitamin K, vitamin KH₂ is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca²⁺ and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KH₂ is converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin K₁ by vitamin K epoxide reductase then back to vitamin KH₂ by vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit 1 and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K₁. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of 8 and 24 hours, with the exception of factor VII which has a half life of 6 hours. Factors IX, X, and finally thrombin degrade later with half lives of 24, 36, and 50 hours resulting in a dominant anticoagulation effect. In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized. It takes approximately 2 days for new coagulation factors to be synthesized in the liver. Vitamin K₂, functionally identical to vitamin K₁, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin K<sub>2</sub supply and result in a greater anticoagulation effect. Animals poisoned by warfarin ... die of tissue hypoxia resulting from massive internal bleeding of 2-5 days onset. Bleeding is due to incr capillary permeability & decr blood coagulability. The exact cause of capillary damage is not known, but its presence is evidenced by the fact that hemorrhages occur in tissues not subjected to much mechanical stress. The coagulation defect is the result decreased blood concentrations of the coagulation proteins factor II (prothrombin), factor VII (proconvertin, autoprothrombin I), factor IX (Christmas factor, autoprothrombin II, PTC), and factor X (Stuart factor, autoprothrombin III). These coagulation factors are decreased because their synthesis in the liver has been inhibited. Biosynthesis of these particular proteins is inhibited becaused each one requires adequate activity of vitamin K for biosynthesis, but the rodenticide interferes with the normal function of vitamin K. Hepatic synthesis of prothrombin and factors VII, IX, and X is dependent upon adequate supplies of vitamin K. The molecular and even the cellular mechanism of the anti-vitamin K action of the coumarin compounds remain uncertain. These drugs seem to act as antimetabolites in synthesis of affected clotting factors. Since large doses of vitamin K can overcome or surmount action of dicumarol, competitive type of interaction is thought to be involved. Perhaps coumarin anticoagulants simply inhibit transport of vitamin K to the cellular sites wheresynthesis takes place. In any event, there is some evidence that dicumarol interferes with involvement of vitamin K in synthesis of a prothrombin precursor that may also be common to factors VII, IX, and X. Anticoagulants interfere with fibrin formation and are used to prevent thrombus development and extension. Their major therapeutic application has traditionally been for venous thromboembolic diso

Source: PubChem (NCBI) · compound 54678486