Indication |
For decreasing blood clotting. Often used along with heparin for treatment of deep vein thrombosis. |
Pharmacodynamics |
Dicumarol is an coumarin-like compound found in sweet clover. It
is used as an oral anticoagulant and acts by inhibiting the hepatic
synthesis of vitamin K-dependent coagulation factors (prothrombin and
factors VII, IX, and X). It is also used in biochemical experiments as
an inhibitor of reductases. |
Mechanism of action |
Dicumarol inhibits vitamin K reductase, resulting in depletion of
the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor
for the carboxylation of glutamate residues on the N-terminal regions of
vitamin K-dependent proteins, this limits the gamma-carboxylation and
subsequent activation of the vitamin K-dependent coagulant proteins. The
synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X
and anticoagulant proteins C and S is inhibited. Depression of three of
the four vitamin K-dependent coagulation factors (factors II, VII, and
X) results in decresed prothrombin levels and a decrease in the amount
of thrombin generated and bound to fibrin. This reduces the
thrombogenicity of clots. |
Absorption |
Not Available |
Volume of distribution |
Not Available |
Protein binding |
Not Available |
Metabolism |
Not Available |
Route of elimination |
Not Available |
Half life |
Not Available |
Clearance |
Not Available |
Toxicity |
LD50=233 mg/kg (orally in mice); LD50=250 mg/kg (orally in rats) |
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