Oral anticoagulants indirect-acting

The oral anticoagulant drugs act indirectly on the process of Glu carboxylation of the vitamin K-dependent proteins. The vitamin K antagonists prevent the reduction of the reaction intermediate, vitamin K epoxide. Blockage of the epoxide reductase reaction results in the accumulation of vitamin K epoxide and other nonfunctional forms of vitamin K. Without regeneration of the vitamin K-related reaction intermediates through the cycle shown in Figure 36-22, a depletion of functional vitamin K occurs. 

The two commonly administered anticoagulant therapies3 are parenteral heparin, a highly sulfated glycosaminoglycan, and oral warfarin 2, a vitamin K antagonist (which acts by indirectly inhibiting several steps of the coagulation pathway). The major... 

As a result of intensive research, derivatives of 4-hydroxycoumarin were found, which proved to be particularly efficient against rodents and resistant to anticoagulant rodenticides. Difenacoum (34) is a chronic rodenticide, which acts as a typical indirect blood anticoagulant similar to warfarin. However, it is effective against rats and mice, which are resistant to warfarin and other anticoagulant rodenticides, and is more toxic than warfarin to susceptible strains of these rodents. The chemical composition of difenacoum is 3-(3-p-biphenyl-1,2,3,4-tetrahydro-naphth-l-yI)-4-hydroxycoumarin. Its acute oral LD50 is 1.8 mg/kg for Norway rats (Hadler et al., 1975a,b). 

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