Anticoagulants coumarin derivatives/warfarin

The isoprene-derived molecule whose structure is shown here is known alternately as Coumarin and warfarin. By the former name, it is a widely prescribed anticoagulant. By the latter name, it is a component of rodent poisons. How can the same chemical species be used for such disparate purposes The key to both uses lies in its ability to act as an antagonist of vitamin K in the body. 

Anticoagulants used therapeutically include heparin, warfarin (a coumarin derivative), and anisindione (an indandione derivative). 

Coumarins are also synthesized by a variety of plant species. Medically, the most significant coumarins are dicoumarol and its derivative, warfarin. Dicoumarol was initially discovered as the active substance in mouldy sweet clover hay, which could induce haemorrhagic disease in cattle. Dicoumarol and warfarin are now used clinically as anticoagulants, as discussed in Chapter 9. 

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

The coumarin anticoagulants include dicumarol, warfarin sodium (coumadin sodium), warfarin potassium (Athrombin-K), acenocoumarol (Sintrom), and phenprocoumon (Liquamar). The inanedione derivatives are phenindione (Hedulin), diphenadione (Dipaxin), and anisindi-... 

Warfarin - altered coagulation parameters and/or bleeding have been reported in patients taking capecitabine concomitantly with coumarin-derivative anticoagulants such as warfarin. Patients taking warfarin... 

The coumarin anticoagulants include dicumarol, warfarin sodium (coumadin sodium), warfarin potassium (Athrom-bin-K), acenocoumarol (Sintrom), and phenprocoumon (Liquamar). The inanedione derivatives are phenindione (Hedulin), diphenadione (Dipaxin), and anisindione (Miradon). The pharmacological properties of oral anticoagulants are identical qualitatively, but their pharmacokinetic parameters and their toxicities vary. Racemic warfarin sodium is the most widely used anticoagulant. Antithrombotic drugs are used clinically either to prevent the formation of blood clots within the circulation (anticoagulant) or to dissolve a clot that has already formed (thrombolytic). 

Classification and Prototypes Anticoagulants reduce the formation of fibrin clots. Two major types of anticoagulants are available heparin and its derivatives, which must be used parenterally and the orally active coumarin derivatives (eg, warfarin). The two groups differ in their chemistry, pharmacokinetics, and pharmacodynamics (Table 34-2). Two other anticoagulant proteins are available lepirudin, a recombinant form of hirudin, a protein found in leech saliva and human antithrombin III, a commercial preparation of an endogenous human anticoagulant. 

Chamomile has been indicated as an herb with the theoretical potential for interacting with warfarin due to the coumarin content of the herb (Heck et al. 2000). The cou-marin content, however, consists of the coumarin derivatives herniarin and umbelliferone. Herniarin has been shown to have hemostatic activity (Ahmad and Misra 1997) and umbelliferone has shown no evidence of anticoagulant activity (Egan et al. 1990 Feuer 1974 Pelkonen et al. 1997). The flavonoid apigenin has been shown to inhibit platelet aggregation in vitro (Landolfi et al. 1984 Teng et al. 1985). 

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