The ways that haemostatic processes may be altered pharmacologically are classified in Figure CP1, while Figure CP2 shows the effects of the commoner drugs on the coagulation system.

Anticoagulants

Anticoagulants are drugs that interfere with the process of fibrin plug formation, to reduce or prevent coagulation. This effect is used to reduce the risk of thrombus formation within normal vessels and vascular grafts. The injectable anticoagulants are also used to prevent coagulation in extracorporeal circuits and in blood product storage. There are two main types of anticoagulants: oral anticoagulants and injectable anticoagulants (heparins).

Oral anticoagulants

Oral anticoagulants inhibit the reduction of vitamin K. Reduced vitamin K is required as a cofactor in γ-carboxylation of the glutamate residues of the glycoprotein clotting factors II, VII, IX and X, which are synthesised in the liver. During this γ-carboxylation process, vitamin K is oxidised to vitamin K 2,3-epoxide. The oral anticoagulants prevent the reduction of this compound back to vitamin K in the liver, and they do this by virtue of their structural similarity to vitamin K. Their action depends on the depletion of these factors, which decline according to their individual half-lives (Figure CP3).

There are two groups of oral anticoagulants:

• Coumarins (warfarin and nicoumalone)

• Inandiones (phenindione)

Warfarin has the most widespread use. Phenindione is more likely to cause hypersensitivity, but is useful when there is intolerance to warfarin.

Warfarin sodium

Warfarin is administered orally as a racemic mixture.