The pharmacology of oral anticoagulants: implications for therapy.

All oral anticoagulants act by producing a functional deficiency of vitamin K, thereby impairing the normal synthesis of factors II, VII, IX and X. All, except dicumarol, are well absorbed after oral administration. They are highly protein bound and are mainly metabolized in the liver. A number of factors such as altered absorption, distribution, elimination, genetic factors, aging, vitamin K excess or deficiency, alterations in the level of vitamin K-dependent coagulation factors and drug interactions may affect response to oral anticoagulants. Adverse effects include hemorrhage, skin necrosis and teratogenicity. Phenindione can also cause serious hypersensitivity reactions. Five oral anticoagulants are available in Europe, although warfarin, phenprocoumon and nicoumalone (acenocumarol) are the most commonly used agents. The choice of oral anticoagulant is often influenced by previous experience and familiarity, but in a survey of 22 clinical pharmacologists in 12 countries of Europe, warfarin (57%) or phenprocoumon (24%) were the agents recommended most often in clinical practice.