American Heart Association/American College of Cardiology Foundation Guide to Warfarin Therapy

摘要: ### Mechanism of Action Coumarin Anticoagulant Drugs Warfarin, a coumarin derivative, produces an anticoagulant effect by interfering with the cyclic interconversion vitamin K and its 2,3 epoxide (vitamin epoxide). Vitamin is cofactor for carboxylation glutamate residues to γ-carboxyglutamates (Gla) on N-terminal regions K–dependent proteins (Figure 1).1–6 These proteins, which include coagulation factors II, VII, IX, X, require γ-carboxylation biological activity. By inhibiting conversion cycle, warfarin induces hepatic production partially decarboxylated reduced coagulant activity.7,8 Figure 1. The cycle link glutamic acid proteins. K1 obtained from food sources KH2 warfarin-resistant reductase. then oxidized (Vit KO) in reaction that coupled factors. This step renders X protein C S functionally active. Vit KO catalyzed reductase, blocks formation KH2, thereby removing substrate KH2) acids. K1, either given therapeutically or derived sources, can overcome bypassing warfarin-sensitive reductase KH2. Carboxylation promotes binding phospholipid surfaces, accelerating blood coagulation.9–11 γ-Carboxylation requires form KH2). Coumarins block …