**2.3.2 Vitamin K antagonists**

Vitamin K antagonist inhibit the hepatic synthesis of factors II, VII, IX and X and protein C and S. There are various vitamina K antagonists, however, warfarin is the most commonly used around the world.

After oral administration warfarin is rapidly absorbed reaching the plasma peak concentration within 90 minutes, the peak therapeutic effect is acquired at 36 hours. Warfarin undergoes oxidative metabolism via the CYP450 system in the liver and less than 1% of the drug is excreted unchanged in the urine. (Ansell, 2008)

The risk of bleeding and thromboembolic complications is increased when using warfarin in the chronic kidney disease population and depends of the INR target, incidence of values outside of the target or other comorbid conditions. Warfarin dosing requirements tend to be lower as renal function declines. (Limdi , 2009) Concurrent drug interactions and acute medical problems such as heart failure or infections can influence the dose response to warfarin. Because the complexity of managing warfarin and increased risk of adverse outcomes in the chronic kidney disease setting, warfarin management in those patients should be referred when possible to dedicated anticoagulant services.(Dager ,2003).
