IJCS | Volume 31, Nº4, July / August 2018

388 Borges et al. Adherence score Int J Cardiovasc Sci. 2018;31(4)383-392 Original Article of warfarin absorption by cholestyramine or by foods in the gastrointestinal tract; increased distribution volume and half-life reduction due to hypoproteinemia; increased metabolism caused by stimulation of CYP2C9 by other drugs (barbiturates); excess intake of vitamin K-rich foods. On the other hand, CYP2C9 inhibition by other drugs (fluoxetine, amiodarone, clopidogrel), protein binding displacement caused by diuretics and sodium valproate, as well as vitamin K deficiency may reduce vitamin K metabolism, and consequently increase its effect. 10 Amiodarone and simvastatin were the main drugs that significantly affected the required dose of OACs. Amiodarone is an antiarrhythmic that inhibits warfarin, due to its role as a potent cytochrome P450 inhibitor including CYP2C9, which is involved in S-warfarin metabolism. 10 Amiodarone inhibits warfarinmetabolism and increases its effect, and the concomitant use of both drugs also affects prothrombin time. Simvastatin potentiates the effect of warfarin by binding to plasma proteins, reduces platelet aggregation and promotes thrombus formation. 11 Besides, it is essential that patients on OAC-T are aware of the consumption of vitamin K-rich foods. Variations in the amount or in the frequency of consumption of these foods may change INR to values outside the therapeutic range. 10 In case of acute alcohol consumption, dehydrogenase pathway plays a key role in ethanol metabolism in the liver. Nevertheless, in case of chronic consumption, the microsomal ethanol oxidizing system, which requires the CYP2E1 enzyme, is used and increases ethanol metabolism by ten-fold. 10 Therefore, in the pharmacokinetics of warfarin, there is an interaction between ethanol and the drug – in case of acute ethanol consumption, warfarin metabolism is decreased by enzymatic inhibition, resulting in increased OAC effect and increased risk of bleeding. 10 In chronic alcohol consumption, enzymatic activity decreases, with consequent increase of warfarin metabolism, reduction Figure 2 - Internal validation of Simonetti adherence score. Score