Drugs Acting on the Cerebral and Peripheral Circulations

Cilostazol caused increased accumulation of donepezil in cardiomyocytes by inhibiting breast cancer resistance protein. This might explain the increased risk of cardiotoxicity when donepezil is co-administered with cilostazol. High-dose vitamin E induced significant changes in biomarkers of inflammation and toxicity in kidney tissue of male, but not female, mice. Furthermore, vitamin E induced a significant increase in phase-I, but not phase-II, carcinogen bio-activating enzymes and a reduction in antioxidant enzyme activities. Benzbromarone significantly inhibited CYP2C9 and CYP3A4 activity in human liver microsomes, suggesting a possible involvement of CYP450 inhibition in the occurrence of benzbromarone-induced hepatotoxicity. In healthy volunteers, diosmin significantly inhibited P-glycoprotein and CYP3A4 activity, with consequent increased exposure to fexofenadine and carbamazepine, respectively. A case of erythema multiforme related to sildenafil use was reported. In an experimental model of epilepsy, the pro-convulsant effects of sildenafil were mediated by oxytocin and cyclic AMP response element-binding protein.