Sildenafil is broken down in the liver by hepatic metabolism using cytochrome p450 enzymes, mainly CYP450 3A4 (major route),but also by CYP2C9 (minor route) hepatic isoenzymes. Unlike previously approved treatments for impotence, sildenafil does not directly cause penile erection; but affects the response to sexual stimulation. The drug acts by enhancing the smooth muscle relaxant effects of nitric oxide (Fig. 2). Drug interactions with sildenafil arise through two principal mechanisms: pharmacodynamic interactions (additive vasodilatory effects) and pharmacokinetic interactions (CYP3A4-mediated alterations in sildenafil plasma concentrations). Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying the plasma levels of sildenafil, increasing the incidence and severity of side effects. Those using protease inhibitors are recommended to limit their use of sildenafil to no more than one 25 mg dose every 48 hours. [4] Learn how sildenafil, a phosphodiesterase-5 (PDE5) inhibitor, can treat erectile dysfunction. Discover its mechanism, dosage, side effects, and more. Viagra works by relaxing the blood vessels in the penis, allowing more blood to flow in when you’re sexually aroused. The active ingredient, sildenafil, blocks an enzyme that normally breaks down a chemical signal responsible for keeping those blood vessels open. Mechanism of Action: The NO/cGMP Pathway and PDE5 Inhibition Sildenafil's therapeutic effect is a direct consequence of its potent and selective inhibition of phosphodiesterase type 5 (PDE5). Sildenafil, which is a specific phosphodiesterase type V inhibitor, enhances erection on sexual arousal by increasing the quantity of cyclic guanosine monophosphate in the corpora cavernosa. This has revolutionized the treatment of erectile dysfunction. Erectile dysfunction: Does not directly cause penile erections but affects the response to sexual stimulation. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation.