Indications & Usage:-
Sildenafil is indicated for the treatment of erectile dysfunction. The studies that established benefits demonstrated improvements in success rates for sexual intercourse compare with placebo.
Properties:-
The physiological mechanism of erection of the penis involves release of Nitric Oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic, guanosine monophosphate (cGMP), producing muscle relaxation in the corpus cavernosum & allowing inflow of blood.
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 degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by Sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation & inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.
Studies in vitro have shown that Sildenafil is selective for PDE5. Its effect is more potent on PDE5 than other known phosphodiesterases (>80-fold for PDE1,>1,000-fold for PDE2, PDE3 and PDE4). The approximately 4000-fold selectively for PDE’s versus PDE3 is important because that PDE is involved in control of cardiac contractility, Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an emztme found in the retina: this lower selectivity is thought to be the basis for abnormalities related to colour vision observed with higher doses or plasma levels.
Pharmacokinetics & Metabolism:-
Sildenafil is rapidly absorbed, maximum plasma concentrations are reached within 30-120mins. 90mins after dosing, less than 0.001% of the administered dose may appear in the semen of patients.
The major circulating metabolite result from N-desmethylation of Sildenafil and is itself further metabolized. After either oral or intravenous administration, Sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% administered oral dose) & to a lesser extent in the urine (approximately 13% of administered oral dose).
