Page 302 - Remedial Andrology

Brief Review on Sildenafil

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increases blood flow to the penis during sexual stimulation. Phos- The physiologic mechanism of erection of the penis involves re-
phodiesterase type 5 inhibitor inhibitors are effective, there are lease of nitric oxide in the corpus cavernosum. Nitric oxide then
differences in their onset and duration of action. activates the enzyme guanylate cyclase, which results in increased
levels of cyclic guanosine monophosphate (cGMP), it produces
smooth muscle relaxation in the corpus cavernosum and allowing
Erectile dysfunction is when a man has difficulty getting an
inflow of blood. Sildenafil has no direct relaxant effect on isolated
erection. Keeping it long enough for sex. It's also known as erec-
human corpus cavernosum, but enhances the effect of nitric ox-
tile dysfunction or impotence. When not enough blood flows to the
ide by inhibiting phosphodiesterase type 5, which is responsible
penis, preventing an erection. Some guys with erectile dysfunction
for degradation of cGMP in the corpus cavernosum. They sexual
find it difficult to either get or keep an erection every time they try
stimulation causes local release of Nitric oxide, and inhibition of
to have sex [3]. Erectile dysfunction is often caused by something
phosphodiesterase type 5 by sildenafil causes increased levels of
physical, such as disease, injury, or side effects from other drugs. In
cyclic guanosine monophosphate in the corpus cavernosum, result-
some men, erectile dysfunction is a side effect of some medication.
ing in smooth muscle relaxation and inflow of blood, In addition
These medications might include drugs used to treat; high blood
to human corpus cavernosum smooth muscle, phosphodiester-
pressure, heart disease, depression.
ase type 5 is also found in lower concentrations in other tissues
including platelets, vascular, visceral smooth muscle, and skeletal
muscle. The inhibition of phosphodiesterase type 5 in these tissues
by sildenafil which may be the basis for the enhanced platelet anti-
aggregant activity of nitric oxide observed in vitro, an inhibition of
platelet thrombus formation in vivo and peripheral arterial-venous
dilatation in vivo.

Pharmacokinetics and Metabolism of sildenafil is rapidly ab-
sorbed after oral administration, with a mean absolute bioavail-
ability of 41%, Its pharmacokinetics of dose-proportional over the
recommended dose range. It is eliminated predominantly by he-
patic metabolism and it is converted to an active metabolite with
properties similar to the parent sildenafil. The metabolite have half
lives of 4 hours. Absorption and Distribution of sildenafil is rap-
idly absorbed. indicating distribution into the tissues. Sildenafil
and its major circulating N-desmethyl metabolite approximately
Figure 1 95% bound to plasma proteins. Protein binding is independent of

total drug concentrations, Based upon measurements of sildenafil
Mechanism of action in semen of healthy volunteers 90 minutes after dosing, less than
0.001% of the administered dose may appear in patients. Metabo-
lism and Excretion of Sildenafil is cleared predominantly by the
CYP3A4 by major route and CYP2C9 by minor route hepatic mi-
crosomal isoenzymes. This metabolite has a PDE selectivity profile
similar to sildenafil and an in vitro potency for phosphodiesterase
type 5 inhibitors approximately 50% of drug. After either oral or
intravenous administration, sildenafil is excreted as metabolites
predominantly in the feces that means approximately 80% of ad-
ministered oral dose and to a lesser extent in the urine that means
approximately 13% of the administered oral dose [4].

It is used to treat the male sexual problems. In combination with
sexual stimulant, sildenafil works by increasing blood flow to the
Figure 2 penis to help to get an erection and keep an erection. These drugs
does not give protection against sexually transmitted diseases such
as

Citation: Lokesh Masagiri., et al. “Brief Review on Sildenafil". Acta Scientific Pharmaceutical Sciences 4.1 (2020): 25-27.