Viagra (sildenafil citrate)

Sildenafil, a selective phosphodiesterase (PDE) type 5 inhibitor, is a vasodilating agent.

Sildenafil is a selective inhibitor of phosphodiesterases (PDEs), with the greatest selectivity for PDE type 5, the principal isoenzyme of PDE involved in the metabolism of cyclic guanosine monophosphate (cGMP) to GMP in the corpora cavernosa of the penis. Sildenafil has no direct relaxant effect on isolated human corpora cavernosa of the penis, but enhances the effect of nitric oxide by inhibiting PDE type 5-mediated hydrolysis of cGMP. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cells in the corpora cavernosa.

By selectively inhibiting PDE type 5, sildenafil causes accumulation of cGMP in various tissues. Because sildenafil potentiates the accumulation of cGMP rather than stimulating its production, the drug is effective only when cGMP production in the penis is increased by sexual arousal. Sildenafil at recommended doses has no effect on erectile function in the absence of sexual stimulation.

Sildenafil also exhibits some activity against other PDE isoenzymes. In vitro, sildenafil is about 10 times more active against PDE type 5 than against PDE type 6, greater than 70-80 times more active against PDE type 5 than against PDE type 1, greater than 1000 times more active against PDE type 5 than against PDE types 2 and 4, and 4000 times more active against PDE type 5 than against PDE type 3. PDE type 3 is involved in cardiac contractility, vascular smooth muscle relaxation (vasodilation), and platelet aggregation, and PDE type 6 (photoreceptor PDE) is found in the retina and involved in phototransduction.

The duration of erectile responsiveness (i.e., the time period in which adequate sexual stimulation can produce an erection) with oral sildenafil has been reported to be approximately 2 hours, with some penile responsiveness persisting for up to 4 hours after oral administration. In the largest clinical study published to date, the onset and duration of action of oral sildenafil were not reported. In most other placebo-controlled studies in which improvement in erection was determined by penile plethysmography, the erectile effect was determined at a fixed time of 60 minutes after an oral dose of the drug.

Sildenafil is rapidly absorbed following oral administration; the mean absolute bioavailability is 41% (range, 25-63%). Although studies indicate that more than 90% of an oral sildenafil dose is absorbed from the GI tract, the drug undergoes extensive metabolism in the GI mucosa during absorption and on first pass through the liver, with only about 40% of a dose reaching systemic circulation unchanged. Pharmacokinetics of the drug (as determined by peak plasma concentrations or AUC) are dose proportional over the single-dose range of 1.25-200 mg.

Peak plasma concentrations of sildenafil and its active N-desmethyl metabolite are achieved within 30-120 (median: 60) minutes following oral administration in fasting adults. Administration with a high-fat meal delays GI absorption, with a reduction in peak plasma concentrations of about 29% and a delay in time to peak plasma concentrations of about 60 minutes; the extent of absorption is not affected.

Sildenafil appears to be widely distributed in the body. Sildenafil and its major circulating N-desmethyl metabolite are each approximately 96% bound to plasma proteins; protein binding reportedly is independent of plasma concentration. Sildenafil is distributed to a limited extent in semen following oral administration, with less than 0.001% of a single dose appearing in semen 90 minutes after dosing in healthy individuals.

Such concentrations are unlikely to cause any effects in sexual partners exposed to the semen. Plasma sildenafil concentrations appear to decline in a biphasic manner following oral administration, with a terminal elimination half-life of about 4 hours (range: 3-5 hours). Sildenafil is metabolized principally via hepatic cytochrome P-450 (CYP) microsomal isoenzymes 3A4 (major route) and 2C9 (minor route).

Plasma concentrations of the active N-desmethyl metabolite are approximately 40% of those observed with sildenafil, and the metabolite reportedly accounts for about 20% of sildenafil's pharmacologic activity. The N-demethylated metabolite, the major circulating metabolite, has a phosphodiesterase selectivity profile similar to that of sildenafil and an in vitro potency for PDE type 5 of approximately 50% of the parent drug. Sildenafil is eliminated mainly in the feces as metabolites following oral administration.

In healthy adults and those with ED, approximately 80% of an oral dose is excreted as metabolites in feces and 13% is excreted in urine.

USES: Sildenafil is used to treat male sexual function problems (impotence or erectile dysfunction-ED). In combination with sexual stimulation, sildenafil works by increasing blood flow to the penis to help a person get and keep an erection. This drug does not protect against sexually transmitted diseases (such as HIV, hepatitis B, gonorrhea, syphilis).

Using an effective barrier method (latex or polyurethane condom/dental dams) during sexual activity will help to decrease your risk of infection.

Generic name: sildenafil citrate
Pronunciation: (sil-DEN-a-fil)

The following indications are listed for Viagra:

• Erectile Dysfunction

Also known as: Impotency.

No ICD codes are available for this drug.