Gynecology Sexual health

Sildenafil Wikipedia

Drugbox|
|IUPAC_name = 1-4-ethoxy-3-(6,7-dihydro-1-methyl-<BR>7-oxo-3-propyl-1H-pyrazolo4,3-dpyrimidin-5-yl)<BR>phenylsulfonyl-4-methylpiperazine citrate
| CAS_number=171599-83-0
| ATC_prefix=G04
| ATC_suffix=BE03
| PubChem=5281023
| DrugBank=APRD00556
| image=PAGENAME
| chemical_formula = C₂₂H₃₀N₆O₄S &middot; C₆H₈O₇
| molecular_weight = base: 474.6 g/mol<br />salt: 666.7 g/mol
| bioavailability= ?
| metabolism = ?
| elimination_half-life=?
| excretion = ?
| pregnancy_category = ?
| legal_status = ?
| routes_of_administration=Oral

Sildenafil citrate, sold under the names Viagra, Revatio and (in the Indian subcontinent) Caverta, is a Medication|drug used to treat male erectile dysfunction (impotence) and pulmonary hypertension|pulmonary arterial hypertension (PAH), developed by the pharmaceutical company Pfizer. Viagra pills, intended to treat impotence, are blue with the words "Pfizer" on one side and "VGR xx" (with xx being either 25, 50 or 100 as the dose of that pill in milligrams) on the other.

Sildenafil, initially known as compound UK-92,480, was initially developed to treat angina pectoris (a form of cardiovascular disease). Phase I clinical trials suggested that the drug had little effect on angina, but that it could induce marked penile erections. Pfizer therefore decided to market it for erectile dysfunction, rather than for angina. The drug was patented in 1996, approved for use in erectile dysfunction by the FDA on March 27, 1998, becoming the first pill approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year. It soon became a great success: annual sales of Viagra in the period 1999&ndash;2001 exceeded $1 billion.

The name "Viagra", like many drug names, is a marketing invention. It was possibly inspired by the Sanskrit word "vyāghra", which means "tiger". The word rhymes with "Niagara" (Niagara Falls is a popular honeymoon destination and Niagara, being such an impressive cataract, evokes a sense of incredible erectile and ejaculatory strength). The sound of the word also suggests the words "vigor" and "virile".

Even though Viagra is only available by prescription from a doctor, it was advertised directly to consumers on TV (famously being endorsed by Bob Dole). Numerous sites on the Internet offer Viagra for sale after an "online consultation," a mere web questionnaire. The "Viagra" name has become so well known that many fake aphrodisiacs now call themselves "herbal Viagra" or are presented as blue tablets imitating the shape and colour of Pfizer's product. A mixture of Viagra and ecstasy (drug)|ecstasy, called sextasy, has become popular among rave partygoers. Viagra is also informally known as "Vitamin V", "the Blue Pill", and goes by various other nicknames.

It has been suggested that Viagra would lead to a marked drop in the demand for certain traditional remedies, such as tiger penises and rhinoceros horns and that the drug may therefore help to preserve these endangered species. However, this is unlikely in that these parts of endangered species are not only used to treat impotence. Rhinoceros horns, for example, are used as a treatment for high fever. Furthermore, since Viagra has not been shown to possess aphrodisiac properties, it is unclear that the natural remedies would compete with this new clinical drug.

Pfizer's worldwide patents on sildenafil citrate will expire in 2011&ndash;2013. The United Kingdom|UK patent held by Pfizer on the use of PDE5 inhibitors (see below) as treatment of impotence has been invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002.

Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection.

Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with Viagra on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include tadalafil (Cialis&reg;) and vardenafil (Levitra&reg;).

Sildenafil is metabolism|metabolised by liver|hepatic enzymes and excreted by both the liver and kidneys.
If taken with a high fat meal, there may be a delay in absorption of Viagra and the net effect might be muted slightly as the plasma concentration will be lowered.

Some reports have claimed that sildenafil causes enhanced sexual pleasure for women by increasing blood flow to the sexual organs.

As with all prescription drugs, proper dosage is at the discretion of a licensed medical doctor. The dose of sildenafil is 25 mg to 100 mg taken once per day between 0.5 to 4 hours before sexual intercourse.

It is usually recommended to start with a dosage of 50 mg and then lower or raise the dosage as appropriate. The drug is sold in three dosages (25, 50, and 100 mg), all three costing about USD$10 per pill. Sildenafil is not scored, meaning there is no guarantee that the drug is evenly distributed throughout the tablet, therefore it is not advisable to cut it to change dosage.

Contraindications include:

• When taking other nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate, sodium nitroprusside, amyl nitrite ("poppers") (Cheitlin et al 1999)

Studies have shown that apart from in erectile dysfunction, sildenafil citrate is also effective in the rare disease pulmonary hypertension|pulmonary arterial hypertension (PAH). It appears to relax the arterial wall, decreasing the pressure on the lung vasculature and improving symptoms of right-sided heart failure. As a result of these studies, Pfizer submitted an additional registration for sildenafil with the FDA, and was approved for this indication in June 2005. Presumably to avoid confusion with Viagra, the preparation is named Revatio and the 20 milligram tablets are white and round. Sildenafil follows bosentan and prostacyclin as therapies for this condition.

• Tadalafil (Cialis)

• Terrett, N. K. et al. Sildenafil (Viagra), a potent and selective inhibitor of Type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction. Bioorg. Med. Chem. Lett. 1996, 6, 1819-1824. <!--not indexed on Medline-->

• http://www.viagra.com/ Home page for Viagra

Last Modified:   2005-12-19