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Old 10-23-2005, 02:19 PM
rushdoony rushdoony is offline
Senior Member
Join Date: Nov 2004
Posts: 556
Default SILDENAFIL ( Viagra )

What health effects to a baby
will result if that baby was conceived
with semen laden with the chemicals
that make up "sildenafil"?
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phenylsulfonyl]-4-methylpiperazine citrate
IUPAC name
CAS number
171599-83-0 ATC code
Chemical formula C22H30N6O4S · C6H8O7
Molecular weight base: 474.6 g/mol
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 at least) Caverta, is a drug used to treat male erectile dysfunction (impotence) and 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.

Contents [hide]
1 History
2 Mechanism of action
3 Dosage and price
4 Contraindications and side effects
5 Use in pulmonary hypertension
6 See also
7 References
8 External links

Sildenafil, initially known as compound UK-92,480, was initially developed to treat angina pectoris (a form of cardiovascular disease). In Phase I clinical trials, the drug turned out to have 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 1999–2001 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, called sextasy, has become popular among rave partygoers. Viagra is also informally known as "Vitamin V", 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 2011–2013. The 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.

Mechanism of action
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®) and vardenafil (Levitra®).

Sildenafil is metabolised by 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.

Dosage and price
As with all prescription drugs, proper dosage is at the discretion of a licensed medical doctor. The dose of sildenafil is 25mg to 100mg 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 and side effects
Contraindications include:

When taking other nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate, sodium nitroprusside, amyl nitrite (Cheitlin et al 1999)
In men for whom sexual intercourse is inadvisable due to cardiovascular risk factors
Severe hepatic impairment (decreased liver function)
Severe impairment in renal function
Hypotension (low blood pressure)
Recent stroke or heart attack
Hereditary degenerative retinal disorders (including genetic disorders of retinal phosphodiesterases)
Amongst sildenafil's serious adverse effects are: priapism, severe hypotension, myocardial infarction, ventricular arrhythmias, sudden death, stroke and increased intraocular pressure.

Common side effects include sneezing, headache, flushing, dyspepsia, prolonged erections, palpitations and photophobia. Visual changes including blurring of vision and a curious bluish tinge have also been reported.

In May of 2005, the U.S. Food and Drug Administration found that sildenafil could lead to vision impairment. An investigation is currently underway. Some patients developed nonarteritic ischemic optic neuropathy (NAION), an eye problem that can result in permanent vision loss. Combined with past reports, this study brings the total number of sildenafil-related NAION cases to 14.

Some users complained of blurriness and some a loss of peripheral vision. It appears that there is a hereditary condition described as a "cup" in the retina that is the constant among all cases.

Use in pulmonary hypertension
Studies have shown that apart from in erectile dysfunction, sildenafil citrate is also effective in the rare disease 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.

See also
Tadalafil (Cialis)
Vardenafil (Levitra)

“...I realized I had to gain more knowledge to protect against evil and to protect myself from not becoming evil myself. This is our major goal in life...\" Terry Lee
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