The mechanism of action of Sildenafil citrate involves the release of nitric oxide (NO) in the corpus cavernosum of the penis.
NO binds to the receptors of the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation (vasodilation) of the intimal cushions of the helicine arteries, 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.
The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections.[
Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. O
ther drugs that operate by the same mechanism include tadalafil (Cialis) and vardenafil (Levitra).
Sildenafil is metabolised by liver enzymes and excreted by both the liver and kidneys.
If taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.
The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete intercourse). It use is now standard treatment for erectile dysfunction in all settings, including diabetes.
People on antidepressants may experience sexual dysfunction, either as a result of their illness or as a result of their treatment.
A 2003 study showed that sildenafil improved sexual function in men in this situation.
Following up to earlier reports from 1999, the same researchers found that sildenafil was able to improve sexual function in female patients on antidepressants as well.
Professional sports players have been using drugs such as Viagra thinking that the opening of their blood vessels will enrich their muscles, therefore enhancing their performance.
Viagra's popularity with young adults has increased over the years.
It is sometimes used recreationally, though this use is somewhat pointless in young, healthy men, as they receive no benefit from the drug.
Some users mix Viagra with methylenedioxymethamphetamine (MDMA, ecstasy) or other stimulants in an attempt to compensate for the side effect common to many amphetamines of erectile dysfunction, a combination known as "sextasy", "rockin' and rollin'", or 'trail mix'." Mixing with amyl nitrite is particularly dangerous, and is potentially fatal.
A low-concentration solution of sildenafil in water significantly prolongs the time before cut flowers wilt; one experiment showed a doubling in time from one week to two weeks.
The mechanism of action is similar to that in humans: nitric oxide leads to the production of cGMP whose degradation by PDE5 is inhibited by sildenafil.
The 2007 Ig Nobel Prize in Aviation went to Patricia V. Agostino, Santiago A. Plano and Diego A. Golombek of Universidad Nacional de Quilmes, Argentina, for their discovery that Viagra aids jet lag recovery in hamsters. Their research was published in the Proceedings of the National Academy of Sciences.
Viagra Pfizer pills are blue and diamond-shaped with the words "Pfizer" engraved on one side, and "VGR xx" (where xx stands for "25", "50" or "100", the dose of that pill in milligrams) engraved on the other. The dose of sildenafil for erectile dysfunction is 25 mg to 100 mg taken not more than once per day between 30 minutes and 4 hours prior to sexual intercourse.
When taking nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate (nitroglycerin), sodium nitroprusside, amyl nitrite ("poppers")
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)
In clinical trials, the most common adverse effects of sildenafil use included headache, flushing, dyspepsia, nasal congestion and impaired vision, including photophobia and blurred vision.
Some sildenafil users have complained of seeing everything tinted blue (cyanopsia).
Some complained of blurriness and loss of peripheral vision. In July 2005, the U.S. Food and Drug Administration found that sildenafil could lead to vision impairment in rare cases and a number of studies have linked sildenafil use with nonarteritic anterior ischemic optic neuropathy.
Rare but serious adverse effects found through postmarketing surveillance include priapism, severe hypotension, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure and sudden hearing loss.
As a result of these postmarketing reports, in October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil, required a more prominent warning of the potential risk of sudden hearing loss.
Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizer's Sandwich, Kent, research facility in England.
It was initially studied for use in hypertension (high blood pressure) and angina pectoris (a symptom of ischaemic heart disease).
The first clinical trials were conducted in Morriston Hospital in Swansea.
Phase I clinical trials under the direction of Ian Osterloh 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 US Food and Drug Administration on March 27, 1998, becoming the first oral treatment 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 19992001 exceeded $1 billion!
The British press portrayed Peter Dunn and Albert Wood as the inventors of the drug, a claim which Pfizer disputes. Their names are on the manufacturing patent application drug, but Pfizer claims this is only for convenience.
Even though sildenafil is available only by prescription from a doctor, it was advertised directly to consumers on U.S. TV (famously being endorsed by former United States Senator Bob Dole and soccer star Pel้).
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.
Viagra is also informally known as "Vitamin V", "the Blue Pill", as well as various other nicknames.
In 2000, Viagra sales accounted for 92 percent of the global market for prescribed erectile dysfunction pills.
By 2007, Viagra's global share had plunged to about 50 percent due to several factors, including the entry of Cialis and Levitra, along with several other counterfeits and clones, and reports of vision loss in people taking PDE5 inhibitors.
In February 2007, it was announced that Boots the Chemist would trial over the counter sales of Viagra in stores in Manchester, England.
Men aged between 30 and 65 would be eligible to buy four tablets after a consultation with a pharmacist.
Pfizer's worldwide patents on sildenafil citrate will expire in 20112013.
The UK patent held by Pfizer on the use of PDE5 inhibitors as treatment of impotence was invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002.