History Viagra was initially developed to treat heart disease (angina). In trial studies, the erection enhancing effects were noticed. The drug was patented in 1996, approved by the FDA on March 27, 1998 (becoming the first pill approved to treat erectile disfunction in the United States) and offered for sale in the United States later that year. It soon became a smashing success. 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. It is likely that many men (and some women) experiment with the drug to increase sexual prowess or pleasure. Annual sales of Viagra in the period 1999 - 2001 exceeded $1 billion (=1000 million).
The undeniable efficacy of Viagra reportedly has led to a marked drop in the demand for certain traditional remedies, such as tiger penises and rhinoceros horns. The drug may therefore help to preserve these endangered species.
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.
Chemistry Chemical name: 1-[4-ethoxy- 3-(6,7-dihydro- 1-methyl- 7-oxo- 3-propyl- 1H-pyrazolo [4,3-d]pyrimidin-5-yl) phenylsulfonyl]- 4-methylpiperazine citrate. Chemical formula: C22H30N6O4S.C6H8O7. Molecular weight: 666.7
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, Viagra should not cause an erection.
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 Viagra also causes enhanced sexual pleasure for women by increasing blood flow to the sexual organs.
Contraindications and side effects Contraindications include:
Common side effects include headache, flushing, dyspepsia, prolonged erections, palpitations and photophobia. Visual changes including blurring of vision and a curious bluish tinge have also been reported.
It is usually recommended to start with a dosage of 50mg and then lower or raise the dosage as appropriate. The drug is sold in three dosages (25mg, 50mg, and 100mg), all three costing about USD$10 per pill. Investing in a pill cutter can therefore be advisable.
Some patients may find various degrees of discomfort at the 25 or 50mg dosage level, including flushing of the face, head pressure, headache, and tachycardia. For these patients a dosage of 10 mg to 12.5 mg may be more appropriate and may be found to be effective.