VIAGRA®, an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1Hpyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate and has the following structural formula: 
Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. VIAGRA (sildenafil citrate) is formulated as blue, film-coated rounded-diamond-shaped tablets equivalent to 25 mg, 50 mg and 100 mg of sildenafil for oral administration. In addition to the active ingredient, sildenafil citrate, each tablet contains the following inactive ingredients: microcrystalline cellulose, anhydrous dibasic calcium phosphate, croscarmellose sodium, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, lactose, triacetin, and FD & C Blue #2 aluminum lake.CLINICAL PHARMACOLOGY Mechanism of ActionThe physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Studies in vitro have shown that sildenafil is selective for PDE5. Its effect is more potent on PDE5 than on other known phosphodiesterases (10-fold for PDE6, >80-fold for PDE1, >700-fold for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11). The approximately 4,000-fold selectivity for PDE5 versus PDE3 is important because PDE3 is involved in control of cardiac contractility. Sildenafil is only about 10-fold as potent for PDE5 compared to PDE6, an enzyme found in the retina which is involved in the phototransduction pathway of the retina. This lower selectivity is thought to be the basis for abnormalities related to color vision observed with higher doses or plasma levels. In addition to human corpus cavernosum smooth muscle, PDE5 is also found in lower concentrations in other tissues including platelets, vascular and visceral smooth muscle, and skeletal muscle. The inhibition of PDE5 in these tissues by sildenafil may be the basis for the enhanced platelet antiaggregatory activity of nitric oxide observed in vitro, an inhibition of platelet thrombus formation in vivo and peripheral arterial-venous dilatation in vivo. What is Viagra®?
Viagra is a new drug developed by Pfizer for the treatment of male impotency. Its pharmacological name is sildenafil citrate. It was approved by the US Food & Drug Administration in March 1998 for the treatment of male impotency. What does Viagra® do?
Viagra increases the body's ability to achieve and maintain an erection during sexual stimulation. Viagra does not produce spontaneous erections; sexual stimulus must be present for erection to occur. How does Viagra® work?
Viagra is dispensed as a pill and ingested orally. After absorption into the bloodstream, it functions as an inhibitor to an enzyme called phosphodiesterase 5 (PDE5) which is found primarily in the penis. The enzyme, PDE5 breaks down cyclic GMP. Cyclic GMP is produced during sexual stimulation, leading to penis erection. The longer the cyclic GMP is allowed to persist, the greater the chance for increased blood flow to the penis, thereby generating an erection. How long does Viagra® remain effective after ingestion?
The half-life is approximately 4 hours. If is recommended that sexual stimulation commence from 30 to 60 minutes after Viagra is taken. What happens if there is no sexual stimulation
after Viagra® is taken?
Sildenafil, or Viagra, is excreted as metabolites from the body in feces and urine. What is Viagra®'s success rate?
Viagra's success rate is about 75%. Are there any side effects?
Yes, a small percentage of the study group experienced headaches, nausea, facial flushing, diarrhea, urinary tract infection and visual changes to color sensitivity. Who should NOT take Viagra?
The main contraindication to prescribing Viagra® are people who suffer from a rare disease, retinitis pigmentosa, or those who are on nitroglycerin or nitrous oxide.
Recently, it has been reported that 16 Viagra® patients have died. While there is no direct evidence that Viagra caused the deaths, readers should be aware that sexual activity increases cardiac risk. Male impotence is often a side effect of more serious cardiovascular problems.
Viagra® MUST NOT be taken by men who are on medications containing nitrates, such as nitroglycerine tablets, as this could lead to dangerous lowering of blood pressure. There is evidence to suggest that Viagra may interact with other medications in such a way as to increase health risk. Men who have medical conditions, such as sickle cell anemia, leukemia, or multiple myeloma, or those with abnormally-shaped penis should also not take Viagra because of a possibility of producing a sustained erection. Can I get Viagra® over-the-counter?
No, Viagra® should only be taken by prescription from a qualified physician. You must tell your doctor exactly what other medications you are taking. FDA regulations do not permit Viagra® to be purchased without a physician's prescription. How often should Viagra be taken?
For those patients who have been prescribed Viagra® by their doctors, Viagra® should only be taken once per day, about 1 hour before sexual activity. What Viagra® dosage is best?
Many physicians are now recommending Viagra therapy begin with 25mg dosage, the minimum. Standard dose is 50mg. Dosages higher than 100mg per day are NOT recommended. Can Viagra® be combined with other treatments for Erectile dysfunction?
The use of such combinations is NOT recommended, since no studies have been done to assess its safety and effectiveness. Are there concerns about taking Viagra®
for long periods of time?
Yes. Some health practitioners are concerned since little is known about Viagra®'s long term effects. Is there Prescribing Information I can read?
Yes, full prescribing information has now been published. Visit http://www.viagra.com for full details.
|