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32 Mechanism of action Crystal structure of human pde5 with bound sildenafil, pdb entry 1udt 33 Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cgmp-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum. Nitric oxide (NO) in the corpus cavernosum of the penis binds to guanylate cyclase receptors, which results in increased levels of cgmp, leading to smooth muscle relaxation ( vasodilation ) of the intimal cushions of the helicine arteries. This smooth muscle relaxation leads to vasodilation and increased inflow of blood into the spongy tissue of the penis, causing an erection. Furchgott, ferid Murad, and louis Ignarro won the nobel Prize in Physiology or Medicine in 1998 for their independent study of the metabolic pathway of nitric oxide in smooth muscle vasodilation. 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. 34 Without sexual stimulation, and therefore lack of activation of the no/cgmp system, sildenafil should not cause an erection.
18 Mixing with amyl nitrite is particularly dangerous and potentially brugge fatal. 18 Jet lag research The 2007 Ig Nobel Prize in aviation went oververhitting to patricia. Plano, and diego. Golombek of Universidad Nacional de quilmes, argentina, for their discovery that sildenafil helps treat jet lag recovery in hamsters. 22 23 Sports Professional athletes have been documented using sildenafil, believing the opening of their blood vessels will enrich their muscles. In turn, they believe it will enhance their performances. 24 25 Analogs Acetildenafil and other synthetic structural analogs of sildenafil which are pde5 inhibitors have been found as adulterants in a number of "herbal" aphrodisiac products sold over-the-counter.
26 These analogs have not undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have unknown side-effect profiles. 27 Some attempts have been made to ban these drugs, but progress has been slow so far, as, even in those jurisdictions that have laws targeting designer drugs, the laws are drafted to ban analogs of illegal drugs of abuse, rather than analogs of prescription. However, at least one court case has resulted in a product being taken off the market. 28 The us fda has banned numerous products claiming to be eurycoma longifolia that, in fact, contain only analogs of sildenafil. Sellers of such fake herbals typically respond by just changing the names of their products. Detection in biological fluids Sildenafil and/or N-desmethylsildenafil, its major active metabolite, may be quantified in plasma, serum, or whole blood to assess pharmacokinetic status in those receiving the drug therapeutically, to confirm the diagnosis in potential poisoning victims, or to assist in the forensic investigation.
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Those using protease inhibitors are recommended to limit their use of sildenafil to no more than one 25 mg dose every 48 hours. 2 Other drugs that interfere with the metabolism of sildenafil include erythromycin and cimetidine, both of which can also lead to prolonged plasma half-life levels. The use of sildenafil and an α1 blocker (typically prescribed for hypertension or for urologic conditions, such as benign prostatic hypertrophy ) at the same time may lead to low blood pressure, but this effect does not occur if they are taken at least. 15 Contraindications Contraindications include: 2 :11 Concomitant use of nitric oxide donors, organic nitrites and nitrates, 16 such as: Concomitant use of soluble guanylyl cyclase stimulators, such as riociguat Known hypersensitivity to sildenafil Sildenafil should not be used if sexual activity is inadvisable due. Citation needed nonmedical use recreational use sildenafil's popularity with young adults has increased over the years. 17 Sildenafil's trade name, viagra, is widely recognized in popular culture, and the drug's association with treating erectile dysfunction has led to its recreational use.
18 The reasons behind such use include the belief that the drug increases libido, improves sexual performance, 18 or permanently increases penis size. 19 Studies on the effects of viagra when used recreationally are limited, but suggest it has little effect when used by those not suffering from erectile dysfunction. In one study, a 25-mg dose was shown to cause no significant change in erectile quality, but did reduce the postejaculatory refractory time. 20 This study also noted a significant placebo effect in the control group. 20 Unprescribed recreational use of sildenafil and other pde5 inhibitors is noted as particularly high among users of illegal drugs. 21 Sildenafil is sometimes used to counteract the effects of other substances, often illicit. 18 Some users mix it with methylenedioxymethamphetamine ( mdma, ecstasy other stimulants, or opiates in an attempt to compensate for the common side effect of erectile dysfunction, a combination known as " sextasy "rockin' and rollin or "trail mix".
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10 Adverse effects In clinical trials, the most common adverse effects of sildenafil use included headache, flushing, indigestion, nasal congestion, and impaired vision, including photophobia and blurred vision. 2 Some sildenafil users have complained of seeing everything tinted blue ( cyanopsia ). 11 Some complained of blurriness and loss of peripheral vision. In July 2005, the fda found that sildenafil could lead to vision impairment in rare cases 12 and a number of studies have linked sildenafil use with non-arteritic anterior ischemic optic neuropathy. 13 Rare but serious adverse effects found through postmarketing surveillance include prolonged erections, severe low blood pressure, myocardial infarction (heart level attack ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss. 2 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. 14 Interactions Care should be exercised by people who are also taking protease inhibitors for the treatment of hiv infection. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying knie the plasma levels of sildenafil, increasing the incidence and severity of side effects.
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Sildenafil should not be taken by people who take nitrates such as nitroglycerin (glycerin trinitrate as this may result in a severe and potentially fatal drop in blood pressure. 3, sildenafil acts by inhibiting cgmp-specific phosphodiesterase type 5 (phosphodiesterase 5, pde5 an enzyme that promotes degradation of cgmp, which regulates blood flow in the penis. Pfizer scientists, andrew Bell, david Brown, and Nicholas Terrett originally discovered sildenafil as a treatment for various cardiovascular disorders. 4 5, since becoming available vastzittend in 1998, sildenafil has been a common treatment for erectile dysfunction; its primary competitors are tadalafil (trade name cialis) and vardenafil (levitra). Contents Medical uses 50mg tablets of sildenafil Sexual dysfunction The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete intercourse). Its use is now one of the standard treatments for erectile dysfunction, including for men with diabetes mellitus. 6 Antidepressant-associated sexual dysfunction Tentative evidence suggests that sildenafil may help men who experience antidepressant -induced erectile dysfunction. 7 Pulmonary hypertension While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of death or serious side effects as of 2014. 8 raynaud's phenomenon Sildenafil and other pde5 inhibitors are used off-label to alleviate vasospasm and treat severe ischemia and ulcers in fingers and toes for people with secondary raynaud's phenomenon ; 9 10 these drugs have moderate efficacy for reducing the frequency and duration.
For other uses, see. Sildenafil, sold as the brand name. Viagra among others, is a medication used to treat erectile dysfunction zwangerschap and pulmonary arterial hypertension. 3, its effectiveness for treating sexual dysfunction in women has not been demonstrated. 3, common side effects include headaches and heartburn, as well as flushed skin. Caution is advised in those who have cardiovascular disease. Rare but serious side effects include prolonged erections, which can lead to damage to the penis, and sudden-onset hearing loss.
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