Sildenafil is broken down in the
liver by hepatic metabolism using cytochrome p450
Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis. [8] It requires sexual arousal to work, and does not by itself cause or increase sexual arousal. [8] It also results in dilation of the blood vessels in the lungs. Pfizer originally discovered the medication in 1989 while looking for a treatment for angina. [11] It was approved for medical use in the United States and in the European Union in 1998.
[5][8][11][12] In 2023, it was the 151st most commonly prescribed medication in the United States, with more than 3 million prescriptions. [13][14] It is available as a generic medication. [15][16] In the United Kingdom, it is available as a pharmacy medicine. The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete sexual intercourse). Its use is now one of the standard treatments for erectile dysfunction, including for males with diabetes mellitus.
Tentative evidence suggests that sildenafil may help males who experience antidepressant-induced erectile dysfunction. 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. 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][21] these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes. [9] As of 2016,[update] their role more generally in Raynaud's was not clear. Sildenafil has shown some potential for improving exercise performance at high altitudes. enzymes, mainly CYP450 3A4 (major route), but
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| Viagra Soft Tabs | 100mg | 20 Pills | 62.99€ 59.99€ | |
| Levitra Generic | 20mg | 90 + 8 Pills | 180.78€ 172.17€ | |
| Cialis Original | 20mg | 12 Pills | 78.32€ 74.59€ | |
| Apcalis SX Oral Jelly | 20mg | 17 + 4 Sachets | 95.52€ 90.97€ | |
| Cialis Generic | 5mg | 180 + 10 Pills | 159.65€ 152.05€ | |
| Cialis Original | 20mg | 4 Pills | 41.99€ 39.99€ | |
| Cialis Black | 80mg | 180 + 10 Pills | 356.64€ 339.66€ | |
| Apcalis SX Oral Jelly | 20mg | 50 + 6 Sachets | 146.39€ 139.42€ | |
| Cialis Original | 20mg | 76 + 4 Pills | 319.19€ 303.99€ | |
| Kamagra Effervescent Tablets | 100 mg | 42 + 7 Pills | 122.97€ 117.11€ | |
| Cialis Generic | 20mg | 60 + 6 Pills | 117.76€ 112.15€ | |
| Kamagra Effervescent Tablets | 100 mg | 28 Pills | 90.83€ 86.50€ | |
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| Viagra Generic | 50mg | 360 + 10 Pills | 225.33€ 214.60€ |
also by CYP2C9 (minor route) hepatic isoenzymes.
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 4 hours apart. Concomitant use of nitric oxide donors, organic nitrites and nitrates,[30] such as: nitroglycerinisosorbide mononitrateisosorbide dinitratesodium nitroprussidealkyl nitrites (commonly known as "poppers") Concomitant use of soluble guanylyl cyclase stimulators, such as riociguat Sildenafil should not be used if sexual activity is inadvisable due to underlying cardiovascular risk factors. Sildenafil's popularity with young adults has increased over the years. [32] Sildenafil's brand name, Viagra, is widely recognized in popular culture, and the drug's association with treating erectile dysfunction has led to its recreational use. [33] The reasons behind such use include the belief that the drug increases libido, improves sexual performance,[33] or permanently increases penis size.
[34] Studies on the effects of sildenafil when used recreationally are limited, but suggest it has little effect when used by those who do not have 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. [35] This study also noted a significant placebo effect in the control group. Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high among users of illegal drugs. [36] Sildenafil is sometimes used to counteract the effects of other substances, often illicit.
[33] 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'", "hammerheading", or "trail mix". [33] Mixing it with amyl nitrite, another vasodilator, is particularly dangerous and potentially fatal. The 2007 Ig Nobel Prize in aviation went to Patricia V. Agostino, Santiago A. Plano, and Diego A. The major product of metabolisation by these
Golombek of Universidad Nacional de Quilmes, Argentina, for their discovery that sildenafil helps treat jet lag recovery in hamsters. 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. 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. [41] These analogs have not undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have unknown side-effect profiles.
[42] 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 medicines. However, at least one court case has resulted in a product being taken off the market. The US Food and Drug Administration (FDA) has banned numerous products claiming to be Eurycoma longifolia that, in fact, contain only analogs of sildenafil. [44][45][46] Sellers of such fake herbals typically respond by just changing the names of their products. 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 in a case of fatal overdose.
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. [49] Robert F. 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. The molecular mechanism of smooth muscle relaxation involves the enzyme CGMP-dependent protein kinase, also known as PKG. enzymes is N-desmethylated sildenafil,
which is metabolised further.
This metabolite also has an affinity for the
PDE receptors, about 40% of that of sildenafil.
| Active Ingredient | Dose per tablet | Purpose | Additional Components |
|---|---|---|---|
| Sildenafil Citrate | 50 mg | Treats Erectile Dysfunction | Microcrystalline cellulose, flavoring agents |
| Dapoxetine HCl | 60 mg | Prevents Premature Ejaculation | Sodium benzoate |
| Excipients | Various | Enhance stability and absorption | Lactose, coloring agents |