Sildenafil Citrate (UK Viagra) Information

Sildenafil citrate, sold as "Viagra" UK, "Revatio" and under various other trade names, is a drug (Viagra UK) used to treat erectile dysfunction and pulmonary arterial hypertension (PAH). Sildenafil citrate (Viagra UK) was developed by and is being marketed by the pharmaceutical company Pfizer. Sildenafil citrate (Viagra UK) acts by inhibiting cGMP specific phosphodiesterase type 5, an enzyme that regulates blood flow in the penis. Since becoming available in 1998, sildenafil citrate (Viagra UK) has been the prime treatment for erectile dysfunction; sildenafil citrate's (Viagra UK) primary competitors on the market are tadalafil (Cialis UK) and vardenafil (Levitra UK).


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Mechanism of action of Genuine Viagra UK
The mechanism of action of sildenafil citrate (viagra UK) involves the release of nitric oxide (NO) in the corpus cavernosum of the penis. NO binds to the receptors of the enzyme guanylate cyclase in the sildenafil citrate (viagra UK), 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.[14] Robert F. Furchgott won the Nobel Prize in Physiology or Medicine in 1998 for his discovery and analysis of endothelium-derived relaxing factor, a key part of the NO mechanism of action.
Sildenafil citrate (viagra UK) 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 citrate (viagra UK) 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.
[14] Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil citrate (viagra UK) should not cause an erection. Other drugs that operate by the same mechanism include tadalafil (Cialis UK) and vardenafil (Levitra UK).
Sildenafil citrate (viagra UK) is metabolised by liver enzymes and excreted by both the liver and kidneys. If sildenafil citrate (viagra UK) is taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration of sildenafil citrate (viagra UK) increases by around one hour, and the maximum concentration itself of sildenafil citrate (viagra UK) is decreased by nearly one-third.
[15]

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Uses of Genuine Viagra UK
Sexual dysfunction uses of Viagra UK
The primary indication of sildenafil citrate (viagra UK) is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete intercourse, also known as "male impotence"). Sildenafil citrate's (viagra UK) use is now standard treatment for erectile dysfunction in all settings, including diabetes.[16]
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 citrate (viagra UK) improved sexual function in men in this situation.
[17] Following up to earlier reports from 1999,[18] the same researchers found that sildenafil citrate (viagra UK) was able to improve sexual function in female patients on antidepressants as well.[19]
Pulmonary hypertension uses of Viagra UK
As well as erectile dysfunction, sildenafil citrate (viagra UK) is also effective in the rare disease pulmonary arterial hypertension (PAH). Sildenafil citrate (viagra UK) relaxes the arterial wall, leading to decreased pulmonary arterial resistance and pressure. This effect of sildenafil citrate (viagra UK), in turn, reduces the workload of the right ventricle of the heart and improves symptoms of right-sided heart failure. Because PDE-5 is primarily distributed within the arterial wall smooth muscle of the lungs and penis, sildenafil citrate (viagra UK) acts selectively in both these areas without inducing vasodilation in other areas of the body. Pfizer submitted an additional registration for sildenafil citrate (viagra UK) to the FDA, and sildenafil citrate (viagra UK) was approved for this indication in June 2005. The preparation is named Revatio, to avoid confusion with Viagra UK, and the 20 milligram tablets are white and round. Sildenafil citrate (viagra UK) joins bosentan and prostacyclin-based therapies for this condition.[20]
Altitude sickness uses of Viagra UK
Sildenafil citrate (viagra UK) has been shown to be useful for the prevention and treatment of High-altitude pulmonary edema associated with altitude sickness such as that suffered by mountain climbers.[21][22] While this effect has only recently been discovered, sildenafil citrate (viagra UK) is already becoming an accepted treatment for this condition, in particular in situations where the standard treatment of rapid descent has been delayed for some reason.[23]
Use in sports of Viagra UK
Professional sports players have been using drugs such as Viagra UK, thinking that the opening of their blood vessels will enrich their muscles, therefore enhancing their performance.[24]

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Non-medical use of Viagra UK
Recreational use of Viagra UK
Sildenafil citrate's (viagra UK) popularity with young adults has increased over the years.[25] Sildenafil citrate's (viagra UK) trade name "Viagra" UK is widely recognized in popular culture, and the sildenafil citrate's (viagra UK) association with treating erectile dysfunction has led to the recreational use of sildenafil citrate (viagra UK).[26] The reasons behind such use of sildenafil citrate (viagra UK) include the belief that sildenafil citrate (viagra UK) increases libido, that sildenafil citrate (viagra UK) improves sexual performance,[26] or that sildenafil citrate (viagra UK) permanently increases penis size. Studies on the effects of viagra UK when used recreationally are limited, but suggest that sildenafil citrate (viagra UK) has little effect when used by those not suffering from erectile dysfunction, and having sex within a stable relationship. In one study, a 25mg dose of sildenafil citrate (viagra UK) was shown to cause no significant change in erectile quality, but the sildenafil citrate (viagra UK)did reduce the post-ejaculatory refractory time.[27] This study also noted a significant placebo effect in the control group for Viagra UK.[27]
Unprescribed recreational use of sildenafil citrate (viagra UK) and other PDE-5 Inhibitors is noted as particularly high among users of illegal drugs.
[28][29] Sildenafil citrate (viagra UK) is sometimes used to counteract the effects of other substances, often illicit.[26] Some users mix sildenafil citrate (viagra UK) 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."[26] Mixing sildenafil citrate (viagra UK) with amyl nitrite is particularly dangerous, and is potentially fatal.[26]
Prevention of plant wilting use of Viagra UK
A low-concentration solution of sildenafil citrate (viagra UK) 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 in the sildenafil citrate (viagra UK) leads to the production of cGMP whose degradation by PDE5 is inhibited by sildenafil citrate (viagra UK).[30]
Jet lag research relating to Viagra UK
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 UK aids jet lag recovery in hamsters.[31] Their research about sildenafil citrate (viagra UK) was published in the Proceedings of the National Academy of Sciences.[32]
Analogues of Sildenafil Citrate (Viagra UK)
Acetildenafil is a structural analogue of sildenafil citrate (viagra UK), one of the PDE5 inhibitors found in a number of "herbal" aphrodisiac products sold over-the-counter (sometimes called "generic Viagra"). This class of analogues have not undergone any of the rigorous testing that drugs like sildenafil citrate (viagra UK) have passed, and thus have an unknown side-effect profile.[33] 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 analogues of illegal drugs of abuse, rather than analogues of prescription medicines. However, at least one court case has resulted in a product (an analogue sildenafil citrate [viagra UK]) being taken off the market.[34]


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Dosage of Viagra UK
Viagra UK pills are blue and diamond-shaped with the words "Pfizer" engraved on one side, and "VGR xx" (where xx stands for "50" or "100", the dose of that Viagra UK pill in milligrams) engraved on the other. The dose of sildenafil citrate (viagra UK) for erectile dysfunction is 50 mg to 100 mg taken not more than once per day between 30 minutes and 4 hours prior to sexual intercourse.
The dosage for pulmonary arterial hypertension (Revatio) is one 20 mg tablet three times a day. Revatio pills are white, round, film-coated tablets imprinted with "RVT 20" embossed on one side (Viagra UK).
[35]


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Contraindications of Viagra UK
Contraindications of sildenafil citrate (viagra UK) include:
• When taking nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate (nitroglycerin), sodium nitroprusside, amyl nitrite ("poppers")[36]
• 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)


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Side-effects of Viagra UK
In clinical trials, the most common adverse effects of sildenafil citrate (viagra UK) use included headache, flushing, dyspepsia, nasal congestion and impaired vision, including photophobia and blurred vision.[37] Some sildenafil citrate (viagra UK) users have complained of seeing everything tinted blue (cyanopsia).[38] Some sildenafil citrate (viagra UK) users complained of blurriness and loss of peripheral vision. In July 2005, the U.S. Food and Drug Administration found that sildenafil citrate (viagra UK) could lead to vision impairment in rare cases[39] and a number of studies have linked sildenafil citrate (viagra UK) use with nonarteritic anterior ischemic optic neuropathy.[40][41][42][43][44][45]
Rare but serious adverse effects found through postmarketing surveillance of sildenafil citrate (viagra UK) include priapism, severe hypotension, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss.
[37] As a result of these postmarketing reports about sildenafil citrate (viagra UK), in October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil citrate (viagra UK), required a more prominent warning of the potential risk of sudden hearing loss.[46]


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Interactions with Viagra UK
Care should be exercised by patients using sildenafil citrate (viagra UK) that are also taking protease inhibitors for the treatment of HIV. Protease inhibitors inhibit the metabolism of sildenafil citrate (viagra UK), effectively multiplying the plasma levels of sildenafil citrate (viagra UK), increasing the incidence and severity of side-effects of sildenafil citrate (viagra UK). It is recommended that patients using protease inhibitors limit their use of sildenafil citrate (viagra UK) to no more than one 25 mg (of sildenafil citrate [viagra UK]) dose every 48 hours.
Concomitant use of sildenafil citrate (viagra UK) and an alpha blocker may lead to low blood pressure, but this effect does not occur if sildenafil citrate (viagra UK) and the alpha blocker are taken at least four hours apart.
[47]


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Chemical synthesis of Sildenafil Citrate (Viagra UK)
The preparation steps for synthesis of sildenafil citrate (viagra UK) are as follows:[48]
1. Methylation of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate.
2. Hydrolysis with aqueous NaOH to free acid.
3. Nitration with oleum/fuming nitric acid.
4. Carboxamide formation with refluxing thionyl chloride/NH4OH.
5. Reduction of nitro group to amino.
6. Acylation with 2-ethoxybenzoyl chloride.
7. Cyclization.
8. Sulfonation to the chlorosulfonyl derivative.
9. Condensation with 1-methylpiperazine.


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Notes about Viagra UK
1. Aubetawe Bro Morgannwg University NHS Trust (2008-07-04). "Research at ABM". Viagra UK
2. "Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction". Int J Impot Res 8 (2): 47–52. 1996. PMID 8858389. Viagra UK
3. Terrett NK et al. (1996). "Sildenafil (Viagra), a potent and selective inhibitor of Type 5 cGMP phosphodiesterase with utility for the treatment of male erectile dysfunction". Bioorg Med Chem Lett 6: 1819–1824. doi:10.1016/0960-894X(96)00323-X. Viagra UK
4. Kling J (1998). "From hypertension to angina to Viagra" . Mod Drug Discov 1: 31–38. Viagra UK
5. Bellis M. "Viagra, the patenting of an aphrodisiac". About.com. Viagra UK
6. "Urban Dictionary: Vitamin V". Urban Dictionary. January 16, 2009.  Viagra UK
7. Keith A (2000). "The economics of Viagra" (PDF). Health Aff (Millwood) 19 (2): 147–57. doi:10.1377/hlthaff.19.2.147. PMID
10718028. Viagra UK
8. McGuire, Stephen (1 January 2007). "Cialis gaining market share worldwide". Medical Marketing & Media. Haymarket Media.  Viagra UK
9. Mullin, Rick (June 20, 2005). "Viagra". Chemical & Engineering News 83 (25).  Viagra UK
10. Berenson, Alex (December 4, 2005). "Sales of Impotence Drugs Fall, Defying Expectations". The New York Times.  Viagra UK
11. Buy Genuine Prescription Viagra UK
12. "Viagra ruling upsets Pfizer". Telegraph Media Group Limited. 23 January 2002.  Viagra UK
13. "Pfizer Loses UK Battle on Viagra Patent". UroToday. Thomson Reuters. 17 June 2002.  Viagra UK
14. Webb, D.J.; Freestone, S.; Allen, M.J.; Muirhead, G.J. (March 4, 1999). "Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist". Am. J. Cardiol. 83 (5A): 21C–28C. doi:10.1016/S0002-9149(99)00044-2. PMID 10078539. Viagra UK
15. "Viagra Clinical Pharmacology". RxList.com. 2008. Viagra UK
16. Vardi M, Nini A (2007). "Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus". Cochrane Database Syst Rev (1): CD002187. doi:10.1002/14651858.CD002187.pub3. PMID 17253475. Viagra UK
17. Nurnberg HG, Hensley PL, Gelenberg AJ, Fava M, Lauriello J, Paine S (January 2003). "Treatment of antidepressant-associated sexual dysfunction with sildenafil: a randomized controlled trial". JAMA 289 (1): 56–64. doi:10.1001/jama.289.1.56. PMID 12503977. Viagra UK
18. Nurnberg HG, Hensley PL, Lauriello J, Parker LM, Keith SJ (August 1999). "Sildenafil for women patients with antidepressant-induced sexual dysfunction". Psychiatr Serv 50 (8): 1076–8. PMID 10445658. Viagra UK 
19. Nurnberg HG, Hensley PL, Heiman JR, Croft HA, Debattista C, Paine S (2008). "Sildenafil Treatment of Women With Antidepressant-Associated Sexual Dysfunction". JAMA 300 (4): 395–404. doi:10.1001/jama.300.4.395. PMID 18647982. Viagra UK
20. Pfizer, Inc. (June 6, 2005). "FDA Approves Pfizer's Revatio as Treatment for Pulmonary Arterial Hypertension". 2005 News Releases. Pfizer.  Viagra UK
21. Richalet JP, Gratadour P, Robach P, et al. (2005). "Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension". Am. J. Respir. Crit. Care Med. 171 (3): 275–81. doi:10.1164/rccm.200406-804OC. PMID 15516532. Viagra UK
22. Perimenis P (2005). "Sildenafil for the treatment of altitude-induced hypoxaemia". Expert Opin Pharmacother 6 (5): 835–7. doi:10.1517/14656566.6.5.835. PMID 15934909. Viagra UK
23. Fagenholz PJ, Gutman JA, Murray AF, Harris NS (2007). "Treatment of high altitude pulmonary edema at 4240 m in Nepal". High Alt. Med. Biol. 8 (2): 139–46. doi:10.1089/ham.2007.1055. PMID 17584008. Viagra UK
24. "Source: Roger Clemens, host of athletes pop Viagra to help onfield performance". Daily News (Daily News). 10 June 2008. 
25. Peterson K (2001-03-21). "Young men add Viagra to their drug arsenal". USAToday.  Viagra UK
26. Smith, K; F Romanelli (2005). "Recreational use and misuse of phosphodiesterase 5 inhibitors". Journal of the American Pharmacists Association 45 (1): 63-75. Viagra UK
27. Mondaini, N; R Ponchietti, G H Muir, F Montorsi, F Di Loro, G Lombardi and M Rizzo (2003). "Sildenafil does not improve sexual function in men without erectile dysfunction but does reduce the postorgasmic refractory time". International Journal of Impotence Research 15: 225–228. Viagra UK
28. McCambridge, J; Mitcheson, L., Hunt, N., Winstock, A. (2006). "The rise of Viagra among British illicit drug users: 5-year survey data". Drug and Alcohol Review 25 (2): 111-113. Viagra UK
29. Eloi-Stiven, M; Channaveeraiah, N.a , Christos, P.J.c , Finkel, M.c , Reddy, R. (November 2007). "Does marijuana use play a role in the recreational use of sildenafil?". Journal of Family Practice 56 (11): 932. Viagra UK
30. Siegel-Itzkovich J (1999). "Viagra makes flowers stand up straight". Student BMJ (9).  Viagra UK
31. "The 2007 Ig Nobel Prize Winners". Improbable Research. 4 October 2007.  Viagra UK
32. Agostino, P. V.; Agostino PV, Plano SA, Golombek DA (2007). "Sildenafil accelerates reentrainment of circadian rhythms after advancing light schedules". Proc. Natl. Acad. Sci. U.S.A. 104 (23): 9834–9. doi:10.1073/pnas.0703388104. PMID 17519328. Viagra UK
33. Oh SS, Zou P, Low MY, Koh HL. Detection of sildenafil analogues in herbal products for erectile dysfunction. Journal of Toxicology and Environmental Health Part A. 2006 Nov;69(21):1951-8. PMID 16982533. Viagra UK
34. Venhuis BJ, Blok-Tip L, de Kaste D. Designer drugs in herbal aphrodisiacs. Forensic Science International. 2008 May 20;177(2-3):e25-7. PMID 18178354. Viagra UK
35. "Pill Identifier". Drugs.com. "This site is intended for viewing by the USA audience only. If you are in another country, local laws may not permit access to the medical information contained in this site." Viagra UK
36. Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM (1999). "ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association". Journal of the American College of Cardiology 33 (1): 273–82. doi:10.1016/S0735-1097(98)00656-1. PMID 9935041. Viagra UK
37. "VIAGRA Prescribing Information" (PDF). Pfizer. October 2007. Viagra UK
38. "Viagra and vision". VisionWeb. 29 October 2001.  Viagra UK
39. "FDA Updates Labeling for Viagra, Cialis and Levitra for Rare Post-Marketing Reports of Eye Problems". United States Food and Drug Administration. 8 July 2005.  Viagra UK
40. "Nonarteritic ischemic optic neuropathy developing soon after use of sildenafil (viagra): a report of seven new cases". J Neuroophthalmol 25 (1): 9–13. 2005. PMID 15756125. Viagra UK
41. "Sildenafil (Viagra) associated anterior ischemic optic neuropathy". Arch Ophthalmol 118 (2): 291–2. 2000. PMID 10676804. Viagra UK
42. Pomeranz, H; Pomeranz HD, Smith KH, Hart WM, Egan RA (2002). "Sildenafil-associated nonarteritic anterior ischemic optic neuropathy". Ophthalmology 109 (3): 584–7. doi:10.1016/S0161-6420(01)00976-9. PMID 11874765. Viagra UK
43. "Anterior ischemic optic neuropathy associated with viagra". J Neuroophthalmol 21 (1): 22–5. 2001. PMID 11315976. Viagra UK
44. "A case of nonarteritic ischemic optic neuropathy (NAION) in a male patient taking sildenafil". Int J Clin Pharmacol Ther 40 (9): 422–3. 2002. PMID 12358159. Viagra UK
45. Akash, Raj; Akash R, Hrishikesh D, Amith P, Sabah S (2005). "Case report: association of combined nonarteritic anterior ischemic optic neuropathy (NAION) and obstruction of cilioretinal artery with overdose of Viagra". J Ocul Pharmacol Ther 24 (4): 315–7. doi:10.1089/jop.2005.21.315. PMID 16117695. Viagra UK
46. "FDA Announces Revisions to Labels for Cialis, Levitra and Viagra". United States Food and Drug Administration. 18 October 2007. Viagra UK
47. Kloner RA (2005). "Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions". Am J Cardiol 96 (12B): 42M–46M. doi:10.1016/j.amjcard.2005.07.011. PMID 16387566. Viagra UK
48. Dunn PJ (2005). "Synthesis of Commercial Phosphodiesterase(V) Inhibitors". Org Process Res Dev 2005 (1): 88–97. doi:10.1021/op040019c. Viagra UK



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