Sildenafil citrate, sold under the names Viagra, Revatio and (in the Indian subcontinent) Caverta, is a drug used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH), developed by the pharmaceutical company Pfizer. It is also capable of arousing women for greater sexual drive. Viagra pills, intended to treat impotence, are blue with the words "Pfizer" on one side and "VGR xx" (with xx representing 25, 50 or 100, the dose of that pill in milligrams) on the other. Its primary competitor on the market is tadalafil (Cialis). Chemical strucutre of citric acid. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules . ... DrugBank is a database available at the University of Alberta that provides information about thousands of products. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos)) is the biochemical modification of chemical compounds in living organisms and cells. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother. ... The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ... Oral (Russian: Уральск, Uralsk, also spelled Uralsk) is a city in western Kazakhstan, along the Ural (Zhayyq) River. ... Composite satellite image of the Indian subcontinent Map of South Asia. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Erectile dysfunction, also known as impotence, is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis for satisfactory sexual intercourse regardless of the capability of ejaculation. ... In medicine, pulmonary hypertension (PH) or pulmonary artery hypertension (PAH) is an increase in blood pressure in the pulmonary artery or lung vasculature. ... A pharmaceutical company (or drug company) is a company licensed to discover, develop, market and distribute drugs. ... Pfizer, Incorporated (NYSE: PFE), is a global pharmaceutical company, with headquarters in New York City. ... Tadalafil is a drug used to treat male erectile dysfunction (impotence). ...

History

Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizer's Sandwich, Kent research facility. It was initially studied for use in hypertension (high blood pressure) and angina pectoris (a form of ischaemic cardiovascular disease). Phase I clinical trials under the direction of Ian Osterloh suggested that the drug had little effect on angina, but that it could induce marked penile erections (Boolell et al 1996). Pfizer therefore decided to market it for erectile dysfunction, rather than for angina. The drug was patented in 1996, approved for use in erectile dysfunction by the FDA on March 27, 1998, becoming the first pill approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year (Kling 1998). It soon became a great success: annual sales of Viagra in the period 1999–2001 exceeded $1 billion. Location within the British Isles Arms of Sandwich Town Council Sandwich is an historic town in Kent, south-east England. ... For other forms of hypertension see hypertension (disambiguation) Hypertension or high blood pressure is a medical condition wherein the blood pressure is chronically elevated. ... In medicine, ischemia (Greek ισχαιμία, isch- is restriction, hema or haema is blood) is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. ... Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). ... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ... An erection of the penis occurs when engorgement of venous blood in two tubular structures at the bottom of the penis, the corpora cavernosa, results from a variety of stimuli. ... A patent is a set of exclusive rights granted by a state to a person for a fixed period of time in exchange for the regulated, public disclosure of certain details of a device, method, process or composition of matter (substance) (known as an invention) which is new, inventive, and... 1996 (MCMXCVI) was a leap year starting on Monday of the Gregorian calendar, and was designated the International Year for the Eradication of Poverty. ... The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... March 27 is the 86th day of the year in the Gregorian Calendar (87th in Leap years). ... 1998 (MCMXCVIII) was a common year starting on Thursday of the Gregorian calendar, and was designated the International Year of the Ocean. ... 1999 (MCMXCIX) was a common year starting on Friday, and was designated the International Year of Older Persons by the United Nations. ... 2001: A Space Odyssey. ... The word billion and its equivalents in other languages refer to one of two different numbers, depending on whether the writer is using the long or short scale. ...

The name "Viagra", like many drug names, is a marketing invention. It was possibly inspired by the Sanskrit word "vyāghra", which means "tiger". The word rhymes with "Niagara" (Niagara Falls is a popular honeymoon destination and Niagara, being such an impressive waterfall, evokes a sense of incredible erectile and ejaculatory strength). The sound of the word also suggests the words "vigor" and "virile". Sanskrit ( संस्कृतम्) is an Indo-European Classical language of India and a liturgical language of Hinduism, Buddhism, and Jainism. ... For other uses, see Niagara Falls (disambiguation). ... Hopetoun Falls near Otway National Park, Victoria, Australia A waterfall is usually a geological formation resulting from water, often in the form of a stream flowing over an erosion-resistant rock formation that forms a sudden break in elevation. ...

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. The "Viagra" name has become so well known that many fake aphrodisiacs now call themselves "herbal Viagra" or are presented as blue tablets imitating the shape and colour of Pfizer's product. A mixture of Viagra and ecstasy, called sextasy, has become popular among rave partygoers. Viagra is also informally known as "Vitamin V", "the Blue Pill", "Hard Drug", and goes by various other nicknames. Robert Joseph Dole (born July 22, 1923) is best known as a former Republican United States Senate Majority Leader and Senator from Kansas from 1969-1996. ... An aphrodisiac is an agent which acts on the mind and causes the arousal of the mood of sexual desire. ... MDMA (3,4-methylenedioxymethamphetamine), most commonly known today by the street name ecstasy, is a synthetic entactogen of the phenethylamine family whose primary effect is to stimulate the secretion of and inhibit the re-uptake of large amounts of serotonin as well as dopamine and noradrenaline in the brain, causing... Sextasy is a drug mixture of methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy, and a prescription drug such as sildenafil citrate (Viagra), which is a PDE5 inhibitor used for erectile dysfunction. ...

It has been suggested that Viagra would lead to a marked drop in the demand for certain traditional remedies, such as tiger penises and rhinoceros horns and that the drug may therefore help to preserve these endangered species. However, this is unlikely in that these parts of endangered species are not only used to treat impotence. Rhinoceros horns, for example, are used as a treatment for high fever. Furthermore, since Viagra has not been shown to possess aphrodisiac properties, it is unclear that the natural remedies would compete with this new clinical drug. Binomial name Panthera tigris (Linnaeus, 1758) Tigers (Panthera tigris) are mammals of the Felidae family and one of four big cats in the Panthera genus. ... The penis (plural penises or penes) or phallus is an external male sexual organ. ... Genera Ceratotherium Dicerorhinus Diceros Rhinoceros Coelodonta (extinct)Elasmotherium (extinct) A rhinoceros (commonly called a rhino for short) is any of five surviving species of odd-toed ungulate in the family Rhinocerotidae. ... The American bison there are as few as 750 in 1890 due to extreme overhunting. ... An aphrodisiac is an agent which acts on the mind and causes the arousal of the mood of sexual desire. ...

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. A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. ...

Mechanism of action

Part of the physiological process of erection involves the parasympathetic nervous sytem causing the release of release nitric oxide (NO) in the corpus cavernosum of the penis. NO binds to the receptors of the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation (vasodilation) in the corpus cavernosum, resulting in increased inflow of blood and an erection. The chemical compound nitric oxide is a gas with chemical formula NO. It is an important signaling molecule in the body of mammals including humans, one of the few gaseous signaling molecules known. ... A corpus cavernosum is one of a pair of a sponge-like regions of erectile tissue which contain most of the blood in the male penis during erection. ... Guanylate cyclase (EC 4. ... Cyclic guanosine monophosphate (cGMP) is a second messenger derived from GTP. Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). ... Smooth muscle is a type of non-striated muscle, found within the walls of hollow organs; such as blood vessels, bladders, uteri. ...

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 cGMP in the corpus cavernosum, resulting in better erections. Without sexual stimulation and no activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include tadalafil (Cialis®) and vardenafil (Levitra®). Image:PDE5 1. ... A corpus cavernosum is one of a pair of a sponge-like regions of erectile tissue which contain most of the blood in the male penis during erection. ... Tadalafil is a drug used to treat male erectile dysfunction (impotence). ... Vardenafil (Levitra) is a PDE5 inhibitor used in the treatment of erectile dysfunction. ...

Sildenafil is metabolised by hepatic enzymes and excreted by both the liver and kidneys. If taken with a high fat meal, there may be a delay in absorption of sildenafil and the peak effect might be reduced slightly as the plasma concentration will be lowered. Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos)) is the biochemical modification of chemical compounds in living organisms and cells. ... The liver is one of the largest internal organs of the human body. ... Ribbon diagram of the catalytically perfect enzyme TIM. An enzyme is a protein that catalyzes, or speeds up, a chemical reaction. ... The liver is one of the largest internal organs of the human body. ... Human kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ...

Some reports have claimed that sildenafil causes enhanced sexual pleasure for women by increasing blood flow to the sexual organs. This lacks firm evidence, and it has also been suggested that this is part of an effort to invent a new disease - female sexual dysfunction - thus doubling the potential size of the market for this class of drugs.

Dosage and price

As with all prescription drugs, proper dosage is at the discretion of a licensed medical doctor. The dose of sildenafil is 25 mg to 100 mg taken once per day between 30 minutes to 4 hours before sexual intercourse. A prescription drug (or POM Prescription Only Medicine, in UK) is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained. ... The missionary position is the most commonly used position for sexual intercourse in humans The cowgirl sex position is a position frequently combined with kissing, caressing, and embracing of the paramour. ...

It is usually recommended to start with a dosage of 50 mg and then lower or raise the dosage as appropriate. The drug is sold in three dosages (25, 50, and 100 mg), all three costing about US$10 per pill. Sildenafil is not scored and it is not advisable to cut it to change dosage since the active compound is not distributed homogenously in the tablet.

Contraindications and side effects

Contraindications include: In medicine, a contraindication is a condition or factor that increases the risk involved in using a particular drug, carrying out a medical procedure or engaging in a particular activity. ...

• When taking nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate, sodium nitroprusside, amyl nitrite ("poppers") (Cheitlin et al 1999)
• 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)

Amongst sildenafil's serious adverse effects are: priapism, severe hypotension, myocardial infarction, ventricular arrhythmias, sudden death, stroke and increased intraocular pressure. Glyceryl trinitrate (GTN) is the pharmaceutical name for nitroglycerin. ... Sodium nitroprusside (Na3Fe(CN)5NO) is a potent peripheral vasodilator which affects both arterioles and venules. ... The chemical compound amyl nitrite (here referring to isoamyl nitrite) is an alkyl nitrite. ... The missionary position is the most commonly used position for sexual intercourse in humans The cowgirl sex position is a position frequently combined with kissing, caressing, and embracing of the paramour. ... In medicine (nephrology) renal function is an indication of the state of the kidney and its role in physiology. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... A stroke or cerebrovascular accident (CVA) occurs when the blood supply to a part of the brain is suddenly interrupted. ... A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream. ... A phosphodiesterase (PDE) is an enzyme that catalyzes the hydrolysis of phosphodiester bonds. ... Priapism (Greek πριαπισμός, the erection) is a painful and potentially harmful medical condition in which the erect penis (erection) does not return to its flaccid state (despite the absence of both physical and psychological stimulation). ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ... A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream. ... A stroke or cerebrovascular accident (CVA) occurs when the blood supply to a part of the brain is suddenly interrupted. ... Intraocular pressure is the fluid pressure inside the eye. ...

Common side effects include sneezing, headache, flushing, dyspepsia, prolonged erections, palpitations and photophobia. Visual changes including blurring of vision and a curious bluish tinge have also been reported.

Care should be exercised by patients who are also taking Protease inhibitors for the treatment of HIV. Protease inhibitors inhibit the metabolism of sildenafil, effectively multiplying the plasma levels of sildenafil, increasing the incidence and severity of side-effects. It is recommended that patients using protease inhibitors limit their use of sildenafil to no more than one 25-mg dose every 48 hours. Protease inhibitors are a class of medication used to treat or prevent viral infections. ... Human immunodeficiency virus, commonly known by the initialism HIV, formerly known as HTLV-III and lymphadenopathy-associated virus, is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. ...

In May of 2005, the U.S. Food and Drug Administration found that sildenafil could lead to vision impairment. An investigation is currently underway. Some patients developed nonarteritic ischemic optic neuropathy (NAION), an eye problem that can result in permanent vision loss. Combined with past reports, this study brings the total number of sildenafil-related NAION cases to 14. Look up May in Wiktionary, the free dictionary. ... 2005 (MMV) was a common year starting on Saturday of the Gregorian calendar. ... For other uses, see United States (disambiguation) and US (disambiguation). ... The Food and Drug Administration (FDA) of the United States is the government agency responsible for regulating food (human and animal), dietary supplements, drugs (human and animal), cosmetics, medical devices (human and animal), biologics, and blood products in the United States. ...

Some users complained of blurriness and some a loss of peripheral vision. It appears that there is a hereditary condition described as a "cup" in the retina that is the constant among all cases. Peripheral vision is a part of vision that occurs outside the very center of gaze. ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ...

Uses outside of erectile dysfunction

Pulmonary hypertension

As well as erectile dysfunction, sildenafil citrate is also effective in the rare disease pulmonary arterial hypertension (PAH). It relaxes the arterial wall, decreasing pulmonary arterial resistance and pressure, and thus the strain on the right side of the heart thus improving symptoms of right-sided heart failure. Because the distribution of PDE-5, which is primarily in the arterial wall smooth muscle in the lungs and penis, sildenafil acts selectively in both these areas without inducing vasodilation in other areas of the body. Pfizer submitted an additional registration for sildenafil to the FDA, and sildenafil was approved for this indication in June 2005. The preparation is named Revatio, avoiding confusion with Viagra, and the 20 milligram tablets are white and round. Sildenafil joins bosentan and prostacyclin, both of which are given by continuous infusion, as therapies for this condition. A rare disease has such a low prevalence in a population that a doctor in a busy general practice would not expect to see more than one case a year. ... In medicine, pulmonary hypertension (PH) or pulmonary artery hypertension (PAH) is an increase in blood pressure in the pulmonary artery or lung vasculature. ... 2005 (MMV) was a common year starting on Saturday of the Gregorian calendar. ... Bosentan is an endothelin receptor antagonist important in the treatment of pulmonary artery hypertension. ... Prostacyclin is a member of the family of lipid molecules known as eicosanoids. ...

Raynaud's phenomenon

In 2005, Dr. Roland Fries and colleagues reported that sildenafil cut the frequency of Raynaud's phenomenon attacks, reduced their duration by roughly one half, and more than quadrupled the mean capillary blood velocity. This was a double-blind, placebo-controlled crossover trial and the patients had both the primary and secondary forms and had all discontinued the more conventional treatments for this (Fries et al 2005). It had earlier been reported to be effective for Raynaud's in a 65-year-old woman with scleroderma and pulmonary hypotension (Rosenkranz et al 2003); (Rosenkranz et al 2004), and in nine women and one man treated by a Dr. Jack R. Lichtenstein of Annapolis, Maryland over a three-year period (Lichtenstein 2003). In medicine, Raynauds phenomenon is discoloration of the fingers or toes due to emotion or cold in a characteristic pattern in time: white, blue and red. ... Scleroderma is a rare, chronic disease characterized by excessive deposits of collagen. ...

See also

• Tadalafil (Cialis)
• Vardenafil (Levitra)
• Sani Abacha, suspected cause of his death

Tadalafil is a drug used to treat male erectile dysfunction (impotence). ... Vardenafil (Levitra) is a PDE5 inhibitor used in the treatment of erectile dysfunction. ... Abacha General Sani Abacha (20 September 1943 - 8 June 1998) was the military dictator of Nigeria from 1993 to 1998. ...

References

• Boolell M, Allen MJ, Ballard SA, Gepi-Attee S, Muirhead GJ, Naylor AM, Osterloh IH, Gingell C. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 1996;8:47-52. PMID 8858389.
• Cheitlin MD, Hutter AM Jr, Brindis RG, Ganz P, Kaul S, Russell RO Jr, Zusman RM. 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. 1999 Jan;33(1):273-82. Full text. PMID 9935041.
• Fries, Roland, Kaveh Shariat, Hubertus von Wilmowsky, and Michael Böhm (November 8, 2005). Sildenafil in the treatment of Raynaud's phenomenon resistant to vasodilatory therapy. Circulation 112 (19): 2980-5. PMID 16275885.
• Kling J. From hypertension to angina to Viagra. Mod Drug Discov 1998;1:31-38. Fulltext.
• Lichtenstein, Jack R. (November 18, 2003). Use of sildenafil citrate in Raynaud's phenomenon: Comment on the article by Thompson et al. Arthritis & Rheumatism 48 (1): 282-3. PMID 12528146.
• Pfizer, Inc. (June 6, 2005). FDA Approves Pfizer's Revatio as Treatment for Pulmonary Arterial Hypertension. (html) 2005 News Releases. Pfizer. URL accessed on December 27, 2005.
• Rosenkranz, Stephan (November 18, 2003). Sildenafil improved pulmonary hypertension and peripheral blood flow in a patient with scleroderma-associated lung fibrosis and the raynaud phenomenon. Annals of Internal Medicine 139 (10): 871-3. PMID 14623635. (PDF)
• Rosenkranz, Stephan (August 13, 2004). Langzeiteffekte von Sildenafil bei Sklerodermie-assoziierter pulmonaler Hypertonie und Raynaud-Syndrom (Long-term effects of sildenafil in a patient with scleroderma-associated pulmonary hypertension and Raynaud’s syndrome). Deutsche Medizinische Wochenschrift 129 (33): 1736-40. PMID 15295684 DOI:10.1055/s-2004-829025.
• Terrett, N. K. et al. 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. 1996, 6, 1819-1824.

November 8 is the 312th day of the year (313th in leap years) in the Gregorian Calendar, with 53 days remaining. ... 2005 (MMV) was a common year starting on Saturday of the Gregorian calendar. ... November 18 is the 322nd day of the year (323rd in leap years), with 43 remaining. ... 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ... December 27 is the 361st day of the year in the Gregorian Calendar. ... 2005 (MMV) was a common year starting on Saturday of the Gregorian calendar. ... November 18 is the 322nd day of the year (323rd in leap years), with 43 remaining. ... 2003 (MMIII) was a common year starting on Wednesday of the Gregorian calendar. ... August 13 is the 225th day of the year in the Gregorian Calendar (226th in leap years), with 140 days remaining. ... 2004 (MMIV) was a leap year starting on Thursday of the Gregorian calendar. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ...

External links

• Home page for Viagra
• Pfizer Pharmaceutical (Company website) - manufacturer of Viagra; prescribing information available in PDF format.
• FDA Web Site for Viagra Consumer Information
• Viagra Misunderstood Article describing what Viagra feels like
• How Viagra Works - Howstuffworks article

HowStuffWorks is a website created by Marshall Brain. ...