banner



Home  ›  What Is The Chemical Makeup Of Viagra

What Is The Chemical Makeup Of Viagra

Written By Sunday, June 5, 2022 Add Comment Edit

Medical drug for erectile dysfunction and pulmonary hypertension

Sildenafil
Sildenafil structure.svg
Sildenafil-from-xtal-3D-balls.png
Clinical data
Pronunciation sil-DEN-ə-fil
Merchandise names Viagra, Revatio, others
AHFS/Drugs.com Monograph
MedlinePlus a699015
License data
  • EU  EMA:past INN
  • US FDA: Sildenafil
Pregnancy
category
  • AU: B1[1]
Routes of
administration		 By mouth (tablets), intravenous
ATC lawmaking
  • G04BE03 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA : ℞-only
  • Great britain: over-the-counter (OTC) / P[2] [iii]
  • United states of america: ℞-but [4]
  • European union: Rx-merely [5] [6]
  • In general: ℞ (Prescription only)
Pharmacokinetic information
Bioavailability 41% (mean)[7]
Protein binding ~96%
Metabolism Liver: CYP3A4 (major route), CYP2C9 (minor route)
Metabolites N-desmethylsildenafil (~50% say-so for PDE5)
Onset of action 20 minutes
Elimination one-half-life 3–four hours
Excretion Feces (~80%), urine (~xiii%)[4]
Identifiers

IUPAC name

  • 5-{two-Ethoxy-v-[(4-methylpiperazin-ane-yl)sulfonyl]phenyl}-ane-methyl-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
CAS Number
  • 139755-83-ii check Y
  • citrate:171599-83-0 check Y
PubChem CID
  • 135398744
  • citrate: 135413523
DrugBank
  • DB00203 check Y
  • citrate:DBSALT000347 check Y
ChemSpider
  • 5023 check Y
  • citrate:56586 check Y
UNII
  • 3M7OB98Y7H
  • citrate:BW9B0ZE037 check Y
KEGG
  • D08514 check Y
  • citrate:D02229 check Y
ChEBI
  • CHEBI:9139 check Y
  • citrate:CHEBI:58987 check Y
ChEMBL
  • ChEMBL192 check Y
  • citrate:ChEMBL1737 check Y
PDB ligand
  • VIA (PDBe, RCSB PDB)
CompTox Dashboard (EPA)
  • DTXSID6023579 Edit this at Wikidata
ECHA InfoCard 100.122.676 Edit this at Wikidata
Chemical and physical data
Formula C 22 H 30 N half dozen O 4 South
Molar mass 474.58 m·mol−one
3D model (JSmol)
  • Interactive image

SMILES

  • CCCC1=NN(C2=C1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)C)OCC)C

InChI

  • InChI=1S/C22H30N6O4S/c1-5-7-17-nineteen-twenty(27(four)25-17)22(29)24-21(23-19)16-xiv-xv(8-9-xviii(16)32-half dozen-2)33(30,31)28-12-10-26(3)11-13-28/h8-ix,14H,5-vii,10-13H2,i-4H3,(H,23,24,29)☒ N

  • Key:BNRNXUUZRGQAQC-UHFFFAOYSA-North☒ N

☒ N check Y  (what is this?) (verify)

Sildenafil, sold under the brand proper noun Viagra among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension.[viii] [4] It is unclear if information technology is effective for treating sexual dysfunction in women.[8] It is taken by mouth or by injection into a vein.[8] Onset is typically within 20 minutes and lasts for about 2 hours.[8]

Mutual side effects include headaches, heartburn, and flushed skin.[8] Circumspection is advised in those with cardiovascular disease.[viii] Rare merely serious side effects include a prolonged erection (priapism) that can lead to damage to the penis, vision problems, and hearing loss.[8] Sildenafil should not be taken by people on nitrates such as nitroglycerin (glycerin trinitrate), as this may upshot in a serious drop in blood force per unit area.[8] Sildenafil should non be taken within four hours of taking an alpha blocker.

Sildenafil acts by blocking phosphodiesterase v (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis.[8] It requires sexual arousal, however, to work.[8] It likewise results in dilation of the blood vessels in the lungs.[8]

Pfizer originally discovered the medication in 1989 while looking for a handling for heart-related chest pain.[9] Information technology was approved for medical utilize in the Us and in the European Spousal relationship in 1998.[5] [eight] [9] [ten] In 2017, it was the 217th about ordinarily prescribed medication in the United states of america, with more than than two million prescriptions.[11] [12] In 2017, it became available as a generic medication subsequently final patents by Pfizer expired.[xiii] In the Britain, information technology is available over the counter.[14] Most of the Active Pharmaceutical Ingredient (API) in Sildenafil, Sildenafil citrate, is produced in Pfizer'south Ringaskiddy complex, County Cork, which is Pfizer's largest product facility outside of the United states.[15]

Medical uses

Pfizer Viagra tablet in the trademark bluish diamond shape

Sexual dysfunction

The principal indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete sexual intercourse). Its utilise is at present one of the standard treatments for erectile dysfunction, including for men with diabetes mellitus.[16]

Antidepressant-associated sexual dysfunction

Tentative evidence suggests that sildenafil may help men who feel antidepressant-induced erectile dysfunction.[17]

Pulmonary hypertension

While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of expiry or serious side furnishings.[18]

Raynaud's phenomenon

Sildenafil and other PDE5 inhibitors are used off-label to alleviate vasospasm and treat astringent ischemia and ulcers in fingers and toes for people with secondary Raynaud's phenomenon;[19] [xx] these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes.[nineteen] Equally of 2016,[update] their function more than generally in Raynaud's was not clear.[20]

High-distance pulmonary edema

Sildenafil has been studied for high-altitude pulmonary edema, merely its use is currently non recommended for that indication.[21]

Adverse effects

In clinical trials, the nigh common adverse furnishings of sildenafil apply included headache, flushing, indigestion, nasal congestion, and impaired vision, including photophobia and blurred vision.[four] Some sildenafil users have complained of seeing everything tinted blue (cyanopsia).[22] This cyanopsia tin be explained because Sildenafil, while selective for PDE5, does have a minor level of selectivity for PDE6, which is the phosphodiesterase found in the retina. Patients thus taking the drug may experience colorvision abnormalities. Some complained of blurriness and loss of peripheral vision. In July 2005, the U.Due south. Nutrient and Drug Assistants (FDA) establish that sildenafil could lead to vision impairment in rare cases,[23] and a number of studies have linked sildenafil apply with non-arteritic anterior ischemic optic neuropathy.[24]

Rare but serious adverse effects institute through postmarketing surveillance include prolonged erections, severe low claret pressure, myocardial infarction (heart attack), ventricular arrhythmias, stroke, increased intraocular pressure, and sudden hearing loss.[4] In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil, required a more prominent alarm of the potential risk of sudden hearing loss.[25]

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, finer multiplying the plasma levels of sildenafil, increasing the incidence and severity of side furnishings. Those using protease inhibitors are recommended to limit their use of sildenafil to no more than than ane 25 mg dose every 48 hours.[four] Other drugs that interfere with the metabolism of sildenafil include erythromycin and cimetidine, both of which tin can also lead to prolonged plasma half-life levels.[26]

The employ of sildenafil and an αone 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 upshot does not occur if they are taken at least 4 hours apart.[27]

Contraindications

Contraindications include:[4]

  • Concomitant use of nitric oxide donors, organic nitrites and nitrates,[28] such every bit:
    • nitroglycerin
    • isosorbide mononitrate
    • isosorbide dinitrate
    • sodium nitroprusside
    • alkyl nitrites (normally known as "poppers")
  • Concomitant use of soluble guanylyl cyclase stimulators, such equally riociguat
  • Known hypersensitivity to sildenafil

Sildenafil should non be used if sex is inadvisable due to underlying cardiovascular risk factors.[29]

Nonmedical employ

Recreational utilise

Sildenafil's popularity with young adults has increased over the years.[30] Sildenafil's trade proper name, Viagra, is widely recognized in popular civilization, and the drug's association with treating erectile dysfunction has led to its recreational utilise.[31] The reasons behind such utilize include the belief that the drug increases libido, improves sexual functioning,[31] or permanently increases penis size.[32] Studies on the effects of sildenafil when used recreationally are limited, but suggest information technology has little outcome when used by those not suffering from erectile dysfunction. In ane report, a 25 mg dose was shown to cause no significant change in erectile quality, but did reduce the postejaculatory refractory time.[33] This study as well noted a pregnant placebo effect in the control group.[33]

Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high amidst users of illegal drugs.[34] Sildenafil is sometimes used to counteract the effects of other substances, often illicit.[31] Some users mix it with methylenedioxymethamphetamine (MDMA, ecstasy), other stimulants, or opiates in an attempt to compensate for the common side consequence of erectile dysfunction, a combination known as "sextasy", "rockin' and rollin'" or "trail mix".[31] Mixing it with amyl nitrite, another vasodilator, is specially dangerous and potentially fatal.[31]

Jet lag research

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 sildenafil helps treat jet lag recovery in hamsters.[35] [36]

Sports

Professional athletes take been documented using sildenafil, assertive the opening of their blood vessels will enrich their muscles. In plough, they believe it will raise their performances.[37] [38]

Analogs

Acetildenafil and other synthetic structural analogs of sildenafil which are PDE5 inhibitors accept been found as adulterants in a number of "herbal" aphrodisiac products sold over-the-counter.[39] These analogs have non undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have unknown side-effect profiles.[40] Some attempts have been fabricated to ban these drugs, just progress has been slow so far, every bit, 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. Even so, at least one court case has resulted in a product being taken off the marketplace.[41]

The U.S. Nutrient and Drug Administration (FDA) has banned numerous products claiming to be Eurycoma longifolia that, in fact, contain only analogs of sildenafil.[42] [43] [44] Sellers of such false 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 in a case of fatal overdose.[45]

Mechanism of action

Crystal structure of human PDE5 with bound sildenafil, PDB entry 1udt [46]

Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation past cGMP-specific phosphodiesterase blazon 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.[47] Robert F. Furchgott, Ferid Murad, and Louis Ignarro won the Nobel Prize in Physiology or Medicine in 1998 for their independent written report of the metabolic pathway of nitric oxide in smooth muscle vasodilation.

The molecular mechanism of smoothen muscle relaxation involves the enzyme CGMP-dependent poly peptide kinase, as well known as PKG. This kinase is activated by cGMP and information technology phosphorylates multiple targets in the smooth musculus cells, namely myosin light chain phosphatase, RhoA, IP3 receptor, phospholipase C, and others.[48] Overall, this results in a decrease in intracellular calcium and desensitizing proteins to the effects of calcium, engendering smooth muscle relaxation.[48]

Sildenafil is a strong and selective inhibitor of cGMP-specific phosphodiesterase blazon 5 (PDE5), which is responsible for deposition of cGMP in the corpus cavernosum. The molecular structure of sildenafil is similar to that of cGMP and acts every bit a competitive binding amanuensis of PDE5 in the corpus cavernosum, resulting in more than cGMP and increased penile response to sexual stimulation.[47] [49] Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should non cause an erection. Other drugs that operate by the aforementioned mechanism include tadalafil (Cialis) and vardenafil (Levitra).

Sildenafil is broken down in the liver by hepatic metabolism using cytochrome p450 enzymes, mainly CYP450 3A4 (major route), but also by CYP2C9 (modest road) hepatic isoenzymes. The major product of metabolisation by these enzymes is Northward-desmethylated sildenafil, which is metabolised further. This metabolite as well has an affinity for the PDE receptors, about 40% of that of sildenafil. Thus, the metabolite is responsible for about 20% of sildenafil's action. Sildenafil is excreted as metabolites predominantly in the feces (about 80% of administered oral dose) and to a lesser extent in the urine (around 13% of the administered oral dose). If taken with a high-fat meal, absorption is reduced; the fourth dimension taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly 1-3rd.[50]

Route of assistants

  • When taken by mouth sildenafil for erectile dysfunction results in an average time to onset of erections of 27 minutes (ranging from 12 to 70 minutes).[51]
  • Under the natural language employ of sildenafil for erectile dysfunction results in an average onset of action of 15 minutes and lasting for an boilerplate of 40 minutes.[52]

There are also mouth spray preparations of sildenafil for faster onset of action.

Chemical synthesis

The preparation steps for synthesis of sildenafil are:[53]

  1. Methylation of 3-propylpyrazole-5-carboxylic acrid ethyl ester with hot dimethyl sulfate
  2. Hydrolysis with aqueous sodium hydroxide (NaOH) to complimentary acid
  3. Nitration with oleum/fuming nitric acid
  4. Carboxamide formation with refluxing thionyl chloride/NH4OH
  5. Reduction of nitro group to amino group
  6. Acylation with 2-ethoxybenzoyl chloride
  7. Cyclization
  8. Sulfonation to the chlorosulfonyl derivative
  9. Condensation with 1-methylpiperazine.

History

Sildenafil (compound Uk-92,480) was synthesized past a group of pharmaceutical chemists working at Pfizer's Sandwich, Kent, research facility in England. It was initially studied for use in hypertension (high claret pressure) and angina pectoris (a symptom of ischaemic heart disease). The first clinical trials were conducted in Morriston Infirmary in Swansea.[54] Phase I clinical trials under the direction of Ian Osterloh suggested the drug had little event on angina, but information technology could induce marked penile erections.[55] [56] Pfizer therefore decided to market place it for erectile dysfunction, rather than for angina; this determination became an oftentimes-cited case of drug repositioning.[57] [58] The drug was patented in 1996, approved for use in erectile dysfunction by the FDA on 27 March 1998, becoming the first oral handling canonical to care for erectile dysfunction in the United States, and offered for sale in the United States later that twelvemonth.[59] It soon became a groovy success: annual sales of Viagra peaked in 2008 at US$i.934 billion.[threescore]

Social club and culture

Marketing and sales

Bulk handbag of counterfeit Viagra

In the Us, even though sildenafil is available but past prescription from a doctor, information technology was advertised direct to consumers on TV (famously existence endorsed by sometime United states of america Senator Bob Dole and football star Pelé). Numerous sites on the Internet offer Viagra for sale after an "online consultation", often a simple web questionnaire.[61] [62] The Viagra name has become and so well known that many faux aphrodisiacs now call themselves "herbal viagra" or are presented as blue tablets imitating the shape and colour of Pfizer'southward product. Viagra is as well informally known as "vitamin V", "the blue pill", or "blueish diamond", also as diverse other nicknames.

In 2000, Viagra sales accounted for 92% of the global market for prescribed erectile dysfunction pills.[63] By 2007, Viagra's global share had plunged to about fifty%[64] due to several factors, including the entry of Cialis and Levitra, along with several counterfeits and clones, and reports of vision loss in people taking PDE5 inhibitors.[65] [66] In 2008, the FDA forced Pfizer to remove Viva Cruiser, an advergame for Viagra, from appearing on Forbes.com, after the game failed to disclose risk information almost the drug.[67] [68]

In Feb 2007, it was announced that Boots, the UK chemist's chain, would try over-the-counter sales of Viagra in stores in Manchester, England. Men between the ages of 30 and 65 would exist eligible to buy four tablets after a consultation with a pharmacist.[69] In 2017, the Medicines and Healthcare products Regulatory Agency (MHRA) enacted legislation that expanded this nationwide,[70] assuasive a item branded formulation of Sildenafil, Viagra Connect (l mg), to be sold over the counter and without a prescription throughout the UK from early 2018. While the sale remains bailiwick to a consultation with a pharmacist, the other restrictions from the trial have been removed, allowing customers over the age of xviii to buy an unlimited number of pills.[71] The decision was made, in function, to reduce online sales of apocryphal and potentially dangerous erectile dysfunction treatments.

On six May 2013, Pfizer, which articles Viagra, told the Associated Press they will brainstorm selling the drug directly to people on its website.[72]

Pfizer's patents on Viagra expired exterior the US in 2012; in the United states they were set to expire, but Pfizer settled litigation with each of Mylan and Teva which agreed that both companies could introduce generics in the The states on xi December 2017.[73] [74] In December 2017, Pfizer released its ain generic version of Viagra.[75] [76]

As of 2018[update], the U.S. Food and Drug Administration has approved 15 drug manufacturers to market place generic sildenafil in the United states of america. Seven of these companies are based in India. This is likely to pb to dramatic cost reductions.[77] [78]

Counterfeits

Apocryphal Viagra, despite mostly being cheaper,[79] can comprise harmful substances or substances that touch how Viagra works, such equally blue printer ink, amphetamines, metronidazole, boric acid, and rat poison.[80]

Viagra is one of the world'southward most counterfeited medicines.[81] [82] According to a Pfizer study, around 80% of sites claiming to sell Viagra were selling counterfeits.[fourscore]

Regional issues

Brazil

Pfizer'south patent on sildenafil citrate expired in Brazil in 2010.[83]

Canada

In Canada, Pfizer'south patent 2,324,324 for Revatio (sildenafil used to treat pulmonary hypertension) was plant invalid by the Federal Courtroom in June 2010, on an application past Ratiopharm Inc.[84] [85]

On 8 November 2012, the Supreme Court of Canada ruled that Pfizer'south patent two,163,446 on Viagra was invalid from the beginning because the company did not provide full disclosure in its application. The decision, Teva Canada Ltd. five. Pfizer Canada Inc., pointed to section 27(3)(b) of The Patent Human activity which requires that disclosure must include sufficient information "to enable whatsoever person skilled in the art or science to which information technology pertains" to produce information technology. It added further: "As a matter of policy and sound statutory interpretation, patentees cannot be allowed to 'game' the system in this way. This, in my view, is the cardinal issue in this entreatment."[86]

Teva Canada launched Novo-Sildenafil, a generic version of Viagra, on the 24-hour interval the Supreme Court of Canada released its conclusion.[87] [88] [89] To remain competitive, Pfizer then reduced the price of Viagra in Canada.[90] Notwithstanding, on 9 November 2012, Pfizer filed a motility for a re-hearing of the appeal in the Supreme Court of Canada,[91] on the grounds that the court accidentally exceeded its jurisdiction past voiding the patent.[92] Finally, on 22 Apr 2013, the Supreme Courtroom of Canada invalidated Pfizer's patent altogether.[93]

China

Manufacture and sale of sildenafil citrate drugs is mutual in China, where Pfizer'south patent claim is not widely enforced.

Arab republic of egypt

Egypt approved Viagra for sale in 2002, but presently after immune local companies to produce generic versions of the drug, citing the interests of poor people who would not exist able to afford Pfizer'due south price.[94]

European Marriage

Sildenafil 100 milligram tablets - (prescription in the European Union)

Pfizer's patent on sildenafil citrate expired in some fellow member countries of the Eu, Austria, Denmark, France, Germany, Ireland, Italy, Holland, Spain, Sweden, the U.k. and Switzerland on 21 June 2013.[95] [96] [97] A UK patent held by Pfizer on the apply of PDE5 inhibitors (come across below) equally handling of impotence was invalidated in 2000 because of obviousness; this conclusion was upheld on entreatment in 2002.[98] [99]

Bharat

Manufacture and sale of sildenafil citrate drugs known as "generic Viagra" is common in Republic of india, where Pfizer'south patent claim does not apply. Trade names include Kamagra (Ajanta Pharma), Silagra (Cipla), Edegra (Sun Pharmaceutical), Penegra (Zydus Cadila), Manly (Cooper Pharma) and Zenegra (Alkem Laboratories).

New Zealand

Sildenafil was reclassified in New Zealand in 2014 so information technology could exist bought over the counter from a pharmacist. Information technology is idea that this reduced sales over the Internet and was safer as men could exist referred for medical advice if appropriate.[100]

South Korea

In 1999 Republic of korea granted two patents to Pfizer related to sildenafil. The beginning certificate guaranteed sole production and auction of the substance until 2012, while the 2d gave Pfizer the exclusive use to treating erectile dysfunction with sildenafil until 2014.[101] In 2011 Hanmi Pharmaceutical and CJ CheilJedang launched a conform against the exclusive apply patent. The Korean Court system made a ruling confronting Pfizer in June 2012, allowing for the unhindered domestic production of generic prescription sildenafil.[102]

During 2012 Viagra lost its position as the peak selling erectile dysfunction treatment in South Korea. This evolution was credited largely "due to the introduction of generic products." Generic sildenafil became publicly available in May. Sales of PalPal past Hanmi Pharmaceuticals totalled ₩22 billion or about 86% the market share of Viagra that yr.[103] Past 2017 at that place were over l generic sildenafil pills available. During that year Viagra sales slumped to 38% that of Palpal.[104]

United Kingdom

At that place were 2,958,199 prescriptions for Sildenafil in 2016 in England, compared with i,042,431 in 2006.[105]

In 2018, Viagra Connect, a particular formulation of Sildenafil marketed by Pfizer, became bachelor for auction without a prescription in the Uk,[71] in an attempt to widen availability and reduce demand for counterfeit products.

United States

Sildenafil is bachelor as a generic drug in the Usa, labeled for pulmonary arterial hypertension.[106] As of 2016[update] branded pills price about 50 times more than than generic ones.[106] In the U.s.a. as of 2015[update] the branded 50 mg pill cost is between 25.17 and US$37.88.[107]

In the United States, Pfizer received ii patents for sildenafil: 1 for its indication to treat cardiovascular disease (marketed as Revatio) and another for its indication to care for erectile dysfunction (marketed as Viagra). The substance is the same nether both trade names.[106]

In 1992, Pfizer filed a patent covering the substance sildenafil and its utilize to treat cardiovascular diseases.[108] This would be marketed equally Revatio. The patent was published in 1993 and expired in 2012. The patent on Revatio (indicated for pulmonary arterial hypertension rather than erectile dysfunction) expired in belatedly 2012. Generic versions of this low-dose form of sildenafil take been available in the U.Due south. from a number of manufacturers, including Greenstone, Mylan, and Watson, since early 2013.[109] Health care providers may prescribe generic sildenafil for erectile dysfunction.[106] However, the generic is not available in the same dosages equally branded Viagra, so using dosages typically required for treating ED requires patients to take multiple pills.[106]

In 1994, Pfizer filed a patent roofing the utilize of sildenafil to treat erectile dysfunction.[110] This would be marketed as Viagra. This patent was published in 2002 and will expire in 2019. Teva sued to have the latter patent invalidated, merely Pfizer prevailed in an Baronial 2011 federal district courtroom instance.[111] An understanding with Pfizer immune Teva to brainstorm to provide the generic drug in December 2017.[106]

References

  1. ^ "Sildenafil Utilise During Pregnancy". Drugs.com. 7 Oct 2019. Retrieved half-dozen October 2020.
  2. ^ "Viagra 25mg film-coated tablets - Summary of Production Characteristics (SmPC)". (emc). 7 Baronial 2020. Retrieved half dozen October 2020.
  3. ^ "Viagra Connect 50 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 5 December 2017. Retrieved 6 Oct 2020.
  4. ^ a b c d due east f thousand "Viagra- sildenafil citrate tablet, film coated". DailyMed . Retrieved 6 October 2020.
  5. ^ a b "Viagra EPAR". European Medicines Bureau . Retrieved 6 October 2020.
  6. ^ "Revatio EPAR". European Medicines Agency . Retrieved half-dozen October 2020.
  7. ^ Nichols DJ, Muirhead GJ, Harness JA (6 March 2002). "Pharmacokinetics of sildenafil later unmarried oral doses in good for you male person subjects: accented bioavailability, food effects and dose proportionality". British Periodical of Clinical Pharmacology. 53 (Suppl one): 5S–12S. doi:10.1046/j.0306-5251.2001.00027.10. PMC1874258. PMID 11879254.
  8. ^ a b c d due east f g h i j thousand 50 "Sildenafil Citrate". The American Society of Health-Organization Pharmacists. Retrieved 1 Dec 2014.
  9. ^ a b Goldstein I, Burnett AL, Rosen RC, Park PW, Stecher VJ (January 2019). "The Serendipitous Story of Sildenafil: An Unexpected Oral Therapy for Erectile Dysfunction". Sexual Medicine Reviews. 7 (i): 115–128. doi:10.1016/j.sxmr.2018.06.005. PMID 30301707. S2CID 52945888.
  10. ^ "Drug Approval Package: Viagra (sildenafil citrate) NDA #020895". U.South. Food and Drug Assistants (FDA). 27 March 1998. Retrieved 15 February 2021.
  11. ^ "The Top 300 of 2020". ClinCalc . Retrieved 11 April 2020.
  12. ^ "Sildenafil - Drug Usage Statistics". ClinCalc . Retrieved 11 April 2020.
  13. ^ Gordon Southward (11 December 2017). "Generic Viagra: Two versions of sildenafil hit the market today". CBS News . Retrieved 24 November 2018.
  14. ^ LaMattina J. "With Viagra At present Available Over-The-Counter In The U.K., Will The U.S. Follow Adjust?". Forbes . Retrieved 24 November 2018.
  15. ^ "Pfizer Synthesis Facility, Ringaskiddy, Ireland - Pharmaceutical Engineering". world wide web.pharmaceutical-engineering science.com . Retrieved 10 April 2021.
  16. ^ Vardi Thou, Nini A (January 2007). "Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus". The Cochrane Database of Systematic Reviews (1): CD002187. doi:x.1002/14651858.CD002187.pub3. PMC6718223. PMID 17253475.
  17. ^ Taylor MJ, Rudkin L, Bullemor-Mean solar day P, Lubin J, Chukwujekwu C, Hawton Thousand (May 2013). "Strategies for managing sexual dysfunction induced by antidepressant medication". The Cochrane Database of Systematic Reviews (v): CD003382. doi:10.1002/14651858.CD003382.pub3. PMID 23728643.
  18. ^ Wang RC, Jiang FM, Zheng QL, Li CT, Peng XY, He CY, et al. (March 2014). "Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review". Respiratory Medicine. 108 (iii): 531–seven. doi:x.1016/j.rmed.2014.01.003. PMID 24462476. Retrieved 5 Nov 2016.
  19. ^ a b Roustit M, Blaise S, Allanore Y, Carpentier PH, Caglayan E, Cracowski JL (Oct 2013). "Phosphodiesterase-5 inhibitors for the treatment of secondary Raynaud's phenomenon: systematic review and meta-analysis of randomised trials". Register of the Rheumatic Diseases. 72 (10): 1696–nine. doi:10.1136/annrheumdis-2012-202836. PMID 23426043. S2CID 33666968. PDE-5 inhibitors appear to have pregnant merely moderate efficacy in secondary [Raynaud's phenomenon].
  20. ^ a b Linnemann B, Erbe M (2016). "Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative handling options". VASA. Zeitschrift Fur Gefasskrankheiten. 45 (three): 201–12. doi:10.1024/0301-1526/a000526. PMID 27129065. Phosphodiesterase inhibitors (eastward.g., sildenafil) can also improve [Raynaud's phenomenon] symptoms and ulcer healing
  21. ^ Nieto Estrada VH, Molano Franco D, Medina RD, Gonzalez Garay AG, Martí-Carvajal AJ, Arevalo-Rodriguez I (June 2017). "Interventions for preventing high altitude illness: Office 1. Ordinarily-used classes of drugs". The Cochrane Database of Systematic Reviews. half-dozen (12): CD009761. doi:10.1002/14651858.CD009761.pub2. PMC6481751. PMID 28653390.
  22. ^ "Viagra and Vision". VisionWeb. 29 October 2001. Archived from the original on x June 2017. Retrieved five Nov 2016.
  23. ^ "FDA Updates Labeling for Viagra, Cialis and Levitra for Rare Post-Marketing Reports of Eye Problems" (Press release). U.S. Food and Drug Administration. 8 July 2005. Archived from the original on 22 October 2016. Retrieved v November 2016.
  24. ^ Laties AM (January 2009). "Vision disorders and phosphodiesterase type 5 inhibitors: a review of the evidence to appointment". Drug Safety. 32 (1): 1–18. doi:10.2165/00002018-200932010-00001. PMID 19132801. S2CID 207296076.
  25. ^ "FDA Announces Revisions to Labels for Cialis, Levitra and Viagra". U.South. Food and Drug Administration (FDA). eighteen October 2007. Archived from the original on 22 October 2016. Retrieved 5 November 2016.
  26. ^ Schwartz BG, Kloner RA (July 2010). "Drug interactions with phosphodiesterase-5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension". Circulation. 122 (1): 88–95. doi:10.1161/CIRCULATIONAHA.110.944603. PMID 20606131. S2CID 13207143.
  27. ^ Kloner RA (December 2005). "Pharmacology and drug interaction effects of the phosphodiesterase 5 inhibitors: focus on alpha-blocker interactions". The American Periodical of Cardiology. 96 (12B): 42M–46M. doi:10.1016/j.amjcard.2005.07.011. PMID 16387566.
  28. ^ Cheitlin Doc, Hutter AM, Brindis RG, Ganz P, Kaul S, Russell RO, Zusman RM (January 1999). "ACC/AHA proficient consensus document. Utilise of sildenafil (Viagra) in patients with cardiovascular illness. American Higher of Cardiology/American Eye Association". Journal of the American College of Cardiology. 33 (1): 273–82. doi:ten.1016/S0735-1097(98)00656-1. PMID 9935041.
  29. ^ "Viagra (Sildenafil Citrate): Side Effects, Interactions, Warning, Dosage & Uses". RxList . Retrieved 11 July 2018.
  30. ^ Peterson K (21 March 2001). "Young men add Viagra to their drug armory". United states Today.
  31. ^ a b c d east Smith KM, Romanelli F (2005). "Recreational use and misuse of phosphodiesterase 5 inhibitors". Periodical of the American Pharmacists Clan. 45 (i): 63–72, quiz 73–5. doi:10.1331/1544345052843165. PMID 15730119.
  32. ^ "Sildenafil Volition Not Affect Libido - Fact!". Retrieved xv July 2016.
  33. ^ a b Mondaini N, Ponchietti R, Muir GH, Montorsi F, Di Loro F, Lombardi G, Rizzo M (June 2003). "Sildenafil does not amend sexual part in men without erectile dysfunction just does reduce the postorgasmic refractory time". International Journal of Impotence Inquiry. fifteen (3): 225–8. doi:ten.1038/sj.ijir.3901005. PMID 12904810.
  34. ^ McCambridge J, Mitcheson 50, Hunt N, Winstock A (March 2006). "The rise of Viagra among British illicit drug users: five-year survey data". Drug and Booze Review. 25 (2): 111–3. doi:x.1080/09595230500537167. PMID 16627299. S2CID 40250895.
    - Eloi-Stiven ML, Channaveeraiah N, Christos PJ, Finkel M, Reddy R (November 2007). "Does marijuana use play a office in the recreational use of sildenafil?". The Journal of Family Exercise. 56 (xi): E1-four. PMID 17976333.
  35. ^ "The 2007 Ig Nobel Prize Winners". Improbable Enquiry. 4 October 2007. Archived from the original on 26 January 2013. Retrieved ten February 2009.
  36. ^ Agostino PV, Plano SA, Golombek DA (June 2007). "Sildenafil accelerates reentrainment of circadian rhythms after advancing lite schedules". Proceedings of the National Academy of Sciences of the United States of America. 104 (23): 9834–nine. Bibcode:2007PNAS..104.9834A. doi:10.1073/pnas.0703388104. PMC1887561. PMID 17519328.
  37. ^ Thompson T, Crimson C, O'Keefffe M, Vinton N (ten June 2008). "Source: Roger Clemens, host of athletes pop Viagra to assist onfield performance". Daily News. Archived from the original on 14 August 2020. Retrieved 10 February 2009.
  38. ^ Busbee J (28 November 2012). "Bears' Brandon Marshall says some NFL players use Viagra … ON THE FIELD". Yahoo! Sports. Archived from the original on five March 2016. Retrieved 28 Nov 2012.
  39. ^ Venhuis BJ, de Kaste D (October 2012). "Towards a decade of detecting new analogues of sildenafil, tadalafil and vardenafil in food supplements: a history, analytical aspects and health risks". Journal of Pharmaceutical and Biomedical Analysis. 69: 196–208. doi:10.1016/j.jpba.2012.02.014. PMID 22464558.
  40. ^ Oh SS, Zou P, Depression MY, Koh HL (November 2006). "Detection of sildenafil analogues in herbal products for erectile dysfunction". Journal of Toxicology and Environmental Health. Role A. 69 (21): 1951–8. doi:10.1080/15287390600751355. PMID 16982533. S2CID 40831895.
  41. ^ Venhuis BJ, Blok-Tip L, de Kaste D (May 2008). "Designer drugs in herbal aphrodisiacs". Forensic Scientific discipline International. 177 (2–three): e25-seven. doi:ten.1016/j.forsciint.2007.eleven.007. PMID 18178354.
  42. ^ "FDA letter to Libidus distributor". U.s. FDA. 11 July 2006. Archived from the original on iv March 2016.
  43. ^ "FDA Warns Consumers Well-nigh Dangerous Ingredients in "Dietary Supplements" Promoted for Sexual Enhancement". US FDA. 12 July 2006. Archived from the original on 18 January 2017.
  44. ^ "Hidden Risks of Erectile Dysfunction 'Treatments' Sold Online". US FDA. 21 Feb 2009. Retrieved eight December 2020.
  45. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Human being, 9th edition, Biomedical Publications, Seal Embankment, CA, 2011, pp. 1552–53. "Sildenafil" (PDF). Biomedical Publications. Archived from the original (PDF) on ten September 2011. Retrieved ane July 2011.
  46. ^ Sung BJ, Hwang KY, Jeon YH, Lee JI, Heo YS, Kim JH, et al. (September 2003). "Construction of the catalytic domain of human phosphodiesterase 5 with bound drug molecules". Nature. 425 (6953): 98–102. Bibcode:2003Natur.425...98S. doi:10.1038/nature01914. PMID 12955149. S2CID 4404590.
  47. ^ a b Webb DJ, Freestone South, Allen MJ, Muirhead GJ (March 1999). "Sildenafil citrate and claret-pressure level-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist". The American Journal of Cardiology. 83 (5A): 21C–28C. doi:10.1016/S0002-9149(99)00044-2. PMID 10078539.
  48. ^ a b Francis SH, Busch JL, Corbin JD, Sibley D (September 2010). "cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action". Pharmacological Reviews. 62 (iii): 525–63. doi:10.1124/pr.110.002907. PMC2964902. PMID 20716671.
  49. ^ Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA (May 1998). "Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group". The New England Journal of Medicine. 338 (20): 1397–1404. doi:10.1056/NEJM199805143382001. PMID 9580646.
  50. ^ "Viagra Clinical Pharmacology". RxList.com. 2008. Retrieved xx August 2008.
  51. ^ Eardley I, Ellis P, Boolell One thousand, Wulff M (2002). "Onset and duration of action of sildenafil for the treatment of erectile dysfunction". British Journal of Clinical Pharmacology. 53 (Suppl one): 61S–65S. doi:10.1046/j.0306-5251.2001.00034.x. PMC1874251. PMID 11879261.
  52. ^ Deveci S, Peşkircioğlu L, Aygün C, Tekin MI, Dirim A, Ozkardeş H (Nov 2004). "Sublingual sildenafil in the treatment of erectile dysfunction: faster onset of activity with less dose". International Journal of Urology. 11 (11): 989–92. doi:x.1111/j.1442-2042.2004.00933.x. PMID 15509203. S2CID 28302024.
  53. ^ Dunn PJ (2005). "Synthesis of Commercial Phosphodiesterase(V) Inhibitors". Org Process Res Dev. 2005 (one): 88–97. doi:10.1021/op040019c. S2CID 93589067.
  54. ^ "Research". ABM. Abertawe Bro Morgannwg University Health Board. 4 July 2008. Archived from the original on 26 September 2008. Retrieved vi August 2008. Our clinicians regularly offer patients the opportunity to take part in trials of new drugs and treatments. Morriston Infirmary in Swansea, was the showtime in the earth to trial Viagra!
  55. ^ Boolell M, Allen MJ, Ballard SA, Gepi-Attee Southward, Muirhead GJ, Naylor AM, et al. (June 1996). "Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction". International Periodical of Impotence Research. 8 (two): 47–52. PMID 8858389.
  56. ^ Terrett NK, Bong AS, Dark-brown D, Elllis P (1996). "Sildenafil (Viagra), a potent and selective inhibitor of Type 5 cGMP phosphodiesterase with utility for the treatment of male person erectile dysfunction". Bioorg Med Chem Lett. half dozen (15): 1819–24. doi:10.1016/0960-894X(96)00323-10.
  57. ^ Ashburn TT, Thor KB (August 2004). "Drug repositioning: identifying and developing new uses for existing drugs". Nature Reviews. Drug Discovery. 3 (8): 673–83. doi:10.1038/nrd1468. PMID 15286734. S2CID 205475073.
  58. ^ Institute of Medicine (2014). Drug Repurposing and Repositioning: Workshop Summary. National Academies Press. ISBN9780309302043.
  59. ^ Kling J (1998). "From hypertension to angina to Viagra". Modern. Drug Discov. one: 31–38. ISSN 1532-4486. OCLC 41105083.
  60. ^ "Portions of the 2010 Financial Report". Retrieved xv July 2016.
  61. ^ Ciment J (Nov 1999). "Health situation in former communist bloc is dire, says Unicef". BMJ. 319 (7221): 1324. doi:10.1136/bmj.319.7221.1324g. PMC1174637. PMID 10567131.
  62. ^ Devine A (29 September 2008). "Chemists plan to sell Viagra on the internet". Daily Tape . Retrieved thirty April 2012.
  63. ^ Keith A (2000). "The economics of Viagra". Health Affairs. 19 (2): 147–57. doi:10.1377/hlthaff.19.2.147. PMID 10718028.
  64. ^ McGuire S (i Jan 2007). "Cialis gaining marketplace share worldwide". Medical Marketing & Media. Haymarket Media. Archived from the original on 3 Jan 2009. Retrieved 10 February 2009.
  65. ^ Mullin R (20 June 2005). "Viagra". Chemical & Engineering News. 83 (25). Retrieved 20 August 2008.
  66. ^ Berenson A (four December 2005). "Sales of Impotence Drugs Fall, Defying Expectations". The New York Times . Retrieved twenty August 2008.
  67. ^ "Pfizer Courting More Controversy with Viagra 'Advergaming'". world wide web.cbsnews.com . Retrieved 19 December 2019.
  68. ^ "FDA gave Pfizer hard fourth dimension over Viagra game". Engadget . Retrieved 19 Dec 2019.
  69. ^ "Over-the-counter Viagra piloted". BBC News. xi February 2007. Retrieved 10 Feb 2009.
  70. ^ "Viagra can be sold over the counter". BBC News. 28 November 2017. Retrieved 5 April 2018.
  71. ^ a b "Viagra at present available over the counter without prescription in the United kingdom of great britain and northern ireland". The Independent. 27 March 2018. Retrieved 5 April 2018.
  72. ^ "Pfizer to sell Viagra online, in outset for Big Pharma: AP". CBS News. Associated Printing. Retrieved half dozen May 2013.
  73. ^ Helfand C (14 April 2015). "The coming generics threat to Pfizer'due south Viagra make just got scarier". FiercePharma.
  74. ^ "Viagra to become generic in 2017 according to Pfizer agreement". CBS News. 17 Dec 2013.
  75. ^ Nocera J (6 December 2017). "Sexual practice, Drugs and That Little Bluish Pill". Bloomberg. Retrieved x December 2017.
  76. ^ Mukherjee S (six December 2017). "Why Pfizer Is About to Slash Viagra'south Price in One-half". Fortune . Retrieved 6 Dec 2017.
  77. ^ Chandna H (vii August 2018). "Pfizer to lose patent of drug Viagra, Indian companies gear up with copycat versions: Pfizer'southward patent for the formulation of Viagra, used to treat impotence in men, ends in the US in 2020". Hindustan Times. New Delhi. Retrieved x August 2018.
  78. ^ "Fix to conquer US, Indian 'Viagras' may give Pfizer a hard Fourth dimension". The Economic Times. Mumbai. 3 August 2018. Retrieved 10 August 2010.
  79. ^ "Record corporeality of counterfeit Viagra seized". www.bbc.com. 12 May 2016. Archived from the original on 19 November 2016. Retrieved 26 December 2016.
  80. ^ a b Amerman D (22 May 2012). "Apocryphal Viagra, Cialis, Levitra: The Ultimate Guide". AccessRx . Retrieved 10 Jan 2017.
  81. ^ Moran B (20 August 2013). "Cracking Down on Apocryphal Drugs — NOVA Next | PBS". PBS NOVA Next. Retrieved x January 2017.
  82. ^ Somra G (31 August 2015). "Online pharmacies suspected of counterfeit drug sales". CNN. Retrieved 10 January 2017.
  83. ^ in-PharmaTechnologist.com. "Viagra patent expires in June, says Brazilian court". Retrieved fifteen July 2016.
  84. ^ "Revatio patent ruled invalid for lack of sound prediction and obviousness". Canadian Engineering & IP Constabulary. Stikeman Elliott. 18 June 2010. Archived from the original on iii March 2016. Retrieved 14 Nov 2012.
  85. ^ "Pfizer Canada Inc. 5. Ratiopharm Inc., 2010 FC 612". CanLII.
  86. ^ Teva Canada Ltd. v. Pfizer Canada Inc., 2012 SCC sixty at par. 80 (8 Nov 2012)
  87. ^ Spears J (8 Nov 2012). "Supreme Court ruling could lead to cheaper versions of Viagra". Toronto Star . Retrieved xiv Nov 2012.
  88. ^ Hanly Thou (8 November 2012). "Canadian Supreme court rules Viagra patent invalid". Digital Journal . Retrieved 14 November 2012.
  89. ^ "Viagra patent tossed out by Supreme Court: Decision allows generic versions of drug to be produced". CBC News. 8 November 2012. Retrieved fourteen November 2012.
  90. ^ "Pfizer Canada drops Viagra price after generic versions get Supreme Courtroom green lite". Financial Postal service. 22 November 2012. Retrieved 9 February 2013.
  91. ^ "SCC Case Information, Docket No. 33951". January 2001. Retrieved 14 November 2012.
  92. ^ Makin K (15 November 2012). "In rare move, Pfizer asks Supreme Courtroom to reconsider ruling that killed Viagra patent". The Globe and Mail . Retrieved 15 November 2012.
  93. ^ Henderson GL, D'Iorio H (22 April 2013). "The Supreme Court of Canada holds Pfizer'southward Viagra patent invalid". Lexology . Retrieved 27 December 2013.
  94. ^ Allam A (4 Oct 2002). "Seeking Investment, Egypt Tries Patent Laws". New York Times . Retrieved 1 April 2013.
  95. ^ "Actavis Launches Generic Viagra in Europe as Patents Elapse". Retrieved 25 October 2013.
  96. ^ Edwards J (21 Oct 2009). "What Will Happen When Viagra Goes Generic?". AccessRx.com. Retrieved 25 March 2011.
  97. ^ "Is Viagra about to lose its pulling power in the UK?". The Guardian. 3 June 2013. Retrieved thirteen June 2013.
  98. ^ Murray R (23 January 2002). "Viagra ruling upsets Pfizer". London: Telegraph Media Group Limited. Archived from the original on 22 August 2009. Retrieved 10 February 2009.
  99. ^ "Pfizer Loses UK Battle on Viagra Patent". UroToday. Thomson Reuters. 17 June 2002. Archived from the original on 25 June 2007. Retrieved ten February 2009.
  100. ^ "Viagra from the pharmacist: insight from reclassification in New Zealand". Pharmaceutical Journal. 31 January 2018. Retrieved 2 April 2018.
  101. ^ Herald, Korea (14 March 2012). "Generic Viagra developers queue upwards, but may take to wait". The Korea Herald . Retrieved 28 December 2021.
  102. ^ "Approved Viagra copies flood drugstores in Korea". Reuters. 1 June 2012. Retrieved 28 Dec 2021.
  103. ^ Herald, Korea (10 April 2013). "Viagra loses top spot in Korean market place". The Korea Herald . Retrieved 28 December 2021.
  104. ^ "Hanmi leads erectile dysfunction drug sales". KBR (in Korean). 12 December 2017. Retrieved 28 Dec 2021.
  105. ^ "Viagra prescriptions most triple in a decade". Pharmaceutical Periodical. 21 August 2017. Retrieved 8 October 2017.
  106. ^ a b c d e f Skinner Yard (iv March 2016). "Aye, In that location Is a Style to Become Generic Viagra". Consumer Reports . Retrieved 4 May 2016.
  107. ^ Langreth R (29 June 2016). "Decoding Big Pharma'due south Secret Drug Pricing Practices". Bloomberg. Retrieved 15 July 2016.
  108. ^ U.S. Patent 5,250,534
  109. ^ "Pfizer's Revatio Goes Generic". Zacks Equity Research. xv November 2012. Retrieved five October 2013.
  110. ^ U.Southward. Patent 6,469,012
  111. ^ "Pfizer Wins Viagra Patent Infringement Case Against Teva Pharmaceuticals". Bloomberg. 15 August 2011. Retrieved one April 2012.

External links

  • "Sildenafil". Drug Data Portal. U.S. National Library of Medicine.
  • "Sildenafil citrate". Drug Information Portal. U.Southward. National Library of Medicine.
  • Viagra at The Periodic Table of Videos (University of Nottingham)

[1]

  1. ^ Kayık Grand, Tüzün NŞ, Durdagi S (Oct 2017). "In silico blueprint of novel hERG-neutral sildenafil-like PDE5 inhibitors". Journal of Biomolecular Structure & Dynamics. 35 (13): 2830–2852. doi:10.1080/07391102.2016.1231634. PMID 27581752. S2CID 21682809.

Source: https://en.wikipedia.org/wiki/Sildenafil

Posted by: moakcamagirse.blogspot.com

0 Response to "What Is The Chemical Makeup Of Viagra"

Post a Comment

Subscribe to: Post Comments (Atom)

Iklan Atas Artikel

Iklan Tengah Artikel 1

Iklan Tengah Artikel 2

Iklan Bawah Artikel