Sildenafil citrate, sold as
Viagra,
Revatio and under various other trade names, is a
drugA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used to treat
erectile dysfunctionErectile dysfunction is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis sufficient for satisfactory sexual performance....
and
pulmonary arterial hypertensionIn medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
(PAH). It was developed and is being marketed by the
pharmaceutical companyThe pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies can deal in generic and/or brand medications. They are subject to a variety of laws and regulations regarding the patenting, testing and marketing of drugs.-History:The...
PfizerPfizer Incorporated is a pharmaceutical company, ranking number one in sales in the world. The company is based in New York City, with its research headquarters in Groton, Connecticut...
. It acts by inhibiting
cGMP specific phosphodiesterase type 5cGMP-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina....
, an
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
that regulates blood flow in the penis. Since becoming available in 1998, sildenafil has been the prime treatment for erectile dysfunction; its primary competitors on the market are
tadalafilTadalafil is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; it has recently been approved for the treatment of pulmonary arterial hypertension, and has been used for other conditions...
(Cialis) and
vardenafilVardenafil is a PDE5 inhibitor used for treating impotence that is sold under the trade name Levitra .-History:...
(Levitra).
History
Sildenafil (compound UK-92,480) was synthesized by a group of pharmaceutical chemists working at Pfizer's
Sandwich, KentSandwich is a historic town in Kent, south-east England. It was one of the Cinque Ports and still has many original medieval buildings. While once a major port, it is now two miles from the sea, its historic centre preserved.....
, research facility in England. It was initially studied for use in
hypertensionHypertension is a chronic medical condition in which the blood pressure is elevated. It is also referred to as high blood pressure or shortened to HT, HTN or HPN. The word "hypertension", by itself, normally refers to systemic, arterial hypertension.Hypertension can be classified as either...
(high blood pressure) and angina pectoris (a symptom of
ischaemic heart diseaseIschaemic or ischemic heart disease , or myocardial ischaemia, is a disease characterized by reduced blood supply to the heart muscle, usually due to coronary artery disease...
). The first clinical trials were conducted in
Morriston HospitalMorriston Hospital is a 750 bed hospital located in Cwmrhydyceirw near Morriston in Swansea, Wales. Morriston is the largest hospital in the city and county of Swansea and is operated by Abertawe Bro Morgannwg University NHS Trust. Alongside its role as a district general hospital, Morriston is a...
in
SwanseaSwansea is a coastal city and county in Wales. Swansea is in the historic county boundaries of Glamorgan. Situated on the sandy South West Wales coast, the county area includes the Gower peninsula and the Lliw uplands...
. Phase I
clinical trialClinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and Health Authority/Ethics Committee approval is...
s under the direction of
Ian OsterlohIan Osterloh is a clinical researcher for Pfizer, Inc. who led the development of sildenafil citrate , as well as a number of Pfizer medications for cardiovascular disease.He was educated at The Portsmouth Grammar School....
suggested that the drug had little effect on angina, but that it could induce marked penile
erectionPenile erection is a physiological phenomenon where the penis becomes enlarged and firm. Penile erection is the result of a complex interaction of psychological, neural, vascular and endocrine factors, and is usually, though not exclusively, associated with sexual arousal. Penile erection can also...
s. Pfizer therefore decided to market it for erectile dysfunction, rather than for angina. The drug was
patentA patent is a set of exclusive rights granted by a state to an inventor or their assignee for a limited period of time in exchange for a public disclosure of an invention....
ed in 1996, approved for use in erectile dysfunction by the US
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
on March 27, 1998, becoming the first oral treatment approved to treat erectile dysfunction in the United States, and offered for sale in the United States later that year. It soon became a great success: annual sales of Viagra in the period 1999–2001 exceeded $1 billion.
The British press portrayed Peter Dunn and Albert Wood as the inventors of the drug, a claim that Pfizer disputes. Their names are on the manufacturing patent application drug, but Pfizer claims this is only for convenience.
Even though sildenafil is available only by prescription from a doctor, it was advertised directly to consumers on U.S. TV (famously being endorsed by former
United States SenatorThe United States Senate is the upper house of the bicameral United States Congress, the lower house being the House of Representatives. The composition and powers of the Senate and the House are established in Article One of the U.S. Constitution . Each U.S state is represented by two senators,...
Bob DoleRobert Joseph "Bob" Dole is an attorney and retired United States Senator from Kansas from 1969–1996, serving part of that time as United States Senate Majority Leader, where he set a record as the longest-serving Republican leader. He was his party's 1996 presidential nominee but lost the...
and
soccerAssociation football, more commonly known as football or soccer, is a team sport played between two teams of eleven players using a spherical ball...
star
PeléEdison Arantes do Nascimento , , best known by his nickname Pelé is a Brazilian football player. He was given the title "Athlete of the Century" by the International Olympic Committee...
). Numerous sites on the Internet offer Viagra for sale after an "online consultation", often a simple web questionnaire. The "Viagra" name has become so well known that many fake
aphrodisiacAn aphrodisiac is a substance which is used in the belief that it increases sexual desire. The name comes from Aphrodite, the Greek goddess of sensuality and love. Throughout history, many foods, drinks, and behaviors have had a reputation for making sex more attainable and/or pleasurable...
s now call themselves "herbal Viagra" or are presented as blue tablets imitating the shape and colour of Pfizer's product. Viagra is also informally known as "Vitamin V", "the Blue Pill", as well as various other nicknames.
In 2000, Viagra sales accounted for 92 percent of the global market for prescribed
erectile dysfunctionErectile dysfunction is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis sufficient for satisfactory sexual performance....
pills. By 2007, Viagra's global share had plunged to about 50 percent due to several factors, including the entry of Cialis and Levitra, along with several other counterfeits and clones, and reports of vision loss in people taking PDE5 inhibitors.
In February 2007, it was announced that Boots the Chemist would trial
over the counterOver-the-counter drugs are medicines that may be sold to a customer without a prescription from a health care professional, as compared to prescription drugs, which may only be sold to customers possessing a valid prescription...
sales of Viagra in stores in
ManchesterManchester is a city and metropolitan borough of Greater Manchester, England. In 2007, the population of the city was estimated to be 458,100...
,
EnglandEngland is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west and the North Sea to the east, with the English Channel to the south separating it from continental...
. Men aged between 30 and 65 would be eligible to buy four tablets after a consultation with a
pharmacistPharmacists are health professionals who practice the science of pharmacy. In their traditional role, pharmacists typically take a request for medicines from a prescribing health care provider in the form of a medical prescription, evaluate the appropriateness of the prescription, dispense the...
.
Pfizer's worldwide patents on sildenafil citrate will expire in 2011–2013. The
UKThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
patent held by Pfizer on the use of
PDE5 inhibitorA 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...
s (see below) as treatment of impotence was invalidated in 2000 because of obviousness; this decision was upheld on appeal in 2002.
Mechanism of action
The mechanism of action of Sildenafil citrate involves the release of
nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
(NO) in the
corpus cavernosumThe corpus cavernosum penis is one of a pair of sponge-like regions of erectile tissue which contain most of the blood in the penis during penile erection...
of the penis. NO binds to the receptors of the enzyme
guanylate cyclaseGuanylate cyclase is a lyase enzyme.-Reaction:It catalyzes the conversion of guanosine triphosphate to 3',5'-cyclic guanosine monophosphate and pyrophosphate:...
, which results in increased levels of
cyclic guanosine monophosphateCyclic guanosine monophosphate is a cyclic nucleotide derived from guanosine triphosphate . cGMP acts as a second messenger much like cyclic AMP, most notably by activating intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell...
(cGMP), leading to
smooth muscleSmooth muscle is an involuntary non-striated muscle, found within the tunica media layer of large and small arteries and veins, the bladder, uterus, male and female reproductive tracts, gastrointestinal tract, respiratory tract, arrector pili of skin, the ciliary muscle, and iris of...
relaxation (vasodilation) of the intimal cushions of the
helicine arteriesThe helicine arteries of penis are arteries in the penis. They are found in the corpora cavernosa penis.They are involved in the process of erection.-Anatomy:...
, resulting in increased inflow of blood and an erection.
Robert F. FurchgottRobert Francis Furchgott was a Nobel Prize-winning American biochemist.Furchgott was born in Charleston, SC, to Arthur Furchgott and Pena Sorentrue Furchgott...
won the
Nobel Prize in Physiology or MedicineThe Nobel Prize in Physiology or Medicine is awarded once a year by the Swedish Karolinska Institute. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in Physics, Chemistry, Literature, Peace, and Physiology or Medicine...
in 1998 for his discovery and analysis of
endothelium-derived relaxing factorEndothelium-derived relaxing factor is produced and released by the endothelium that results in smooth muscle relaxation. The most well characterized is nitric oxide , and some older sources consider the two terms to be equivalent....
, a key part of the NO mechanism of action.
Sildenafil is a potent and selective inhibitor of
cGMP specific phosphodiesterase type 5cGMP-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina....
(PDE5), which is responsible for degradation of cGMP in the
corpus cavernosumThe corpus cavernosum penis is one of a pair of sponge-like regions of erectile tissue which contain most of the blood in the penis during penile erection...
. The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection. Other drugs that operate by the same mechanism include
tadalafilTadalafil is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; it has recently been approved for the treatment of pulmonary arterial hypertension, and has been used for other conditions...
(Cialis) and
vardenafilVardenafil is a PDE5 inhibitor used for treating impotence that is sold under the trade name Levitra .-History:...
(Levitra).
Sildenafil is
metabolisedDrug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
by
liverThe liver is a vital organ present in vertebrates and some other animals; it has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
s and excreted by both the liver and
kidneyThe kidneys are paired organs, which have the production of urine as their primary function. Kidneys are seen in many types of animals, including vertebrates and some invertebrates. They are part of the urinary system, but have several secondary functions concerned with homeostatic functions. ...
s. If taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.
Sexual dysfunction
The primary indication of sildenafil is treatment of
erectile dysfunctionErectile dysfunction is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis sufficient for satisfactory sexual performance....
(inability to sustain a satisfactory erection to complete intercourse). Its use is now standard treatment for erectile dysfunction in all settings, including
diabetesDiabetes mellitus —often referred to simply as diabetes—is a condition in which the body either does not produce enough, or does not properly respond to, insulin, a hormone produced in the pancreas. Insulin enables cells to absorb glucose in order to turn it into energy...
.
People on
antidepressantAn antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia. Drugs including the monoamine oxidase inhibitors , tricyclic antidepressants , tetracyclic antidepressants , selective serotonin reuptake inhibitors , and serotonin-norepinephrine...
s may experience sexual dysfunction, either as a result of their illness or as a result of their treatment. A 2003 study showed that sildenafil improved sexual function in men in this situation. Following up to earlier reports from 1999, the same researchers found that sildenafil was able to improve sexual function in female patients on antidepressants as well.
Pulmonary hypertension
As well as erectile dysfunction, sildenafil citrate is also effective in the
rare diseaseA rare disease, sometimes known as an orphan disease, is any disease that is not common. Typically, a rare disease has such a low prevalence in a population that a physician in a busy general practice would not expect to see more than one case a year....
pulmonary arterial hypertensionIn medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
(PAH). It relaxes the arterial wall, leading to decreased pulmonary arterial resistance and pressure. This, in turn, reduces the workload of the right
ventricleIn the heart, a ventricle is a heart chamber which collects blood from an atrium and pumps it out of the heart...
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 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, to avoid confusion with Viagra, and the 20 milligram tablets are white and round. Sildenafil joins
bosentanBosentan is a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension . It is licensed in the United States, the European Union and other countries by Actelion Pharmaceuticals for the management of PAH under the trade name Tracleer.-Mechanism of...
and
prostacyclinProstacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably. -History:During the 1960s a U.K...
-based therapies for this condition.
Altitude sickness
Sildenafil 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. While this effect has only recently been discovered, sildenafil 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.
Use in sports
Professional sports players have been using drugs such as Viagra, thinking that the opening of their blood vessels will enrich their muscles, therefore enhancing their performance.
Recreational use
Sildenafil's popularity with young adults has increased over the years. Sildenafil's trade name "Viagra" is widely recognized in popular culture, and the drug's association with treating erectile dysfunction has led to its recreational use. The reasons behind such use include the belief that the drug increases libido, improves sexual performance, or permanently increases penis size. Studies on the effects of viagra when used recreationally are limited, but suggest that it 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 was shown to cause no significant change in erectile quality, but did reduce the post-ejaculatory
refractory timeIn sexuality, the refractory period is the recovery phase after orgasm during which it is physiologically impossible for an individual to have additional orgasms...
. This study also noted a significant
placebo effectPlacebo effect may refer to:* Placebo effect, the tendency of any medication or treatment, even an inert or ineffective one, to exhibit results simply because the recipient believes that it will work...
in the control group.
Unprescribed recreational use of Sildenafil and other PDE-5 Inhibitors is noted as particularly high among users of illegal drugs. Sildenafil is sometimes used to counteract the effects of other substances, often illicit. Some users mix it with
methylenedioxymethamphetamineMDMA is a psychoactive amphetamine drug with entactogenic, psychedelic, and stimulant effects....
(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." Mixing with
amyl nitriteAmyl nitrite is the chemical compound with the formula C5H11ONO. A variety of isomers are known, but they all feature an amyl group attached to the nitrito functional group. The alkyl group is unreactive and the chemical and biological properties are mainly due to the nitrite...
is particularly dangerous, and is potentially fatal.
Prevention of plant wilting
A low-concentration solution of sildenafil 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 leads to the production of cGMP whose degradation by PDE5 is inhibited by sildenafil.
Jet lag research
The 2007
Ig Nobel PrizeThe Ig Nobel Prizes are a parody of the Nobel Prizes and are given each year in early October for ten achievements that "first make people laugh, and then make them think"...
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 aids
jet lagJet lag, also jetlag, medically referred to as "desynchronosis" is a physiological condition which is a consequence of alterations to circadian rhythms; it is classified as one of the circadian rhythm sleep disorders...
recovery in hamsters. Their research was published in the
Proceedings of the National Academy of SciencesThe Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences...
.
Analogues
AcetildenafilAcetildenafil is a designer drug which acts as a phosphodiesterase inhibitor. It is a structural analogue of sildenafil which has been detected in numerous different brands of supposedly "herbal" aphrodisiac products sold to boost libido and alleviate erectile dysfunction.A range of designer...
is a structural analogue of sildenafil, one of the
PDE5 inhibitorscGMP-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina....
found in a number of "herbal" aphrodisiac products sold over-the-counter. This class of analogues have not undergone any of the rigorous testing that drugs like sildenafil have passed, and thus have an unknown side-effect profile. 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 being taken off the market.
Dosage
Viagra pills are blue and diamond-shaped with the words "Pfizer" engraved on one side, and "VGR xx" (where xx stands for "25", "50" or "100", the dose of that pill in milligrams) engraved on the other. The dose of sildenafil for erectile dysfunction is 25 mg to 100 mg taken not more than once per day between 30 minutes and 4 hours prior to
sexual intercourseSexual intercourse, also known as copulation or coitus, commonly refers to the act in which the male reproductive organ enters the female reproductive tract. The two entities may be of opposite sexes or not, or they may be hermaphroditic, as is the case with snails...
.
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.
Contraindications
Contraindications include:
- When taking nitric oxide donors, organic nitrites and nitrates, such as glyceryl trinitrate
Glyceryl trinitrate may refer to:* Glyceryl trinitrate , drug* Nitroglycerin, explosive...
(nitroglycerin), sodium nitroprussideSodium nitroprusside is the inorganic compound with the formula Na2[Fe5NO]·2H2O. This red-coloured salt, which is often abbreviated SNP, is a potent vasodilator.-Properties:...
, amyl nitriteAmyl nitrite is the chemical compound with the formula C5H11ONO. A variety of isomers are known, but they all feature an amyl group attached to the nitrito functional group. The alkyl group is unreactive and the chemical and biological properties are mainly due to the nitrite...
("poppersPoppers is the street term for various alkyl nitrites taken for recreational purposes through direct inhalation, particularly amyl nitrite, butyl nitrite, isopropyl nitrite and isobutyl nitrite. Amyl nitrite has a long history of safe medical use in treating angina, as well as an antidote to...
")
- In men for whom sexual intercourse
Sexual intercourse, also known as copulation or coitus, commonly refers to the act in which the male reproductive organ enters the female reproductive tract. The two entities may be of opposite sexes or not, or they may be hermaphroditic, as is the case with snails...
is inadvisable due to cardiovascular risk factors
- Severe hepatic impairment
Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.- Causes :...
(decreased liver function)
- Severe impairment in renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
- Hypotension
In physiology and medicine, hypotension refers to an abnormally low blood pressure. This is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the opposite of hypertension, which is high blood...
(low blood pressure)
- Recent stroke
A stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...
or heart attackMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, is the interruption of blood supply to part of the heart, causing some heart cells to die...
- Hereditary degenerative retinal disorders (including genetic disorders of retinal phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
s)
Side-effects
In
clinical trialClinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices. These trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and Health Authority/Ethics Committee approval is...
s, the most common
adverse effectAn adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dose. The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial...
s of sildenafil use included
headacheIn medicine a headache or cephalalgia is a symptom of a number of different conditions of the head. Some of the causes are benign while others are medical emergencies.There are a number of different classification systems for headaches...
,
flushingFor a person to flush is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or...
,
dyspepsiaDyspepsia , popularly known as indigestion, meaning hard or difficult digestion, is a medical condition characterized by chronic or recurrent pain in the upper abdomen, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating, belching, nausea...
,
nasal congestionNasal congestion is the blockage of the nasal passages usually due to membranes lining the nose becoming swollen from inflamed blood vessels. It is also known as nasal blockage, nasal obstruction, blocked nose, runny nose, stuffy nose, or stuffed up nose.Nasal congestion has many causes and can...
and impaired vision, including
photophobiaPhotophobia is a symptom of excessive sensitivity to light and the aversion to sunlight or well-lit places. In ordinary medical terms photophobia is not a morbid fear, but an experience of discomfort or pain to the eyes due to light exposure....
and blurred vision.
Some sildenafil users have complained of seeing everything tinted blue (
cyanopsiaCyanopsia is a medical term for seeing everything tinted with blue. It is also referred to as blue vision. Cyanopsia often occurs for a few days, weeks, or months after removal of a cataract from the eye. Cyanopsia also sometimes occurs as a side-effect of taking sildenafil, Cialis, or Levitra...
). Some complained of blurriness and loss of
peripheral vision Peripheral vision is a part of vision that occurs outside the very center of gaze. There is a broad set of non-central points in the field of view that is included in the notion of peripheral vision...
. In July 2005, the
U.S.The United States of America is a federal constitutional republic comprising fifty states and a federal district...
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
found that sildenafil could lead to vision impairment in rare cases and a number of studies have linked sildenafil use with
nonarteritic anterior ischemic optic neuropathyAnterior ischemic optic neuropathy is a medical condition involving loss of vision due to damage to the optic nerve from insufficient blood supply. AION is generally divided into two types: arteritic AION and non-arteritic AION...
.
Rare but serious adverse effects found through
postmarketing surveillancePostmarketing surveillance is the practice of monitoring a pharmaceutical drug or device after it has been released on the market. Since drugs are approved on the basis of clinical trials which involve relatively small numbers of people who have been "controlled" for this purpose - meaning that...
include
priapismPriapism is a potentially harmful and painful medical condition in which the erect clitoris or penis does not return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours...
, severe
hypotensionIn physiology and medicine, hypotension refers to an abnormally low blood pressure. This is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the opposite of hypertension, which is high blood...
,
myocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, is the interruption of blood supply to part of the heart, causing some heart cells to die...
(heart attack),
ventricular arrhythmiaVentricular tachycardia is a tachycardia, or fast heart rhythm, that originates in one of the ventricles of the heart...
s,
strokeA stroke is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by thrombosis or embolism or due to a hemorrhage...
, increased
intraocular pressureIntraocular pressure is the fluid pressure inside the eye.-Physiology and measurement:Intraocular pressure is mainly determined by the coupling of the production of aqueous humor and the drainage of aqueous humor mainly through the trabecular meshwork located in the anterior chamber...
, and
sudden hearing lossA hearing impairment or deafness is a full or partial decrease in the ability to detect or understand sounds. Caused by a wide range of biological and environmental factors, loss of hearing can happen to any organism that perceives sound...
. As a result of these postmarketing reports, in October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including sildenafil, required a more prominent warning of the potential risk of sudden hearing loss.
Interactions
Care should be exercised by patients that are also taking
protease inhibitorsProtease inhibitors are a class of medications used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new...
for the treatment of
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid,...
. 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.
Concomitant use of sildenafil and an
alpha blockerAlpha-1 blockers constitute a variety of drugs which block α1-adrenergic receptors in arteries and smooth muscles.-Pharmacology:...
may lead to low blood pressure, but this effect does not occur if they are taken at least four hours apart.
Chemical synthesis
The preparation steps for synthesis of sildenafil are as follows:
- Methylation
Methylation in the chemical sciences denotes the attachment or substitution of a methyl group on various substrates. Methylation is a form of alkylation with specifically a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate.
- Hydrolysis
Hydrolysis is a chemical reaction during which one or more water molecules are split into hydrogen and hydroxide ions, which may go on to participate in further reactions. It is the type of reaction that is used to break down certain polymers, especially those made by step-growth polymerization...
with aqueous NaOH to free acid.
- Nitration
Nitration is a general chemical process for the introduction of a nitro group into a chemical compound. Examples of nitrations are the conversion of glycerin to nitroglycerin and the conversion of toluene to trinitrotoluene...
with oleum/fuming nitric acid.
- Carboxamide formation with refluxing thionyl chloride/NH4OH.
- Reduction
Redox describes all chemical reactions in which atoms have their oxidation number changed....
of nitro group to amino.
- Acylation
In chemistry, acylation is the process of adding an acyl group to a compound. The compound providing the acyl group is called the acylating agent....
with 2-ethoxybenzoyl chloride.
- Cyclization.
- Sulfonation to the chlorosulfonyl derivative.
- Condensation
Condensation is the change of the physical state of aggregation of matter from gaseous phase into liquid phase and the reverse of evaporation. When the transition happens from the gaseous phase into the solid phase directly, bypassing the liquid phase, the change is called deposition...
with 1-methylpiperazine.
See also
- Tadalafil
Tadalafil is a PDE5 inhibitor, currently marketed in pill form for treating erectile dysfunction under the name Cialis; it has recently been approved for the treatment of pulmonary arterial hypertension, and has been used for other conditions...
(Cialis)
- Vardenafil
Vardenafil is a PDE5 inhibitor used for treating impotence that is sold under the trade name Levitra .-History:...
(Levitra)
- Acetildenafil
Acetildenafil is a designer drug which acts as a phosphodiesterase inhibitor. It is a structural analogue of sildenafil which has been detected in numerous different brands of supposedly "herbal" aphrodisiac products sold to boost libido and alleviate erectile dysfunction.A range of designer...
(Viagra analogue)
External links