Sildenafil, sold under the brand name Viagra, among others, is a medication used to treat erectile dysfunction and pulmonary arterial hypertension. It is also sometimes used off-label for the treatment of certain symptoms in secondary Raynaud’s phenomenon. It is unclear if it is effective for treating sexual dysfunction in females. It can be taken orally (swallowed by mouth), intravenously (injection into a vein), or through the sublingual route (dissolved under the tongue). Onset when taken orally is typically within twenty minutes and lasts for about two hours.
Viagra is a brand name for the drug sildenafil, which is commonly used to treat erectile dysfunction (ED) in men. Erectile dysfunction is a condition where a man has difficulty achieving or maintaining an erection sufficient for sexual activity. Sildenafil works by increasing blood flow to the penis, helping to achieve and sustain an erection when the individual is sexually aroused.
Sildenafil acts by blocking phosphodiesterase 5 (PDE5), an enzyme that promotes breakdown of cGMP, which regulates blood flow in the penis. It requires sexual arousal to work, and does not by itself cause or increase sexual arousal. It also results in dilation of the blood vessels in the lungs.
Pfizer originally discovered the medication in 1989 while looking for a treatment for angina. It was approved for medical use in the United States and in the European Union in 1998. In 2020, it was the 183rd most commonly prescribed medication in the United States, with more than 2 million prescriptions. It is available as a generic medication. In the United Kingdom, it is available over the counter. Most of the active pharmaceutical ingredient, sildenafil citrate, is produced in Pfizer’s Ringaskiddy complex in County Cork, Ireland, which is Pfizer’s largest production facility outside of the United States.
Viagra is used to treat erectile dysfunction (impotence) in men. Another brand of sildenafil is Revatio, which is used to treat pulmonary arterial hypertension and improve exercise capacity in men and women. This page contains specific information for Viagra, not Revatio.
Medical Uses of Viagra
Sexual dysfunction
The primary indication of sildenafil is treatment of erectile dysfunction (inability to sustain a satisfactory erection to complete sexual intercourse). Its use is now one of the standard treatments for erectile dysfunction, including for males with diabetes mellitus.
Antidepressant-associated Sexual Dysfunction
Tentative evidence suggests that sildenafil may help males who experience antidepressant-induced erectile dysfunction.
Pulmonary Arterial Hypertension (PAH)
While sildenafil improves some markers of disease in people with pulmonary arterial hypertension, it does not appear to affect the risk of death or serious side effects. Sildenafil, the active ingredient in Viagra, is also used in the treatment of pulmonary arterial hypertension. In this condition, high blood pressure occurs in the arteries that supply the lungs. By relaxing the blood vessels in the lungs, sildenafil helps to improve blood flow and reduce the strain on the heart.
Raynaud’s Phenomenon
Some studies have suggested that Viagra may be beneficial in treating the symptoms of Raynaud’s phenomenon, a condition where certain areas of the body, usually the fingers and toes, experience reduced blood flow in response to cold or stress. Sildenafil and other PDE5 inhibitors are used off-label to alleviate vasospasm and treat severe ischemia and ulcers in fingers and toes for people with secondary Raynaud’s phenomenon; these drugs have moderate efficacy for reducing the frequency and duration of vasospastic episodes. As of 2016, their role more generally in Raynaud’s was not clear.
High-altitude Pulmonary Edema
Sildenafil has been studied for high-altitude pulmonary edema, but its use is currently not recommended for that indication.
Warnings of Taking Viagra
Some medicines can cause unwanted or dangerous effects when used with Viagra. Tell your doctor about all your current medicines, especially riociguat (Adempas) and nitrates.
Do not take Viagra if you are also using a nitrate drug for chest pain or heart problems, including nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, and some recreational drugs such as “poppers”. Taking sildenafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.
Contact your doctor or seek emergency medical attention if your erection is painful or lasts longer than 4 hours. A prolonged erection (priapism) can damage the penis.
Stop using Viagra and get emergency medical help if you have sudden vision loss.
Before taking this medicine
You should not use Viagra if you are allergic to sildenafil, or:
- if you take other medicines to treat pulmonary arterial hypertension, such as riociguat (Adempas).
- if you take nitrates.
Do not take Viagra if you are also using a nitrate drug for chest pain or heart problems. This includes nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates are also found in some recreational drugs such as amyl nitrate or nitrite (“poppers”). Taking sildenafil with a nitrate medicine can cause a sudden and serious decrease in blood pressure.
To make sure Viagra is safe for you, tell your doctor if you have ever had:
- heart disease or heart rhythm problems, coronary artery disease;
- a heart attack, stroke, or congestive heart failure;
- high or low blood pressure;
- liver or kidney disease;
- a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
- a bleeding disorder such as hemophilia;
- a stomach ulcer;
- retinitis pigmentosa (an inherited condition of the eye);
- a physical deformity of the penis (such as Peyronie’s disease); or
- if you have been told you should not have sexual intercourse for health reasons.
Viagra can decrease blood flow to the optic nerve of the eye, causing sudden vision loss. This has occurred in a small number of people taking sildenafil, most of whom also had heart disease, diabetes, high blood pressure, high cholesterol, or certain pre-existing eye problems, and in those who smoked or were over 50 years old. It is not clear whether sildenafil is the actual cause of vision loss.
Viagra is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.
It is not known whether sildenafil passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.
Do not give this medicine to anyone under 18 years old without medical advice.
Who may not be able to take sildenafil?
Sildenafil is not suitable for some people. To make sure it’s safe for you, speak to your doctor or pharmacist before taking sildenafil if you:
- have ever had an allergic reaction to sildenafil or any other medicine
- are taking medicines called nitrates for chest pain (angina)
- have a serious heart or liver problem
- have recently had a stroke, heart attack or a heart problem – your doctor should carefully check whether your heart can take the additional strain of having sex
- have low blood pressure (hypotension)
- have a rare inherited eye disease, such as retinitis pigmentosa
- have sickle cell anaemia (an abnormality of red blood cells), leukaemia (cancer of blood cells) or multiple myeloma (cancer of bone marrow)
- have a deformity of your penis or Peyronie’s disease (curved penis)
- have a stomach ulcer
- have a bleeding problem like haemophilia
Pregnancy, breastfeeding and fertility while taking sildenafil
Sildenafil and pregnancy
Pulmonary hypertension is an extremely serious condition in pregnancy. If you have pulmonary hypertension, it’s important to use reliable contraception (for example a contraceptive implant or a coil). Talk to your doctor before trying for a baby as your heart condition will need to be assessed and you will need to be advised on the risks of pregnancy.
If you do become pregnant while taking sildenafil then it is recommended that you continue to take it throughout pregnancy. This is because the risks from pulmonary hypertension are potentially life threatening without treatment.
It’s important that you let your doctors know that you are pregnant as early as possible, as you will need to be reviewed in a specialist pregnancy and heart clinic throughout your pregnancy. You will be considered a very high risk pregnancy and will have additional care.
Sildenafil and breastfeeding
If your doctor or health visitor says that your baby is healthy, it’s OK to take sildenafil for pulmonary hypertension while you’re breastfeeding.
Sildenafil only passes into breast milk in tiny amounts, and is unlikely to cause any side effects in your baby.
It is important to keep taking sildenafil to keep you well. Breastfeeding will also benefit both you and your baby.
If you notice that your baby is not feeding as well as usual, is unusually sleepy, much paler than usual, or flushed, or if you have any other concerns about your baby, talk to your health visitor, midwife or doctor as soon as possible.
Sildenafil and fertility
There’s no clear evidence to suggest that taking sildenafil reduces fertility in either women or men.
Speak to your doctor before taking it if you’re trying to get pregnant.
How Should I Take Viagra?
Take Viagra exactly as it was prescribed for you. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.
Viagra is usually taken only when needed, 30 minutes to 1 hour before sexual activity. You may take it up to 4 hours before sexual activity. Do not take Viagra more than once per day.
Viagra can help you have an erection when sexual stimulation occurs. An erection will not occur just by taking a pill. Follow your doctor’s instructions.
During sexual activity, if you become dizzy or nauseated, or have pain, numbness, or tingling in your chest, arms, neck, or jaw, stop and call your doctor right away. You could be having a serious side effect of sildenafil.
Store at room temperature away from moisture and heat.
Mechanism of Action of Viagra
Sildenafil protects cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 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. Robert F. Furchgott, Ferid Murad, and Louis Ignarro won the Nobel Prize in Physiology or Medicine in 1998 for their independent study of the metabolic pathway of nitric oxide in smooth muscle vasodilation.
The molecular mechanism of smooth muscle relaxation involves the enzyme CGMP-dependent protein kinase, also known as PKG. This kinase is activated by cGMP and it phosphorylates multiple targets in the smooth muscle cells, namely myosin light chain phosphatase, RhoA, IP3 receptor, phospholipase C, and others. Overall, this results in a decrease in intracellular calcium and desensitizing proteins to the effects of calcium, engendering smooth muscle relaxation.
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 PDE5 in the corpus cavernosum, resulting in more cGMP and increased penile response to sexual stimulation. 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 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 (minor route) hepatic isoenzymes. The major product of metabolisation by these enzymes is N-desmethylated sildenafil, which is metabolised further. This metabolite also has an affinity for the PDE receptors, about 40% of that of sildenafil. 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 time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.
Chemical Synthesis
The preparation steps for synthesis of sildenafil are:
- Methylation of 3-propylpyrazole-5-carboxylic acid ethyl ester with hot dimethyl sulfate
- Hydrolysis with aqueous sodium hydroxide (NaOH) to free acid
- Nitration with oleum/fuming nitric acid
- Carboxamide formation with refluxing thionyl chloride/NH4OH
- Reduction of nitro group to amino group
- Acylation with 2-ethoxybenzoyl chloride
- Cyclization
- Sulfonation to the chlorosulfonyl derivative
- Condensation with 1-methylpiperazine.
What Happens if I Miss a dose?
Since Viagra is used as needed, you are not likely to miss a dose.
What Happens if I Overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
What to Avoid
Drinking alcohol with this medicine can cause side effects.
Grapefruit and grapefruit juice may interact with sildenafil and lead to unwanted side effects. Avoid the use of grapefruit products while taking sildenafil.
Avoid using any other medicines to treat impotence, such as alprostadil or yohimbine, without first talking to your doctor.
Viagra Side Effects
Get emergency medical help if you have signs of an allergic reaction to Viagra: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Stop taking Viagra and get emergency medical help if you have:
- heart attack symptoms–chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
- vision changes or sudden vision loss; or
- erection is painful or lasts longer than 4 hours (prolonged erection can damage the penis).
Call your doctor at once if you have:
- ringing in your ears, or sudden hearing loss;
- irregular heartbeat;
- swelling in your hands, ankles, or feet;
- shortness of breath;
- seizure (convulsions); or
- a light-headed feeling, like you might pass out.
Common Viagra side effects may include:
- flushing (warmth, redness, or tingly feeling);
- headache, dizziness;
- abnormal vision (blurred vision, changes in color vision)
- runny or stuffy nose, nosebleeds;
- sleep problems (insomnia);
- muscle pain, back pain; or
- upset stomach.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What Other Drugs Will Affect Viagra?
Do not take Viagra with similar medications such as avanafil (Stendra), tadalafil (Cialis) or vardenafil (Levitra). Tell your doctor about all other medications you use for erectile dysfunction.
Tell your doctor about all your current medicines and any you start or stop using, especially:
- drugs to treat high blood pressure or a prostate disorder;
- an antibiotic – clarithromycin, erythromycin, or telithromycin;
- antifungal medicine – ketoconazole or itraconazole; or
- medicine to treat HIV/AIDS – atazanavir, indinavir, ritonavir, or saquinavir;
- nitrates;
- medications used to treat pulmonary artery hypertension.
Contraindications
Contraindications include:
- Concomitant use of nitric oxide donors, organic nitrites and nitrates, such as:
- nitroglycerin
- isosorbide mononitrate
- isosorbide dinitrate
- sodium nitroprusside
- alkyl nitrites (commonly known as “poppers”)
- Concomitant use of soluble guanylyl cyclase stimulators, such as riociguat
- Known hypersensitivity to sildenafil
Sildenafil should not be used if sexual activity is inadvisable due to underlying cardiovascular risk factors.
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 sildenafil when used recreationally are limited, but suggest it has little effect when used by those who do not have erectile dysfunction. In one study, a 25 mg dose was shown to cause no significant change in erectile quality, but did reduce the postejaculatory refractory time. This study also noted a significant placebo effect in the control group.
Unprescribed recreational use of sildenafil and other PDE5 inhibitors is noted as particularly high among users of illegal drugs. Sildenafil is sometimes used to counteract the effects of other substances, often illicit. Some users mix it with methylenedioxymethamphetamine (MDMA, ecstasy), other stimulants, or opiates in an attempt to compensate for the common side effect of erectile dysfunction, a combination known as “sextasy”, “rockin’ and rollin'” or “trail mix”. Mixing it with amyl nitrite, another vasodilator, is particularly dangerous and potentially fatal.
Can you Take Viagra With High Blood Pressure?
You can take Viagra (sildenafil) if you have high blood pressure that is controlled by blood pressure medications. Viagra (sildenafil) works by blocking an enzyme called PDE-5, which, in turn, prevents the break down of another substance called cGMP, which causes smooth muscle to relax and dilate. This allows more blood to flow to the penis and also causes blood vessels around the heart to open wider. This effect is called vasodilation, and it lowers blood pressure.
Viagra is used to treat erectile dysfunction in men. You should tell your doctor if you have high or low blood pressure before starting Viagra.
Caution is warranted in some cases:
- If you take Viagra with a blood pressure medication that also works by lowering blood pressure through vasodilation, your blood pressure could drop low enough to make you dizzy or make you pass out
- Taking Viagra with a blood pressure or prostate medication called an alpha blocker can be dangerous. If you take an alpha blocker and you need Viagra, your doctor may need to lower the dose of the alpha blocker or lower the dose of Viagra
- Another type of drug that lowers blood pressure is a nitrate drug. Nitrate drugs are used in people with heart disease to relieve chest pain called angina. You should not use Viagra if you use a nitrate drug. This can also lead to a dangerous drop in blood pressure.
Blood pressure is measured in units called millimeters of mercury (mmHg). The higher number in a blood pressure measurement is the pressure in your arteries when your heart pumps, called the systolic pressure. The lower number is the pressure between heartbeats, called the diastolic pressure. Studies in healthy volunteers show that a single dose of Viagra lowers systolic blood pressure by about 8 mmHg and diastolic pressure by about 5 mmHg.
You should tell your doctor if you have high or low blood pressure before starting Viagra. You should also tell your doctor about all the medications or supplements you take. If you take a medication or supplement that lowers blood pressure along with Viagra, it may drop your blood pressure too much, which could make you dizzy or fall over. This is called hypotension.
Key Facts:
- It usually takes 30 to 60 minutes for sildenafil to work for erectile dysfunction. You can take it up to 4 hours before you want to have sex.
- Taking sildenafil alone will not cause an erection. You need to be sexually excited for it to work.
- The most common side effects are headaches, feeling sick, indigestion and dizziness. Many people have no side effects or only mild ones.
- It can be dangerous to take sildenafil if you also take medicines called nitrates (often given for chest pain). The combination can cause a dangerous fall in your blood pressure. If you’re not sure if you’re taking a nitrate, ask your doctor or pharmacist.
- Do not drink grapefruit juice if you’re taking sildenafil (Revatio) for pulmonary hypertension. It affects the way the medicine works.