Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor widely prescribed for erectile dysfunction (ED) in adult men across the UK. Understanding how sildenafil works helps patients use the medication safely and effectively. When a man is sexually aroused, sildenafil enhances natural erectile processes by preventing the breakdown of cyclic guanosine monophosphate (cGMP), a chemical that relaxes smooth muscle in penile blood vessels. This allows increased blood flow to the penis, facilitating an erection. Sildenafil requires sexual stimulation to be effective and does not cause spontaneous erections. This article explains the mechanism of action, onset time, factors affecting efficacy, and what to expect when taking sildenafil.

What Is Sildenafil and What Does It Treat?

Sildenafil is a medicine primarily used to treat erectile dysfunction (ED) in adult men. It belongs to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors. Originally developed for cardiovascular conditions, sildenafil was found to be highly effective for ED and holds a UK marketing authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA). In the UK, sildenafil 50mg is available as a Pharmacy (P) medicine (Viagra Connect) without prescription following pharmacist assessment, while other strengths remain prescription-only. Sildenafil is also licensed under the brand name Revatio for treating pulmonary arterial hypertension, though this article focuses on its use for erectile dysfunction.

Erectile dysfunction is the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual activity. It affects millions of men in the UK and can result from various causes including diabetes, cardiovascular disease, psychological factors, or certain medications. Sildenafil does not cure ED but provides symptomatic relief by facilitating the physiological processes required for an erection when sexual stimulation occurs.

How sildenafil works at a cellular level:

When a man is sexually aroused, nerve signals trigger the release of nitric oxide in the erectile tissue of the penis. This nitric oxide activates an enzyme that produces cyclic guanosine monophosphate (cGMP), which relaxes smooth muscle cells in the blood vessels of the penis, allowing increased blood flow and resulting in an erection. The enzyme PDE5 naturally breaks down cGMP, which can limit erectile function. Sildenafil works by selectively inhibiting PDE5, thereby preventing the breakdown of cGMP. This allows cGMP levels to remain elevated for longer, promoting sustained smooth muscle relaxation and improved blood flow to the penis during sexual stimulation.

It is important to understand that sildenafil requires sexual arousal to be effective—it does not cause spontaneous erections and will not work without appropriate stimulation. For men with unstable cardiovascular disease, sexual activity may be inadvisable, and clinical assessment should be sought before using sildenafil.

How Long Does Sildenafil Take to Work?

Sildenafil typically begins to take effect within 30 to 60 minutes after oral administration, though this can vary between individuals. The medication reaches peak plasma concentrations approximately one hour after ingestion when taken on an empty stomach. For optimal results, most healthcare professionals recommend taking sildenafil about one hour before planned sexual activity.

The duration of action is generally four to five hours, during which time the medication can facilitate erections in response to sexual stimulation. This does not mean an erection will last for this entire period; rather, it represents the window during which the drug remains sufficiently active in the body to support erectile function when arousal occurs. After this time, the effects gradually diminish as the medication is metabolised and eliminated from the body.

Factors affecting onset time:

• Food intake: Taking sildenafil with a large or high-fat meal can significantly delay absorption and reduce peak effectiveness. The medication may take up to two hours to work when consumed with food. For faster onset, it is advisable to take sildenafil on an empty stomach or after a light meal.

• Dosage: Sildenafil is available in various strengths (typically 25mg, 50mg, and 100mg). The typical starting dose is 50mg as needed, with 25mg recommended for adults over 65 years, those with hepatic or renal impairment, or patients taking certain interacting medicines. Higher doses may produce more pronounced effects but do not necessarily work faster. The appropriate dose should be determined by a healthcare professional based on individual response and tolerability.

• Individual metabolism: Age, liver function, kidney function, and concurrent medications can all influence how quickly sildenafil is absorbed and metabolised. Older adults or those with hepatic or renal impairment may experience prolonged effects and should discuss appropriate dosing with their GP.

Patients should not take more than one dose within a 24-hour period, regardless of whether the first dose was effective. Grapefruit juice may increase sildenafil blood levels and should be avoided when taking this medication.

Factors That Affect How Well Sildenafil Works

Several factors can influence the effectiveness of sildenafil, and understanding these can help optimise treatment outcomes whilst maintaining safety.

Underlying health conditions:

Certain medical conditions may reduce sildenafil's effectiveness. Severe cardiovascular disease, uncontrolled diabetes with significant vascular damage, or advanced neurological conditions can impair the physiological mechanisms necessary for erectile function, even with PDE5 inhibition. Endocrine disorders such as hypogonadism (low testosterone) may also affect response. Men with these conditions should have realistic expectations and discuss alternative or adjunctive treatments with their healthcare provider.

Psychological factors:

Anxiety, depression, stress, and relationship difficulties can significantly impact sexual function. Sildenafil addresses the physical aspects of ED but cannot resolve psychological barriers. In cases where psychological factors predominate, cognitive behavioural therapy, counselling, or treatment of underlying mental health conditions may be beneficial alongside medication. NICE guidance recognises the multifactorial nature of ED and recommends a holistic approach to management.

Medication interactions:

Sildenafil is absolutely contraindicated with:

• Nitrates (such as glyceryl trinitrate used for angina) due to the risk of severe, potentially life-threatening hypotension

• Recreational nitrates ('poppers' containing amyl nitrite)

• Guanylate cyclase stimulators such as riociguat

Alpha-blockers used for prostate conditions or hypertension can also cause blood pressure drops when combined with sildenafil. If taking alpha-blockers, ensure you are haemodynamically stable, start sildenafil at 25mg, and consider separating dosing times to reduce the risk of postural hypotension.

Other medications that affect the cytochrome P450 3A4 enzyme system can alter sildenafil levels in the blood:

• Strong CYP3A4 inhibitors (ritonavir, cobicistat) may significantly increase sildenafil levels; avoid or limit use

• Moderate inhibitors (clarithromycin, ketoconazole, erythromycin) require caution and possibly lower sildenafil doses

• CYP3A4 inducers (rifampicin) may reduce sildenafil effectiveness

Always inform your GP or pharmacist of all medications you are taking.

Lifestyle factors:

• Alcohol consumption: Excessive alcohol can impair erectile function and reduce sildenafil's effectiveness. Moderate alcohol intake is unlikely to cause problems, but heavy drinking should be avoided.

• Smoking: Tobacco use damages blood vessels and can worsen ED over time, potentially reducing treatment response.

• Physical fitness: Regular exercise and maintaining a healthy weight improve cardiovascular health and can enhance sildenafil's effectiveness.

Realistic expectations:

Many men with ED respond well to sildenafil, but response varies. Some men may require dose adjustment or may respond better to alternative PDE5 inhibitors. It is reasonable to try sildenafil on 4-8 separate occasions before concluding it is ineffective. If sildenafil has been ineffective after several attempts at the maximum appropriate dose, patients should consult their GP to discuss alternative management strategies rather than exceeding recommended doses.

What to Expect When Taking Sildenafil

Understanding what to expect when taking sildenafil can help ensure safe and effective use whilst minimising anxiety about the medication.

Do not take sildenafil if you:

• Are taking nitrate medicines (including recreational 'poppers') or riociguat

• Have severe hypotension (low blood pressure)

• Have had a heart attack or stroke within the past 6 months

• Have unstable cardiovascular disease where sexual activity is inadvisable

• Have a known allergy to sildenafil or any ingredients in the tablet

Common side effects:

Most men tolerate sildenafil well, but some may experience mild to moderate side effects, typically related to its vasodilatory properties:

• Headache (most common, affecting approximately 10-15% of users)

• Facial flushing or warmth

• Indigestion or dyspepsia

• Nasal congestion

• Visual disturbances, such as mild colour tinge (usually blue) or increased light sensitivity

• Dizziness

These effects are generally mild, temporary, and resolve as the medication is eliminated from the body. If side effects are troublesome or persistent, consult your GP, who may adjust the dose or suggest an alternative treatment.

Serious adverse effects requiring immediate medical attention:

Whilst rare, certain serious side effects require urgent medical assessment:

• Priapism: An erection lasting more than four hours is a medical emergency requiring immediate treatment to prevent permanent damage. Men with conditions such as sickle cell disease, multiple myeloma, leukaemia, or penile deformity have a higher risk of priapism. Seek urgent care at A&E if this occurs.

• Sudden vision loss: Very rarely, sildenafil has been associated with non-arteritic anterior ischaemic optic neuropathy (NAION). Those with a history of NAION or retinitis pigmentosa should seek medical advice before using sildenafil. Stop taking the medication and seek immediate medical advice if sudden vision loss occurs.

• Sudden hearing loss or tinnitus: Discontinue use and contact your GP promptly.

• Chest pain during sexual activity: Stop activity immediately and seek emergency medical help, as this may indicate cardiovascular problems. Do not take nitrate medicines if you have taken sildenafil within the past 24 hours.

Practical guidance for use:

Take sildenafil approximately one hour before sexual activity, with water. Sexual stimulation is necessary for the medication to work. Do not take more than the prescribed dose or use more frequently than once daily. Store tablets at room temperature away from moisture and heat.

When to contact your GP:

Consult your healthcare provider if sildenafil is ineffective after several attempts, if you experience troublesome side effects, if your ED worsens, or if you develop new symptoms. Regular review is important, particularly for men with cardiovascular risk factors. The MHRA and NICE recommend that men with ED receive appropriate cardiovascular risk assessment, as ED can be an early indicator of cardiovascular disease.

If you experience any suspected side effects, report them to the MHRA through the Yellow Card Scheme (yellowcard.mhra.gov.uk).

Sildenafil is an effective, well-established treatment for erectile dysfunction when used appropriately under medical supervision. Open communication with healthcare professionals ensures optimal outcomes and safety.

Frequently Asked Questions