What is the role of Sildenafil (Phosphodiesterase type 5 inhibitor) in treating Erectile Dysfunction (ED)?

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Last updated: July 7, 2025View editorial policy

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From the Guidelines

Sildenafil is an effective treatment for erectile dysfunction (ED) and works by inhibiting phosphodiesterase type 5 (PDE5), enhancing the effects of nitric oxide and increasing blood flow to the penis, as supported by the most recent and highest quality study 1.

How Sildenafil Works

Sildenafil enhances the effects of nitric oxide, a natural chemical that relaxes muscles in the penis and increases blood flow, facilitating erection when sexual stimulation occurs.

Dosage and Administration

The typical starting dose is 50mg taken approximately one hour before sexual activity, with adjustments possible between 25-100mg based on effectiveness and tolerability, as recommended by the American College of Physicians 1.

Important Considerations

Sildenafil should be taken no more than once daily, and its effects last about 4-5 hours. The medication requires sexual stimulation to work and doesn't automatically cause an erection.

Side Effects and Contraindications

Common side effects include headache, flushing, indigestion, and nasal congestion. Sildenafil should not be taken with nitrate medications (like nitroglycerin) as this combination can cause dangerous drops in blood pressure, as warned by the American College of Physicians 1. Patients with certain cardiovascular conditions, severe liver impairment, or recent stroke should use sildenafil cautiously or avoid it altogether.

Optimal Use

For optimal results, sildenafil should be taken on an empty stomach, as high-fat meals can delay absorption and reduce effectiveness, as suggested by the evidence 1.

Key Points to Consider

  • Sildenafil is effective for treating ED by inhibiting PDE5 and increasing blood flow to the penis.
  • The typical starting dose is 50mg, with adjustments possible between 25-100mg.
  • Sildenafil should be taken no more than once daily and requires sexual stimulation to work.
  • Common side effects include headache, flushing, and indigestion.
  • Sildenafil should not be taken with nitrate medications and should be used cautiously in patients with certain cardiovascular conditions or severe liver impairment.

From the FDA Drug Label

Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE-5) in the smooth muscle of the pulmonary vasculature, where PDE-5 is responsible for degradation of cGMP. In addition to pulmonary vascular smooth muscle and the corpus cavernosum, PDE-5 is also found in other tissues including vascular and visceral smooth muscle and in platelets.

Sildenafil will help in treating Erectile Dysfunction (ED) by increasing cGMP within the smooth muscle cells of the corpus cavernosum, resulting in relaxation and vasodilation.

  • The mechanism of action of sildenafil is to inhibit the PDE-5 enzyme, which is responsible for the degradation of cGMP.
  • The increased levels of cGMP will lead to smooth muscle relaxation and vasodilation, allowing for increased blood flow to the penis, resulting in an erection 2.

From the Research

Role of Sildenafil in Treating Erectile Dysfunction

Sildenafil, a phosphodiesterase type 5 inhibitor, plays a significant role in treating erectile dysfunction (ED) by:

  • Enhancing the relaxant effect of nitric oxide on the corpus cavernosum, causing smooth muscle relaxation and increased blood flow into the penis, resulting in an erection 3
  • Inhibiting the degradation of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum, leading to improved erections 3
  • Allowing for successful penetrative sexual intercourse in men with ED of various etiologies, including organic, psychogenic, or mixed origin 4, 5

Efficacy and Safety of Sildenafil

The efficacy and safety of sildenafil have been extensively investigated in various studies, demonstrating that:

  • Sildenafil is effective in improving erections and allowing successful sexual intercourse in men with ED, regardless of age, including those over 75 years old 6
  • The drug is well-tolerated, with common adverse events being transient and mild or moderate, including headache, flushing, and dyspepsia 4, 5, 6
  • Sildenafil can be used in various dosages, selected depending on comorbidities, tolerability, and efficacy of the drug, allowing for a personalized approach to treatment 7

Dosage and Administration

Sildenafil is typically administered in doses of 25-100mg, taken 1 hour before sexual activity, with the maximum dose being 100mg once daily 4, 7. The dosage can be adjusted based on individual characteristics, such as age, comorbidities, and response to treatment 7.

Contraindications and Precautions

Sildenafil is contraindicated in men taking organic nitrates, due to the potential for a precipitous decrease in blood pressure 4, 3. Additionally, men with severe cardiac failure, unstable angina, or recent stroke or myocardial infarction should be excluded from treatment with sildenafil 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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