What is the mechanism of action (MOA) and details of Sildenafil (phosphodiesterase type 5 inhibitor) in treating erectile dysfunction?

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Last updated: July 1, 2025View editorial policy

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From the Guidelines

Sildenafil is a highly effective treatment for erectile dysfunction, working by inhibiting phosphodiesterase type 5 (PDE5) and increasing cyclic guanosine monophosphate (cGMP) levels, which enhances and prolongs erections. The mechanism of action involves the release of nitric oxide in the penis during sexual stimulation, activating guanylate cyclase to produce cGMP, which relaxes smooth muscles in the corpus cavernosum and increases blood flow, facilitating erection 1.

Key Points:

  • The typical dose of sildenafil is 50mg taken 30-60 minutes before sexual activity, with a range of 25-100mg based on response and tolerability 1.
  • Sildenafil should be taken on an empty stomach for optimal absorption, as high-fat meals can delay onset 1.
  • Common side effects include headache, flushing, indigestion, and nasal congestion 1.
  • It's contraindicated with nitrates due to dangerous blood pressure drops and should be used cautiously with alpha-blockers, certain antihypertensives, and in patients with cardiovascular disease, liver or kidney impairment, or anatomical penile conditions 1.

Important Considerations:

  • Phosphodiesterase type 5 inhibitors, including sildenafil, should not be used concomitantly with nitrate medications, often used to treat chronic coronary disease, because of the potential for severe hypotension 1.
  • Patients on sildenafil should avoid taking nitroglycerine for at least 24 hours 1.

Recommendation:

Sildenafil is recommended as a first-line treatment for erectile dysfunction, due to its efficacy and safety profile, with the dose and administration guided by individual patient needs and medical history.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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