Sildenafil works by selectively inhibiting the enzyme phosphodiesterase type 5 (PDE5), which is responsible for breaking down cyclic guanosine monophosphate (cGMP). cGMP is a key mediator of smooth muscle relaxation and blood vessel dilation. The mechanism of action involves:

1. Erectile Dysfunction:
   • During sexual stimulation, nitric oxide (NO) is released in the penile tissue, which activates the enzyme guanylate cyclase.
   • This increases the production of cGMP, leading to relaxation of smooth muscles in the penile arteries and increased blood flow to the corpus cavernosum, resulting in an erection.
   • By inhibiting PDE5, sildenafil prevents the breakdown of cGMP, enhancing and prolonging the erectile response.
2. Pulmonary Arterial Hypertension (PAH):
   • In PAH, sildenafil inhibits PDE5 in the pulmonary vasculature, leading to increased cGMP levels, relaxation of pulmonary smooth muscles, and reduced pulmonary artery pressure.

Sildenafil is approved for the following conditions:

1. Erectile Dysfunction (ED):
   • Treatment of erectile dysfunction in adult men.
2. Pulmonary Arterial Hypertension (PAH):
   • Treatment of PAH to improve exercise capacity and delay clinical worsening. For PAH, sildenafil is marketed under the brand name Revatio.

The dosage of sildenafil varies depending on the indication and patient response. Below are general guidelines:

1. Erectile Dysfunction:
   • Adults: 50 mg taken orally approximately 1 hour before sexual activity. The dose may be adjusted to 25 mg or 100 mg based on efficacy and tolerability.
   • Maximum Frequency: Once daily.
2. Pulmonary Arterial Hypertension (PAH):
   • Adults: 20 mg taken orally three times daily, 4–6 hours apart.
   • Children: Dosage is weight-based and should be determined by a healthcare provider.
3. Administration:
   • Sildenafil can be taken with or without food, but high-fat meals may delay its absorption.
   • Avoid excessive alcohol consumption while taking sildenafil, as it may increase the risk of side effects.

Sildenafil is generally well-tolerated, but some side effects may occur. These include:

1. Common Side Effects:
   • Headache
   • Flushing
   • Nasal congestion
   • Dyspepsia (indigestion)
   • Dizziness
   • Visual disturbances (e.g., blurred vision, changes in color perception)
2. Less Common Side Effects:
   • Nausea
   • Muscle pain
   • Back pain
3. Rare but Serious Side Effects:
   • Priapism: Prolonged and painful erection lasting more than 4 hours. This is a medical emergency and requires immediate treatment.
   • Sudden Hearing Loss: Rare cases of hearing impairment have been reported.
   • Cardiovascular Events: Hypotension, myocardial infarction, or stroke, particularly in patients with pre-existing cardiovascular disease.
   • Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION): Sudden vision loss in one or both eyes.

1. Contraindications:
   • Hypersensitivity to sildenafil or any component of the formulation.
   • Concurrent use of nitrates (e.g., nitroglycerin) or nitric oxide donors, as this can cause severe hypotension.
   • Severe cardiovascular disease (e.g., unstable angina, recent myocardial infarction).
2. Warnings:
   • Cardiovascular Risk: Use with caution in patients with a history of cardiovascular disease, as sexual activity may increase cardiac workload.
   • Priapism: Patients should seek immediate medical attention if an erection lasts longer than 4 hours.
   • Vision or Hearing Loss: Discontinue sildenafil and consult a healthcare provider if sudden vision or hearing loss occurs.
3. Monitoring:
   • Monitor for signs of hypotension, especially in patients taking antihypertensive medications.
   • Regular cardiovascular assessment in patients with pre-existing heart conditions.

Sildenafil interacts with several medications, including:

1. Nitrates (e.g., nitroglycerin): Concurrent use can cause severe hypotension and is contraindicated.
2. Alpha-Blockers (e.g., doxazosin): May cause additive hypotensive effects.
3. Protease Inhibitors (e.g., ritonavir): Increase sildenafil levels, requiring dose adjustment.
4. CYP3A4 Inhibitors (e.g., ketoconazole, erythromycin): Increase sildenafil levels, increasing the risk of side effects.
5. Antihypertensive Medications: May cause additive hypotensive effects.

Sildenafil is available under its generic name as well as brand names. Some common formulations include:

• Generic Name: Sildenafil citrate
• Brand Names: Viagra (for erectile dysfunction), Revatio (for pulmonary arterial hypertension).