What is Viagra (sildenafil)?

What is Viagra (Sildenafil)?

Viagra (sildenafil citrate) is an oral phosphodiesterase type 5 (PDE-5) inhibitor that treats erectile dysfunction by enhancing nitric oxide-mediated vasodilation in penile tissue, allowing corpus cavernosum smooth muscle to relax and potentiate erections during sexual stimulation. 1, 2

Mechanism of Action

• Sildenafil selectively inhibits PDE-5, the main phosphodiesterase enzyme in human corpus cavernosum tissue, preventing the breakdown of cyclic guanosine monophosphate (cGMP) 2
• By preserving cGMP levels, sildenafil enhances the natural erectile response that occurs with sexual stimulation, but sexual stimulation is necessary for the drug to be effective 3
• The drug does not cause erections independently—it only amplifies the body's natural erectile mechanism when arousal is present 2

Clinical Efficacy

• Sildenafil is recommended as first-line therapy for erectile dysfunction by the American Urological Association, unless contraindicated 4
• High-quality evidence demonstrates that 69% of men using sildenafil achieve successful sexual intercourse attempts compared to 35.5% with placebo 5
• The drug improves erections in 73-88% of patients compared to 26-32% with placebo 5
• Sildenafil is effective across all tested causes of ED, including organic (diabetes, spinal cord injury), psychogenic, and mixed etiologies 6, 7

Pharmacokinetics and Dosing

• Sildenafil is rapidly absorbed with peak plasma concentrations within 1 hour of administration 6
• The elimination half-life is 3-5 hours, with duration of action approximately 4-5 hours 5, 6
• Standard starting dose is 50 mg taken approximately 1 hour before sexual activity, with maximum frequency of once daily 1, 6
• Dose can be increased to 100 mg or decreased to 25 mg based on efficacy and tolerability 6
• Improvement in erectile function is dose-related for sildenafil (25 mg to 50 mg), though less additional benefit occurs when increasing from 50 mg to 100 mg 4

Adverse Effects

• Common side effects include headache, flushing, dyspepsia, nasal congestion, and abnormal vision—these are typically transient and mild to moderate 8, 6
• Less common adverse effects include visual disturbances, myalgia, nausea, diarrhea, vomiting, dizziness, and chest pain 8
• Serious adverse events occur in less than 2% of patients, with no significant difference from placebo 8, 4
• Higher doses are associated with greater risk for adverse effects, necessitating dose titration 4

Critical Safety Considerations

Absolute Contraindications

• Never prescribe sildenafil with any form of nitrate therapy (nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, or recreational "poppers")—this combination can cause dangerous, potentially fatal hypotension 8, 1
• If a patient on sildenafil requires emergency nitrate administration, wait at least 24 hours after the last sildenafil dose before giving nitrates, under close medical supervision 3

Cardiovascular Screening

• Most ED patients fall into the low-risk category and can safely receive sildenafil, including those with asymptomatic coronary artery disease with <3 risk factors, controlled hypertension, mild stable angina, successful coronary revascularization, uncomplicated past MI, mild valvular disease, and CHF (NYHA class I) 3, 4
• Patients whose cardiovascular risk is indeterminate or who cannot perform moderate physical activity should be referred to cardiology before prescribing 3

Special Populations

• Men with diabetes and post-prostatectomy patients have more severe ED at baseline and may respond less robustly, but sildenafil remains effective 3, 4
• For men with both ED and confirmed testosterone deficiency, combining sildenafil with testosterone therapy may be more effective than sildenafil alone 3, 4
• Lower doses (25 mg) should be used in elderly patients, those with hepatic or renal impairment, or those receiving CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin) 6
• Sildenafil is generally not recommended in severe hepatic impairment 3, 4

Optimizing Treatment Success

Adequate Trial Requirements

• Before declaring treatment failure, ensure at least 5 separate attempts at maximum dose 3, 4
• Many apparent failures are due to inadequate trials, improper timing, lack of sexual stimulation, or modifiable factors 3

Common Pitfalls to Address

• Verify adequate sexual stimulation is occurring 3
• Confirm proper timing (approximately 1 hour before sexual activity) 6
• Assess for heavy alcohol use, which can impair response 3
• Evaluate for hormonal abnormalities (check testosterone if response is suboptimal) 3
• Review for drug interactions, particularly CYP3A4 inhibitors that increase sildenafil levels 1
• Consider relationship issues with partner that may be limiting effectiveness 3

Ongoing Management

• Periodic follow-up should verify that cardiovascular health hasn't changed, review new medications, assess treatment effectiveness, and evaluate side effects 3, 4
• Sildenafil efficacy is maintained in long-term (1-year) studies 6
• The drug improves quality of life for both patients and their sexual partners 6

Additional Formulations

• Sildenafil is also marketed as sildenafil tablets 20 mg for pulmonary arterial hypertension (PAH), a completely different indication 1
• Patients should not take both the ED formulation (25-100 mg) and the PAH formulation (20 mg) or combine with other PDE-5 inhibitors 1