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 smooth muscle relaxation in the corpus cavernosum, allowing erections to occur during sexual stimulation. 1
Mechanism of Action
- Sildenafil selectively inhibits PDE-5, the primary enzyme responsible for breaking down cyclic GMP (cGMP) in penile tissue 2
- By blocking PDE-5, sildenafil increases intracellular cGMP levels, which triggers smooth muscle relaxation in the corpus cavernosum and allows blood flow into the penis 3
- Sexual stimulation is required for sildenafil to work—the drug enhances the natural erectile response but does not cause erections without arousal 4
Clinical Efficacy
- High-quality evidence demonstrates that sildenafil improves erections in 73-88% of patients compared to 26-32% with placebo 4
- The success rate for sexual intercourse attempts is 69% with sildenafil versus 35.5% with placebo 5
- Sildenafil is effective across multiple etiologies of erectile dysfunction, including diabetes, cardiovascular disease, depression, spinal cord injury, and post-prostatectomy 4, 6
Pharmacokinetics
- Sildenafil is rapidly absorbed with peak plasma concentrations occurring within 1 hour of oral administration 6
- The elimination half-life is 3-5 hours, with duration of action typically 4-5 hours 5
- The drug is metabolized primarily by CYP3A4 (major route) and CYP2C9 (minor route) 1
- Approximately 80% is excreted in feces and 13% in urine as metabolites 1
Dosing
- Standard starting dose is 50 mg taken approximately 1 hour before sexual activity, with a maximum frequency of once daily 6
- Dose can be titrated to 100 mg for improved efficacy or reduced to 25 mg for better tolerability 6
- Sildenafil shows dose-dependent improvement from 25 mg to 50 mg, but less additional benefit from 50 mg to 100 mg 5
- Lower doses (25 mg) should be used in elderly patients, those with hepatic or renal impairment, or those taking CYP3A4 inhibitors 6
Common Adverse Effects
- The most frequent side effects are headache, flushing, dyspepsia, nasal congestion, and abnormal vision 7, 6
- Less common adverse effects include myalgia, nausea, diarrhea, vomiting, dizziness, and chest pain 7
- Serious adverse events occur in less than 2% of patients, with no difference compared to placebo 7
- Sildenafil is associated with fewer adverse events than non-PDE-5 inhibitor treatments for erectile dysfunction 7
Critical Safety Considerations
- Absolute contraindication: Never use sildenafil with nitrates in any form (nitroglycerin, isosorbide, amyl nitrite "poppers") due to risk of severe, potentially fatal hypotension 1
- If emergency nitrate administration is required, wait at least 24 hours after sildenafil use before giving nitrates 8
- Patients should be assessed for cardiovascular risk before prescribing—those unable to perform moderate physical activity should be referred to cardiology 8
- Low-risk cardiovascular patients (controlled hypertension, mild stable angina, successful revascularization, uncomplicated past MI, NYHA class I heart failure) can safely receive sildenafil 8
Special Populations
- Men with diabetes respond to sildenafil but may have less robust responses due to more severe baseline erectile dysfunction 8
- Post-prostatectomy patients also respond but typically require higher doses or combination therapy 8
- In men with testosterone deficiency and erectile dysfunction, combining sildenafil with testosterone therapy may be more effective than sildenafil alone 4
Clinical Pearls
- An adequate trial consists of at least 5 separate attempts at maximum dose before declaring treatment failure 8
- Many apparent failures are due to inadequate sexual stimulation, improper timing, food interactions, or relationship issues that should be addressed before switching therapies 8
- Sildenafil has been prescribed to over 23 million men by more than 750,000 physicians since its 1998 market launch, establishing an extensive safety and efficacy record 9