sildenafil
Brand: Viagra, Revatio
Beers Criteria Prototype Drug
Drug Class: PDE-5 inhibitor
Drug Family: GU agent
Subclass: phosphodiesterase type-5 inhibitor
Organ Systems: reproductivecardiovascular
Mechanism of Action
Inhibits PDE-5, the enzyme that degrades cyclic GMP (cGMP) in smooth muscle cells. In penile erectile tissue, sexual stimulation releases nitric oxide (NO), which activates guanylyl cyclase to produce cGMP, causing smooth muscle relaxation and increased blood flow; PDE-5 inhibition prolongs cGMP accumulation, enhancing and sustaining erections. In pulmonary vasculature (Revatio), the same mechanism produces pulmonary arterial vasodilation.
phosphodiesterase type-5 (PDE-5)
Indications
- erectile dysfunction (Viagra)
- pulmonary arterial hypertension (Revatio)
- Raynaud's phenomenon (off-label)
Contraindications
- concurrent nitrate use (organic nitrates — contraindicated; severe hypotension)
- concurrent alpha-blocker use (use cautiously; some are acceptable)
- recent myocardial infarction or stroke (<6 months)
- hypotension
Adverse Effects
Common
- headache (most common)
- flushing
- dyspepsia
- nasal congestion
- visual disturbances (blue-green color tingling)
Serious
- severe hypotension (with nitrates)
- priapism
- non-arteritic anterior ischemic optic neuropathy (NAION)
- sudden hearing loss
- cardiovascular events in susceptible patients
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~41% (high-fat meal reduces Cmax and delays absorption) |
| Distribution | Vd ~105 L; 96% protein bound |
| Metabolism | hepatic via CYP3A4 (major) and CYP2C9 (minor) to active metabolite N-desmethylsildenafil |
| Excretion | fecal (80%) and renal (13%) |
| Half-life | 3–5 hours |
| Onset | 30–60 minutes |
| Peak | 0.5–2 hours |
| Duration | 4–6 hours |
| Protein Binding | 96% |
| Vd | 105 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| nitrates (nitroglycerin, isosorbide) | synergistic cGMP elevation causes catastrophic hypotension; ABSOLUTE CONTRAINDICATION | contraindicated |
| ritonavir, ketoconazole (CYP3A4 inhibitors) | dramatically increase sildenafil levels (11-fold with ritonavir); dose reduction required | major |
| alpha-blockers (tamsulosin, doxazosin) | additive hypotension; use caution with timing | major |
Nursing Considerations
- CRITICAL: absolute contraindication with any nitrate (nitroglycerin, isosorbide mononitrate/dinitrate, amyl nitrite); severe life-threatening hypotension can occur; if patient takes nitroglycerin, sildenafil is contraindicated.
- Advise patients to take 30–60 minutes before sexual activity; avoid high-fat meals which delay onset.
- For pulmonary hypertension (Revatio): administered three times daily; monitor blood pressure and exercise tolerance regularly.
- Counsel patients to seek emergency care for erection lasting >4 hours (priapism) and for sudden vision or hearing changes.
Clinical Pearls
- Sildenafil was initially developed as an anti-anginal agent; its erectile effects were discovered incidentally in phase II trials, leading to one of the most commercially successful drug repurposings in history.
- The absolute contraindication with nitrates is the most important clinical safety rule: even if nitrates are needed urgently for chest pain in a patient who took sildenafil, nitrates must be withheld for 24–48 hours (or longer with tadalafil).
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.