Sildenafil relaxes blood vessels by blocking an enzyme that normally breaks down a chemical messenger responsible for smooth muscle relaxation. This single mechanism is why the same drug treats two very different conditions: erectile dysfunction (sold as Viagra) and pulmonary arterial hypertension (sold as Revatio). In both cases, the core action is the same: widening blood vessels in specific parts of the body.
How Sildenafil Works in the Body
When your body needs to relax smooth muscle tissue, it uses nitric oxide to trigger production of a signaling molecule called cGMP. Think of cGMP as the “relax” signal for blood vessel walls. Normally, an enzyme called PDE5 breaks down cGMP fairly quickly, keeping the relaxation effect short-lived.
Sildenafil blocks PDE5. With that enzyme out of the way, cGMP accumulates and the relaxation signal persists much longer. In lab studies, sildenafil increased cGMP concentrations up to 28-fold when nitric oxide was already present. That last detail matters: sildenafil amplifies a process that’s already happening rather than starting one from scratch. For erectile dysfunction, this means sexual arousal still needs to occur first. The drug doesn’t create arousal on its own.
Treating Erectile Dysfunction
PDE5 is heavily concentrated in the erectile tissue of the penis. By blocking it there, sildenafil allows blood to flow in and stay, producing and maintaining an erection when a person is sexually stimulated.
The standard starting dose is 50 mg, taken roughly an hour before sexual activity, though it can be taken anywhere from 30 minutes to 4 hours beforehand. In clinical testing, 71% of men experienced the onset of an erection within 30 minutes, and 82% responded within 45 minutes. The median time to onset was 27 minutes. The dose can be adjusted down to 25 mg or up to a maximum of 100 mg depending on how well it works and how well it’s tolerated, but it should not be taken more than once per day.
The effect is strongest in the first two hours. In one study, men who were sexually stimulated two hours after taking 100 mg maintained firm erections for a median of about 20 minutes, with 75% of men achieving adequate rigidity. Even at four hours, 81% of men still responded, though the duration of firm erections was shorter (a median of about 5 minutes). So while the drug stays active for several hours, its peak window is earlier.
Food and Timing
A high-fat meal slows absorption and reduces peak blood levels of the drug. If you eat a heavy meal beforehand, expect a longer wait before it kicks in and a potentially weaker effect. Taking it on an empty stomach or after a light meal gives the most reliable results.
Treating Pulmonary Arterial Hypertension
PDE5 is also abundant in the blood vessels of the lungs. In pulmonary arterial hypertension, those vessels become abnormally narrow, forcing the heart to work much harder to push blood through. Sildenafil relaxes the smooth muscle in pulmonary blood vessels, lowering the pressure and easing the workload on the heart.
The dosing for this condition looks completely different from the ED use. Instead of a single larger dose taken as needed, it’s prescribed as 20 mg three times a day, spaced about 4 to 6 hours apart, with or without food. It’s marketed under the brand name Revatio for this purpose.
Common Side Effects
Most side effects stem directly from the blood-vessel-relaxing mechanism and are mild to moderate. In clinical trials of the 50 mg dose, the most frequently reported were:
- Headache: 11.4%
- Facial flushing: 9.3%
- Indigestion: 2.9%
- Nasal congestion: 2.0%
- Dizziness: 2.0%
At the 100 mg dose, indigestion became somewhat more common (4.8%), and visual changes appeared more frequently. About 1 to 3% of men at the higher dose noticed temporary color-tinted vision, most often a blue tinge. This happens because sildenafil has a mild effect on a related enzyme found in the retina. The visual changes are transient and resolve as the drug clears the body.
The Nitrate Interaction
The most dangerous interaction is with nitrate medications, which are commonly prescribed for chest pain (angina). Nitrates work by boosting nitric oxide, and sildenafil amplifies that same pathway. Combining the two can cause a severe, potentially fatal drop in blood pressure. On its own, sildenafil lowers systolic blood pressure by about 8 to 10 points and diastolic by 5 to 6 points. Paired with nitrates, those drops become far more dramatic and unpredictable.
This applies to all forms of nitrates: long-acting prescription nitrates, fast-acting nitroglycerin tablets, and recreational “poppers” (amyl nitrite). The American Heart Association has flagged this combination as capable of causing major cardiovascular collapse. There is no safe waiting period that makes the combination acceptable.
Rare but Serious Risks
Post-marketing reports have linked sildenafil (and other drugs in the same class) to a rare eye condition called non-arteritic anterior ischemic optic neuropathy, or NAION. It causes sudden, painless partial vision loss in one eye. Most reported cases occurred in people who already had risk factors: age over 50, diabetes, high blood pressure, coronary artery disease, high cholesterol, smoking, or a specific optic nerve anatomy known as a “crowded disc.” The condition is rare enough that a direct cause-and-effect relationship hasn’t been firmly established, but the FDA updated prescribing information to warn about it. Any sudden vision loss while using the drug warrants immediate medical attention.
Sudden hearing loss has also been reported in rare cases, sometimes accompanied by ringing in the ears or dizziness.
Dosing Adjustments for Specific Groups
Several factors cause the body to process sildenafil more slowly, which raises blood levels and increases both effectiveness and side-effect risk. Adults over 65 have about 40% higher blood levels than younger adults on the same dose. People with significant liver disease (such as cirrhosis) see levels rise by roughly 80%, and those with severe kidney impairment see levels approximately double. For all of these groups, a lower starting dose of 25 mg is recommended.
The same 25 mg starting dose applies to anyone taking certain medications that interfere with the liver enzyme responsible for breaking sildenafil down. Alpha-blockers, used for prostate enlargement or high blood pressure, also interact. If you’re already on an alpha-blocker, sildenafil should be started at the lowest dose only after you’ve been stable on that medication.