How Does Sildenafil (Viagra) Work?
Sildenafil was discovered by accident while researchers were looking for a heart medication—and the science behind how it works is actually fascinating. Here's the complete picture of what happens in your body when you take it.
The Simple Version
Sildenafil blocks an enzyme (PDE5) that normally breaks down a chemical (cGMP) responsible for relaxing blood vessel walls in the penis. With more cGMP available, blood flows in more easily, producing a firmer erection. It doesn't create arousal—it makes the body's natural arousal response work better.
Understanding how sildenafil works requires understanding how erections work in the first place. Once you grasp the basic mechanism, the drug's effects—and its limitations—make complete sense.
How Erections Actually Work
An erection is a hydraulic event. The penis contains two spongy chambers called the corpora cavernosa that fill with blood during arousal. When these chambers fill and the blood is trapped, the penis becomes rigid. The key to this process is relaxation of smooth muscle in the blood vessel walls.
Here's the sequence of events during a normal erection:
Sexual stimulation occurs
Visual, mental, or physical arousal sends nerve signals to the penis.
Nitric oxide is released
Nerve endings and blood vessel lining cells release nitric oxide (NO)—a small molecule that acts as a signaling chemical.
cGMP is produced
Nitric oxide activates an enzyme called guanylate cyclase, which converts GTP into cyclic GMP (cGMP).
Smooth muscle relaxes
cGMP causes the smooth muscle cells in blood vessel walls to relax. This allows arteries to dilate and blood to flow into the corpus cavernosum.
Blood fills the chambers
As the chambers fill, they compress the veins that normally drain blood away, trapping blood and maintaining rigidity.
PDE5 breaks down cGMP
An enzyme called phosphodiesterase type 5 (PDE5) continuously breaks down cGMP. When arousal ends and nitric oxide release stops, PDE5 clears the remaining cGMP and the erection subsides.
The discovery of this pathway—the nitric oxide/cGMP signaling system—was so significant that three scientists won the Nobel Prize in Physiology or Medicine in 1998 for their work on it.
Where Sildenafil Enters the Picture
Sildenafil is a PDE5 inhibitor. It blocks the enzyme (PDE5) responsible for breaking down cGMP. When PDE5 is inhibited, cGMP accumulates to higher levels and persists longer.
The result: when sexual stimulation triggers nitric oxide release and cGMP production, the cGMP isn't broken down as quickly. More cGMP means more smooth muscle relaxation, more blood flow, and a firmer, more sustained erection.
The Critical Point
Sildenafil doesn't create an erection on its own. Research shows it has no direct relaxant effect on penile tissue in the absence of sexual stimulation. It only enhances the natural process—you still need arousal to trigger nitric oxide release. Without that initial signal, there's nothing for sildenafil to amplify.
The Accidental Discovery
Sildenafil wasn't designed to treat erectile dysfunction. Pfizer researchers in the late 1980s were investigating compounds to treat angina (chest pain caused by reduced blood flow to the heart) and high blood pressure. They knew PDE5 was present in blood vessel walls and thought inhibiting it might help dilate coronary arteries.
In early clinical trials, sildenafil didn't work particularly well for angina. But male participants reported an unexpected side effect: improved erections. Researchers pivoted, recognizing that the corpus cavernosum of the penis has high concentrations of PDE5, and the rest is pharmaceutical history.
Sildenafil (brand name Viagra) was approved by the FDA in 1998 and became the first effective oral treatment for erectile dysfunction.
How Quickly Does It Work?
Sildenafil is typically absorbed within 30-60 minutes when taken on an empty stomach. Several factors affect how quickly it works:
Food
High-fat meals significantly delay absorption. If you've eaten a heavy meal, sildenafil may take longer to kick in and may be less effective at peak.
Alcohol
Moderate alcohol intake doesn't significantly affect absorption, but excessive alcohol impairs erection quality regardless of medication.
Age
Older men may metabolize sildenafil more slowly, leading to higher blood levels and potentially more pronounced effects.
Other medications
Some drugs (like certain antibiotics and HIV medications) can slow sildenafil metabolism, increasing its effects and duration.
Why Sildenafil Works for Most Men
PDE5 inhibitors like sildenafil are effective for many different causes of erectile dysfunction because they work downstream in the erection process. Whether ED is caused by:
- • Vascular issues (reduced blood flow from diabetes, atherosclerosis, or high blood pressure)
- • Nerve damage (from diabetes, prostate surgery, or spinal injury)
- • Psychological factors (performance anxiety, stress, depression)
- • Hormonal factors (low testosterone contributing to reduced libido and function)
...sildenafil can help by amplifying whatever cGMP signal is present. It doesn't fix the underlying problem, but it compensates by making the existing signaling more effective.
When Sildenafil May Not Work
Sildenafil isn't universally effective. It tends to work less well when:
- ✗ Severe nerve damage: If the nerves that trigger nitric oxide release are completely damaged (not just impaired), there may be minimal signal to amplify.
- ✗ Severe vascular disease: If arteries are severely blocked, even enhanced blood vessel relaxation may not produce adequate flow.
- ✗ Very low testosterone: Men with extremely low T may have reduced libido and arousal, meaning less nitric oxide release to amplify.
- ✗ Post-prostatectomy: Radical prostate surgery can damage the cavernous nerves. Recovery varies, and some men don't respond to PDE5 inhibitors.
If sildenafil doesn't work, other options include trying a different PDE5 inhibitor (they have slightly different properties), addressing underlying conditions like low testosterone, or considering injection therapy or other interventions.
Why the Nitrate Warning Matters
You've probably seen warnings about not taking sildenafil with nitrate medications (like nitroglycerin used for chest pain). Here's why this interaction is dangerous:
Nitrates work by releasing nitric oxide throughout the body, which causes blood vessel dilation. Sildenafil amplifies the effects of nitric oxide in any tissue where PDE5 is present—including the heart and systemic blood vessels.
Combining the two creates a double hit: nitrates flood the system with nitric oxide, and sildenafil prevents the breakdown of the resulting cGMP. The result can be profound, dangerous drops in blood pressure.
Critical Warning
Never take sildenafil within 24 hours of taking any nitrate medication. This includes nitroglycerin tablets, patches, or sprays, as well as recreational "poppers" (amyl nitrite). The combination can cause life-threatening hypotension.
Why Some Men See a Blue Tint
One of sildenafil's more curious side effects is visual changes—some men report seeing a blue tint to their vision or increased brightness. This happens because sildenafil isn't perfectly selective for PDE5.
It also inhibits PDE6, an enzyme found in the retina that plays a role in the visual signaling pathway. Sildenafil is about 10-fold more selective for PDE5 than PDE6, so it doesn't affect vision dramatically, but at higher doses, this cross-reactivity can cause temporary visual effects.
This is also why tadalafil (Cialis) causes fewer visual side effects—it's more selective for PDE5 over PDE6.
Common Side Effects Explained
Understanding the mechanism helps explain sildenafil's side effects. Because it causes vasodilation (blood vessel relaxation) throughout the body, not just in the penis:
Headache (most common)
Blood vessel dilation in the brain can trigger headaches in more than 10% of users.
Flushing
Dilation of blood vessels near the skin surface causes the characteristic facial flushing.
Nasal congestion
Vasodilation in the nasal passages causes swelling and that stuffed-up feeling.
Indigestion
Effects on smooth muscle in the digestive tract can cause dyspepsia or heartburn.
Sildenafil vs. Other PDE5 Inhibitors
Sildenafil isn't the only PDE5 inhibitor available. Tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) all work through the same basic mechanism but differ in their pharmacology:
| Property | Sildenafil | Tadalafil |
|---|---|---|
| Onset | 30-60 minutes | 30-45 minutes |
| Duration | 4-6 hours | Up to 36 hours |
| Food effect | Significantly delayed by high-fat meals | Minimal food effect |
| Daily dosing | Not typical | Available (5mg daily) |
Men who don't respond well to one PDE5 inhibitor sometimes do better with another, likely due to individual differences in drug metabolism and tissue distribution.
Ready to Try Sildenafil?
Online telehealth platforms make it easy to consult with a licensed provider, get a prescription if appropriate, and have medication delivered discreetly to your door.
The Bottom Line
Sildenafil works by blocking the enzyme that breaks down cGMP, a chemical that causes blood vessels in the penis to relax. It doesn't create arousal—it makes the body's natural arousal response more effective. It's a well-understood medication with decades of safety data, and it works for most men with erectile dysfunction regardless of the underlying cause.