Viagra works by relaxing muscles in blood vessel walls to help increase blood flow to the penis, making it easier to get and maintain an erection. Viagra is only effective if there is sexual stimulation, such as that occurring during sexual intercourse. When stimulation first happens, Viagra helps increase blood flow to the penis and then works to help maintain an erection.

According to the Boston University School of Sexual Medicine, erectile dysfunction affects up to 52% of men between the ages of 40-70, many of whom turn to erectile dysfunction medications to help with their symptoms. Viagra is a type of erectile dysfunction drug called a phosphodiesterase 5 inhibitor. PDE5 inhibitors keep a particular enzyme called phosphodiesterase type-5 (PDE5) from acting too quickly. If PDE5 acts slower, then a substance that’s responsible for relaxing muscles and widening blood vessels can do its job.

Viagra will not be as effective for people with certain conditions. You may not get the full benefits of Viagra if you are sick, fatigued, or intoxicated. Alcohol can worsen the side effects of viagra and potentially make erectile dysfunction worse.

You should take Viagra on an empty stomach about one hour before sex. It starts working within 30 to 60 minutes, but an erection requires sexual stimulation.

“Some patients experience the effects of Viagra within 20 to 30 minutes after taking the medication,” says Amber Williams, Pharm.D., a compounding pharmacist at Family Pharmacy in Sarasota. “However, if the dose is taken with a high-fat meal, the peak response may be delayed for up to 60 minutes.

In most patients, the effects of Viagra will last for up to two hours. A duration of two hours or less indicates that an appropriate dose was taken. If the duration is greater than four hours, medical attention should be sought out immediately to avoid damaging effects on the tissues.”

VIAGRA works for men with ED by increasing blood flow to the penis so you can get and keep an erection hard enough for sex.* VIAGRA only works when you are sexually stimulated. It has been proven to help guys with all degrees of ED. VIAGRA usually starts to work within 30-60 minutes. And you only take it when you need it.

How Does Viagra Work?

Viagra (sildenafil) is a phosphodiesterase type 5 (PDE5) inhibitor, primarily used to treat erectile dysfunction (ED). It enhances erectile function by improving blood flow to the penis — but only in response to sexual stimulation. Here’s a comprehensive, detailed explanation of how Viagra works, step by step:

? 1. The Physiology of an Erection (Before Viagra Acts)

To understand how Viagra works, first we need to understand the normal erectile process:

➤ Sexual Stimulation Triggers:

Psychogenic (brain signals from arousal) and/or
Reflexogenic (touch or stimulation of the genitals)

➤ Neurovascular Mechanism:

Nitric Oxide (NO) Release:
- Parasympathetic nerves in the penis release nitric oxide (NO) during arousal.
Activation of Guanylate Cyclase:
- NO stimulates the enzyme guanylate cyclase in smooth muscle cells.
cGMP Formation:
- Guanylate cyclase converts GTP (guanosine triphosphate) into cGMP (cyclic guanosine monophosphate).
Smooth Muscle Relaxation:
- cGMP causes the smooth muscle of the corpus cavernosum (erectile tissue) and arterial walls to relax.
Increased Blood Flow:
- Relaxation leads to vasodilation → increased blood flow into penile sinusoids.
- Blood fills the corpora cavernosa, compressing venous outflow, resulting in penile erection.

? 2. Role of PDE5: Natural Turn-Off Mechanism

The enzyme PDE5 (phosphodiesterase type 5) breaks down cGMP into inactive GMP.
This reduces smooth muscle relaxation, ending the erection by restoring baseline vascular tone.

? 3. How Viagra Works: PDE5 Inhibition

➤ Viagra Mechanism of Action:

Selective PDE5 Inhibition:
- Sildenafil (Viagra) competitively inhibits PDE5.
- This prevents the breakdown of cGMP in the corpus cavernosum.
Increased cGMP Levels:
- As PDE5 is blocked, cGMP levels remain elevated.
- This prolongs smooth muscle relaxation in penile arteries and erectile tissues.
Enhanced and Prolonged Erection:
- Sustained vasodilation and blood pooling leads to a firmer and longer-lasting erection.

? Note:

Viagra does not initiate an erection on its own.
Sexual stimulation is still required to trigger the NO–cGMP pathway.

⏱️ 4. Pharmacokinetics of Viagra

Property	Details
Onset	~30 to 60 minutes after oral intake
Peak effect	~60–120 minutes
Duration	Up to 4 hours
Absorption	Delayed with high-fat meals
Metabolism	Liver (via CYP3A4, minor CYP2C9)
Elimination	Mainly fecal (via bile), some in urine
Half-life	~3–5 hours

? 5. Tissue Selectivity and Other PDEs

Viagra is most selective for PDE5, found in:

Corpus cavernosum (penis)
Pulmonary vascular smooth muscle
Platelets and vascular endothelium

But it also partially inhibits other PDEs at higher doses:

Enzyme	Location	Effects of Inhibition
PDE6	Retina (photoreceptors)	May cause visual disturbances (blue/green color tinge, light sensitivity)
PDE1	Heart, brain, vessels	Mild vasodilation, headache, flushing
PDE11	Skeletal muscle, testes	Clinical significance unclear

⚠️ 6. Why Certain Patients Should Avoid Viagra

Contraindications:

Nitrate therapy (e.g. nitroglycerin) → Risk of severe hypotension
Severe cardiovascular disease
Recent stroke or heart attack
Retinitis pigmentosa (due to PDE6 interaction)

Drug Interactions:

Nitrates – life-threatening drop in blood pressure
Alpha-blockers – additive hypotension
CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) – increase sildenafil levels

✅ 7. Clinical Uses of Viagra

1. Erectile Dysfunction (ED):

Primary and most common use.
Effective across a broad range of ED etiologies (diabetes, post-prostatectomy, psychogenic, etc.)

2. Pulmonary Arterial Hypertension (PAH):

Under brand Revatio (also sildenafil).
Works via vasodilation of pulmonary arteries, reducing pulmonary vascular resistance.

? Summary Diagram: Viagra Mechanism of Action

Sexual Arousal → Nitric Oxide ↑ → Guanylate Cyclase ↑ → cGMP ↑ → Smooth Muscle Relaxation → Blood Flow ↑ → Erection

    ↓ (Normally broken down by PDE5)
Viagra → Inhibits PDE5 → cGMP stays high → Longer & Stronger Erection

If you’d like, I can also provide a diagram, slide deck, or infographic illustrating the whole mechanism.