PDE5 Inhibitors: Common ED Drugs & How They Work

Kristin Hall, FNP
Medically reviewed by Kristin Hall, FNP Written by Our Editorial Team Last updated 8/28/2020

If you’ve searched online for information about treating erectile dysfunction (ED), you’ve likely heard of medications called PDE5 inhibitors. 

PDE5 inhibitors are medications that improve blood flow to certain tissues, including the tissue of the penis. Although they were originally designed to treat cardiovascular conditions, they’re most commonly used today to treat erectile dysfunction.

Common PDE5 inhibitors available today include Viagra® (which contains the active ingredient sildenafil), Cialis® (tadalafil), Levitra® (vardenafil) and Stendra® (avanafil). 

Below, we’ve explained what PDE5 inhibitors are, how they work and how you may be able to use them to treat erectile dysfunction. We’ve also explained several important topics related to PDE5 inhibitors, from side effects, to frequently asked questions and more. 

What Are PDE5 Inhibitors?

PDE5 inhibitors, or phosphodiesterase type 5 inhibitors, are medications that block the actions of cGMP-specific phosphodiesterase type 5 — an enzyme that’s responsible for regulating the flow of blood to the penis and other areas of the body.

By inhibiting PDE5, these medications make it easier for men to get and maintain an erection when sexually aroused.

Originally, PDE5 inhibitors were developed as treatments for cardiovascular conditions such as angina and hypertension (high blood pressure).

During clinical trials in the early 1990s, patients who received the first PDE5 inhibitor — a substance named UK-92,480 — reported several side effects, including penile erections.

Initially, the researchers testing UK-92,480 (now known as sildenafil, or Viagra), viewed this as of minor significance. However, over time, the focus of the trials changed from conditions such as angina and hypertension to the use of PDE5 inhibitors to treat erectile dysfunction (ED).

Today, PDE5 inhibitors such as sildenafil and others are used by tens of millions of men in the United States and many more worldwide.

List of PDE5 Inhibitors

In the late 1990s, the first PDE5 inhibitors became available. Today, several PDE5 inhibitors are sold in the United States and internationally. The four most common PDE5 inhibitors are:

  • Sildenafil. Sold under the brand name Viagra, sildenafil is one of the most common and well-known PDE5 inhibitors. It’s been available since the late 1990s and is prescribed to treat erectile dysfunction (ED).

    Sildenafil is a relatively short-acting PDE5 inhibitor that provides relief from ED for around four hours after taking the medication. It’s available in a range of dosages and typically starts working in 30 to 60 minutes.
  • Tadalafil. Sold under the brand name Cialis, tadalafil is a long-acting PDE5 inhibitor that is occasionally referred to as the “weekend pill.” Cialis was approved by the FDA in 2003, a few years after sildenafil.

    Tadalafil’s “weekend pill” nickname comes from its long-lasting effects — one tadalafil tablet can provide relief from erectile dysfunction for up to 36 hours after it’s taken, making it a good option for people that want to avoid taking multiple tablets over several days.
  • Vardenafil. Sold under the brand name Levitra, vardenafil was introduced in 2003 as an alternative to sildenafil. Vardenafil works similarly to sildenafil, although it lasts for slightly longer, providing relief from ED for four to six hours per tablet.
  • Avanafil. Sold under the brand name Stendra, avanafil is a newer, “second-generation” PDE5 inhibitor. It works similarly to sildenafil and vardenafil but is more selective in the tissue it targets, making it less likely to cause certain side effects.

    Avanafil was approved by the FDA in 2012, making it the newest PDE5 inhibitor on the market. It’s available in a range of dosages and starts working a half hour after being taken.

All four of these medications are only available with a prescription, meaning you’ll need to talk to your healthcare provider before being able to use them. 

In addition to the medications listed above, there are several other PDE5 inhibitors that are sold internationally but are not available in the United States. These include udenafil (sold under the brand name Zydena®) and mirodenafil (sold as Mvix®).

How PDE5 Inhibitors Work

PDE5 inhibitors work by blocking the effects of the enzyme cGMP-specific phosphodiesterase type 5, or PDE5.

The PDE5 enzyme breaks down a cyclic nucleotide called cyclic guanosine monophosphate, or cGMP, which is responsible for relaxing smooth muscle tissue and regulating blood flow to parts of the body, including the erectile tissue of the penis.

By blocking the effects of PDE5, blood can more easily flow into the penis when you’re sexually aroused, making it easier for you to develop and maintain an erection.

Like other medications, the effects of most PDE5 inhibitors aren’t immediate. Depending on the specific medication you take, you’ll usually need to wait for 15 to 60 minutes before you’ll find it easier to get an erection. 

One important point to note is that PDE5 inhibitors won’t cause you to get erections randomly. Instead, they’ll make it easier for you to develop and maintain an erection only when you feel sexually aroused or stimulated. 

PDE5 Inhibitor Side Effects and Safety

PDE5 inhibitors are generally safe to use when taken according to their instructions. However, like other medications, PDE5 inhibitors such as sildenafil, tadalafil, vardenafil and avanafil can cause certain side effects.

Most of the side effects caused by PDE5 inhibitors are mild and temporary. However, there are several severe side effects that can occur when PDE5 inhibitors are misused, taken with other medications or used by people with underlying health conditions. 

Common side effects of PDE5 inhibitors include: 

  • Headaches
  • Flushed skin
  • Nasal congestion
  • Nasopharyngitis (swelling of the nasal passages and cold-like symptoms)
  • Dyspepsia (indigestion)

As a newer PDE5 inhibitor with a more selective mechanism of action, Stendra (avanafil) is less likely to cause some common side effects than other PDE5 inhibitors such as Viagra (sildenafil), Cialis (tadalafil) and Levitra (vardenafil). 

According to data from the FDA, common side effects occur about a third as frequently among men who use Stendra as they do among those who use older medications.

Severe side effects from PDE5 inhibitors are uncommon. However, they can occur. Rare and serious side effects of PDE5 inhibitors can include:

  • Priapism. Priapism is a prolonged, painful erection that can last for several hours and potentially lead to permanent damage to the erectile tissue of the penis.

    Priapism is a very uncommon side effect that requires urgent medical attention if it occurs, as failure to treat priapism may lead to lasting tissue damage.
  • Hearing issues. A very small number of men who use PDE5 inhibitors such as Viagra (sildenafil) report an issue called sudden sensorineural hearing loss (SSHL). This is an uncommon side effect that, like priapism, requires immediate medical attention.
  • Vision issues. Some PDE5 inhibitors may cause vision issues, such as sudden loss of vision in one or both eyes. Like other potentially serious side effects, this is something that requires immediate medical help.
  • Cardiovascular issues in people with existing conditions. PDE5 inhibitors may be unsafe for people with cardiovascular health issues, such as people who have recently suffered a stroke, severe arrhythmia or myocardial infarction (heart attack).

    If you have a history of heart-related issues, or if you have resting hypertension (high blood pressure) or hypotension (low blood pressure), it’s important that you talk to your healthcare provider before using any type of PDE5 inhibitor.

You can learn more about the potential side effects of PDE5 inhibitors in our detailed guides to Viagra, Cialis, Levitra and Stendra side effects. 

PDE5 inhibitors may also interact with other medications, foods and beverages, including some medications used to treat cardiovascular health issues and hypertension. We’ve provided more information about these drug interactions below. 

Frequently Asked Questions About PDE5 Inhibitors

Can PDE5 Inhibitors Interact With Other Medications?

Yes. PDE5 inhibitors can interact with other medications. In some cases, these interactions can be dangerous and even life-threatening. 

PDE5 inhibitors can interact with nitrates — a class of prescription medications that are used to treat heart conditions such as angina. Using a PDE5 inhibitor at the same time as a nitrate can cause a sudden, significant and potentially dangerous drop in your blood pressure. Do not take these two types of medications together. 

Some PDE5 inhibitors may also interact with other medications, whether sold over the counter or with a prescription. To stay safe, inform your healthcare provider about any medications you currently use or have recently used before discussing the use of a PDE5 inhibitor to treat ED.

Finally, like other medications, PDE5 inhibitors may take longer to start working if taken with fatty foods. 

Are PDE5 Inhibitors Available Over the Counter?

PDE5 inhibitors such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra) and avanafil (Stendra) are all prescription medications in the United States. In order to purchase these medications, you’ll need to talk to your healthcare provider first. 

We offer several prescription ED medications online with discreet, convenient delivery to your home address following an online consultation with a healthcare profressional.

Do PDE5 Inhibitors Lower Blood Pressure?

Yes. Because of their vasodilation effects, PDE5 inhibitors like sildenafil (Viagra) produce a small reduction in blood pressure. This effect is mild, with an average decrease of 8.4/5.5 mmHg following a normal dosage of sildenafil for erectile dysfunction.

In fact, sildenafil is even used as a treatment for pulmonary arterial hypertension (a form of hypertension that affects the arteries of the lungs) under the brand name Revatio®

What’s the Best PDE5 Inhibitor?

There’s no “best” PDE5 inhibitor for everyone. Research indicates that Viagra (sildenafil), Cialis (tadalafil) and Levitra (vardenafil) are of similar effectiveness as treatments for erectile dysfunction. In general:

  • Short-acting PDE5 inhibitors such as Viagra (sildenafil) and Levitra (vardenafil) may be the best options for treating erectile dysfunction for short periods, such as one night at a time.

  • Cialis (tadalafil), which lasts for up to 36 hours, may be the best PDE5 inhibitor if you prefer to use one medication every few days, rather than taking a PDE5 inhibitor just before sex.

  • Stendra (avanafil), which is a newer PDE5 inhibitor, is more selective in its effects and may be the best option if you’re prone to side effects from older ED medications. 

If you’re currently prescribed a certain PDE5 inhibitor and think that a different medication may be a better choice for you, it’s best to talk to your healthcare provider. 

Learn More About Treating Erectile Dysfunction (ED)

Erectile dysfunction can occur for a variety of reasons, from physical causes such as diabetes and heart disease to psychological ones such as stress, anxiety, relationship issues and even overuse of porn.

Our detailed guide to erectile dysfunction goes into more detail about the causes of ED, as well as the treatments — from medication to lifestyle changes — that are available today.

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.