Phosphodiesterase 5 (PDE5) inhibitors are a type of drug that can affect blood flow and how cells communicate in the body. PDE5 inhibitors can also appear in some foods and supplements.

People may take PDE5 inhibitors to manage conditions such as erectile dysfunction or pulmonary hypertension.

In this article, we explain how PDE5 inhibitors work and the potential risks and side effects of taking them. We also provide a list of drugs and substances that contain them.

An image of Kaempferia parviflora (KP) rootstalk, known as black ginger, which is on a list of pde5 inhibitors.Share on Pinterest
Kaempferia parviflora is a plant that naturally contains PDE5 inhibitors.

PDE5 is an enzyme in the walls of blood vessels. It affects blood flow and how cells signal within the body.

PDE5 inhibitors block the PDE5 enzyme to prevent it from working. This inhibition relaxes the blood vessels and increases blood flow.

People may take PDE5 inhibitors to treat erectile dysfunction or pulmonary hypertension.

In people with erectile dysfunction, PDE5 inhibitors increase blood flow to the penis, improving erectile function.

In people with pulmonary hypertension, PDE5 inhibitors can help by:

  • controlling blood flow to the arteries in the lungs
  • increasing blood flow to the lungs
  • lowering blood pressure

Research also suggests that PDE5 inhibitors may be helpful in treating heart disease, diabetes, and cancer.

Current research is looking into whether PDE5 inhibitors are also effective in treating cognitive disorders, such as dementia.

Various PDE5 inhibitor drugs are available, and people will usually take them in tablet form.

In the United States, the following PDE5 inhibitors are available:

  • avanafil (Stendra), to treat erectile dysfunction
  • vardenafil (Levitra), for the treatment of erectile dysfunction
  • tadalafil (Cialis, Adcirca), for the treatment of erectile dysfunction and pulmonary hypertension
  • sildenafil (Viagra, Revatio), to treat erectile dysfunction and pulmonary hypertension

Other PDE5 inhibitors include:

  • phentolamine (Regitine)
  • yohimbine (Yocon)
  • L-arginine

Read more about the best pills for erectile dysfunction here.

People who are taking nitrate medication should avoid taking PDE5 inhibitors. The combination of both medications can cause a severe decrease in blood pressure, which can potentially be fatal.

People may be taking nitrate medications for chest or heart issues. These drugs include:

  • nitroglycerin (Nitrostat)
  • isosorbide dinitrate (Dilatrate-SR, Isordil) or isosorbide mononitrate (Imdur, Monoket)
  • amyl nitrate, or “poppers”

PDE5 inhibitors can also potentially be harmful to people with certain conditions. Before taking these medications, a person should make their doctor aware if they:

  • have a history of heart attack, severe arrhythmia, or stroke in the last 6 months
  • have hypotension or hypertension
  • have a history of heart failure or angina
  • are currently using alpha-blockers

Common, and usually mild, side effects of PDE5 inhibitors can include:

  • headaches
  • flushing
  • symptoms resembling those of the common cold
  • stomach upset
  • muscle and back pain

Rare side effects may include:

  • changes in vision, or sudden loss of vision, for which people with heart disease or diabetes are more at risk
  • sudden loss of hearing
  • prolonged or painful erections that will require treatment to prevent lasting damage

PPDE5 inhibitors may interact negatively with grapefruit juice and alcohol. They can potentially also interact with other medications, so people should make their doctor aware if they are taking other drugs or supplements.

Some herbs contain PDE5 inhibitors, so people may find them in certain supplements or herbal remedies.

Kaempferia parviflora (KP) rootstalk, known as black ginger or Thai ginseng, contains PDE5 inhibitors.

Laboratory and animal studies have shown that compounds in KP have moderate blocking effects on PDE5. In relation to erectile dysfunction, KP can widen blood vessels and increase blood flow to the penis.

Horny goat weed contains icariin, an extract from the Epimedium plant. Icariin is effective as a PDE5 inhibitor.

An older study in rats found that horny goat weed extract may be a potential treatment for erectile conditions and nerve injuries in humans.

However, herbs and supplements may contain additional unlisted ingredients, cause adverse side effects, or interact with other drugs.

The Food and Drug Administration (FDA) warn that herbal or natural remedies for conditions such as erectile dysfunction may contain active ingredients that are also present in prescription drugs.

It is advisable to speak to a doctor before taking substances and supplements that contain PDE5 inhibitors or promise results equivalent to those of PDE5 inhibitor prescription drugs.

PDE5 inhibitors block PDE5, an enzyme in the walls of blood vessels. Blocking PDE5 causes blood vessels to relax, increasing blood flow to certain areas of the body.

This effect means that they can help manage conditions such as erectile dysfunction and pulmonary hypertension.

People taking nitrate medication should not take PDE5 inhibitors because the combination of drugs can cause a dangerous drop in blood pressure, which can be life threatening.

Other drugs, foods, supplements, or herbal remedies may contain PDE5 inhibitors. These may not have FDA regulation and could contain unlisted ingredients or contaminants, or interact with other medications.

People should discuss any potential side effects or drug interactions of PDE5 inhibitors with their doctor before taking these medications.