Phosphodiesterase inhibitors are a class of medications that interfere with certain types of chemical reactions in your blood. This helps blood vessels relax, reduces inflammation and more. They are best-known for their use in treating erectile dysfunction, but also have many other uses related to the heart and circulatory system.
Phosphodiesterase inhibitors are medications that cause blood vessels to relax and widen, improving circulation and lowering blood pressure. That makes them useful for treating a wide range of medical conditions, including problems with your skin and joints, your heart and lungs, and even sexual dysfunction.
Phosphodiesterases (foss-fo-dy-ess-ter-aze-s) are enzymes, a type of molecule that helps chemical reactions happen much faster and easier than normal. PDEs come in several different types in humans, with numbers assigned to each type to tell them apart. These different types of PDEs usually occur in specific places in your body.
Phosphodiesterase (PDE) inhibitors are medications that block those enzymes. Some PDE inhibitors are selective, meaning they target a specific type of PDE. Other PDE inhibitors are nonselective, meaning they can interfere with all PDEs to some extent.
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PDE inhibitors have approval from the U.S. Food and Drug Administration to treat over a dozen different medical concerns, conditions and diseases. These include:
PDE inhibitors prescriptions are very common, especially PDE-5 inhibitors for the treatment of treat erectile dysfunction. In 2019, there were more than 4 million prescriptions for just the top two PDE inhibitor medications, sildenafil and tadalafil. Both rank in the top 300 among most commonly prescribed medications in the United States.
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As of Sept. 2021, there are 14 PDE inhibitors with FDA approval. U.S. Food and Drug Administration.
PDE-3 | PDE-4 | PDE-5 | Non-selective |
---|---|---|---|
Amrinone/Inamrinone | Apremilast | Avanafil | Caffeine* |
Anagrelide | Crisaborole | Sildenafil | Pentoxifylline |
Cilostazol | Roflumilast | Tadalafil | Theophylline |
Dipyridamole | Vardenafil | ||
Milrinone | |||
PDE-3 | |||
Amrinone/Inamrinone | |||
PDE-4 | |||
Apremilast | |||
PDE-5 | |||
Avanafil | |||
Non-selective | |||
Caffeine* | |||
Anagrelide | |||
PDE-4 | |||
Crisaborole | |||
PDE-5 | |||
Sildenafil | |||
Non-selective | |||
Pentoxifylline | |||
Cilostazol | |||
PDE-4 | |||
Roflumilast | |||
PDE-5 | |||
Tadalafil | |||
Non-selective | |||
Theophylline | |||
Dipyridamole | |||
PDE-4 | |||
PDE-5 | |||
Vardenafil | |||
Non-selective | |||
Milrinone | |||
PDE-4 | |||
PDE-5 | |||
Non-selective | |||
*Caffeine does act as a PDE inhibitor and comes in medicinal forms. One of those forms, caffeine citrate, comes in specific dosages for medical use.
PDE inhibitors have several advantages that make them beneficial — if not ideal — for treating certain conditions. These advantages include:
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The major side effects and complications for PDE inhibitors strongly depend on the type in question.
PDE-3 inhibitor side effects and complications
PDE-4 inhibitor side effects and complications
PDE-5 inhibitor side effects and complications
If you take nitroglycerin under your tongue for chest pain, you should immediately go to the emergency room if you have chest pain within 24 hours after taking any PDE-5 inhibitor.
A severe side effect of PDE-5 inhibitors is priapism. This is an erection you don't want or that happens without sexual arousal; these last at least four hours but can happen on and off for several hours. Other side effects include:
Nonselective PDE inhibitor side effects and complications
There are several reasons, including personal circumstances and medical conditions, which mean you shouldn't take a PDE inhibitor. These are contraindications, and they come in two types: absolute (meaning you definitely shouldn’t take this medication) or relative (meaning providers should be cautious when prescribing these medications, and you should be cautious when taking them).
Absolute contraindications include:
Other contraindications include:
You may want to avoid taking certain PDE inhibitors if you are pregnant or trying to become pregnant. While there’s limited evidence to show a risk to a fetus in humans, there are studies in animals that show potential problems with these medications:
PDE inhibitors can interact with a wide range of medications, especially those that affect your heart, lungs or circulatory systems. Your healthcare provider can provide more information and advise you on what to avoid when taking these medications.
How long you need to take a PDE inhibitor depends on the reason you take it. Some people may only need to take them temporarily. Others may need to take them indefinitely.
Your healthcare provider can best explain the signs or symptoms that mean you need to call their office or go to the hospital right away. This is especially true if your symptoms start to change and affect your daily life or routine.
In general, you should go to the hospital immediately if you have any of the following:
A note from Cleveland Clinic
Phosphodiesterase inhibitors are medications that can help people with a wide range of medical conditions and needs. Though they are well-known because they can help with erectile dysfunction, their uses go far beyond sexual health. However, you should not take these medications unless you have a prescription. Taking any of these medications without a doctor’s prescription can cause dangerous or even deadly medical conditions.
Last reviewed on 06/08/2022.
Learn more about the Health Library and our editorial process.
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Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy