overview
What are phosphodiesterase inhibitors?
Phosphodiesterase inhibitors are drugs that relax and dilate blood vessels, improving circulation and lowering blood pressure. This makes them useful in treating a wide range of conditions, including skin and joint problems, heart and lung problems, and even sexual dysfunctions.
How do they work?
Phosphodiesterases (foss-fo-dy-ess-ter-aze-s) are enzymes, a type of molecule that make chemical reactions happen much faster and easier than normal. In humans, PDE comes in several different types, with numbers assigned to each type to distinguish them. These different types of PDE usually occur in specific areas of the body.
- PDE-3: This type of PDE is specific to the heart and circulatory system. It also plays a role in blood clotting.
- PDE-4: This type is characteristic of the lungs and causes constriction and tension of the muscles in the airways (especially the bronchi).
- PDE-5: Are found in the lungs and penis (in the case of people who were assigned male at birth).
Phosphodiesterase (PDE) inhibitors are drugs that block these enzymes. Some PDE inhibitors are selective, meaning they act on a specific type of PDE. Other PDE inhibitors are non-selective, meaning they can interfere with all PDEs to some extent.
What diseases does this group of drugs treat?
PDE inhibitors are approved by the US Food and Drug Administration to treat more than a dozen different medical problems, conditions and illnesses. They include:
Heart and circulatory diseases
- decompensated heart failure. When a system in your body goes awry, it tries to compensate so you can keep going. Decompensation occurs when the heart stops working because the body cannot keep up with the problem(s). Decompensated heart failure occurs when long-term problems make the heart too weak to pump blood on its own.
- Pulmonary hypertension. This is high blood pressure in the lungs. It is usually associated with heart problems.
- Peripheral Arterial Disease (PAD). This happens when the body has difficulty getting enough blood flow to the extremities, especially the legs.
- Prevention of postoperative thromboembolism (thrombosis).. Blood clots after surgery can be dangerous because of the risk of stroke, heart attack, or pulmonary embolism (a blood clot that becomes trapped and blocks blood flow in the lungs).
- Trombocitemia. This happens when the body makes too many platelets – a type of blood cell that helps the blood to clot.
inflammatory diseases
- Eczema. This condition, also called atopic dermatitis, causes the skin to become inflamed, irritated, and itchy.
- Psoriasis. This is a condition where the immune system causes inflammation in areas of the skin.
- Psoriatic arthritis. The condition is arthritis, which begins with immune-mediated inflammation in the form of psoriasis.
Reproductive disorders (male).
- Benign prostatic hyperplasia.This is an enlargement of the prostate that is not related to cancer.
- erectile dysfunction.
respiratory conditions
- Chronic obstructive pulmonary disease. It is a condition, also called COPD, which includes several specific diseases that cause breathing problems.
- neonatal apnea. These are breathing problems in premature babies, especially those born at least seven weeks early.
Are phosphodiesterase inhibitors commonly prescribed?
PDE inhibitors are very commonly prescribed, especially PDE-5 inhibitors used to treat erectile dysfunction. In 2019, over 4 million prescriptions were written for the two most popular PDE inhibitors, sildenafil and tadalafil. Both are among the top 300 most prescribed drugs in the United States.
How many phosphodiesterase inhibitors are there?
As of September 2021, there are 14 FDA-approved PDE inhibitors. US Food and Drug Administration.
PDE Inhibitors by Type
| PDE-3 | PDE-4 | PDE-5 | non-selective |
|---|---|---|---|
| Amrynon/Inamrynon | you rushed | Avanafila | caffeine* |
| Anagrelid | Crisiborol | sildenafil | Pentoxifylline |
| Cilostazol | Roflumilaste | Tadalafil | theophylline |
| dipyridamole | Wardenafila | ||
| Milrinon |
*Caffeine acts as a PDE inhibitor and comes in medicinal forms. One of these forms, caffeine citrate, comes in specific dosages for medical use.
Risk/Benefits
What are the benefits of phosphodiesterase inhibitors?
PDE inhibitors have several advantages that make them beneficial - if not ideal - for treating certain conditions. These benefits include:
- convenient forms. PDE inhibitors come in a variety of forms, including those taken by mouth, creams applied to the skin, and medications given as injections into a vein (IV). Depending on the medication, some medications can be taken daily and others as needed or when the situation requires it.
- targeted treatment. Selective targeting of a specific PDE allows the condition to be treated without affecting other parts of the body (which can cause unwanted side effects).
- many beneficial effects. There are certain conditions that PDE inhibitors can treat that often occur together. Examples of this are benign prostatic hyperplasia and erectile dysfunction. Tadalafil, a PDE-5 inhibitor, has FDA approval for both drugs. Another example is apremilast, which can treat both psoriasis and psoriatic arthritis.
What are the possible side effects and risks of complications associated with using these medications?
The main side effects and complications of PDE inhibitors strongly depend on the type of drug in question.
PDE-3 inhibitor side effects and complications
Common symptoms or side effects with PDE-3 inhibitors include:
| Lek | Mild to moderate side effects | serious side effects (call your doctor or seek medical attention immediately) |
|---|---|---|
| Amrinon / Inamrinon | • Thrombocytopenia (low platelet count). • Gastrointestinal effects (nausea, vomiting and abdominal pain). • Liver damage. | • Irregular heart rhythm (arrhythmia). • Immune system hypersensitivity (overreaction). |
| Anagrelid | • Headache. • Weakness. • Edema. • Gastrointestinal effects (nausea, vomiting, indigestion, diarrhoea). | • Heart palpitations. • Low blood pressure. |
| Cilostazol | • Headache. • Gastrointestinal effects (nausea, diarrhea or bloody/tarry stools). | • Fast heartbeat (tachycardia) or palpitations. |
| dipyridamole | • Dizziness or fainting. • Stomach pain or other gastrointestinal symptoms. • Skin irritation. • Headache. • Higher than normal liver enzyme test results. | • Unusual bleeding or bruising. • Jaundice (liver disease causing yellowing of the skin and eyes). • Chest pain. |
| Milrinon | • Headache. • Low potassium level. • Shaking or shaking. | • Irregular heart rhythm (arrhythmia). |
PDE-4 inhibitor side effects and complications
| Lek | Mild to moderate side effects | serious side effects (call your doctor or seek medical attention immediately) |
|---|---|---|
| you rushed | • Gastrointestinal problems (weight loss, nausea, vomiting, diarrhoea). • Illnesses and infections of the upper respiratory tract. • Headache. | • Depression that gets worse. • Suicidal thoughts. |
| Crisiborol | • Burning sensation when applied to the skin. | • Hypersensitivity (itching, swelling, rash). |
| Rofumilaste | • Gastrointestinal problems (loss or decrease in appetite, nausea, vomiting, diarrhoea). • Anxiety, nervousness or insomnia (difficulty sleeping). • Headache. • Dizziness. | • Depression that gets worse. |
PDE-5 inhibitor side effects and complications
| Lek | Mild to moderate side effects | serious side effects (call your doctor or seek medical attention immediately) |
|---|---|---|
| Avanafila | • Headache. • Reddened skin. • Back pain. • Nasal congestion. | • Priapism (an erection that is unwanted or occurs without sexual arousal; lasts at least four hours, but may occur intermittently for several hours). • Hearing loss (partial or complete) or ringing in the ears. • Changes in your vision. • If you take nitroglycerin under your tongue for chest pain, go to the emergency room immediately if you experience chest pain within 24 hours of taking any PDE-5 inhibitor. • Itching, rash or swelling around the eyes. |
| sildenafil | • Headache. • Reddened skin. • Gastrointestinal problems (nausea, indigestion). • In high doses, this can make the lights turn blue or appear brighter than normal (this is a temporary phenomenon). • Feeling dizzy or vertigo. • Low blood pressure. • Back pain. • Skin irritation. | • Changes in your vision. • Priapism (an erection that is unwanted or occurs without sexual arousal; lasts at least four hours, but may occur intermittently for several hours). • Hearing loss (partial or complete). • Liver damage. • If you are taking nitroglycerin under your tongue for chest pain, you should go to the emergency room immediately if you experience chest pain within 24 hours of taking any PDE-5 inhibitor. |
| Tadalafil | • Headache. • Low blood pressure. • Nasal congestion or irritation. • Muscle aches. | • Changes in your vision. • Priapism (an erection that is unwanted or occurs without sexual arousal; lasts at least four hours, but may occur intermittently for several hours). • Hearing loss (partial or complete). • If you are taking nitroglycerin under your tongue for chest pain, you should go to the emergency room immediately if you experience chest pain within 24 hours of taking any PDE-5 inhibitor. |
| Wardenafila | • Headache. • Reddened skin. • Flu-like symptoms. • Sinus congestion. • Gastrointestinal problems (nausea, indigestion). | • Hearing loss (partial or complete). • Priapism (an erection that is unwanted or occurs without sexual arousal; lasts at least four hours, but may occur intermittently for several hours). |
Side effects and complications of non-selective PDE inhibitors
| Lek | Mild to moderate side effects | serious side effects (call your doctor or seek medical attention immediately) |
|---|---|---|
| caffeine* | • Irritability or restlessness. • Trouble sleeping. • Agitation and agitation. • Gastrointestinal problems (nausea, vomiting and diarrhoea). | • Fast heartbeat or palpitations. |
| Pentoxifylline | • Gastrointestinal problems (nausea, vomiting and diarrhoea). • Dizziness. • Headache. | • Chest pain. • Irregular heart rhythm (arrhythmias). |
| theophylline | • Low blood pressure. • Rapid heartbeat. • Gastrointestinal problems (nausea, vomiting and diarrhoea). | • Convulsions. • Irregular heart rhythm (arrhythmias). |
What are the reasons why I shouldn't take these medications?
There are a number of reasons, including personal circumstances and medical conditions, that mean you shouldn't take a PDE inhibitor. These are contraindications that come in two types: absolute (meaning you definitely shouldn't take this drug) or relative (meaning providers must be careful when prescribing these drugs and be careful when taking them).
Absolute contraindications are:
- All PDE inhibitors: If you have had hypersensitivity issues in the past, when your immune system has reacted strongly to something. It could be a type of allergy or a situation where the immune system has caused inflammation or damage to a part of the body.
- Cilostazol: Heart failure of any kind means you should not take this medication.
- PDE-5 inhibitory (avanafil, sildenafil, tadalafil, wardenafil): Heart (circulatory system) diseases and high-risk conditions such as unstable angina, severe heart failure, recent heart attack or heart valve problems, and severe heart rhythm problems.
Other contraindications include:
- PDE-5 inhibitory (avanafil, sildenafil, tadalafil, wardenafil): If you are taking nitrites or nitrates, use caution when taking these medications. They can cause very low blood pressure, which can make you pass out. This can also happen with alpha blockers (also known as alpha antagonists).
- Amrinon e Milrinon: People with aortic or pulmonary valve disease should not take amrinone. People who are already taking disopyramide should discuss this with their doctor thoroughly before taking amrinone. Milrinone can cause problems in acute kidney injury and/or end-stage kidney disease. This is because the kidneys are responsible for removing it from the body.
- Cilostazol: If you have a medical condition that causes bleeding problems, you should not take this medication.
- Pentoxifylline: Avoid using this medication if you have recently had bleeding from your eyes or brain.
Pregnancy
You may want to avoid taking certain PDE inhibitors if you are pregnant or trying to become pregnant. While there is limited evidence of fetal risk in humans, there are animal studies that show potential problems with these drugs:
- Anagrelid.
- Avanafila.
- Cilostazol.
- Milrinon
- Roflumilaste.
- Sildenafil.
- theophylline.
Do phosphodiesterase inhibitors interact with other medications?
PDE inhibitors can interact with a wide range of medications, especially those that affect the heart, lungs, and circulatory system. Your doctor can provide you with more information and advice on what to avoid when taking these medications.
Recovery and prospects
How long can I take phosphodiesterase inhibitors?
How long you take a PDE inhibitor depends on why you are taking it. Some people may only need to take them temporarily. Others may need to take them indefinitely.
When to call a doctor
When should I call my doctor?
Your doctor can better explain the signs and symptoms that require you to contact your GP 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 right away if you experience any of the following symptoms:
- Symptoms of a heart attack. they includechest painbreathing problems, sweating, dizziness, nausea, etc.
- priapism. This is an erection that lasts at least four hours or comes on and lasts for several hours. Priapism occurs without sexual arousal and can be uncomfortable or painful.
- Vision or hearing loss. Any sudden deterioration in vision or hearing requires immediate medical attention. If you delay getting help, these problems could be permanent.
Cleveland clinic note
Phosphodiesterase inhibitors are medications that can help people with a wide range of conditions and needs. While they are well known for their ability to help with erectile dysfunction, their use goes far beyond sexual health. However, you should not take these medications unless you have a prescription. Taking any of these medications without a prescription can cause dangerous or even fatal conditions.