Phosphodiesterase Inhibitors: Types, Uses, Side Effects

Phosphodiesterase Inhibitors are a class of drugs that inhibit or block an enzyme known as phosphodiesterase (PDE).

PDEs naturally break down phosphate groups and lower cAMP or cGMP into target cells.

PDE inhibitors are classified according to the enzymes for which they act as non-specific inhibitors of PDE5, PDE4, and PDE3.

Inhibitors of PDE3 have positive inotropic, vasodilatory, and antiplatelet effects in acute heart failure and peripheral vascular disease.

PDE3 inhibitors are not recommended for long-term use because of their strong cardiostimulatory effect in heart failure patients.

PDE4 inhibitors allow bronchial dilatation in severe COPD.

PDE5 inhibitors cause pulmonary vasodilation and slackening of the smooth muscle of the penis. They are used in pulmonary arterial hypertension and erectile dysfunction.

Its important to understand that Nitrates or alpha-blockers are highly contraindicated in patients already taking PDE5 inhibitors because of the risk of life-threatening hypotension.

Phosphodiesterase inhibitors are classified into PDE3 and PDE5 inhibitors

• PDE3 inhibitors
  • Milrinone
  • Amrinone
  • Cilostazol
• PDE5 inhibitors
  • Sildenafil
  • Tadalafil
  • Vardenafil
  • Udenafil

Phosphodiesterase Inhibitors Type 3 (PDE3 Inhibitors)

Highlights

Some key highlights of this Phosphodiesterase inhibitors class are

• Milrinone is used for the treatment of congestive heart failure
• Amrinone is indicated  for the treatment of congestive heart failure (CHF).
• It can also be used to reduce the symptoms of intermittent claudication (pain in the legs that occurs with walking and disappears with rest).

Milrinone: It is a vasodilator and can be used as a short-term treatment for treat life-threatening heart failure. Milrinone belongs to a group of drugs known as inotropes, which work by assisting the heart to pump more blood through the body.

Uses

Congestive heart failure.

Side Effects

Common side effects of milrinone include

• Abnormal heart rhythm, and
• Dizziness or fainting.
• Easy bruising or bleeding.
• Tremors

Less common and more severe side effects include

• feeling like you might pass out,
• chest pain,
• low potassium
• bronchospasm (wheezing, chest tightness, trouble breathing)

Consult Your healthcare provider if you have the above side effects.

Precautions

• Do not drive or operate heavy machinery until you know how milrinone affects you.
• Get out of bed slowly to avoid dizziness or fainting.

1. Amrinone

Amrinone (or inamrinone) is a type 3 pyridine phosphodiesterase inhibitor. It is a positive inotropic with vasodilating properties.

Mechanism

Phosphodiesterase 3 inhibitor activity and how to stimulate the influx of calcium ions into the heart cell. Amrinone is an inhibitor of phosphodiesterase (PDE3), leading to increased cAMP and cGMP, resulting in increased calcium input, resulting in an increased inotropic effect. The main excretion route in humans is urine, both by inamrinone and by various metabolites (N-glycolyl, N-acetate, glucuronide, and N-glucuronide). The chemical interaction with precipitates occurs with amrinone and dextrose or furosemide. Therefore, a mixture of drugs should be avoided.

Uses

It is used in the treatment of

• congestive heart failure.

Side Effects

Common side effects of amrinone include

• Upset stomach,
• Lowered platelet counts, and
• A sudden drop in blood pressure (hypotension).

1. Cilostazol

Cilostazol is an antiplatelet aggregate and a vasodilator. It works by preventing blood cells, called platelets, from clumping together and preventing harmful clots’ formation. It also dilates the blood vessels in the legs.

Cilostazol helps the blood to move more quickly and ensures the fluidity of blood in your body. Inhibition of platelet aggregation and vasodilation are important cilostazol mechanisms; it is used to treat intermittent claudication in peripheral arterial disease. Cilostazol appears to have less cardio stimulant effects than milrinone.

Uses

Cilostazol is used to improve the symptoms of a particular blood flow problem in the legs.

• intermittent claudication
• Cilostazol can decrease the muscle pain/cramps that occur during exercise/walking.

Side Effects

The most common adverse effects of cilostazol are:

• abdominal pain,
• abnormal stool
• headache,
• diarrhea,
• nausea,
• upper respiratory tract infections,
• fluid retention,
• abnormal heartbeats.
• dizziness and
• runny nose.

Phosphodiesterase Inhibitors Type 5 (PDE5 Inhibitors)

Highlights

• These drugs are used for the treatment of erectile dysfunction
• They are also used for pulmonary hypertension.

1. Sildenafil

Sildenafil belongs to a group of drugs known as Phosphodiesterase Inhibitors type 5 (Phosphodiesterase 5 inhibitors) and is used to treat male sexual function problems (impotence or erectile dysfunction-ED). In combination with sexual stimulation, sildenafil works by increasing blood flow to the penis to help a man get and keep an erection.

Uses

It is most commonly used for two primary conditions such as

• Erectile dysfunctions
• Pulmonary hypertension

Side Effects

The most common side effects include:

• Nasal congestion
• Headaches
• Indigestion
• Impaired vision
• Photophobia, or sensitivity to light

Less commonly, some users have experienced cyanopsia, where everything appears to have a tinted blue tinge.

1. Tadalafil

It is in a class of Phosphodiesterase Inhibitors type-5 (PDE5) inhibitors that also include sildenafil and vardenafil.

Uses

Tadalafil is an oral drug that is used for

• Treating impotence (the inability to attain or maintain a penile erection) and
• Benign prostatic hyperplasia (BPH).

Side Effects

The most common side effects of tadalafil are

• headaches,
• facial flushing
• stomach upset,
• blurred vision,
• flu-like symptoms, and
• diarrhea,
• abnormal ejaculation.
• Tadalafil also may cause low blood pressure,
• changes in color vision

1. Vardenafil

This drug also belongs to a group of drugs known as Phosphodiesterase Inhibitors type -5 (PDE5) inhibitors. Other agents of this group are sildenafil and udenafil. The mechanism of action is the same as that of sildenafil.

Uses

It is used in the treatment of

• Erectile dysfunction

Side Effects

Common side effects includ

• Headache
• stuffy or runny nose
• dizziness
• flushing
• stomach upset