How Do PDE-3 Inhibitors Work?

Phosphodiesterase-3 (PDE-3) inhibitors are medications used to prevent and treat platelet aggregation and intermittent claudication (cramping in the legs because of decreased blood flow during exercise or walking).

PDE-3 inhibitors work by inhibiting the enzyme phosphodiesterase and prevent the breaking down of intracellular secondary messengers, cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) molecules leading to an increase in the levels of cAMP and cGMP in the cells.

Increased cAMP molecules decrease the levels of calcium in the smooth muscle cells. cAMP also inhibits the enzyme myosin light chain kinase that causes contraction of the smooth muscle. So, increased cAMP promotes dilation of blood vessels.

cAMP and cGMP strongly inhibit the normal platelet function. Increased cAMP in the platelets increases the active form of an enzyme, protein kinase A (PKA). PKA is directly associated with inhibition of platelet aggregation and prevention of clot formation.

PDE-3 inhibitors are used to treat:

• Intermittent claudication in peripheral arterial disease
• Thrombocythemia secondary to malignant neoplasms (excessive production of platelets by bone marrow)
• Essential thrombocytosis (excessive number of platelets in the blood)
• Thrombocytosis in patients with chronic myeloid leukemia

Side effects associated with PDE-3 inhibitors include:

• Headache
• Diarrhea
• Fatigue
• Alopecia
• Nausea
• Abnormal stools
• Severe heat intolerance
• Hypotension (low blood pressure)
• Rapid and irregular heartbeat

Other rare but serious side effects of PDE-3 inhibitors may include:

• Complete heart block
• Thrombocytopenia
• Neutropenia
• Stroke
• Pulmonary hypertension
• Renal impairment

The information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of PDE-3 inhibitor drugs include:

• Anagrelide (Agrylin)
• Cilostazol (Pletal)