cilostazol

Cilostazol inhibits phosphodiesterase III, an enzyme that degrades cyclic AMP (cAMP) in platelets and vascular smooth muscle. By increasing intracellular cAMP, cilostazol produces two main effects: (1) inhibition of platelet aggregation, and (2) vasodilation, particularly in the peripheral arterial vasculature. This combination makes it uniquely effective for improving walking distance in patients with intermittent claudication secondary to PAD.

Clinically, cilostazol is a second-line agent (after exercise therapy and risk factor modification) for symptomatic relief of claudication. It is not used for treatment of acute coronary syndromes or as an antiplatelet for stroke prevention (unlike aspirin or clopidogrel).

An important boards concept: cilostazol belongs to the same drug class as milrinone and inamrinone (PDE3 inhibitors), which are used in acute decompensated heart failure for their inotropic and vasodilatory effects. However, chronic PDE3 inhibition has been shown to increase mortality in heart failure patients due to increased myocardial oxygen demand and arrhythmogenic potential from elevated intracellular calcium. Therefore, cilostazol carries a black box warning and is contraindicated in patients with any degree of heart failure.

Common side effects include headache, diarrhea, and palpitations (due to vasodilation and mild positive inotropic/chronotropic effects). It should be used cautiously with other antiplatelet agents due to increased bleeding risk, and its metabolism via CYP3A4 and CYP2C19 means it has interactions with strong inhibitors of these enzymes (e.g., diltiazem, omeprazole), requiring dose adjustment.

Mechanism summary for boards: PDE3 inhibition → ↑cAMP → vasodilation + platelet inhibition (peripheral vasculature) vs. ↑cAMP → ↑Ca2+ influx → positive inotropy (cardiac muscle, relevant to milrinone).