Cilostazol is a phosphodiesterase III inhibitor that leads to arterial vasodilation and decreased platelet aggregation. It is a first-line medication for the treatment of claudication caused by peripheral artery disease (PAD).
Cilostazol inhibits the activation of intracellular phosphodiesterase III. This leads to decreased breakdown of cAMP and subsequent increased cAMP concentrations in platelets and within the blood vessel walls. This increased concentration of cAMP is thought to lead to decreased platelet aggregation and arterial vasodilation. According to the American Heart Association guidelines, cilostazol is a Class I recommended medication for the treatment of intermittent claudication.
Rudisill and Safranek review current guidelines for treatment of intermittent claudication. In patients with stable claudication, exercise regimens have been shown to increase walking distance without symptoms. In addition to cilostazol, additional antiplatelet agents, statins, and pentoxifylline have varying effects on maximal walking distance, depending on the study. Lastly, in the majority of patients, percutaneous transluminal angioplastly is not recommended.
Hankey et al. discuss the prevalence and diagnosis of PAD. Approximately 20% of adults over 55 years of age are affected, and the prevalence increases with age, a history of smoking, hypertension, and diabetes. The diagnosis is typically made using an ultrasound to determine the ankle-brachial index (ABI), which is the ratio of the ankle systolic blood pressure to the brachial systolic blood pressure. An ABI <0.9 is generally accepted as diagnostic.
Illustration A demonstrates the mechanism for how cilostazol inhibits phosphodiesterase III.
Answer 1: An irreversible cyclooxygenase inhibitor describes the mechanism of action of aspirin and other NSAIDs such as ibuprofen.
Answer 2: Glycoprotein IIB/IIIA inhibitors work on the glycoprotein IIb/IIIa receptor on the surface of the platelets. This prevents platelet aggregation and thrombus formation. Abciximab is a member of this drug class.
Answer 3: Thromboxane synthesis inhibitors affect the final step in the synthesis of thromboxane and include drugs such as ifetroban.
Answer 4: Adenosine diphosphate receptor inhibitors target P2Y receptors, a family of G protein-coupled receptors on platelets. Examples include clopidogrel and ticlopidine.
Rudisill HM, Kelsberg G, Safranek S. FPIN's clinical inquiries. Effective therapies for intermittent claudication. Am Fam Physician. 2011 Sep 15;84(6):699, 703-4
PMID:21916397 (Link to Abstract)
Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006 Feb 1;295(5):547-53
PMID:16449620 (Link to Abstract)