A 68-year-old man comes to the office due to thigh and leg pain that worsens with exertion. He is unable to walk through the local mall with his wife without discomfort. Past medical history is significant for hypertension and diabetes mellitus. The patient smokes 2 packs of cigarettes a day and consumes alcohol occasionally. Physical examination of the extremities shows weak dorsalis pedis pulses in both feet. Further evaluation confirms moderate peripheral arterial disease involving both lower extremities. Which of the following drugs would best provide symptomatic improvement due to direct dilation of arteries and inhibition of platelet aggregation?

Question

A 68-year-old man comes to the office due to thigh and leg pain that worsens with exertion.  He is unable to walk through the local mall with his wife without discomfort.  Past medical history is significant for hypertension and diabetes mellitus.  The patient smokes 2 packs of cigarettes a day and consumes alcohol occasionally.  Physical examination of the extremities shows weak dorsalis pedis pulses in both feet.  Further evaluation confirms moderate peripheral arterial disease involving both lower extremities.  Which of the following drugs would best provide symptomatic improvement due to direct dilation of arteries and inhibition of platelet aggregation?

Quizplus · Accepted Answer

Several molecules, including thrombin, adenosine diphosphate, and thromboxane A2, activate platelets by acting on cell surface receptors. However, interference with post-receptor signaling can alter platelet function. In particular, cyclic adenosine monophosphate (cAMP) activates a family of enzymes known as the cAMP-dependent protein kinases, or protein kinase A, and leads to inhibition of platelet aggregation. Agents that increase intra-platelet cAMP levels decrease platelet aggregation by preventing platelet shape change and granule release. Cilostazol reduces platelet activation by inhibiting platelet phosphodiesterase, the enzyme responsible for the breakdown of cAMP. It is also a direct arterial vasodilator. The net effect is a decrease in claudication symptoms and an increase in pain-free walking distances in patients with peripheral arterial disease (PAD). Patients with PAD should be initiated on a graded exercise program, which has also been shown to improve symptoms. (Choices A, E, and F) Abciximab is a monoclonal antibody that inhibits platelet aggregation by targeting the platelet IIb/IIIa receptor. Heparin is an anticoagulant that potentiates antithrombin III, resulting in the inactivation of thrombin and other factors. Tissue plasminogen activator (alteplase) converts plasminogen to plasmin and causes fibrinolysis. These agents are used in the acute management of cardiovascular events but are not useful for long-term management. (Choice B) Argatroban is a direct thrombin inhibitor primarily used in the treatment of heparin-induced thrombocytopenia. (Choice C) Aspirin is an irreversible cyclooxygenase 1 & 2 inhibitor that has been shown to reduce the risk of cardiovascular events in high-risk patients. Patients with clinically significant PAD should take antiplatelet agents (aspirin or clopidogrel) to reduce the risk of cardiovascular events (secondary prevention), but antiplatelet agents do not improve PAD symptoms. (Choice G) Warfarin is an oral anticoagulant that is a competitive inhibitor of vitamin K epoxide reductase and reduces production of vitamin K-dependent coagulation factors (II, VII, IX, X, protein C, protein S). It is used in the long-term treatment and prevention of thromboembolic events but does not reduce claudication in symptomatic PAD. Educational objective: Symptomatic management of peripheral artery disease (PAD) includes a graded exercise program and cilostazol. Cilostazol is a phosphodiesterase inhibitor that inhibits platelet aggregation and acts as a direct arterial vasodilator. Patients with PAD should also receive an antiplatelet agent (aspirin or clopidogrel) for secondary prevention of coronary heart disease and stroke. __________ References: Safety and efficacy of cilostazol in the management of intermittent claudication. (http://www.ncbi.nlm.nih.gov/pubmed/19337533) Management of lower extremity peripheral arterial disease. (http://www.ncbi.nlm.nih.gov/pubmed/19008688)

A 68-Year-Old Man Comes to the Office Due to Thigh