Intermittent claudication cilostazol

The PDE3 inhibitor, cilostazol, has been used as an antithrombotic agent and is currently being used in patients being treated for intermittent claudication. Cilostazol is also used for the prevention of restenosis after treatments such as angioplasty. Another PDE3 selective inhibitor, milrinone, has been used in the treatment of congestive heart failure. Milrinone also has been shown to increase the conductance of the CFTR transporter in vitro. 

Intermittent claudication is a group of symptoms characterized by pain in the calf muscle of one or both legp, caused by walking and relieved by rest. It is a manifestation of peripheral vascular disease, in which atherosclerotic lesions develop in the femoral artery, diminishing blood supply to the lower leg. Cilostazol is used to treat intermittent claudication. 

WARNING Renal impair is the major tox foUow administration instructions Uses CMV retinitis w/ HIV Action Selective inhibition of viral DNA synth Dose Rx 5 mg/kg IV over 1 h once/wk for 2 wk w/ probenecid Maint 5 mg/kg IV once/2 wk w/ probenecid (2 g PO 3 h prior to cidofovir, then 1 g PO at 2 h 8 h after cidofovir) X in renal impair Caution [C, -] Contra Probenecid or sulfa allergy Disp Inj SE Renal tox, chills, fever, HA, NA /D, thrombocytopenia, neutropenia Interactions t Nephrotox W/ aminoglycosides, amphot icin B, foscar-net, IV pentamidine, NSAIDs, vancomycin t effects W/zidovudine EMS Monitor ECG for hypocalcemia (t QT int val) and hypokalemia (flattened T waves) OD May cause renal failure hydration may be effective in reducing drug levels/effects Cilostazol (Pletal) TAntiplatelet, Arterial Vasodilator/ Phosphodiesterase Inhibitor] Uses Reduce Sxs of intermittent claudication Action Phosphodiesterase in inhibitor t s cAMP in pits blood vessels, vasodilation inhibit pit aggregation Dose 100 mg PO bid, 1/2 h before or 2 h after breakfast dinner Caution [C, +/-] Contra CHE, hemostatic disorders. 

Cilostazol is a selective cAMP phosphodiesterase inhibitor. It inhibits platelet aggregation and is a direct arterial vasodilator. It is used for the symptoms of intermittent claudication in individuals with peripheral vascular disease. Side-effects of cilostazol include headache, diarrhea, increased heart rate, and palpitations. Drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure. 

Cilostazol is a newer phosphodiesterase inhibitor that promotes vasodilation and inhibition of platelet aggregation. Cilostazol is used primarily to treat intermittent claudication. 

Cilostazol is indicated for symptomatic relief of intermittent claudication (46,47). With recent attention focusing on new antiplatelet modalities in percutaneous coronary intervention, renewed interest in cilostazol has emerged. Although cilostazol has not been associated with the same increase in cardiac mortality noted with other PDE3 inhibitors used in patients with heart failure (such as milrinone), it is not recommended for use in patients with coexistent heart failure. 

Thompson PD, Zimet R, Forbes WR et al. Meta-analysis of results from eight randomized, placebo-controlled trials on hthe effects of cilostazol on patients with intermittent claudication. Am J Cardiol 2002 90 13 14-13 19. 

Dawson DL, Cutler BS, Meissner MH, et al, Cilostazol has beneficial effects in treatment of intermittent claudication results from a multicenter, randomized, prospective, doubleblind trial, Circulation 1998 98 678-686,... 

Money SR, Herd JA, Isaacsohn JL, et al, Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease, J Vase Surg I 998 27 267-274. 

Strandnessjr DE, Dalman RL, Panian S, et al. Effect of cilostazol in patients with intermittent claudication randomized, double-blind, placebo-controlled study. Vase Endovasc Surg 2002 36 83-91. 

Regensteiner JG, WareJrJE, McCarthy WJ, etal. Effect of cilostazol on treadmill walking, community-based walking ability, and health-related quality of life in patients with intermittent claudication due to peripheral arterial disease meta-analysis of six randomized controlled trials. J Am Geriatr Soc 2002 50 1939-1946. 

Cilostazol is a phosphodiesterase inhibitor that suppresses platelet aggregation and also acts as a direct arterial vasodilator. Small studies in Japan suggested that it might be useful for treating chronic arterial disease and symptoms of intermittent claudication. A trial in 81 patients with claudication substantiated this claim claudication distance was improved by 35% for initial and 41% for absolute claudication distance. 

Six multicenter placebo-controUed trials have been conducted in the USA (3,4). They involved more than 2000 patients with intermittent claudication and established the efficacy of cilostazol in improving walking distance in these patients. 

Comp PC. Treatment of intermittent claudication in peripheral arterial disease. Recent clinical experience with cilostazol. Today s Ther Trends 1999 17 99-112. 

Dawson DL, Cutler BS, Hiatt WR, Hobson RW 2nd, Martin JD, Bortey EB, Forbes WP, Strandness DE Jr. A comparison of cilostazol and pentoxifylline for treating intermittent claudication. Am J Med 2000 109(7) 523-30. 

Cariski AT. Cilostazol a novel treatment option in intermittent claudication. Int J Clin Pract Suppl 2001 (119) 11-18. 

After appropriate exercise therapy and therapeutic lifestyle changes have been implemented, patients who continue to experience severe intermittent claudication may benefit from additional pharmacologic therapy with cilostazol. 

Cilostazol (Pletal), a selective inhibitor of PDE III, is used for the treatment of intermittent claudication, an occlusive disease of blood vessels in the legs, which causes pain on walking. It acts as a vasodilator and inhibitor of platelet aggregation. Warfarin, initially developed as a rat poison, and a number of similar compounds, are effective anti-clotting agents by their action as vitamin K antagonists. 

The inhibition of platelet activation is a critical component in the treatment and prevention of cardiovascular diseases and cerebral ischemia/thrombotic disorders. Nitric oxide and prostacyclins inhibit platelet activation by elevating intracellular levels of both cGMP and cAMP, respectively. In platelets, the most abundant PDE is PDE3A, which lowers the intracellular concentration of cAMP. Inhibitors of PDE3A serve as potential antiplatelet agents by elevating cAMP levels. One PDE3-type selective inhibitor cilostazol, which has both antiplatelet, antithrombotic, and vasodilatory effects, is used for the treatment of intermittent claudication and for the prevention of short- and medium-term vessel closure (22). 

Cilostazol has been used to treat intermittent claudication in individuals widi peripheral vascular disease. A similar molecule as cilostazol may have the risk of death in patients with congestive heart failure. The synthesis of cilostazol contains a 1,3-dipolar addition for the construction of the tetrazole ring, and the resulting tetrazole was coupled with 6-hydroxy-3,4-dihydroquinolin-2(l//)-one with the aide of potassium hydroxide. ... 

Several prospective randomized trials have reported that cilostazol improves walking distance in patients with intermittent claudication by 40 to 50%, compared to placebo after 12 to 24 weeks of treatment (20,21). One of these placebo-controlled trials evaluated both pentoxifylline and cilostazol (17). Pentoxifylline demonstrated no benefit in either onset of claudication or absolute claudication distance as compared to placebo. Cilostazol, however, significantly improved both distances compared to placebo (17). A prevalent side effect of cilostazol is headache. Transient diarrhea, palpitations, and dizziness have also been reported. The FDA has issued a warning regarding the use of cilostazol in patients with congestive heart failure, because of the increased possibility of sudden cardiac death observed with other forms of diesterase type III inhibitors. Thus, it has become routine practice to assess cardiac function clinically and echocardiographically prior to initiating therapy with cilostazol for claudication, and periodically thereafter. As a result of the modest vasodilatation, heart rate may increase by a mean of 5.1 and 7.4 beats per... 

Elam MD, Heckman J, Crouse JR, et al. Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. Arterioscl Thromb Vase Biol 1998 18 1942-1947. 

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