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Intermittent Claudication

cilostazol - Pletal ® pentoxifylline - Trental ®

cilostazol - Pletal ®  top of page icon

Mechanism of Action:
The mechanism of the effects of cilostazol tablets on the symptoms of intermittent claudication is not fully understood. Cilostazol tablets and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively.

Cilostazol tablets reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress. Effects on circulating plasma lipids have been examined in patients taking cilostazol tablets.

INDICATIONS AND USAGE
Cilostazol is indicated for the reduction of symptoms of intermittent claudication, as indicated by an increased walking distance.

CONTRAINDICATIONS
Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV congestive heart failure. Cilostazol is contraindicated in patients with congestive heart failure of any severity.

Cilostazol is contraindicated in patients with haemostatic disorders or active pathologic bleeding, such as bleeding peptic ulcer and intracranial bleeding. Cilostazol inhibits platelet aggregation in a reversible manner.

Cilostazol is contraindicated in patients with known or suspected hypersensitivity to any of its components.

Dosing (Adults): Peripheral vascular disease: 100 mg orally twice daily taken at least 30 minutes before or 2 hours after breakfast and dinner. Dosage should be reduced to 50 mg twice daily during concurrent therapy with inhibitors of CYP3A4 or CYP2C19.

Supplied: 50 mg, 100 mg tablet.

pentoxifylline  - Trental ®  top of page icon

Mechanism of Action:
Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity. In patients with chronic peripheral arterial disease, this increases blood flow to the affected microcirculation and enhances tissue oxygenation. The precise mode of action of pentoxifylline and the sequence of events leading to clinical improvement are still to be defined. Pentoxifylline administration has been shown to produce dose-related hemorrheologic effects, lowering blood viscosity, and improving erythrocyte flexibility. Leukocyte properties of hemorrheologic importance have been modified in animal and in vitro human studies. Pentoxifylline has been shown to increase leukocyte deformability and to inhibit neutrophil adhesion and activation. Tissue oxygen levels have been shown to be significantly increased by therapeutic doses of pentoxifylline in patients with peripheral arterial disease.

Dosing (Adults): Peripheral vascular disease: 400 mg orally 3 times/day with meals. Maximal therapeutic benefit may take 2-4 weeks to develop. Recommended to maintain therapy for at least 8 weeks. May reduce to 400 mg twice daily if GI or CNS side effects occur.

Supplied: 400 mg extended release tablet.
 

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
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David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.
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