Claudication, treatment

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. 

PI (adenosine) receptors were explored as therapeutic targets before P2 receptors. Adenosine was identified early and is in current use to treat supraventricular tachycardia. A2a receptor antagonists are being investigated for the treatment of Parkinson s disease and patents have been lodged for the application of PI receptor subtype agonists and antagonists for myocardial ischaemia and reperfusion injury, cerebral ischaemia, stroke, intermittent claudication and renal insufficiency. 

Claudication and nonhealing foot ulcers are common in type 2 DM. Smoking cessation, correction of dyslipidemia, and antiplatelet therapy are important treatment strategies. 

A systematic literature review showed ten controlled studies of ginkgo for treatment of intermittent claudication (Ernst 1996). Many studies... 

Ernst E. (1996). [Ginkgo biloba in treatment of intermittent claudication. A systematic research based on controlled studies in the literature]. Fortschr Med. 114(8) 85-87. 

Isoxsuprine has been used to arrest premature labor, where it is given in a loading dose of 0.2-1 mg/min for 10 minutes and then reduced to 0.1-0.3 mg/min [40, 41], It has been also used in the treatment of cerebral and peripheral vascular diseases [42], intermittent claudication [43], and obliterative arterial diseases [44]. 

Cilostazol has been shown, in a multicenter, randomized, double-blind study (DP-PARA 2), to be superior to pentoxifylline for treatment of claudication symptoms... 

Unlabeled Uses Prevention of postoperative deep vein thrombosis (DVT), protection of aortocoronary bypass grafts, reduction of graft loss after renal transplant, treatment of intermittent claudication, sickle cell disease, subarachnoid hemorrhage, diabetic microangiopathy, ischemic heart disease... 

Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication. A meta-analysis. Am J Med 2000 108 276-281. 

TREATMENT OF PERIPHERAL ARTERY DISEASE AND INTERMITTENT CLAUDICATION... 

Methylxanthines decrease blood viscosity and may improve blood flow under certain conditions. The mechanism of this action is not well defined, but the effect is exploited in the treatment of intermittent claudication with pentoxifylline, a dimethylxanthine agent. However, no evidence suggests that this therapy is superior to exercise conditioning. 

Treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease... 

The contraindications to the use of 6-blockers are asthma and other bronchospastic conditions, severe bradycardia, atrioventricular blockade, bradycardia-tachycardia syndrome, and severe unstable left ventricular failure. Potential complications include fatigue, impaired exercise tolerance, insomnia, unpleasant dreams, worsening of claudication, and erectile dysfunction. Katzung PHARMACOLOGY, 9e > Section III. Cardiovascular-Renal Drugs > Chapter 12. Vasodilators the Treatment of Angina Pectoris > ... 

The clinical manifestations of PAD are associated with reduction in functional capacity and quality of life, but because of the systemic nature of the atherosclerotic process there is a strong association with coronary and carotid artery disease. Consequently, patients with PAD have an increased risk of cardiovascular and cerebrovascular ischemic events [myocardial infarction (Ml), ischemic stroke, and death] compared to the general population (4,5). In addition, these cardiovascular ischemic events are more frequent than ischemic limb events in any lower extremity PAD cohort, whether individuals present without symptoms or with atypical leg pain, classic claudication, or critical limb ischemia (6). Therefore, aggressive treatment of known risk factors for progression of atherosclerosis is warranted. In addition to tobacco cessation, encouragement of daily exercise and use of a low cholesterol, low salt diet, PAD patients should be offered therapies to reduce lipid levels, control blood pressure, control blood glucose in patients with diabetes mellitus, and offer other effective antiatherosclerotic strategies. A recent position paper... 

Two studies evaluated the effects of lipid-lowering therapy on clinical endpoints in the leg. The Program on the Surgical Control of the Hyperlipidemias was a randomized trial of partial ileal-bypass surgery for the treatment of hyperlipidemia in 838 patients (9). After five years, the relative risk (RR) of an abnormal ankle-brachial index value (ABI) was 0.6 (95% Cl, 0.4 to 0.9, absolute risk reduction, 15% points, p < 0.01), and the RR of claudication or limb-threatening ischemia was 0.7 (95% Cl, 0.2 to 0.9, absolute risk reduction, 7% points, p < 0.01), as compared with the control group. 

Intermittent claudication decreases exercise capacity and overall functional capacity, Impaired walking ability is coupled with the inability to perform activities of daily living and results in a decrease in overall quality of life (60). Pharmacologic and nonpharmacologic measures aimed in improving mobility and consequently the quality of life is important treatment goals for patients with PAD,... 

After 180 days of treatment there was a significant improvement of 73 9% (mean SE) in maximal walking distance in PAD patients treated with propionyl-L-carnitine compared to placebo (80). Propionyl-L-camitine has been shown to improve treadmill performance and quality of life in patients with claudication. After six months of treatment, subjects randomly assigned to propionyl-L-carnitine increased their peak walking time by 162 222 seconds (a 54% increase) as compared with an improvement of 75 191 seconds (a 25% increase) for those on placebo (p < 0.001) (81). 

Girolami B, Bemardi E, Prins MH, etal. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl a meta-analysis. Arch Intern Med 1999 ... 

Gardner AW, Phoelman ET. Exercise rehabilitation programs for the treatment of claudication pain a meta-analysis. JAMA 1995 274 975-980. 

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,... 

Beebe HG, Dawson DL, Cutler BS, et al, A new pharmacological treatment for intermittent claudication results of a randomized, multicenter trial, Arch Intern Med 1999 159 2041-2050. 

Jacoby D, Mohler ER III. Drug treatment of intermittent claudication. Drugs 2004 64(15) 1657-1670. 

Mobler ER III, Hiatt WR, OlinJW, etal. Treatment of intermittent claudication with beraprost sodium, an orally active prostaglandin 12 analogue a double-blinded, randomized,... 

These elfects on cerebrovascular events and on intermittent claudication suggest that simvastatin and other elfective lipid-lowering treatments may have a general antiatherosclerotic elfect not limited to the coronary bed. Definitive evidence on the elfects of statin therapy in stroke prevention and peripheral vessel disease is likely to be provided by the Heart Protection Study (MRC/BHF Heart Protection Study Collaborative Group, 1999). As noted above, this UK study has randomized over 20,000 patients aged up to 80 to simvastatin 40 mg or placebo, and the 5-year treatment period is scheduled for completion in 2001. Among these patients are 3288 patients with a history of cerebrovascular disease. Because of its size and the broad array of patient types randomized, this study should also provide reliable evidence of the elfect of simvastatin on coronary morbidity and mortality in women, elderly patients, patients with low levels of LDL and HDL cholesterol, patients with peripheral vascular disease, and diabetic patients with or without coronary disease (MRC/BHF Heart Protection Study Collaborative Group, 1999). 

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

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