Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2 (1H)-quinolinone, OPC-13013) is an anti-platelet aggregating and vasodilating drug. But cilostazol is known to have a tendency to cause headache, which is thought to be due to the dilatation of the external carotid artery. In the present study the effect of cilostazol on the blood flow in the carotid arteries was established by the Doppler ultrasound technique. Twelve patients with cerebral infarction (mean age 66.3 years) were divided into two groups consisting of 9 patients (Group 1) who did not have headache during treatment with cilostazol and 3 patients (Group II) who complained of headache. The systolic peak frequency (PEAK) of the common and external carotid arteries was measured using a Doppler ultrasound device. The PEAK of the common and external carotid arteries were examined before and 4 weeks after oral administration of 200 mg/d, 100 mg twice a day, cilostazol. In Group I, the PEAK in bilateral common carotid arteries increased significantly after treatment with cilostazol, but the PEAK in bilateral external carotid arteries showed no significant change. In Group II, the PEAK in both common carotid arteries showed no significant change after treatment with cilostazol, but the PEAK in the right external carotid artery increased significantly.
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PMID:Increased external carotid artery blood flow in headache patients induced by cilostazol. Preliminary communication. 238 1

Cilostazol is a selective orally active phosphodiesterase (PDE) III inhibitor. This study was conducted to evaluate whether inhibition of PDE subtype III can reduce bronchial responsiveness. We examined the effects of cilostazol on bronchial responsiveness to methacholine in eight normal subjects by a single-blinded, crossover study. Each subject received 200 mg of cilostazol or placebo in random order. The subjects underwent methacholine challenge test 3 h after administration of each drug on two occasions separated by 5 d or more. The geometric mean value of provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) and the mean value (+/- SEM) of maximum expiratory flow on partial flow-volume curve at isovolume of 40% FVC above residual volume (PEF40) after administration of cilostazol were 25.3 (geometric standard error of the mean [GSEM], 1.35) mg/ml and 3.78 +/- 0.31 L/s, which were significantly (p < 0.02 and p < 0.05) greater than those after the placebo administration (6.81 [GSEM, 1.42] mg/ml and 2.71 +/- 0.39 L/s). All subjects complained of mild to severe headache when cilostazol was given. These findings suggest that PDE III inhibitors such as cilostazol have bronchodilator and bronchoprotective effects in humans. Further studies regarding smaller oral dosing of or aerosol administration of cilostazol or the other PDE III inhibitors are needed to determine clinical usefulness.
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PMID:Bronchodilator and bronchoprotective effects of cilostazol in humans in vivo. 781 59

Whether phosphodiesterase inhibitors increase the heart rate in patients with bradyarrhythmias is not known. We attempted to determine whether the oral phosphodiesterase inhibitor cilostazol exhibits beneficial chronotropic effects in patients with symptomatic bradyarrhythmias. Twenty patients comprising eight with bradycardic atrial fibrillation, eight with sick sinus syndrome, and four with Wenckebach-type atrioventricular block, whose 24-h total heart-beat count was < or =70,000 beats and whose maximal RR interval was > or =2.5 s, were enrolled. Holter recordings (24-h) were made before and 2 weeks after oral daily administration of 200 mg of cilostazol. Cilostazol increased the 24-h total heart-beat count from 77,429 +/- 11,168 to 107,981 +/- 13,536 (95% confidence interval, 24,605-36,497; p < 0.0001), the minimal heart rate from 33 +/- 9 47 +/- 13 beats/min (95% confidence interval, 9-19 beats/min; p < 0.0001), and the maximal RR interval from 3,149 +/- 1,018 to 2,087 +/- 601 ms (95% confidence interval, -1,517 to -608 ms; p = 0.0001). Only two patients had headaches as adverse effects. In conclusion, cilostazol had a beneficial positive chronotropic effect in patients with bradyarrhythmias, especially with bradycardic atrial fibrillation and sick sinus syndrome.
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PMID:Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with bradyarrhythmias. 955 1

This report deals with a study of the effectiveness, safety, and usefulness of long-term administration of Cilostazol for the improvement of cerebral blood flow and clinical symptoms in 24 patients with Chronic Cerebral Circulatory Insufficiency. Cerebral blood flow was investigated quantitatively using the Patlak plot method. Cilostazol was orally administered for 209 days on average. In the global improvement rating assessed on the basis of all subjective symptoms, the final improvement rate, comprising all cases showing moderate or better improvement, was 52.2%. Regarding individual symptoms, dizziness, orthostatic syncope, dull headache, and headache showed improvement rates of 30% or more. Regional cerebral blood flow (rCBF) was increased in both cerebral and cerebellar hemispheres. The global improvement rating for subjective symptoms and the delta % rCBF for every region except the cerebral hemispheres were positively correlated. However, there was no positive correlation between the global improvement rating for psychiatric symptoms and the delta % rCBF for any region. Regarding individual subjective symptoms, dizziness showed an especially high positive correlation of above 0.7 between the improvement rating and the delta % rCBF in the left temporal lobe, basal ganglia, and cerebellum. Headache was observed as an adverse drug reaction in 8 of 24 patients, but it disappeared with reduction of the dose or discontinuation of administration. No other severe adverse drug reactions were noticed. In summary, it was concluded that Cilostazol was useful for treating chronic cerebral circulatory insufficiency.
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PMID:[Effects of long-term administration of cilostazol on chronic cerebral circulatory insufficiency--with special reference to cerebral blood flow and clinical symptoms]. 978 6

Cilostazol is an antiplatelet agent with vasodilating properties that has been used in the treatment of patients with peripheral ischaemia such as intermittent claudication. The drug inhibits platelet aggregation induced by ADP, collagen and arachidonic acid. Unlike aspirin (acetylsalicylic acid), cilostazol inhibits both primary and secondary aggregation. It also acts as a vascular vasodilator by inhibiting calcium-induced contractions while having no direct effect on contractile proteins. In double-blind randomised trials, patients with intermittent claudication receiving cilostazol showed significant improvements versus placebo in terms of time to initial pain and maximal walking or absolute claudication distance; these findings were confirmed by cilostazol patients' positive responses on subscales measuring physical functioning and quality of life. In a 24-week randomised double-blind trial in patients with intermittent claudication, cilostazol 100mg twice daily produced significant improvements in pain-free and maximum walking distances, compared with pentoxifylline (oxpentifylline) 400mg 3 times daily and placebo. Cilostazol has been well tolerated, with the most common adverse events being headache, diarrhoea, abnormal stools and dizziness.
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PMID:Cilostazol. 1006 9

Cilostazol is a phosphodiesterase III inhibitor with antiplatelet, antithrombotic and vasodilatory effects. It raises plasma high-density lipoprotein cholesterol levels by approximately 10% and lowers plasma triglycerides by approximately 15%. Eight US/UK randomized, multicentre, double-blind, placebo-controlled trials lasting 12-24 weeks have been conducted with cilostazol 50, 100 or 150 mg twice daily in more than 2,000 patients with moderate to severe intermittent claudication. In constant- or variable-load treadmill tests, cilostazol increased maximal walking distance by 28-100%, and pain-free walking distance by 45-96%. Comparable changes for patients on placebo were -10 to 30% for maximal walking distance and 9 to 50% for pain-free walking distance. Responses were observed as early as the first observation point of 2 or 4 weeks and increased with time. The response was greater for 100 mg twice daily than for 50 mg twice daily. For the 100 mg twice daily dose, there was no evidence of a plateau in effect. In both the US and the UK, cilostazol is indicated to increase walking distance in patients with intermittent claudication. Cilostazol is generally well tolerated. In clinical trials, the most common adverse effects were headache, palpitation, tachycardia, abnormal stools and diarrhoea. Adverse events were generally mild to moderate in intensity.
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PMID:Cilostazol: a novel treatment option in intermittent claudication. 1135 74

Cilostazol, a type III phosphodiesterase inhibitor, was approved in the United States in 1999 for the reduction of the symptoms of intermittent claudication. This article summarizes the safety data from 8 cilostazol phase 3 controlled clinical trials, involving 2,702 patients: 1,374 receiving cilostazol, 973 assigned to placebo, and 355 taking pentoxifylline. The trials ranged from 12 to 24 weeks in duration. There were a total of 475 patient-exposure years on cilostazol, 357 patient-exposure years on placebo, and 135 patient-exposure years on pentoxifylline. Headache, diarrhea, and other gastrointestinal complaints were seen more often in cilostazol-treated than placebo-treated patients; pharyngitis and nausea were more common in pentoxifylline-treated than placebo-treated patients. Headache requiring discontinuation occurred in 1.3% of patients taking cilostazol 50 mg bid and 3.7% of those receiving cilostazol 100 mg bid, compared with 0.3% of placebo-treated patients. Discontinuations due to diarrhea, palpitations, or myocardial infarction were similar in cilostazol-, placebo-, and pentoxifylline-treated patients. The rate of serious cardiovascular events was similar in all 3 treatment groups. Myocardial infarction occurred in 1.0% of cilostazol-treated, 0.8% of placebo-treated, and 1.1% of pentoxifylline-treated patients. The incidence of stroke was 0.5% in both cilostazol- and placebo-treated patients and 1.1% in pentoxifylline-treated patients. Total cardiovascular morbidity and all-cause mortality was 6.5% for cilostazol 100 mg bid, 6.3% for cilostazol 50 mg bid, and 7.7% for placebo. There were 16 deaths occurring in 0.6%, 0.5%, and 0.6% of cilostazol-, placebo-, and pentoxifylline-treated patients, respectively. The evaluations showed no trend toward increased cardiovascular morbidity or mortality risk in patients receiving cilostazol. In addition, postmarketing surveillance in the United States, representing 70,430 patient-years of cilostazol exposure, has shown minimal accounts of myocardial infarction, stroke, or death. The safety profile of cilostazol in doses of 50 mg bid and 100 mg bid appears to offer an acceptable risk-benefit ratio in patients with intermittent claudication.
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PMID:Analysis of the cilostazol safety database. 1143 97

Intermittent claudication (IC) is leg muscle pain, cramping and fatigue brought on by exercise and is the primary symptom of peripheral arterial disease. The goals of pharmacotherapy for IC are to increase the walking capacity/quality of life and to decrease rates of amputation. In 1988, pentoxifylline was the only drug that had reasonable supportive clinical trial evidence for being beneficial in IC. Since then a number of drugs have shown benefit or potential in IC. Cilostazol, a specific inhibitor of phosphodiesterase 3 and activator of lipoprotein lipase, clearly increases pain-free and absolute walking distances in claudicants. However, cilostazol does cause minor side effects including headache, diarrhoea, loose stools and flatulence. Naftidrofuryl, a serotonin (5-HT2) receptor antagonist and antiplatelet drug, is beneficial in claudicants. Inhibitors of platelet aggregation (including nitric oxide from L -arginine or glyceryl trinitrate) and anticoagulants (low molecular weight heparin, defibrotide) probably have both short and long-term benefits in IC. In addition, intravenous infusions of prostaglandins (PGs) PGE1 and PGI2 have an established role in severe peripheral arterial disease and the recent introduction of longer lasting and/or oral forms of the PGs makes them more likely to be useful in the IC associated with less severe forms of the disease. There are some exciting new approaches to the treatment of IC, including propionyl-L-carnitine and basic fibroblast growth factor (bFGF).
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PMID:Pharmacotherapy of intermittent claudication. 1182 12

Cilostazol (Pletal), a quinolinone derivative, has been approved in the U.S. for the treatment of symptoms of intermittent claudication (IC) since 1999 and for related indications since 1988 in Japan and other Asian countries. The vasodilatory and antiplatelet actions of cilostazol are due mainly to the inhibition of phosphodiesterase 3 (PDE3) and subsequent elevation of intracellular cAMP levels. Recent preclinical studies have demonstrated that cilostazol also possesses the ability to inhibit adenosine uptake, a property that may distinguish it from other PDE3 inhibitors, such as milrinone. Elevation of interstitial and circulating adenosine levels by cilostazol has been found to potentiate the cAMP-elevating effect of PDE3 inhibition in platelets and smooth muscle, thereby augmenting antiplatelet and vasodilatory effects of the drug. In contrast, elevation of interstitial adenosine by cilostazol in the heart has been shown to reduce increases in cAMP caused by the PDE3-inhibitory action of cilostazol, thus attenuating the cardiotonic effects. Cilostazol has also been reported to inhibit smooth muscle cell proliferation in vitro and has been demonstrated in a clinical study to favorably alter plasma lipids: to decrease triglyceride and to increase HDL-cholesterol levels. One, or a combination of several of these effects may contribute to the clinical benefits and safety of this drug in IC and other disease conditions secondary to atherosclerosis. In eight double-blind randomized placebo-controlled trials, cilostazol significantly increased maximal walking distance, or absolute claudication distance on a treadmill. In addition, cilostazol improved quality of life indices as assessed by patient questionnaire. One large randomized, double-blinded, placebo-controlled, multicenter competitor trial demonstrated the superiority of cilostazol over pentoxifylline, the only other drug approved for IC. Cilostazol has been generally well-tolerated, with the most common adverse events being headache, diarrhea, abnormal stools and dizziness. Studies involving off-label use of cilostazol for prevention of coronary thrombosis/restenosis and stroke recurrence have also recently been reported.
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PMID:Cilostazol (pletal): a dual inhibitor of cyclic nucleotide phosphodiesterase type 3 and adenosine uptake. 1183 Jul 53

We examined the effect of cilostazol, a type III phosphodiesterase inhibitor, on pain-free and maximal walking distance and quality of life measures. The present study examined adverse effects in 2,702 patients with stable, moderate to severe claudication enrolled in 8 randomized, double-blind, placebo-controlled trials. Treatment duration ranged from 12 to 24 weeks. Cilostazol therapy increased maximal and pain-free walking distances by 50% and 67%, respectively. In subgroup analysis, cilostazol increased pain-free and maximal walking distance similarly in men and women, in older (>/=65 years) and younger patients, and in patients with and without diabetes. Quality-of-life assessments revealed enhanced scores for physical well-being. Cilostazol-treated patients reported a higher incidence of headache, bowel complaints, and palpitations than patients given placebos. Cilostazol decreased triglycerides by 15.8% and increased high-density lipoprotein cholesterol by 12.8%, but there were no deleterious effects on any hematologic or serum markers. We conclude that cilostazol significantly increases walking distance and quality-of-life measures in patients with claudication without major adverse effects.
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PMID:Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. 1248 40


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