Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epoprostenol (Prostacyclin) has been studied with various success in patients with peripheral vascular disease (PVD). We investigated the tolerance of a new, stable prostacyclin derivative ciprostene (9-beta-methyl carbacyclin) in 9 PVD patients. The drug was infused intravenously for 8 hours a day, once a week for 4 consecutive weeks, at a dose of 120 ng/kg/min. There were 6 men and 3 women with a mean age of 63 years (42-78). The PVD was verified by arteriography (9 patients) and by clinical findings. Patient #9 was lost to follow up after the first infusion and, consequently, was excluded from further evaluation. In patient #5 with a history of arrhythmias, the last ciprostene infusion had to be discontinued at 4.5 hours due to arrhythmias but his data were included into the evaluation. The cardiac disturbances were not judged to be ciprostene-related. Patients were followed monthly for 3 months after last infusion. Ciprostene was well tolerated although it produced adverse medical events (AMEs); most of them were rated as mild. The most frequent were those typical of prostacyclin: headache, facial flushing and warmth, body warmth, jaw pain and sleepiness. No consistent changes in blood pressure and heart rate were observed. One patient who initially had 9 ischemic ulcers underwent transmetatarsal amputation at month 4. The absolute and relative claudication time was measured by treadmill. As compared to baseline, the absolute claudication time increased significantly at week 2 and 4 of the infusion period and also at the end of month 3, but not at the end of month 4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ciprostene in patients with peripheral vascular disease (PVD). An open-label, tolerance trial. 306 80

Iloprost is a synthetic stable analogue of prostacyclin (PGI2), which shares its antiaggregating and vasodilating properties. Iloprost has been administered by i.v. route to patients with critical limb ischaemia (CLI) of different origin (maximal dosage: 2 ng/kg/min 6 hours/day infusion for 14-28 days). In patients with claudicatio intermittens (Fontaine stage II) iloprost improved the time to claudication and the maximal walking distance on treadmill, with an effect still lasting 60 days after suspension. This benefit was not related to a significant improvement in blood flow. Five multicentric, perspective, randomized versus placebo studies in patients with more severe CLI (Fontaine stage III-IV) susceptible to surgical treatment, showed that iloprost was able to reduce pain and ulcer dimensions. Furthermore, tha amputation rate of the ischemic limb was significantly lower in patients treated with iloprost during a 6 month follow-up (p < 0.01). Iloprost was also more effective than aspirin in causing pain relief and ulcer healing in patients with thromboangiitis obliterans and more effective than nifedipine in reducing frequency, intensity and duration of ischemic episodes in patients with Raynaud's phenomenon. Minor side effects of iloprost administration are represented by facial flushing, tachycardia, headache, nausea, vomiting, abdominal cramping, diarrhoea, whose frequency ranges from 16% to 70%; major collateral effects, occurring in less than 5% of patients, are above all represented by severe hypotension and angina pectoris. Clinical data indicate therefore that iloprost treatment can allow to improve the clinical conditions and the prognosis in patients with critical ischemia of the limbs, not candidate to surgical revascularization, by causing a relief of pain, a reduction in ulcer dimensions and deferring amputation.
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PMID:[The role of iloprost in the treatment of critical ischemia of the limbs]. 750 14

Parenteral compounds present special drug delivery challenges. This open-label study evaluated a portable infusion pump as a means to deliver intravenous ciprostene, a stable prostacyclin analog. Ten patients with peripheral vascular disease and claudication received ciprostene (titrated to 120 ng/kg/min) infused over 8 hours 1 day per week for 4 consecutive weeks. Patients successfully maintained the pump strapped to the waist. The mean +/- standard deviation delivery error, with volumes of 6 to 10 mL over 8 hours, was -0.895 +/- 3.177%. Accordingly, the pump performed well with a potent drug under these clinical conditions. Headache, flushing, and infusion site irritation during infusion were the most frequent side effects. Blood pressure remained unchanged during infusion; however, heart rate increased significantly (P < .05, maximum increase was 13.9 +/- 2.1 beats per minute [mean +/- standard error of the mean]. Mean (+/- standard error of the mean) relative claudication times on treadmill remained unchanged; however, absolute claudication times increased (P < .05) from 6.6 +/- 1.8 to 10.0 +/- 2.2 minutes. Ciprostene inhibited adenosine diphosphate-induced platelet aggregation by 56.0 +/- 12.7% (mean +/- standard error of the mean). Mean template bleeding times and plasma concentrations of platelet-specific proteins (beta-thromboglobulin, platelet factor 4) did not change.
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PMID:Continuous intravenous dosing with ciprostene using a portable pump in ambulatory patients. 844 Jul 64

In patients with peripheral artery disease (PAD), statins may improve the symptoms of claudication. The Intermittent Claudication Proof of Principle (ICPOP) study tested the hypothesis that the combination of extended release niacin plus lovastatin would improve exercise performance in patients with PAD and claudication compared with a diet intervention. A phase 3 double-blind, parallel-group, multi-center, 28-week multi-national study evaluated subjects with a history of claudication who had an ankle-brachial index (ABI) < or = 0.90, a reproducible peak treadmill walking time (PWT) of 1-20 minutes, and a low-density lipoprotein (LDL)-cholesterol level < 160 mg/dl (< 4.1 mmol/l). Subjects were randomly assigned to low-dose niacin 1000 mg plus lovastatin 40 mg (low niacin-statin), high-dose niacin 2000 mg plus lovastatin 40 mg (high niacin-statin), or diet intervention (diet). The co-primary efficacy endpoint of percent change in PWT and claudication onset time (COT) at 28 weeks was assessed using a graded treadmill protocol. At completion, 385 subjects were analyzed for safety and 370 subjects were analyzed for efficacy. The primary efficacy analysis showed no statistical significance for overall treatment effect at week 28 for the co-primary endpoint of PWT and COT. The PWT component of the primary endpoint increased 26.5% on diet, 37.8% on high niacin-statin (p = 0.137) and 38.6% on low niacin-statin (p = 0.096). Flushing as the most common event leading to discontinuation and treatment was associated with increases in liver enzymes, fasting blood glucose concentration and a decrease in platelet count.
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PMID:Effect of niacin ER/lovastatin on claudication symptoms in patients with peripheral artery disease. 2021 73