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)

Iloprost is an analogue of epoprostenol (prostacyclin; PGI2; a potent but short-lived prostanoid mainly produced in the vascular endothelium) and mimics the pharmacodynamic properties of this compound, namely: inhibition of platelet aggregation, vasodilatation and, as yet ill-defined, cytoprotection. Improved metabolic and, in particular, chemical stability enhance the clinical utility of iloprost. When administered as an intermittent intravenous infusion at less than or equal to 2 ng/kg/min for 2 to 4 weeks, iloprost reduced rest pain and improved ulcer healing in 40 to 60% of patients with critical leg ischaemia, including diabetic patients, and delayed amputation in the majority of responding individuals. Similar benefits have been seen in thromboangiitis obliterans and, in patients with severe Raynaud's phenomenon, shorter courses of therapy reduced the frequency, intensity and duration of ischaemic episodes for at least 6 weeks. The very few comparative trials reported to date (i.e. vs nifedipine in Raynaud's phenomenon; vs low-dose aspirin in thromboangiitis obliterans) have favoured iloprost, but comparisons with more established agents are needed to assess this drug's value in less severe forms of peripheral ischaemia, such as intermittent claudication. At present, iloprost is administered intravenously and this is a limitation to treatment. The potent, rapidly reversible antiplatelet activity of iloprost suits it for use in extracorporeal circulation and for the intraoperative management of heparin-induced platelet activation. Although results in animal models of ischaemic myocardial injury are encouraging, preliminary clinical experience in patients with myocardial ischaemia or infarction has been disappointing. Most patients tolerate iloprost infusion rates of up to 2 ng/kg/min. Headache and flushing are extremely common and are the suggested end-point of dose titration, as higher doses are associated with a significant incidence of gastrointestinal distress and, ultimately, hypotension. Thus, iloprost provides a pharmacotherapeutic option for patients with severe peripheral vascular disease, a condition for which few alternative drug therapies exist. Its potent but short-lived effects make it well-suited to certain therapeutic niches such as the management of intraoperative platelet activation. Prostanoid analogues have far-reaching therapeutic potential and further experience with iloprost will no doubt help to define its clinical applications.
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PMID:Iloprost. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures. 137 60

The efficacy of iloprost, a stable prostacyclin analog, was investigated in a placebo-controlled trial in 109 diabetics with ischemic lesions. 56 patients were randomly allocated to iloprost and 53 patients to placebo. Iloprost was intravenously applied for 6 hours daily on 28 consecutive days at an individually tolerated dose up to 2 ng/kg/min. The control group received identical solvent volumes. In addition all patients had an intensive basic, mainly local, therapy. At the end of the treatment in the iloprost group 31 of 50 patients (62%) showed partial (greater than 30%) or total healing of the lesion(s). In the placebo group this was the case in 12 of 51 patients (22.5%). The difference of 38.5% was statistically significant (p less than 0.05, chi 2-test, alpha = 0.05, beta = 0.1). The percentage of patients who were free of pain increased from 23% to 42% (+19%) in the iloprost group and from 38% to 48% (+10%) in the placebo group. After dose-titration iloprost was well tolerated. Flush, headache and abdominal complaints were the most frequent side effects. Heart rate and blood pressure were not influenced and the control of diabetes was not altered.
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PMID:[Iloprost in the treatment of ischemic tissue lesions in diabetics. Results of a placebo-controlled multicenter study with a stable prostacyclin derivative]. 169 72

Transcutaneous oxygen pressure (tcPo2), laser Doppler flux and capillary microscopy have been used to examine the forefoot skin in 5 healthy men and 8 patients with severe peripheral arterial occlusive disease in order to evaluate the dose dependent effects of iloprost on skin microcirculation. Iloprost was infused IV starting at 0.0625 ng.kg-1.min-1 and doubling the dose every 15 min up to 2 ng.kg-1.min-1. While tcPo2 at an electrode core temperature of 44 degrees C decreased in both patients and controls, there was a significant dose dependent increase in tcPo2 (37 degrees C) in the controls from 0.25 ng.kg-1.min-1. In the patients the reaction was variable: it was decreased in two and increased in 6, with a maximum either at 0.25-0.5 ng.kg-1.min-1 (n = 3) or at the highest dose (1.0 or 2.0 ng.kg-1.min-1; n = 3). Mean laser Doppler flux in both groups was increased, although the reaction was not consistent in the patients. Density of forefoot skin capillaries was reduced in 3 patients, and in the others the flow velocity was very low. During infusion of iloprost, both an increase in capillary density and blood cell velocity were observed. The effects were of variable intensity and occurred at varying doses, some appeared early and diminished as the dose was increased, and others were found only at 2 ng.kg-1.min-1. Adverse effects were numerous, extending from harmless skin flushing to mental changes and a quickly reversible attack of angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous infusion of iloprost in arterial occlusive disease: dose-dependent effects on skin microcirculation. 172 Jul 38

Iloprost, a stable prostacyclin analogue, was given by intravenous infusion to 29 patients with severe Raynaud's phenomenon, 26 of whom had systemic sclerosis (SS), and compared with placebo infusion in a double blind crossover trial. Iloprost significantly lessened the number and the severity of attacks compared with placebo. Nine patients expressed a preference for effectiveness of treatment, eight of these in favour of Iloprost. Thermography failed to show any long term effect of Iloprost. Side effects of headache, flushing, nausea, and vomiting were common, and the inconvenience of intravenous administration may limit its routine use.
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PMID:Infusion of iloprost, a prostacyclin analogue, for treatment of Raynaud's phenomenon in systemic sclerosis. 244 71

Prostacyclin (PGI2) has proven beneficial effects on organ preservation. Iloprost (ZK 36 374), a stable synthetic analogue with a longer half-life of 14 minutes is reported to have less hypotensive effects than PGI2 while offering increased cytoprotective and antiaggregation action. In this study its effects on lung-preservation were investigated. The heart lung block of 12 Beagle dogs was harvested after flushing of the pulmonary artery with 60 ml/kg modified Eurocollins (MEC) solution, the left lung was stored for 4 hours and then transplanted into 12 weight-matched dogs. Prior to operation the animals were randomized into two groups with MEC solution as the only preservative in group A and an additional i.v. infusion of 1 microgram/kg/min Iloprost during 15 minutes prior to flushing and 15 micrograms/kg Iloprost administered to the perfusate in group B. Arterial pO2, alveolo-arterial oxygen difference (AaDO2) and pulmonary artery pressure (PAP) of the transplanted lungs were measured 1, 4, 12, and 24 hours after transplantation during occlusion of the contralateral pulmonal artery. The application of Iloprost resulted in a significant improvement of pO2 (p = 0.047), AaDO2 (p = 0.002) and PAP (p = 0.018) after 1 hour. Results in group B at later time points were improved without reaching statistical significance. Iloprost therefore showed beneficial effects on pulmonary function early after lung preservation with MEC.
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PMID:Beneficial effect of iloprost on early pulmonary function after lung preservation with modified eurocollins solution. 247 70

Iloprost, a stable prostacyclin analogue, is known to have beneficial effects on the disturbed microcirculation. To develop a topical application for venous leg ulcers it is necessary to know the extent to which iloprost might be absorbed through the ulcer base. The aim of this study was to measure the absorption kinetics of iloprost solutions in increasing concentrations and doses (0.004% [15 micrograms]-0.006% [30 micrograms]) in 23 patients. There was considerable variation amongst the patients in the amount of iloprost absorbed. In 40% of patients no iloprost could be detected in the plasma, whereas in others up to 82% of the iloprost applied was absorbed through the ulcer base. High iloprost plasma levels provoked flushing in two patients. The highest plasma levels were always reached during the first hour after application. There was no direct relation between the ulcer size and the amount of iloprost absorbed. Iloprost concentrations up to the highest concentration applied (0.006%) were well tolerated locally.
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PMID:Absorption of the stable prostacyclin analogue iloprost through the ulcer base in chronic venous insufficiency. 750 5

The no-reflow phenomenon is a dreaded complication in free tissue transplantations. After a critical period of warm ischemia, insufficient reflow is observed after vessel anastomosis and opening of the artery. In an experimental study in 72 rats, groin flaps were harvested with the nutrient superficial epigastric vessels and transplanted to the neck using a microvascular technique with anastomoses to the carotid artery and jugular vein. Before transplantation, the isolated flaps were perfused either with saline solution, with Iloprost, with and without heparin, or the nutrient vessels were simply flushed with heparin solution. After saline perfusion, there was no venous reflow, after pure Iloprost perfusion, there was venous return in 26% of the flaps, after Heparin-Iloprost perfusion in 88% and after flushing with heparin alone in 93%. The addition of heparin to Iloprost seems to improve the reflow rate. The most effective protection against a no-reflow phenomenon, however, is flushing the nutrient vessels with a heparin solution.
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PMID:[Experimental studies of the no-reflow phenomenon with prostacyclin]. 750 60

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

Twelve patients with systemic sclerosis were treated with intravenous infusions of the prostacyclin-stable analogue iloprost 0.5-2.0 ng/kg/min for 6 h from 8 to 13 days. Imminent gangrene was stopped in 2 patients and followed by healing. In 4 of 6 patients iloprost led to complete healing of ischaemic ulcers and in the remaining 2 patients to partial healing. One patient with severe Raynaud's phenomenon discontinued the study after 3 days due to severe headache. The 2 remaining patients with Raynaud's phenomenon as an indication improved, while no improvement was recorded in a patient with vasculitis of the lower leg. Side-effects such as headache, nausea and flushing were the reason that only 5 patients reached the maximum infusion rate. No statistical differences were recorded in digital bloodflow before and after the study or in plasma endothelin in the 9 patients investigated. Three of the 6 patients with healing ulcers, however, showed a pronounced decrease in plasma endothelin. Iloprost appears useful as a treatment of imminent gangrene and ischaemic ulcers in systemic sclerosis. This reparatory capacity could also be of a more general importance in therapy of this disease.
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PMID:Treatment of ischaemic digital ulcers and prevention of gangrene with intravenous iloprost in systemic sclerosis. 880 Mar 8

Iloprost is a stable prostacyclin analogue with a pharmacokinetic profile allowing nebulised administration in patients with primary pulmonary hypertension (PPH). Inhaled iloprost is a potent acute pulmonary vasodilator with a duration of action of about 60 minutes. It may exert additional long-term benefit through antiproliferative and antithrombotic effects. Inhaled iloprost 2.5 or 5 microg six or nine times daily for 12 weeks (n = 101) significantly (p < 0.01) improved a combined clinical endpoint of a > or =10% increase in distance walked in 6 minutes and an improvement of > or =1 class in New York Heart Association functional class without clinical deterioration or death (16.8 versus 4.9% of placebo recipients, n = 102) in patients with severe PPH or selected forms of nonprimary pulmonary hypertension. Statistical analysis of the response for the PPH subgroup (20.8 versus 5.5% with placebo; n = 51 and 51) was not reported. Improvements from baseline in exercise capacity and haemodynamic/gas exchange variables have been reported in patients with PPH with continued use of inhaled iloprost. In addition, improvement in preinhalation vascular resistance occurred after 12 weeks of inhaled iloprost (p < 0.01 versus placebo) in a large randomised trial. Increased cough, headache, flushing and an influenza-like syndrome were the most common adverse events in the largest trial of patients receiving inhaled iloprost. Headache, flushing and jaw pain occurred significantly more frequently with inhaled iloprost than with placebo.
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PMID:Inhaled iloprost: in primary pulmonary hypertension. 1502 51


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