Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

Iloprost, a stable carbaprostacyclin analog, was infused (up to 2-4 ng/kg/min) for 12 h daily on 5 consecutive days into the forearm vein of 13 patients with peripheral arterial occlusive disease (PAOD) of legs (stages IIb-III). All vasodilatory and antiplatelet drugs were stopped three weeks earlier. For comparison, dextran was infused in a randomized, crossover, double-blind manner with an average interval of 3 months. Iloprost increased significantly ankle systolic pressure and ankle/arm pressure ratio for the follow-up period of one month. Foot skin temperature increased insignificantly. Pain-free walking distance was prolonged up to 1.51 times by iloprost and 1.14 times by dextran (p less than 0.05). Venous occlusion plethysmography showed no improvement in the blood flow of legs. Eight patients experienced a subjective improvement in their clinical status with iloprost. Ten patients suffered from mild to severe headache, nausea, transient rest pain of legs, and hypotension. One patient with gastric ulcer history was withdrawn because of mild hematemesis, not definitely drug-related. No significant changes occurred in standard laboratory safety control or in hemostasis. The results suggest that a 5-day iloprost infusion exerts a mild favourable effect on patients with PAOD.
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PMID:A randomized, double-blind, crossover comparison of iloprost with dextran in patients with peripheral arterial occlusive disease. 169 31

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

Iloprost, a stable prostacyclin analog, was evaluated clinically for its ability to ameliorate the symptoms of peripheral neuropathy associated with diabetes. In an open, nonrandomized trial, 13 diabetic patients with neuropathy but without proliferative retinopathy received an intravenous infusion of Iloprost at a dose of 10 micrograms, at a rate of 0.1 micrograms/kg/h, twice daily for two weeks. The administration of Iloprost relieved the majority of such subjective symptoms as pain, numbness or sensation of cold and to a lesser extent, such autonomic symptoms as dizziness. In contrast, there was little evidence of objective improvement, e.g., in motor nerve conduction velocity. Iloprost treatment significantly inhibited the platelet aggregation rate stimulated by collagen in vitro. In the one patient tested, thermography revealed an increase in skin temperature by more than 2 degrees C. Side effects associated with Iloprost included headache (3 patients) or aggravation of pain in the extremities (2 patients) and could be ameliorated by slowing the infusion rate or by discontinuing the drug (one patient). Iloprost appears to be safe and effective for relieving the symptoms of diabetic neuropathy. Our results provide the rationale for a double-blind, clinical trial in larger populations of diabetics with peripheral neuropathy.
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PMID:Clinical efficacy of a stable prostacyclin analog, iloprost, in diabetic neuropathy. 170 9

Iloprost is a potent chemically stable PGI2-mimetic. Therapeutic efficacy was shown after i.v. infusion treatment in several states of peripheral vascular disease. For out-patient therapy an oral dosage form should be developed. Based upon dissolution profiles and in vivo data of a pig model, three different film-coated pellet formulations were selected for pharmacokinetic characterization in nine healthy volunteers. In the first part of the study groups of three test subjects were treated with increasing dosages (150-300 micrograms) of iloprost. At 300 micrograms flush and headache led to the discontinuation of those titration. All formulations exhibited dose-dependent serum level profiles. The cross-over characterization in all test subjects showed that one formulation, which exhibited a modified in vitro dissolution of 60% of the dose within 1 h in pH 7.4 phosphate buffer, was optimal from the pharmacokinetic profile. After oral administration of this formulation the bioavailable dose fraction was highest and half-maximal serum levels lasted for 2.4 h (mean); therapeutic serum levels were maintained for 2.1-5.0 h. This formulation was chosen for further investigation to imitate therapeutic serum level profiles as obtained after i.v. infusion for 4-6 h with a once-a-day dosage form.
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PMID:Oral iloprost in healthy volunteers. 172 88

The plasma levels and excretion of tritium-labeled iloprost in healthy elderly male and female volunteers have been measured after i.v. infusion of 2 ng X kg-1 X min-1 for 4 h and oral administration of 0.1 and 0.48 microgram/kg. During infusion, a steady-state of labeled compounds in the plasma was not achieved. Total radioactivity declined from a mean of 408 pg equiv/ml in three phases, with half-lives of 24 min, 1.7 h and 5.0 h, respectively. A steady-state of unchanged iloprost was reached rapidly with a peak of 81 pg/ml. Plasma levels declined biphasically with half-lives of 6 min and 31 min. Total clearance was 24 ml X min-1 X kg-1. Maximum concentrations of labeled substances after oral administration were 307 and 1,051 pg equiv/ml after 29 and 39 min, respectively. The peak of unchanged iloprost (116 pg/ml) was observed 7.5 min after an oral dose of 0.48 microgram/kg. Bioavailability was 16%. Iloprost was totally metabolized and the metabolites were mainly excreted in urine. The main biotransformation products in plasma and urine were tentatively identified by cochromatography as dinor- and tetranoriloprost and their glucuronides. ADP-induced platelet aggregation was reduced by 60% during the i.v. infusion and 15 min after oral administration of 0.48 microgram/kg. Heart rate and blood pressure were virtually unaffected. Common side-effects were facial flush, headache and nausea.
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PMID:Pharmacokinetics and pharmacodynamics of radio-labeled iloprost in elderly volunteers. 244 64

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

The effectiveness of iloprost, a prostacyclin derivative, was assessed in a placebo-controlled multicentre trial on 101 patients with chronic arterial disease, stage IV. All patients were on a basic local treatment, 53 randomly being assigned to the iloprost group, 48 to the placebo one. Both groups received identical saline infusions, one with the other without iloprost. Infusions were given on 28 consecutive days, iloprost being added at a dose of up to 2 ng/kg.min over six hours. At the end of the treatment period, 32 of 52 patients (61.5%) of the iloprost group and eight of the 47 in the placebo group (17%) had partial or complete healing of ulcers (P less than 0.05), the treatment effect persisting in both groups for a mean duration of at least one year. Iloprost was well tolerated, once individual dosages had been appropriately adjusted. Facial flushes, headache and nausea were the most common side effects. Heart rate and blood-pressure variations did not differ between the two groups.
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PMID:[Iloprost, a stable prostacyclin derivative, in stage 4 arterial occlusive disease. A placebo-controlled multicenter study]. 247 May 69

The effect of a range of prostanoids on human and rabbit basilar arteries precontracted in vitro in the presence of the thromboxane receptor-blocking drug AH23848B was investigated. On the rabbit basilar artery and in the presence of AH23848B the thromboxane A2 mimetic U-46619 produced further concentration-related contractions of the tissue. All other prostaglandins (except ICI81008 and PGF2 alpha which had no effect) produced concentration-related relaxations with the rank order of relaxant potency being PGE2 greater than Iloprost greater than PGI2 = PGE1 = 16,16-dimethyl PGE2 = PGD2. On the human basilar artery PGI2 and iloprost produced concentration-related relaxations with iloprost being more potent than PGI2. At high concentrations both these compounds produced reduced relaxant responses. All other prostanoids (except ICI81008 and PGD2 which had no effect) contracted the tissue, the rank order of contractile potency being 16,16-dimethyl PGE2 greater than PGE2 greater than PGF2 alpha = PGE1 greater than U46619 much greater than ICI81008 and PGD2. It is concluded that the human basilar artery possesses two contractile prostanoid receptors, a TP receptor and one which may be of the EP-type in addition to a prostanoid receptor mediating relaxation which may be of the IP-type. The prostanoid receptor(s) mediating relaxation of the rabbit in vitro basilar artery is difficult to determine. The relevance of the observations to cerebrovascular disorders such as migraine and vasospasm is discussed.
Cephalalgia 1989 Sep
PMID:Effects of prostanoids on human and rabbit basilar arteries precontracted in vitro. 252 33

Iloprost is a chemically stable derivative of carbaprostacyclin. We studied its hemodynamic effects in 10 patients in an intensive care unit. Iloprost was infused intravenously for 3 days for the treatment of advanced obliterative arterial disease of the lower extremities. Clinically significant hemodynamic responses were obtained with an infusion rate of 0.5 ng/kg/min. All subjects tolerated the dose of 4 ng/kg/min, which increased heart rate an average of 11% and cardiac index an average of 26%. This infusion rate decreased mean arterial pressure by 15%, total peripheral resistance by 31%, and pulmonary vascular resistance by 34%. Mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left and right ventricular stroke work indices, and rate pressure product did not change. At higher doses of up to 8 ng/kg/min, responses were augmented only slightly, but side effects such as headache, nausea, and abdominal colics became more prominent. The data show iloprost to be a potent vasodilator that reduces both pre- and afterload and presumably induces a compensatory increase in cardiac output and heart rate, but does not increase the work load or oxygen demand of the heart.
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PMID:Hemodynamic effects of iloprost, a prostacyclin analog. 620 78


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