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 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 ionic monomer, sodium diatrizoate at 150 mg I/ml (726 mosmol/kg) and the non-ionic monomer, iopamidol, diluted to the same iodine concentration but at 324.3 mosmol/kg, were randomly allocated to patients undergoing transfemoral intra-arterial digital subtraction angiography for lower limb peripheral vascular disease. The agents produced images of comparable quality and diagnostic efficacy. There were no significant differences between the media regarding sensations of pain and warmth. Minor neurological symptoms (headache and dizziness) occurred 7 times more frequently with the ionic monomer. There was a slight but temporary rise in plasma potassium one hour after injection of the ionic monomer but no evidence of appreciable intravascular haemolysis. The non-ionic monomer caused a slight fall in haemoglobin and haematocrit one hour after injection which is attributed to osmotic haemodilution. It is concluded that a diluted high osmolar contrast agent is an acceptable alternative to a low osmolar agent in transfemoral digital subtraction lower limb aortography.
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PMID:Transfemoral digital subtraction aortography. Are diluted high osmolar contrast media acceptable? 203 98

This randomized, double-blind study investigated the effect of ciprostene, a stable epoprostenol (prostacyclin) analog in patients with peripheral vascular disease (PVD) characterized by ischemic ulcers. A total of 211 patients (106 ciprostene, 105 placebo) received IV infusions of ciprostene (120 ng/kg/min in 8-hour daily infusions for 7 days) or placebo. The two groups were comparable with regard to demographic data. Only 45% of the patients receiving ciprostene and 55% of the placebo patients completed the trial. The groups were similar in frequency of amputations, vascular surgery, and development of new ulcers. Among those who completed the trials an insignificantly higher percentage of patients receiving ciprostene had all ulcers heal completely. The reduction of ulcer size by at least 50% was higher in the ciprostene-treated group at month 4 (P = .005). Both ciprostene and placebo reduced the severity of a patient's rest pain. There was no difference in the ankle brachial index between the groups. Ciprostene induced a higher incidence of headache, nausea, and flushing during infusion when compared with the placebo group. The results confirmed inherent problems with studies in PVD, namely, scarcity of patients with ischemic ulcers, inclusion of severely ill patients leading to a high dropout rate, and a high placebo effect. Good tolerance and safety of ciprostene was documented in this patient population, and the therapeutic benefit was limited to partial reduction of ulcer size. Selection of patients with less advanced disease and a longer infusion of ciprostene may improve the clinical benefit of this agent.
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PMID:The effect of ciprostene in patients with peripheral vascular disease (PVD) characterized by ischemic ulcers. The Ciprostene Study Group. 204 33

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

The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with beta-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with beta-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as alpha-adrenergic blockers, beta-adrenergic blockers, digoxin, quinidine, and disopyramide.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium channel antagonists. Part III: Use and comparative efficacy in hypertension and supraventricular arrhythmias. Minor indications. 315 29

The purpose of this study was to evaluate the effects of the alpha 1-blocking agent terazosin on blood pressure (BP) and blood lipids in a large, variant population of patients with hypertension. A total of 16,917 patients with hypertension were evaluated at 2214 primary and community care facilities; 7808 of these patients had not been treated previously for hypertension; 3928 were switched to terazosin from another antihypertensive agent; and 5181 received terazosin in addition to an agent that had not controlled their hypertension. Terazosin produced highly significant reductions in systolic (-18.2 +/- 0.2 mm Hg) and diastolic (-13.2 +/- 0.1 mm Hg) BP when used as monotherapy (mean dose, 3.1 mg; range, 2 to 10 mg) without causing a significant increase in heart rate. Equal antihypertensive efficacy was demonstrated in men, women, blacks, and whites of all ages, with particular benefit to elderly patients (> or = 65 years of age) with systolic hypertension. Comparative studies indicated that terazosin had equal antihypertensive efficacy in combination with diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Patients who had not responded to monotherapy with one of these classes of antihypertensive drugs showed significant reductions of BP after terazosin, in the following average doses, was added to diuretics, 3.1 mg; beta-blockers, 3.4 mg; calcium channel blockers, 3.3 mg; and ACE inhibitors, 3.4 mg. Terazosin produced highly significant reductions in blood levels of total cholesterol (-5.0%), triglycerides (-6.1%), and low-density lipoprotein cholesterol (-7.6%) without change in high-density lipoprotein cholesterol when used as monotherapy. Similar favorable effects on blood lipid levels were demonstrated when terazosin was used in combination with all other classes of antihypertensive drugs. The greatest reductions in blood cholesterol (-9.2%) were observed among patients with hyperlipidemia (total cholesterol > or = 240 mg/dL). Terazosin maintained its antihypertensive efficacy and was well tolerated by patients with a variety of concomitant diseases, including congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, benign prostatic hyperplasia, diabetes, and obesity. Adverse effects occurred in 17.9% of patients and caused 2.2% to drop out of the study. The most frequent adverse effects were dizziness (4.8%), headache (2.5%), and asthenia (2.4%). Only 0.4% suffered syncope and 0.2% impotence. These data demonstrate the usefulness of terazosin as monotherapy or add-on therapy for treatment of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha 1-blockade for the treatment of hypertension: a megastudy of terazosin in 2214 clinical practice settings. 792 16

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

Nicardipine is a second generation dihydropyridine calcium antagonist which selectively inhibits vascular smooth muscle contraction. In elderly patients, the drug has demonstrated clinical efficacy in the management of hypertension, angina pectoris and ischaemia-related cerebrovascular disease. In particular, nicardipine effectively controls blood pressure in elderly hypertensive patients with or without coexistent disease. In noncomparative trials, a regimen containing nicardipine has been associated with an improvement of symptoms in hypertensive patients with concurrent coronary artery, cerebrovascular or peripheral vascular disease, while in essentially 'healthy' elderly hypertensive patients, nicardipine monotherapy has resulted in improved indices of mobility and cognitive function. As yet, however, there is no evidence that nicardipine (and/or other calcium channel antagonists) decreases cardiovascular morbidity and mortality in elderly patients, as has been demonstrated for more established antihypertensive therapies, namely diuretics and/or beta-blockers. The pharmacokinetic properties of nicardipine in elderly hypertensive patients appear to be similar to those in younger patients. The main adverse events associated with nicardipine in the elderly are related to the vasodilator properties of the drug and include pedal oedema, headache and flushing. However, the drug does not exacerbate spontaneous postural hypotension in the elderly, nor does it adversely affect the coronary artery disease risk profile, even in patients with type II diabetes mellitus. In summary, widespread clinical experience in the elderly indicates that nicardipine monotherapy or a regimen containing nicardipine is useful for the treatment of hypertension, particularly in patients with coexistent coronary artery, cerebrovascular or peripheral vascular disease. Nicardipine monotherapy has also demonstrated efficacy in angina pectoris and shown promise in the management of ischaemia-related cerebrovascular diseases, notably subarachnoid haemorrhage.
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PMID:Nicardipine. A review of its pharmacology and therapeutic efficacy in older patients. 847 49

Takayasu's arteritis, also known as pulseless disease, is an unusual cause of symptomatic peripheral vascular disease. It was first reported in 1908 by a Japanese ophthalmologist who described retinal arteriovenous shunts which appeared in a wreath-like distribution around the optic disc and microaneurysms of the retinal vessels in a 19-year-old Japanese woman. Onishi found similar findings in association with cool, pulseless upper extremities. Since that time the syndrome has been described as Takayasu's arteritis. The current report is of a 36-year-old black woman who presented with the complaints of blurred vision, dysphagia, headaches, and near syncopal episodes who had been diagnosed with Takayasu's arteritis 12 years previously. The presentation and operative management is described and this report also reviews the literature on the management of this syndrome.
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PMID:Takayasu's arteritis: management of a complex case and literature review. 923 28


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