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)

Blood pressure and clinical status of 1,736 patients with cerebrovascular disease were observed during 12 months of treatment with nicardipine. The most common diagnoses were chronic cerebral ischemia (53.2%), transient ischemic attacks (TIA; 25.1%), and cerebral infarct (8.7%); 50.1% of patients were classed as hypertensive [systolic blood pressure (SBP) > or = 160 mm Hg or diastolic blood pressure (DBP) > or = 90 mm Hg]. Most patients (91.2%) received a daily dose of 60 mg nicardipine. Additional treatments included diuretics (37%), beta-blockers (11.5%), other antihypertensive drugs (15.8%), platelet antiaggregants (25.1%), and cardiotonic drugs (15.1%). A total of 282 patients (16.2%) were lost to follow-up, 21 (1.2%) patients withdrew due to side effects, 32 (1.8%) died, and 9 (0.5%) patients had treatment interrupted due to concomitant illness. In the hypertensive subgroup, blood pressure (SBP/DBP) was reduced from a mean baseline value of 175 +/- 22/97 +/- 14 mm Hg to 152 +/- 17/85 +/- 11 mm Hg at 3 months and 149 +/- 23/81 +/- 11 mm Hg after 12 months of treatment. The incidence of TIA or stroke among these patients was reduced from 29 cases (3.5%) during the first 3 months to 11 cases (1.54%) during months 4-12 (p < 0.01). In normotensive patients there were 18 (2.15%) cases during months 1-3 and 13 (1.55%) cases during months 4-12 (difference not significant). In the 280 patients treated with nicardipine alone, the most frequent side effects during the first month were facial flushing (6.8%), gastrointestinal problems (5%), dizziness (3.2%), headache (3.2%), drowsiness (3.2%), and hypotension (1.1%). Most of these side effects were transient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The influence of nicardipine in patients with high risk of stroke. 136 3

Isradipine is a new dihydropyridine calcium antagonist with a high degree of selectivity for the coronary, cerebral, and skeletal muscle vasculature. The drug has minimal depressant activity on sinoatrial node automaticity and negligible negative chronotropic, dromotropic, and inotropic actions. Isradipine reduces blood pressure and systemic vascular resistance without changes in cardiac output and stroke volume. Renal blood flow is maintained while renal vascular resistance is reduced; this is accompanied by both short- and long-term diuretic and natriuretic effects. Doses of 1.25 to 5 mg twice daily lowers blood pressure effectively over 24 h. In open as well as placebo-controlled trials, 2.5 to 10 mg isradipine twice daily was safe and well tolerated, and reduced systolic and diastolic values in up to 85% of patients with mild-to-moderate hypertension. Efficacy is similar to those of nifedipine and nitrendipine, and potentially superior to those of propranolol, atenolol, prazosin, hydrochlorothiazide, and diltiazem. The drug can be safely combined with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and diuretics. Adverse effects are dose-dependent and secondary to arterial vasodilatation, such as headache, flushing, ankle edema, dizziness, palpitations, and tachycardia. At the recommended dose of 2.5 mg twice daily, the total incidence of side effects does not differ from that with placebo. The antiatherosclerotic, antitrophic, and cerebroprotective effects seen in experimental animal models are promising for the drug in the treatment of human hypertension. Isradipine may not only reduce blood pressure, but may also reduce the risk for the consequences of this peril, namely, cerebral stroke and myocardial infarction.
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PMID:The place of isradipine in the treatment of hypertension. 182 26

Eosinophilic endocarditis is a potentially lethal complication of chronic peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase (EPO), an abundant eosinophil (EO) cationic granule protein, promotes eosinophilic endocarditis by binding to negatively charged endocardium, and there generating cytotoxic oxidants. Using an immunocytochemical technique, we demonstrated endocardial deposition of EPO in the heart of a patient with hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at physiologic halide concentrations, we characterized the Br(-)-dependent toxicity of both activated EOs and purified human EPO towards several types of endothelial cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-, phorbol myristate acetate-activated EOs, but not polymorphonuclear leukocytes, caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates. We further modeled eosinophilic endocarditis by instilling EPO into the left ventricles of isolated rat hearts, flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br- and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous decrement in rate pressure product, stroke volume work, aortic output, and MVO2 to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or H2O2 completely abrogated. These findings raise the possibility that EPO bound to endocardial cells might utilize H2O2 generated either by overlying phagocytes or endogenous cardiac metabolism along with the virtually inexhaustible supply of Br- from flowing blood to fuel HOBr-mediated cell damage. By this mechanism, EPO may play an important role in the pathogenesis of eosinophilic endocarditis.
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PMID:Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis. 198 18

Acylated plasminogen-streptokinase activator complex (APSAC; antistreplase) is an inactive complex of human plasminogen and streptokinase. When it is injected, a controlled deacylation of the catalytic center occurs, activating the complex so that thrombolysis may begin. This process extends the half-life of streptokinase, allowing for 4-6 hours of fibrinolytic activity. Anistreplase has demonstrated equivalent efficacy to intracoronary streptokinase with regard to reperfusion rates in acute myocardial infarction. In addition, patients have shown a 56% reduction in mortality at 28 days with anistreplase compared to heparin. The adverse effect profile of anistreplase includes minor bleeding and hematoma formation at the site of venipuncture, hypotensive and bradycardic episodes, arrhythmias, facial flushing, fever, and rarely, allergic reactions. Serious bleeding reactions are uncommon, with the frequency of cerebrovascular accident reported at 0.4-0.6%. The special advantage of anistreplase is its administration as a 30-U intravenous bolus injected over 5 minutes, eliminating the need for long infusions and increasing the ease of administration. Based on its efficacy and ease of administration, anistreplase may become the drug of choice in the emergency treatment of acute myocardial infarction.
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PMID:Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy. 214 Aug 89

Calcium antagonists, particularly those derived from the dihydropyridine class, have shown remarkable efficacy in the treatment of hypertension and other cardiovascular disorders. This review will concentrate on the use of one of the newer compounds in this category, isradipine, in the treatment of arterial hypertension. Isradipine is a calcium antagonist with marked vascular selectivity and, in practical terms, is devoid of cardiac effects. Its usefulness in hypertension is well documented, both when used as single drug treatment and in combination with other agents, particularly beta-blockers. Isradipine is well tolerated, does not cause metabolic disturbances and, apart from the typical dihydropyridine-type vascular adverse effects, e.g. flushing and ankle oedema, it does not cause any specific side effect. Some results obtained with isradipine in animal studies, e.g. the antiatherosclerotic effect and the brain tissue preserving effect seen in experimental stroke, appear to hold great promise for future important clinical applications for isradipine.
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PMID:Isradipine in hypertension. 215 Jun 33

From a hemodynamic point of view, the calcium antagonists represent an interesting way of treating hypertension, because they reduce total peripheral resistance without compromising cardiac output. Blood flow is also maintained during muscular exercise. Verapamil and diltiazem induce slight reduction in heart rate, but this is compensated by increase in stroke volume. Verapamil and diltiazem also prolong atrioventricular conduction time, in contrast to the dihydropyridines. Most clinical data are available for verapamil, diltiazem, and nifedipine. In patients with mild-to-moderate hypertension, these compounds seem as effective as diuretics and beta-blockers. They do not induce disturbances in glucose metabolism, serum uric acid, or serum potassium, and unwanted disturbances in blood lipids have not been described. The dihydropyridines may safely be combined with beta-blockers, but the combination of either verapamil or diltiazem with a beta-blocker should be avoided (because of the high risk of bradycardia). The calcium antagonists seem particularly useful in patients with the combination of hypertension and angina pectoris or peripheral vascular diseases or chronic obstructive lung diseases or diabetes. They are also effective in hypertensive crises. They may also be tried as a first line drug in patients with mild and moderate essential hypertension, particularly when diuretics or beta-blockers are contraindicated. Temporary side effects due to vasodilatation (headache, flushing, and palpitations) are seen frequently, particularly on the dihydropyridines. Edema is the most frequent serious side effect of the dihydropyridines, and constipation is most common with verapamil. At this point, few long-term data are available and it is not known whether the calcium antagonists will give better or worse results, with respect to morbidity and mortality, than the beta-blockers, diuretics, or other more recent antihypertensive agents.
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PMID:Clinical use of calcium antagonists in hypertension: update 1986. 245 35

1. A novel formulation of nicardipine (50% standard (short acting), 50% sustained release) was evaluated in mild hypertension in a double-blind, randomized, placebo-controlled study, using clinic measurements (Hawksley) augmented by home recorded blood pressures (Copal UA 251). 2. Nicardipine 60 mg twice daily for 28 days produced a highly significant reduction in sitting blood pressure compared with placebo both pre dose (mean difference 17/8 mm Hg) and 2 h post dose (mean difference 34/26 mm Hg). 3. Home recordings confirmed the hypotensive effect and also revealed a consistent 'peak' effect between 2-4 h after dosing (mean difference 32/22) mm Hg). 4. Doppler aortovelography at 2 h post-dose showed a significant increase in in stroke and minute distance (linear analogues of stroke volume and cardiac output respectively) compared with placebo. The increase in stroke distance was linearly related to change in plasma concentration of nicardipine. 5. Of the 14 patients enrolled in the study, nine experienced troublesome adverse effects on nicardipine (headaches, facial flushing, palpitations, ankle oedema) and two of these were unable to complete the study as a result. 6. This formulation of nicardipine, in the fixed dosage used in this study, is characterized by an effective antihypertensive action but also by an unacceptable adverse effect profile, presumably due to an excess of its 'short acting' component.
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PMID:Evaluation of a long acting formulation of nicardipine in hypertension by clinic and home recorded blood pressures and Doppler aortovelography. 275 80

Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.
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PMID:Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications. 332 59

Paroxysmal hypertension associated with diaphoresis and facial flushing occurs after brain injury and after spinal cord lesion above the level of sympathetic outflow. This excessive sympathetic activity is due to the failure of inhibitory impulses from supraspinal vasomotor centers to reach the spinal sympathetic outflow. A case of brainstem stroke, with weakness in all four extremities, is presented. The patient experienced paroxysms of hypertension with bladder spasms, which subsided after treatment of the spasms resulting from bladder infection. Serum levels of dopamine, norepinephrine, and epinephrine were elevated during the episode and were normal after subsidence of the paroxysms.
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PMID:Hypertension after brainstem stroke. 334 93

The therapeutic efficacy of prostacyclin in nonhemorrhagic cerebral infarction was assessed in a placebo-controlled double-blind trial. A total of 80 patients with stroke onset within 24 hours were randomized into placebo (37 patients) and prostacyclin (43 patients) groups. Demographic data and risk factors were comparable. Patients in the prostacyclin group received a continuous i.v. infusion of prostacyclin at an average rate of 8.5 ng/kg/min for an average of 64 hours. The placebo group received vehicle only in a similar fashion. During treatment hemodynamic changes were more prominent in the patients receiving prostacyclin and included reduction of systolic and diastolic blood pressure and increase in pulse rate. In contrast there was only a slight (but significant) reduction of diastolic blood pressure in the placebo group. Neurologic deficit scores were determined on admission, at Day 3, and at Weeks 1, 2, and 4. Mean neurologic deficit scores upon entry were comparable in the placebo and prostacyclin groups, and a significant improvement in the score for neurologic deficit was noted in both. The placebo group tended to fare better throughout the study, with a significant difference in neurologic deficit score favoring the placebo group at Week 2 (p = 0.0048). Two patients in the placebo and one in the prostacyclin group died. The only difference in adverse reactions was flushing (6 patients in prostacyclin vs. 0 in placebo group, p less than 0.05). The results of this study suggest a lack of therapeutic efficacy of prostacyclin in a defined population of patients with nonhemorrhagic cerebral infarction.
Stroke
PMID:Intravenous prostacyclin in acute nonhemorrhagic stroke: a placebo-controlled double-blind trial. 355 Dec 12


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