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)

Felodipine, a dihydropyridine calcium-channel antagonist, significantly reduces systolic and diastolic blood pressure (BP) in patients with hypertension and has been associated with beneficial hemodynamic effects in patients with chronic stable angina pectoris or congestive heart failure (CHF). In hypertensive patients, felodipine does not appear to significantly affect glomerular filtration rate, creatinine clearance, glucose tolerance, or plasma lipoprotein concentrations. Studies comparing felodipine with other agents as monotherapy in mild to moderate hypertension have demonstrated felodipine to be at least as efficacious as hydrochlorothiazide (HCTZ) and HCTZ plus amiloride hydrochloride in combination. Comparisons of felodipine with other agents as adjuncts to beta-blocker or diuretic therapy have shown felodipine to be at least as effective as HCTZ, propranolol hydrochloride, prazosin hydrochloride, and nifedipine. Evaluations of patients with chronic stable angina are limited, and additional studies are needed before felodipine can be recommended for the routine management of angina pectoris. Similarly, additional studies are essential to delineate the role of felodipine, if any, in the management of CHF. In the management of hypertension, felodipine 5-40 mg/d significantly reduces systolic and diastolic BP. Although some patients may be controlled throughout the entire dosing interval when felodipine is administered bid, many patients will require more frequent dosing to obtain adequate BP control. Adverse effects associated with felodipine are similar to those of other dihydropyridine calcium-channel antagonists and include peripheral edema, headache, dizziness, flushing, and fatigue. A potentially clinically important drug interaction was observed when felodipine was administered concomitantly with theophylline aminopropanol; significant decreases in theophylline concentrations were noted. In summary, felodipine appears to be safe and effective for the management of hypertension when used alone or in combination with other antihypertensive agents. The efficacy of felodipine in the management of chronic stable angina pectoris and CHF requires further investigation.
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PMID:Felodipine: a new dihydropyridine calcium-channel antagonist. 176 37

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

This study compared the efficacy and safety of 8 weeks of open treatment with the dihydropyridine calcium antagonists amlodipine and nitrendipine in mild-to-moderate hypertension. Interim analysis of data from 74 patients (43 male, 31 female) showed that amlodipine normalized diastolic blood pressure (less than or equal to 90 mmHg) in 95% of patients compared with 83% of nitrendipine-treated patients. Nitrendipine produced a statistically significant increase in heart rate at 2 and 4 weeks of therapy but there was no significant change in heart rate in amlodipine-treated patients. Amlodipine-treated patients reported fewer adverse events (26%) than did the nitrendipine-treated group (47%), with two patients from the nitrendipine group discontinuing treatment due to treatment-related adverse events. Adverse events in the amlodipine-treated group were mild to moderate. The incidence of flushing was higher in nitrendipine-treated patients (25%) than in amlodipine-treated patients (10%). This relative difference in the incidence of vasodilator-related side effects is probably explained by the gradual onset of effect with amlodipine.
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PMID:Amlodipine compared to nitrendipine for the treatment of mild-to-moderate hypertension. 183 37

Treatment with the somatostatin analogue octreotide, SMS 201-995 (Sandostatin), has been carried out in a series of 23 patients with malignant midgut carcinoid tumours. The patients received initially 50 micrograms twice a day for six months, thereafter a median of 100 micrograms twice daily. Six of 22 evaluable patients (28%) showed objective tumour response lasting for 6 to 30 months. Stable disease was observed in 8 of the 22 patients (36%) and progressive disease in a further 8 patients (36%). A subjective response with decrease of diarrhoea or flushing was noted in 11 out of 22 patients (50%). Two out of 6 patients with objective response demonstrated a significant decrease of tumour size lasting for 6 and 30 months respectively. In order to maintain the clinical response, the dose had to be increased in all 6 responders. The adverse effects included development of diabetic blood glucose levels in 8 out of 22 patients (36%). Albumin-modified serum calcium levels were significantly reduced after treatment with octreotide 50 micrograms twice a day. One patient developed symptoms of hypocalcemia which was reversed by supplementation with calcium and D-vitamins. The somatostatin analogue SMS 201-995 has a beneficial effect in the treatment of patients with the carcinoid syndrome. However, the precise role of the drug in the long-term management of these patients has to be further investigated.
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PMID:Treatment of malignant midgut carcinoid tumours with a long-acting somatostatin analogue octreotide. 185 8

Nitrendipine, a new calcium-channel antagonist, was used to treat 25 children (aged 6 months to 17 years) with severe hypertension. Systolic and diastolic blood pressures (mean +/- SEM) fell from 148 +/- 2/99 +/- 2 mm Hg to 128 +/- 4/77 +/- 3 mm Hg after 24 hours and to 121 +/- 2/75 +/- 2 mm Hg after 2 weeks. No further reductions in systolic or diastolic blood pressure were observed after continued therapy. Transient reflex tachycardia occurred during the first week of therapy. Other adverse effects were uncommon and included headaches, flushing, palpitations, and edema. Pharmacokinetic parameters were estimated at steady state after an oral dose of 0.56 +/- 0.04 mg/kg in 13 children. Although absolute oral bioavailability could not be determined, estimates of the area under the plasma concentration versus time curve, the apparent peak serum concentration, and the apparent time at which the peak serum concentration occurred indicated that both the rate of absorption and oral bioavailability are variable. Coadministration of nitrendipine with food decreased the rate of absorption and may have reduced oral bioavailability. A relationship between age and the apparent plasma elimination half-life of nitrendipine was not observed. Nitrendipine, 0.25 to 0.5 mg/kg per dose administered orally every 6 to 12 hours, appeared to be an effective and safe treatment for resistant hypertension in infants and children.
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PMID:Antihypertensive effect and pharmacokinetics of nitrendipine in children. 200 42

There have been major advances in the understanding of the basic pharmacology of drugs acting upon voltage-dependent and receptor-activated calcium channels using patch-clamp techniques. The structure of the L channel is known and the (different) binding sites for various calcium antagonists have been identified using the methods of molecular biology. Although calcium slow-channel antagonists are very widely used in the treatment of hypertension, advances in the clinical pharmacology of angina and, to a lesser extent, cardiac arrhythmias, have not kept up with the basic research in molecular biology. All of the calcium antagonists in current use dilate arteries, and their therapeutic action largely depends on this property. There is evidence of differences in response between arteries and veins, and some degree of selectivity between vascular territories, but the goal of much more specific or localized vasodilation has not been achieved. The most prominent difference between the three main classes of antihypertensive drugs is the mild reflex increase of heart rate seen with the dihydropyridines and the bradycardia seen with verapamil. Most of the side effects of calcium antagonists are also based on vasodilatation, such as flushing and headache. The mild edema often seen with the dihydropyridines probably depends on the changes in capillary pressure brought about by arterial dilatation. Despite their undoubted efficacy as vasodilators, there are no studies thus far which allow any conclusions as to the long-term effect of calcium antagonists on the morbidity and mortality due to hypertension.
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PMID:Clinical pharmacology of calcium antagonists. 202 57

Calcitonin gene-related peptide (CGRP) is a neuropeptide with potent cardiovascular effects that include positive inotropic and chronotropic actions systemic vasodilation, and hypotension in animals and in man. The mechanism of action of CGRP is still, however, not clear, and in particular it is not known whether vasodilation by CGRP occurs by changes in cutaneous or in muscular blood flow, or both. The aim of the study was, therefore, to evaluate the cutaneous and muscular blood flow, at rest and after ischemic test, induced by an IV bolus 25 micrograms human CGRP infusion in 5 healthy normotensive volunteers, using a strain gauge plethysmographic procedure with venous occlusion. Human CGRP provoked a transient but significant decrease in systolic and diastolic blood pressure, associated with tachycardia, marked flushing, a significant increase in plasma noradrenaline, adrenaline, and cyclic AMP levels, and a slight, but significant, decrease in serum total calcium. Moreover, a significant increase in the carpal cutaneous blood flow at rest was observed, with no significant change in the lower extremity muscular blood flow at rest and after ischemic test. Finally human CGRP produced a significant increase in the venous partial O2 pressure and in the hematocrit and a significant decrease in the venous partial CO2 pressure. The results of the present study confirm the acute cardiovascular and metabolic effects of CGRP. In fact, hypotension, tachycardia, flushing, and the increased cutaneous blood flow indicate a systemic vasodilation by the neuropeptide, with a secondary sympathetic response, as documented by the augmented catecholamine and cyclic AMP plasma levels.
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PMID:Plethysmographic evaluation of the vascular effects of human calcitonin gene-related peptide in man. 204 94

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, the therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.
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PMID:Cadralazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. 208 13

The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37 degrees C and 6 days at 4 degrees C were 80.3 +/- 5.2 and 31.6 +/- 2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0 +/- 3.9% (P less than 0.001) after 6 h of warm ischemia, while this inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 microM of verapamil, 21.2 +/- 5.8% (P less than 0.001) after 6 h of warm ischemia and 25.2 +/- 3.3% (P less than 0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 mM of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 microM of verapamil followed by incubation for 6 h at 37 degrees C. In the livers that were flushed and stored at a warm temperature for 6 h, verapamil reduced the increase of tissue lipid peroxidation product (P less than 0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is thought that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.
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PMID:Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver. 208 35

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


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