Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper summarizes the results of 4 double-blind studies of antihypertensive therapy in which mibefradil was compared with other commonly used calcium antagonists (diltiazem CD, amlodipine, nifedipine SR, and nifedipine GITS) at the recommended dose range. A total of 640 patients were included, with 361 randomized to mibefradil, 98 to diltiazem CD, 119 to amlodipine, 71 to nifedipine SR, and 36 to nifedipine GITS. Trials included an active treatment phase of 6 or 12 weeks in duration. Compared with diltiazem CD or nifedipine SR, mibefradil demonstrated statistically significant greater efficacy. Decreases in sitting diastolic blood pressure (SDBP) after treatment with mibefradil 100 mg once daily were 14.0 +/- 7.8 mm Hg compared with 9.5 +/- 7.5 mm Hg with diltiazem CD 360 mg once daily (p = 0.001), and 12.8 +/- 8.4 mm Hg compared with 8.1 +/- 19.2 mm Hg with nifedipine SR 40 mg twice daily (p = 0.014). Patients on mibefradil also had higher normalization (SDBP reduced to < or = 90 mm Hg) and response (SDBP reduction > or = 10 mm Hg or normalization) rates than did those on diltiazem CD or nifedipine SR. The overall incidence of adverse events was similar among these 3 compounds, but the number of premature withdrawals due to adverse events was greater with both comparators than with mibefradil. Treatment with 100 mg mibefradil or 10 mg amlodipine once daily resulted in statistically significant decreases from baseline in SDBP of 11.5 +/- 8.2 mm Hg and 13.2 +/- 7.9 mm Hg, respectively, which were statistically equivalent. However, patients treated with amlodipine had a considerably greater incidence of leg edema than did those treated with mibefradil (33.6% vs 4.2%, respectively). Similarly, 100 mg mibefradil was equivalent in efficacy to 60 mg nifedipine GITS once daily, but patients on mibefradil experienced fewer vasodilatory related adverse events. In summary, mibefradil demonstrated superior efficacy to diltiazem CD and nifedipine SR and equivalent efficacy to amlodipine and nifedipine GITS in the treatment of hypertension.
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PMID:Mibefradil in the treatment of systemic hypertension: comparative studies with other calcium antagonists. 928 51

Mibefradil belongs to a new class of calcium antagonists, the tetralol derivatives. It selectively blocks T-type calcium channels in contrast to other calcium antagonists which block only L-type channels. Mibefradil relaxes coronary arteries without suppressing myocardial contractility and causes a dose-related decrease in heart rate. When given orally once daily to patients with hypertension mibefradil produces a dose-related decrease in blood pressure which is sustained for 24 hours and improves exercise performance in patients with stable angina pectoris. In patients with generally mild to moderate hypertension oral mibefradil was superior to nifedipine SR and diltiazem CD, tended to be more effective than nifedipine GITS and had similar efficacy to amlodipine. Mibefradil 50 to 100mg once daily also has antianginal and anti-ischaemic effects. The drug improves the duration of symptom-limited exercise and the time to onset of ischaemia, and reduces the frequency of anginal attacks and consumption of nitroglycerin. Its efficacy is similar to that of diltiazem and tends to be greater than that of amlodipine in patients with stable angina. Mibefradil is generally well tolerated and is associated with a lower incidence of leg oedema than amlodipine and nifedipine. Thus, mibefradil is a calcium antagonist with a predictable cardiovascular profile, which, on the basis of available clinical data, is an effective alternative to other drugs widely used in the treatment of hypertension and stable angina pectoris.
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PMID:Mibefradil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the management of hypertension and angina pectoris. 936 62

MIBEFRADIL IN THE TREATMENT OF HYPERTENSION: The antihypertensive efficacy of mibefradil, a new selective transient (T)-channel calcium antagonist, was studied in eight randomized, double-blind, parallel-design trials: four placebo-controlled and four active drug-controlled versus other calcium antagonists. These studies established that at doses of 50 and 100 mg, mibefradil is an effective, well tolerated and safe treatment for high blood pressure. The antihypertensive effect of mibefradil was achieved gradually, with the full activity reached within 1-2 weeks. The decrease in arterial pressure was smooth and sustained over the entire 24-h dosing interval. The antihypertensive action was associated with a dose-related reduction in the heart rate. The efficacy results were similar across all demographic subpopulations studied, including high-risk groups: individuals with chronic renal failure; the elderly; and hydrochlorothiazide-treated patients. In studies comparing mibefradil with other calcium antagonists at their recommended doses, 100 mg mibefradil demonstrated significantly better antihypertensive efficacy than controlled-dose (CD) diltiazem at 360 mg or slow release (SR) nifedipine at 40 mg twice a day, and similar efficacy to that of 10 mg amlodipine or 60 mg nifedipine gastrointestinal therapeutic system (GITS). MIBEFRADIL IN THE TREATMENT OF ANGINA PECTORIS: The efficacy, safety, and tolerability of 50 and 100 mg mibefradil in the treatment of chronic stable angina pectoris was tested in six randomized parallel-design studies. Significant increases in exercise duration and a significant delay in the onset of ischemia during exercise were found in most studies with the 50-mg dose and in all studies with the 100-mg dose. Weekly anginal attacks and nitroglycerine consumption decreased significantly in a dose-related manner and, similarly, a significant dose-related decrease in the number and duration of silent ischemic episodes was observed on 48-h Holter monitoring. In the two studies with active drug controls, 100 mg mibefradil was significantly better than 10 mg amlodipine and equivalent to 120 mg diltiazem SR twice a day in improving anti-anginal and anti-ischemic parameters. In all studies, mibefradil treatment produced a dose-related reduction in the heart rate and the rate-pressure product at rest and at the end of exercise, and the magnitude of these decreases was larger than that observed with the other two calcium antagonists. SAFETY AND TOLERABILITY: An integrated analysis of combined data on the safety and tolerability of mibefradil from studies on hypertension and angina pectoris confirmed that mibefradil and diltiazem were equally well tolerated, but the incidence of leg edema was clearly higher in patients treated with the dihydropyridine calcium antagonists amlodipine and nifedipine.
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PMID:Differential properties of mibefradil in hypertension and angina. 948 14

During the last 2 decades, remarkable progress has been made in the treatment of hypertension with the discovery of new drugs lowering blood pressure by various mechanisms, e.g. calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin II antagonists. These antihypertensive agents are now widely used as first-line therapy although there is still no definite proof that they have a cardioprotective effect and reduce the mortality rate in patients with coronary heart disease. Mibefradil is a new calcium antagonist with a novel mechanism of action since it is the only drug available so far able to block T channels. This compound might be particularly effective in preventing cardiac morbidity and mortality. It reduces heart rate when lowering blood pressure, has no negative inotropic effect, allows regression of cardiac hypertrophy and is effective in the treatment of angina. Mibefradil produces a sustained blood pressure reduction with a close to optimal trough:peak ratio. A major advantage of this novel compound is its excellent tolerability over the dose range recommended (50-100 mg/day). In particular, leg edema is seen clearly less often during mibefradil treatment than during therapy with dihydropyridines. Mibefradil has therefore an attractive profile in terms of both efficacy and safety and represents a promising first-line option to treat hypertensive patients.
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PMID:Potential cardioprotective effect of mibefradil in the long-term treatment of hypertension. 957 Apr 25

Mibefradil is the prototype of a new class of calcium antagonists that selectively block T-type voltage-gated plasma membrane calcium channels in vascular smooth muscle. The drug is structurally and pharmacologically different from traditional calcium antagonists. It does not have negative inotropism at therapeutic concentrations, and is not associated with reflex activation of neurohormonal and sympathetic systems. In clinical studies of hypertension, mibefradil 50 and 100 mg/day reduced trough sitting diastolic and systolic blood pressures in a dose-related manner. Dosages exceeding 100 mg/day generally did not result in significantly greater efficacy, but were associated with a higher frequency of adverse events. No first-dose hypotensive phenomenon was observed. Mibefradil has antiischemic properties resulting from dilation of coronary and peripheral vascular smooth muscle, and a slight reduction in heart rate. In clinical studies of chronic stable angina pectoris, dose-related increases in exercise duration, time to onset of angina, and time to 1-mm ST-segment depression during exercise tolerance tests occurred. Mibefradil reduced the number and duration of ischemic events recorded by 48-hour ambulatory electrocardiograph (ECG) monitoring, as well as number of anginal episodes and nitroglycerin consumption. Favorable hemodynamic and clinical profiles are reported, including high trough:peak ratios (> 80%), high oral bioavailability, and long elimination half-life (17-25 hrs) permitting once/day dosing. Dizziness, headache, leg edema, and lightheadedness are frequently reported, but overall the agent is well tolerated. First-degree atrioventricular block and sinus bradycardia are the most frequent ECG changes caused by the drug. In vitro studies indicate mibefradil inhibits cytochrome P450 1A2, 2D6, and 3A4, resulting in elevated plasma concentrations of drugs metabolized by those isoenzymes. Therefore, it is contraindicated in patients receiving terfenadine, astemizole, cisapride, lovastatin, or simvastatin.
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PMID:Mibefradil, a pharmacologically distinct calcium antagonist. 962 98

A 72-year-old woman had been treated for hypertension and hyperthyroidism by a local doctor. In May 1998, she came to this institution with a chief complaint of leg edema. Based on the clinical findings, she was diagnosed as having nephrotic syndrome with massive proteinurea, hypoproteinemia and hyperlipidemia. Renal biopsy findings showed minimal change nephrotic syndrome (MCNS). No substantial improvement was obtained by steroid therapy. We therefore additionally administered angiotensin-converting enzyme inhibitor (enalapril maleate). The urinary protein concentration significantly decreased. On decreasing the dose of steroids, the urinary protein concentration increased. Cyclophosphamide helped us to decrease the steroid dosage. This treatment resulted in type II incomplete remission. The final diagnosis was refractory MCNS. During steroid therapy, she developed hyperglycemia. She had no histology of diabetes mellitus. There is therefore a possibility that steroids can induce hyperglycemia even in patients without a history of diabetes mellitus. These results suggest that careful monitoring of plasma glucose is necessary during steroid therapy and that the administration of an angiotensin-converting enzyme inhibitor is effective in elderly patients with refractory primary nephrotic syndrome.
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PMID:[A decrease in urinary proteins in an elderly patient with refractory minimal change nephrotic syndrome administration of an angiotensin converting enzyme inhibitor in combination with steroids]. 1057 51

Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.
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PMID:Treatment of hypertensive children with amlodipine. 1104 Nov 59

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin disorders) is a rare multisystemic disease associated with plasma cell dyscrasia. A 68-year-old woman with chronic renal insufficiency and arterial hypertension included in her medical history was admitted to the hospital with confusion, somnolence and asthenia. She presented ascites, hepatosplenomegaly, leg oedema, distal dysesthesias, leuconychia and multiple nodular purple red angiomas on the trunk, upper limbs and fingers. Hypothyroidism was revealed in the laboratory investigations and monoclonal IgG peak in immunoelectrophoresis. Electromyography showed both demyelinisating and axonal degenerative neuropathy. The diagnosis of POEMS syndrome was based on the dermatopathological examination of a cutaneous angioma; histology revealed features of glomeruloid angioma, a specific marker of this syndrome.
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PMID:POEMS syndrome revealed by multiple glomeruloid angiomas. 1207 35

This study was undertaken to clarify whether pulmonary hypertension is a useful marker for underlying obstructive sleep apnea in patients with edema. Twenty-eight ambulatory adults with bilateral leg edema and a normal echocardiogram were enrolled. Sixteen subjects had pulmonary hypertension, and 12 subjects had normal pulmonary artery pressures. Spirometry, pulse oximetry on room air, and polysomnography were obtained for each subject. Ten of 16 (63%) pulmonary hypertension subjects and 9 of 12 (75%) nonpulmonary hypertension subjects had obstructive sleep apnea (P =.48). Eleven of 16 (69%) pulmonary hypertension subjects and 11 of 12 (92%) nonpulmonary hypertension subjects were obese (P =.20). If these results are generalizable, obstructive sleep apnea is frequently associated with bilateral leg edema and obesity, regardless of the presence of pulmonary hypertension. Thus, especially in obese patients, bilateral leg edema may be a useful clinical marker for underlying obstructive sleep apnea.
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PMID:Bilateral leg edema, pulmonary hypertension, and obstructive sleep apnea: a cross-sectional study. 1210 Jul 81

A 52-year-old man with a history of chronic hypertension presented with worsening dyspnea and leg edema. He had been on minoxidil for 10 years. The cardiac silhouette was markedly enlarged. Echocardiography and computed tomography showed a large pericardial effusion. His cardiac status was stable and he was in no cardiorespiratory distress. No attempt was made to drain the fluid. Minoxidil was discontinued, and a month later, the effusion had virtually disappeared. Cessation of minoxidil administration and conservative management may suffice, even though the pericardial effusion is large.
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PMID:Very large pericardial effusion attributable to minoxidil: resolution without drainage of fluid. 1235 48


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