Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235886 (leg edema)
 674 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 50-year-old male with unresectable hepatocellular carcinoma (HCC) had a hypercalcemic crisis with a serum calcium concentration of 7.8 mEq/zeta, without any evidence for bone metastases or parathyroid lesions. The hypercalcemia was thought to be due to increased renal reabsorption of calcium and increased bone resorption, which was probably caused by humoral factors derived from the HCC, some being parathyroid hormone-like factors. Since conservative therapy for hypercalcemia was not sufficiently effective and was accompanied by progressive exacerbation of ascites and leg edema, transcatheter arterial chemo-embolization (TACE) was performed. On the following day, serum calcium concentration decreased from 6.3 mEq/zeta to the normal range, although serum alpha-fetoprotein levels decreased only slightly. Thereafter hypercalcemia did not develop for about 4 weeks. The results demonstrated that TACE can be effective for humoral hypercalcemia of HCC.
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PMID:Transcatheter arterial chemo-embolization for humoral hypercalcemia of hepatocellular carcinoma. 283 39

Excessive accumulation of intracellular calcium in Duchenne muscular dystrophy (DMD) may be a necessary step in the process that causes muscle damage in this disease. Because of this possibility, a controlled trial of the calcium channel blocking agent nifedipine was undertaken. One hundred and five patients were randomized and treated in a double-blind manner for 18 months. Muscle strength, contractures, functional ability, cardiopulmonary changes, and laboratory data were monitored. The dose of nifedipine was 0.75-1 mg/kg/day in the first 6 months and 1.5-2 mg/kg/day for the next 12 months. Satisfactory blood levels of nifedipine were attained. The study had a power greater than 0.99 to detect a slowing of the illness to 25% of its original rate of progression. No significant improvement was demonstrated in the treated group. One or more of the frequent mild side effects of flushing, dizziness, and leg edema, often associated with the use of nifedipine in adults, occurred transiently in approximately one-half of the patients in the nifedipine group and in 21% of the placebo group. Four patients died, two on nifedipine and two on placebo. This study demonstrates that nifedipine is safe to administer in children, but that it is without beneficial effect on the course of DMD.
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PMID:Clinical investigation in Duchenne dystrophy. VI. Double-blind controlled trial of nifedipine. 355 Apr 55

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

The ability of mibefradil, a new T-channel-selective calcium antagonist, to improve exercise tolerance and silent ischemic parameters in patients with chronic stable angina was compared in 3 separate trials with 2 other commonly used calcium antagonists: diltiazem SR (120 mg/twice daily) and amlodipine (10 mg/day). Compared with amlodipine, mibefradil 100 mg given once daily over a 3-week period resulted in a statistically significantly larger increase from baseline in total exercise tolerance test (ETT) duration (treatment difference of 40.9 sec, p = 0.04), time to onset of angina (treatment difference 61.2 sec, p < 0.001), and time to onset of ischemia (treatment difference of 54.4 sec, p = 0.004). The decrease in weekly anginal episodes was 58% with mibefradil versus 19% with amlodipine, and the reduction in nitroglycerin consumption was 58% with mibefradil versus a 10% increase with amlodipine. The decrease in the number of silent ischemic episodes detected by a 48-hour Holter recording was significantly larger (p = 0.03) with mibefradil 100 mg (88%) compared with amlodipine 10 mg (38%). Similarly, a larger decrease in the duration of silent ischemia was observed with mibefradil (69%) compared with that seen with amlodipine (38%). The preliminary results of a second trial comparing mibefradil with amlodipine were consistent with the first demonstrating that the improvement for all 3 ETT parameters was larger for mibefradil (ETT duration: 55.2 sec; delay in onset angina: 74.2 sec; time to onset of ischemia: 63.6 sec), but in this trial the treatment differences did not reach statistical significance. In the trial comparing mibefradil (100 mg once daily) with diltiazem SR (120 mg twice daily), both compounds had equivalent effects on all ETT parameters tested. Mibefradil produced a 21% increase in exercise duration compared with a 20% increase with diltiazem. Although mibefradil yielded larger increases in the time to onset of angina and the time to onset of 1-mm ST-segment depression (42% and 38%, respectively) than did diltiazem (34% and 25%, respectively), the treatment differences did not reach statistical significance. Both mibefradil and diltiazem SR were associated with at least a 70% reduction from baseline in anginal frequency and nitroglycerin consumption. Mibefradil-treated patients showed greater decreases in heart rate and the rate-pressure product at each stage of the ETT than patients treated with amlodipine or diltiazem SR. All 3 drugs were well tolerated. However, compared with mibefradil, amlodipine and diltiazem SR produced a higher incidence of leg edema. In conclusion, the effectiveness of mibefradil in improving all 3 ETT parameters was greater than that of amlodipine and equivalent to that of diltiazem SR. Moreover, mibefradil provided greater reductions in the heart rate and cardiac workload than did the other 2 drugs.
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PMID:Mibefradil in the treatment of chronic stable angina pectoris: comparative studies with other calcium antagonists. 928 52

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 first of a new class of calcium antagonists (CAs), the tetralol derivatives, that selectively blocks the T-type calcium channel. The anti-anginal and anti-ischemic efficacy of mibefradil in patients with chronic stable angina pectoris was established in five placebo-controlled trials (2 monotherapy trials, 3 trials with background beta-blocker or long-acting nitrate therapy). At the recommended doses of 50 and 100 mg, mibefradil treatment was associated with a significant dose-related increase in exercise test variables regardless of demographic subpopulation or background therapy. Significant reductions in weekly anginal attacks, silent ischemic parameters, heart rate (HR) and rate-pressure product were also observed. Two active-controlled trials compared mibefradil 100 mg with amlodipine 10 mg or diltiazem SR 120 mg b.i.d., respectively. Patients receiving mibefradil showed significantly larger improvements than did those treated with amlodipine and similar improvements as those treated with diltiazem SR in all variables measured. In both studies, treatment with mibefradil was associated with a greater decrease in HR and rate-pressure product. Mibefradil was found to be well tolerated and safe; this held true for patients on chronic anti-anginal background therapy. The overall incidences of adverse events and premature withdrawals were only slightly higher than those of placebo-treated patients. Asymptomatic sinus bradycardia and first-degree atrioventricular block were the most frequently occurring mibefradil dose-related ECG changes. Mibefradil was better tolerated than amlodipine (mainly with regard to leg edema) and similarly well tolerated as diltiazem CD.
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PMID:Anti-anginal and anti-ischemic effects of mibefradil, a new T-type calcium channel antagonist. 957 Apr 26

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

Primary pulmonary hypertension (PPH) is a condition characterized by sustained elevation of pulmonary artery pressure (PAP) without demonstrable cause. The most common symptom at presentation is dyspnea. Other complaints include fatigue, chest pain, syncope, leg edema, and palpitations. Right heart catheterization is diagnostic, showing a mean PAP >25 mmHg at rest and >30 mmHg during exercise, with a normal pulmonary capillary wedge pressure. In the National Institutes of Health-PPH registry, the median survival period was 2.8 years. Treatment is aimed at lowering PAP, increasing cardiac output, and decreasing in situ thrombosis. Vasodilators have been used with some success in the treatment of PPH. They include prostacyclin, calcium-channel blockers, nitric oxide and adenosine. Anticoagulation has also been advised for the prevention of deep vein thrombosis, pulmonary embolism, and in situ thromboses of the lungs. New drug treatments under investigation include L-arginine, plasma endothelin-I, and bosentan. Use of oxygen, digoxin, and diuretics for symptomatic relief have also been recommended. Patients with severe PPH refractory to medical management should be considered for surgery.
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PMID:Primary pulmonary hypertension. 1172 93


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