Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bepridil is a calcium antagonist with direct negative chronotropic, dromotropic, inotropic and vasodilatory actions which reduces myocardial oxygen consumption and increases coronary blood flow, leading to a significant anti-ischaemic and antianginal effect in the absence of reflex tachycardia. In contrast to other calcium channel blockers, bepridil produces only modest peripheral vasodilatation and displays weak antihypertensive activity. Its plasma elimination half-life of 1 to 2 days permits once daily administration. Results of short term clinical trials have shown bepridil to be of comparable efficacy to nifedipine, verapamil, diltiazem, propranolol and nadolol in decreasing the frequency of anginal attacks and consumption of nitroglycerin (glyceryl trinitrate) in patients with stable angina. Bepridil is more effective than nifedipine in improving exercise performance in patients with stable angina. Although bepridil proved superior to diltiazem in improving exercise performance in patients refractory to diltiazem, further studies are required to confirm the efficacy of bepridil in patients refractory to, or intolerant of, other antianginal agents. Bepridil in therapeutic doses is well tolerated, and appears to have a similar adverse effect profile to the established calcium antagonists. However, rate-dependent prolongation of the QTc interval and development of torsade de pointes have been associated with the use of bepridil. Therefore, bepridil is contraindicated in patients with hypokalaemia, those receiving other drugs that may prolong the QT interval, and those with congenital QT interval prolongation. Future clinical research will help to further define the position of bepridil as an antianginal treatment relative to the traditional calcium antagonists; in the interim, bepridil is indicated for the treatment of patients with angina refractory to or intolerant of other agents.
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PMID:Bepridil. A review of its pharmacological properties and therapeutic use in stable angina pectoris. 128 May 69

The antianginal efficacy of bepridil, a calcium antagonist with an extended plasma elimination half-life, has been compared with placebo and the calcium antagonists nifedipine and diltiazem in patients refractory to diltiazem. The earliest observations in the United States of antianginal effects of bepridil were revealed in a single-blind, multicenter, placebo-controlled trial of 77 patients with chronic stable angina pectoris that demonstrated that bepridil (300 mg/day) improved exercise duration by 26%, from 6.9 +/- 0.4 (standard error of the mean) to 8.7 +/- 0.5 minutes (p less than 0.001), and exercise work by 52%, from 2.7 +/- 0.3 to 4.1 +/- 0.4 x 10(-3) KPM (p less than 0.001), on a standardized treadmill protocol, and it reduced angina frequency by 68%, from 8.5 +/- 1.1 to 2.7 +/- 0.7 attacks per week, and nitroglycerin use by 76% (p less than 0.001). Minor side effects such as nausea, epigastric discomfort, and tremor were infrequent and no major side effects occurred. Double-blind, parallel-design treatment evaluations confirmed beneficial effects of bepridil alone and in combination with beta blockade. Chronic efficacy was confirmed by evaluations up to 24 months in a controlled withdrawal study. Antianginal effects of nifedipine were compared with those of bepridil in a double-blind, parallel group study of 101 patients with chronic stable angina treated for 3 months. Bepridil (mean final dose 284 mg/day; range 200-400 mg/day) produced modest but statistically significantly (p less than 0.05) greater improvements in exercise work, time to angina, or 1 mm ST-segment change than nifedipine (mean final dose 59 mg/day; range 30-120 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bepridil treatment of chronic stable angina: a review of comparative studies versus placebo, nifedipine, and diltiazem. 153 68

Bepridil is a calcium antagonist with a unique chemical composition and a long elimination half-life (42 hours). We evaluated the efficacy of bepridil 300 mg once/day in a crossover comparison with placebo in 45 patients with angina. Patients had an average of 7.6 anginal episodes/week during the placebo baseline phase of the trial. After 4 weeks of bepridil therapy, anginal frequency decreased to 2.9 episodes/week (p less than 0.05). Likewise, mean nitroglycerin consumption declined from 7.4 tablets/week during the placebo baseline phase to 4.0 tablets/week during bepridil therapy (p less than 0.05). Statistically significant increases over the previous period (placebo baseline or double-blind placebo) were seen in total exercise time, time to angina, and total work (p less than 0.05). During bepridil therapy, 13 of 45 patients (29%) no longer experienced angina as an exercise end point despite the increase in work and exercise time. Bepridil significantly prolonged both the QT and corrected QT (QTc) intervals; the mean increases were 10.0% and 5.6%, respectively. Side effects were reported with equal frequency in the placebo and bepridil arms of the trial, and no serious side effects were reported. In an intermediate fixed dose of 300 mg/day, bepridil relieved anginal symptoms with few side effects. Bepridil appears to be a safe and effective treatment for stable angina.
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PMID:Bepridil hydrochloride compared with placebo in patients with stable angina pectoris. 155 90

The efficacy and safety of once-daily doses of 200, 300, and 400 mg of bepridil hydrochloride were compared with placebo in a 14-week multi-center, double-blind parallel study. All doses of bepridil significantly reduced weekly anginal attacks and nitroglycerin consumption from baseline levels. Bepridil also significantly improved total exercise time, time to angina, time to 1 mm ST-segment depression, and total work. Reduction in heart rate (maximum mean decreases of 7-8 beats/min) and prolongation of QT and corrected QT (QTc) intervals were associated with bepridil therapy. Bepridil was well tolerated; most adverse reactions reported were mild and tolerable even at the 400-mg dose. This study provides strong support for the use of bepridil in patients with chronic stable angina pectoris that is not optimally controlled by other available antianginal therapies. A double-blind withdrawal study is also reported, in which patients stabilized on bepridil were randomized to either continue on bepridil therapy or receive placebo. Patients who were withdrawn from bepridil therapy showed significant increases in the number of weekly anginal attacks and nitroglycerin consumption compared with levels seen during long-term treatment. Patients withdrawn from bepridil therapy showed significant deterioration in exercise tolerance compared with baseline and with those maintained on bepridil.
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PMID:Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies. 155 91

The current classification system for antiarrhythmic drugs has several shortcomings; for example, electrophysiologic effects are defined in normal tissue, whereas antiarrhythmic drugs are often used clinically in diseased or injured tissue. Consideration of the electrophysiologic effects of bepridil in humans emphasizes the drawbacks of the classification system. Bepridil is primarily a calcium antagonist with class IV action. However, because the drug has class IA action as well, it should not be considered a typical class I or class IV agent. Bepridil has been observed to prolong the QT interval in the majority of patients in whom it is used for treatment of angina. However, in US clinical trials, including open extensions, only 7 cases of torsades de pointes have been recorded. In France, where the drug is approved for treatment of angina, the incidence of torsades de pointes was 0.01% in 1989. No consensus currently exists regarding what degree of QT prolongation constitutes increased risk for a ventricular proarrhythmic event. Based on current information, bepridil should be used cautiously in patients with a propensity toward hypokalemia, which can exacerbate or induce a proarrhythmic state. The drug should not be used in patients with a prolonged QT interval at baseline, a history of torsades de pointes, or long QT interval syndrome. Bepridil also should be avoided in patients with sinus node dysfunction or second- or third-degree atrioventricular block.
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PMID:Effects of bepridil on cardiac electrophysiologic properties. 155 93

The efficacy and safety of bepridil hydrochloride (HCl) and propranolol HCl monotherapy were investigated in a double-blind, parallel-group crossover study in 75 patients with chronic stable angina pectoris. For the first double-blind segment, both drugs reduced the frequency of weekly anginal attacks and nitroglycerin consumption. On exercise testing, bepridil was significantly more effective in terms of increasing time to angina and total work. Heart rate and ST-segment depression decreased to a greater degree with propranolol than bepridil. Bepridil produced a greater increase in QT interval than propranolol; corrected QT (QTc) interval was increased by bepridil and slightly decreased by propranolol. The incidence of adverse effects was roughly comparable for the two active drugs and higher than that for placebo during washout periods. It was concluded that bepridil, at a mean maintenance dosage of 324 mg/day, was at least as effective as propranolol in improving exercise tolerance--specifically time to angina and total work--and that tolerability of the 2 drugs was comparable. In another study, the efficacy and safety of bepridil combined with propranolol were compared with that of placebo plus propranolol in 56 patients who had not been well controlled on propranolol alone. The addition of bepridil significantly reduced the frequency of anginal attacks and weekly nitroglycerin consumption compared with baseline. The combination of propranolol and bepridil also produced significant improvements in total exercise time, time to angina, and total work compared with baseline. The QTc interval increased significantly from baseline in the bepridil combination group and decreased significantly in the propranolol plus placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative efficacy and concomitant use of bepridil and beta blockers in the management of angina pectoris. 155 92

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.
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PMID:Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. 185 72

Bepridil is an anti-anginal agent with a novel chemical structure. Its main pharmacological effects are an increase in coronary blood flow, a reduction in myocardial oxygen demand, reduction in cardiac work, primarily by a decrease in after-load and a dose-dependent negative chronotropic effect, and anti-arrhythmic properties. These are mainly due to a calcium-antagonistic action. There is evidence that fast sodium channels in heart muscle are also inhibited. Trials have shown that bepridil is effective in the prophylactic treatment of various forms of angina pectoris and accompanying arrhythmias. Pharmacokinetic data justify once-daily administration. The evidence suggests that bepridil is generally well tolerated. This paper reviews already published studies and the results of recent investigations on the pharmacological and clinical efficacy of bepridil.
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PMID:Bepridil: a review of its pharmacology and clinical efficacy as an anti-anginal agent with anti-arrhythmic properties. 241 84

The acute hemodynamic and antiischemic effects of intravenous bepridil (3 mg/kg/5 minutes followed by 1 mg/kg/hour) were studied in 19 patients with coronary artery disease under basal conditions and during 2 identical pacing stress tests 30 minutes before (pace test I) and 15 minutes after (pace test II) onset of infusion. Bepridil immediately decreased coronary and systemic vascular resistance (26 and 17%, respectively). This resulted in a 19 and 21% reduction in left ventricular systolic and mean aortic pressures and a 15% increase in coronary flow and stroke index (p less than 0.05 vs control for each). These vasodilating effects were short lasting, persisting for 5 minutes after the bolus infusion, followed by significant reductions in heart rate (15%) and contractility (10%) and a temporary 46% increase in left ventricular filling pressure. During both pace tests heart rate, contractility, coronary flow and myocardial O2 consumption were comparable. In contrast, bepridil prevented the significant increase in systemic resistance and mean aortic pressure observed during pace test I (11 and 15%, respectively). Subsequently, myocardial O2 demand was significantly less during pacing after bepridil, due to an 11% reduction in left ventricular systolic pressure (p less than 0.05 vs control and pacing test II vs I). This resulted in marked antiischemic effects: normalization of lactate extraction and reduction in ST-segment depression (-14 +/- 7 vs 3 +/- 6% and 0.2 +/- 0.02 vs 0.13 +/- 0.02 mV, respectively, pace test I vs II, p less than 0.05), and in less or no angina in 18 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute hemodynamic and antiischemic properties of intravenous bepridil in coronary artery disease. 278 81

The chemistry, pharmacology, pharmacokinetics, clinical uses, and adverse effects of nicardipine, nitrendipine, and bepridil are reviewed. Nicardipine, nitrendipine, and bepridil are calcium antagonists under investigation for the treatment of cardiovascular disorders. Nicardipine and nitrendipine share a common dihydropyridine nucleus with the calcium antagonist nifedipine; bepridil is unrelated to other known calcium antagonists. Like nifedipine, nicardipine and nitrendipine produce peripheral vasodilation as their predominant in vivo effect. Bepridil has vascular, sinoatrial and atrioventricular nodal, and myocardial effects qualitatively similar to those of the calcium antagonist verapamil; it also interferes with the fast sodium channel and prolongs refractoriness in atrial and ventricular tissue. Nicardipine and nitrendipine undergo extensive first-pass hepatic extraction after oral administration; oral bioavailability of bepridil is about 60%. All three drugs are highly protein bound and have been reported to increase plasma digoxin concentrations. Both nicardipine and nitrendipine are effective antihypertensive agents used alone or combined with diuretics, beta blockers, or angiotensin-converting enzyme inhibitors. Nicardipine and bepridil effectively control angina, and preliminary studies indicate that nitrendipine has antianginal properties. Bepridil may be useful in the treatment of various cardiac arrhythmias; however, its tendency to cause or worsen cardiac arrhythmias and its association with torsade de pointes may limit its usefulness. Nicardipine and nitrendipine have similar adverse effect profiles, with vasodilation-related complaints being most common. Since nicardipine, nitrendipine, and nifedipine are similar in efficacy and safety, the eventual availability of sustained-release dosage forms may determine how these drugs are ultimately used. Bepridil is an effective antianginal drug, but, because of its proarrhythmic potential, it should probably not be used as a first-line agent.
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PMID:Nicardipine, nitrendipine, and bepridil: new calcium antagonists for cardiovascular disorders. 328 Feb 22


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