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)

In 43 patients with variant angina, the cardiovascular event rate during diltiazem therapy was compared with that in an equal time period before initiation of therapy. Cardiovascular events, that is, myocardial infarction, sudden death and hospitalization for prolonged angina, were decreased significantly (p less than 0.01) during the initial 6 months and mean 19.6 months of therapy. Based on the binomial principle, there were 22 events during the mean 19.6 months before therapy and 2 events during the equal time period on therapy. No patient died during follow-up. The frequency of angina was decreased by 94%. Diltiazem was well tolerated by all patients and no patient had to discontinue therapy because of adverse effects. It is concluded that long-term diltiazem therapy reduces cardiovascular events in patients with variant angina.
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PMID:Prevention of cardiovascular events in variant angina by long-term diltiazem therapy. 685 3

Sixty-three patients completed a multicenter 10 week, double-blind, parallel group protocol evaluating the efficacy of diltiazem versus placebo with respect to rate of attacks of angina, nitroglycerin consumption and duration of treadmill exercise. An additional 36 patients were evaluated for drug safety. A 4 week placebo lead-in phase was followed by a 2 week dose titration period and two treatment evaluation periods of 2 weeks each. Both diltiazem and placebo were associated with a significant reduction in weekly frequency of angina from the baseline rate. Intergroup comparison disclosed a significantly greater reduction for the patients receiving diltiazem than for those receiving placebo. A similar reduction was noted for nitroglycerin consumption. Total exercise duration at week 10 was statistically greater in patients treated with diltiazem. Diltiazem was well tolerated. No abnormalities in hematologic profiles or in routine serum chemistry values were observed; electrocardiographic P-R and QRS intervals were unaffected. Adverse effects that could have been related to drug administration were reported in 11 patients who received diltiazem and in 12 patients who received placebo. Of the 17 episodes in the diltiazem group only 3 were considered significant and drug-related, and only one of these resulted in discontinuation of the drug.
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PMID:Safety and efficacy of diltiazem hydrochloride for the treatment of stable angina pectoris: report of a cooperative clinical trial. 703 9

To assess the efficacy of a new calcium entry blocker, diltiazem (Cardizem), for prophylaxis of Prinzmetal's angina, 48 patients were studied in randomized, multiple crossover multiclinic study (2 weeks single-blind, 8 weeks double-blind). Diltiazem dosage in one crossover phase was 120 mg per day; in the other, 240 mg per day. Therapeutic response was measured by patients' diary records of angina frequency and nitroglycerin tablet consumption. Treatment with 120 mg of diltiazem per day reduced angina by 41 percent from the entry placebo period and 20 percent from the paired placebo period (p less than 0.005). Treatment with 240 mg of diltiazem per day reduced angina frequency by 68 percent from the entry placebo period and 43 percent from the paired placebo period (p less than 0.01). There were similar reductions in nitroglycerin consumption. Adverse experiences that may have been related to the medication were noted in only 5 percent of patients. There were no alterations in blood pressure or heart rate. The PR interval increased 3 percent at the 240 mg dosage level. We conclude that diltiazem is an effective and safe agent for control of symptoms of Prinzmetal's angina.
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PMID:Multiclinic controlled trial of diltiazem for Prinzmetal's angina. 703 26

Recently it has been recognized that coronary vasospasm plays a significant role in precipitating myocardial ischemic pain in a significant minority of individuals with coronary atherosclerosis (approximately 27-35% of patients with angina pectoris at rest). In these individuals normal physiological vasoconstrictor stimuli appear to trigger a spasm of the large epicardial coronary vessels; evidence suggests that it may be caused by the release of increased amounts of calcium from augmented sarcolemmal storage sites. The calcium entry blockers are remarkably effective in preventing coronary spasm by reducing intracellular calcium, but by different mechanisms. Verapamil appears to reduce intracellular and, more specifically, sarcolemmal calcium stores directly. Diltiazem appears to reduce intracellular calcium by stimulating the sarcolemmal sodium-potassium pump and reducing intracellular sodium, and by this mechanism. potentiating passive sodium-calcium exchange. The effects of the calcium entry blockers on myocardial contractility, cardiac pacemaker and conduction tissue, and regional vascular smooth muscle are also different. This makes some of these agents more suitable than others for therapy of other clinical problems such as chronic stable angina pectoris, supraventricular tachycardia, hypertension, hypertropic cardiomyopathy, and protection of the ischemic myocardium during cardiac surgery.
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PMID:Clinical use of calcium entry blockers. 730 98

In this study, the systemic and coronary hemodynamic changes associated with the administration of diltiazem, a recent calcium antagonist, were evaluated in three different situations as follows: following a 200 microgram/kg intravenous bolus of the drug in 12 open-chest anesthetized dogs; following two successive intravenous infusions of diltiazem (15 microgram/kg/min and 30 microgram/kg/min), each for a period of ten minutes, in eight patients with angina pectoris investigated by coronary arteriography; and following a single oral dose of 120 mg of diltiazem in 17 patients undergoing hemodynamic monitoring in the coronary care unit after a recent myocardial infarction. Diltiazem was found to be a coronary vasodilator acting on the large coronary arteries and on collaterals. Its effects on myocardial oxygen requirements were variable; as a rule, the predominant effect was a drop in systemic vascular resistance or in heart rate. When systemic vascular resistance changed little, heart rate tended to decrease significantly; however, when systemic vascular resistance decreased notably, heart rate remained unchanged because of a relfex attempt to increase systemic blood pressure. Cardiac performance and left ventricular end-diastolic pressure were not affected and this lack of change in cardiac inotropism may confer and advantage to diltiazem over other calcium antagonistic drugs in patients with coronary heart disease.
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PMID:Hemodynamics and coronary flow following diltiazem administration in anesthetized dogs and in humans. 739 10

The effects of diltiazem, a calcium antagonist drug, we compared with those of placebo on exercise performance during a series of symptom-limited upright exercise tests. Ten patients with chronic stable angina were studied over a period of 7 weeks. The drug was administered in a random double-blind fashion and was evaluated at increasing dose levels of 120, 180 and 240 mg/day. Diltiazem was effective in increasing the total duration of exercise (p < 0.001) and the time the first onset of angina (p < 0.02) and to the first appearance of 1 mm of S-T depression (p < 0.02). These effects were most marked at the highest dose level of diltiazem. The heart rate was reduced at rest (p < 0.05) and during submaximal exercise (p < 0.001). There was a reduction in diastolic blood pressure during submaximal exercise (p < 0.04) but no change in systolic pressure. Pressure-rate product was significantly reduced at submaximal (p < 0.001) but not maximal exercise. The reduction in pressure-rate product is postulated as the mechanism by which diltiazem enhances duration of exercise. There was no reduction in electrocardiographic evidence of myocardial ischemia at peak exercise by either clinical observation or computer analysis of spatial electrocardiographic variables Five of the six patients who continued to take the drug maintained or improved their exercise performance on follow-up study 8 to 10 months later.
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PMID:Improved exercise performance in persons with stable angina pectoris receiving diltiazem. 745 15

We investigated whether analysis of heart rate (HR) variability may be used to predict the efficacy of drug treatment of myocardial ischemia. In a double-blind, crossover study, 28 patients with stable angina pectoris, proven coronary artery disease, and myocardial ischemia during Holter monitoring received metoprolol controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a placebo run-in phase and after each treatment period, 72-hour Holter recordings were obtained for HR variability and ST-segment analysis. At baseline, the total duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24 hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol significantly reduced the total duration of ischemia by -8.7 minutes (95% CI -14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients with a low SD of normal-to-normal intervals at baseline (SDNN), using the median value of 50 ms as a cut-off value. In contrast, significant treatment effects were not observed in patients with a high SDNN at baseline. Similar results were obtained using baseline total power or low-frequency power, but not when using baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9 minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to metoprolol, efficacy of diltiazem was not related to baseline HR variability. In conclusion, patients with reduced HR variability at baseline responded to treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris. 757 50

Diltiazem (DTZ) is a calcium channel blocker widely used in the treatment of angina and hypertension. DTZ undergoes extensive metabolism yielding several metabolites, some of which are active like N-desmethyldiltiazem (MA), desacetyldiltiazem (M1) and N-desmethyl,desacetyldiltiazem (M2). Due to the nature of its biotransformation, several organs should have the ability to metabolize DTZ, however it is still assumed that the liver is the only organ implicated in its elimination. In this study, the fate of DTZ, MA and M1 was assessed in several organs that could contribute to their biotransformation. To this purpose, DTZ (48.2 microM) was incubated in the 10,000 x g supernatant of homogenates of rabbit tissues for 60 min at 37 degrees C. Multiple samples were withdrawn, and DTZ and its metabolites were assayed by HPLC. The elimination rate constant of DTZ in 10,000 x g supernatants varied between the organs: liver 334 +/- 45, proximal small intestine 69 +/- 11, distal small intestine 25 +/- 3, lungs 15 +/- 6 and kidneys 8 +/- 6 (10(-4) min-1). The metabolism of DTZ in the liver generated large amounts of MA but no M1, and in the small intestine, modest amounts of both metabolites. When MA (50.0 microM) or M1 (53.7 microM) were incubated in liver homogenates, the estimated elimination rate constant were 166 +/- 23 and 468 +/- 53 (10(-4) min-1), respectively. The rate of degradation of the metabolites in the small intestine was much slower.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolism of diltiazem in hepatic and extrahepatic tissues of rabbits: in vitro studies. 759

1. This placebo-controlled study assessed once daily sustained-release (SR) diltiazem, 200 and 300 mg, in 182 stable angina patients with positive exercise test. 2. Exercise testing was performed at baseline after a 7 day placebo run-in period, and repeated after 7 days of treatment, 25.0 +/- 0.1 h postdose. 3. Diltiazem (200 and 300 mg) produced respectively a 68% and a 64% decrease in weekly angina episodes, and placebo a 15% decrease (P < 0.05). Similarly, both dose levels produced a 70% decrease in nitroglycerin consumption, whereas no difference was obtained with placebo (P < 0.01). The increase in time to ischaemic threshold was significantly superior for 200 mg and 300 mg diltiazem when compared with placebo (75.2 and 91.5 s respectively vs 47.0 s) (P < 0.05); increase in time to anginal threshold was also significantly greater for diltiazem when compared with placebo (84.6 and 85.9 s respectively vs 43.9 s) (P < 0.05). 4. Only one patient experienced worsening of angina and had to be withdrawn from the study. 5. This study demonstrates 200 and 300 mg SR diltiazem is effective when given once-a-day in the prophylaxis of stable exertional angina. This once daily formulation should improve patients' compliance and comfort.
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PMID:Twenty-four hour efficacy of two dose levels of a once daily sustained-release diltiazem formulation in stable angina: a placebo-controlled trial. The Dildurang Study Group. 761 69

Diltiazem is a calcium channel blocking agent known to be effective in the treatment of angina pectoris, hypertension and supraventricular arrhythmias. To improve the conditions of diltiazem administration in the treatment of hypertensive patients, a sustained-release formulation (Mono-Tildiem LP 300 mg) allowing a single daily oral administration has been developed. The aim of the present study was to first evaluate the influence of food intake and second to evaluate those of the time of administration on the pharmacokinetic parameters and the bioavailability of this sustained-release formulation. The influence of these factors was investigated over two different open, randomized, cross-over studies in 12 healthy volunteers. Although a significant decrease in Tmax and an increase in Cmax occurred when diltiazem sustained-release was administered with food intake, AUC0-48, and therefore the fraction absorbed, were not modified either by concurrent food intake or by different times of administration. The minor modifications of pharmacokinetic parameters of diltiazem sustained release observed were unlikely to induce any clinical consequence.
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PMID:Pharmacokinetic and bioavailability of diltiazem sustained-release: influence of food and time of administration. 762 34


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