Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of studies have addressed the response to calcium antagonists, used alone or combined with other therapy, in patients with silent myocardial ischemia (SMI). Nifedipine, the first calcium antagonist to be studied, was shown to be superior to pindolol in patients with effort angina. Although both nifedipine and diltiazem significantly reduced episodes of ST depression, compared with placebo, in patients with stable effort angina, the addition of nifedipine to diltiazem removed the beneficial effect of diltiazem in another study. Studies have shown a reduced incidence of ischemic episodes during nicardipine treatment in patients with ambulatory ischemia, predominantly SMI, and rest angina due to coronary artery spasm. Other workers similarly reported that verapamil was superior to both placebo and propranolol in reducing painful and painless ischemia in patients with angina at rest. It has been demonstrated that, compared with placebo, nifedipine reduced ischemic episodes by 50% and also markedly reduced total ischemic time in totally asymptomatic men with coronary artery disease and SMI. It was suggested that the well-documented increase in SMI occurring between 0600 and 1200 h was reduced, but not eliminated, by nifedipine. Diltiazem may also attenuate the circadian variation in SMI. Nifedipine has been shown to be particularly effective in SMI when combined with a beta-blocker. This has been substantiated in a large group of patients; both drugs reduced the number of episodes of SMI when used as monotherapy, and the combination decreased the incidence by 95%. These findings collectively indicate that calcium antagonists are effective in reducing or preventing SMI.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical effects of calcium antagonists in silent ischemia. 136 8

The antianginal efficacy and duration of action of slow-release (SR) diltiazem were evaluated in 12 patients with stable angina. Patients underwent maximal symptom limited bicycle exercise testing and 24-hour Holter monitoring at the end of 1-week placebo run-in phase and after 1-month therapy with either placebo or SR-diltiazem (120 mgs bid) using a placebo controlled, double-blind, randomized cross-over trial. No concomitant antianginal therapy, except sublingual nitroglycerin, was allowed during the trial. Exercise testing was performed 3 and 12 hours after drug administration. Blood samples were obtained for the determination of diltiazem plasma concentrations. After diltiazem administration, peak exercise duration increased significantly in comparison both with placebo and the run-in phase: from 292 +/- 48 to 378 +/- 113 s at 3 hours and from 286 +/- 59 to 366 +/- 109 s 12 hours after drug administration. Similarly, ST depression time increased from 240 +/- 59 to 374 +/- 123 s at 3 hours and from 231 +/- 57 to 332 +/- 123 s 12 hours after diltiazem. No significant changes of heart rate, blood pressure and double product were detected. Diltiazem plasma concentrations averaged, respectively, 175 +/- 86 pg/ml and 109 +/- 43 pg/ml 3 and 12 hours after its administration. No correlation was found between plasma concentrations and antianginal effects of diltiazem. At 24 hours Holter monitoring, SR-diltiazem induced a significant decrease of mean heart rate with a reduction in the number and duration of ischemic episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The antianginal effects of a new delayed-release formulation of diltiazem in patients with stable angina pectoris: its evaluation by the ergometry test and dynamic electrocardiogram]. 139 48

1. The effects of BRL 34915 (cromakalim), a potassium channel opener, have been tested on the epileptiform activity elicited by high dose/concentrations of some calcium antagonists in in vivo (diltiazem) and in vitro (diltiazem and verapamil) experiments in rats. 2. Diltiazem (150-300 mg kg-1, i.p.) induced behavioural and electroencephalographic (EEG) seizures that were completely prevented by cromakalim (10 nmol/10 microliters, i.c.v.). Whereas, pentobarbitone (5-10 mg kg-1, i.p.) only prevented the behavioural component of the seizures. 3. In hippocampal slices, verapamil (1.5-2.0 mM) produced, within 30-60 min of perfusion, a CA1 epileptiform bursting in 80% of the experiments. This epileptiform activity was prevented by the cromakalim concentration (50 microM) that did not affect the control CA1 synaptic transmission per se. Pentobarbitone also prevented verapamil-induced epileptiform bursting only at the concentration (100 microM) that also reduced control CA1 synaptic transmission. 4. Diltiazem (1.5 mM) produced a biphasic excitatory-depressant effect within 60 min of perfusion. A CA1 epileptiform bursting appeared in 100% of the experiments within 30 min of perfusion. These excitatory effects were followed by a depression phase, characterized by a reduction of the magnitude of CA1 excitatory postsynaptic potentials (e.p.s.ps) and population spike. 5. The diltiazem-induced epileptiform bursting was prevented by cromakalim at a concentration (50 microM) that did not affect the control CA1 synaptic transmission per se. Pentobarbitone also prevented the diltiazem-induced epileptiform bursting only at a concentration (100 microM) that also reduced the control CA1 synaptic transmission. Both cromakalim (50 microM) and pentobarbitone (100 microM) failed to affect the depressant effects of diltiazem on CA1 hippocampal area. On the contrary, high (3.3mM) calcium solutions prevented both the excitatory and the depressant effects of 1.5 mm diltiazem within 60 min.6. These data indicate an involvement of potassium currents in the epileptiform activity elicited by high doses of diltiazem and verapamil.
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PMID:Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil in rats. 166 91

In a 6-week, randomized, double-blind trial, the drug effects of the calcium antagonists, fendiline (75 mg twice daily) and diltiazem (90 mg twice daily), as measured by subjective and objective parameters of coronary heart disease, were studied in 79 patients with stable angina pectoris. The statistical analysis included the data of 71 patients. The results of exercise-ECG tests showed that both medications were effective anti-ischaemic agents. Fendiline was found to be effective in reducing ST-segment depression at maximum comparable load (71 watts) as well as at the time of reaching the individual maximum tolerated load (discontinuation of exertion). Diltiazem, on the other hand, proved effective only at maximum comparable load (72 watts). There was no significant difference between the groups with regard to the reduction after 6 weeks. As regards work tolerance, the duration of exercise and time until appearance of a ST-segment depression of 0.1 mV, before and after treatment comparisons revealed significant changes only in the group receiving diltiazem and the differences between fendiline and diltiazem were statistically significant with regard to these three parameters. Reduction in the frequency of anginal attacks and the diminution of nitroglycerin consumption were comparable in both medication groups, and the changes from baseline were statistically significant. Assessment of the efficacy and tolerability of the medications by patients as well as by investigators revealed no statistically significant differences between the two groups. Blood pressure and heart rate were clearly lowered by diltiazem, whereas fendiline induced only a slight decrease in blood pressure. The results indicate that both medications are equally suited for the treatment of stable angina pectoris.
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PMID:Double-blind, randomized study of the anti-anginal and anti-ischaemic efficacy of fendiline and diltiazem in patients with coronary heart disease. 176 56

The effects of diltiazem on hemodynamics, plasma catecholamine and plasma renin activity were studied during treadmill exercise test in 9 cases with moderate essential hypertension. Diltiazem of 120 mg/day was orally administered for 4 weeks. At maximum exercise, significant decrease in systolic blood pressure (-32 mmHg), heart rate (-16/min), pressure-rate product (-7,883 mmHg/min), plasma norepinephrine (-195 ng/L) and plasma epinephrine (-11 ng/L) were observed; while, diastolic blood pressure, ST depression and plasma renin activity showed no significant change. Also, a significant correlation between systolic blood pressure and plasma norepinephrine (r = 0.57, p < 0.001), especially after diltiazem therapy (r = 0.68, p < 0.001), was observed. These findings indicated that diltiazem can reduce the secretion of catecholamine from the sympathetic nerves during exercise in patients with essential hypertension.
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PMID:[Effects of diltiazem on hemodynamics, plasma catecholamine and renin activity during exercise in hypertension]. 184 25

Using an isolated perfused rat heart preparation, the protective effects of lidocaine and diltiazem on ischemic derangements of myocardial energy metabolism were studied with 31P-nuclear magnetic resonance spectroscopy. The hearts were perfused with a solution containing lidocaine (4.27 x 10(-5), 12.80 x 10(-5) M) or diltiazem (2.22 x 10(-7), 2.22 x 10(-6) M) for 15 min prior to the induction of global ischemia. The decrease in myocardial oxygen consumption rate, assessed as the product of heart rate and left ventricular systolic pressure (HR x LVP), was greater in diltiazem-treated than in lidocaine-treated hearts. Diltiazem and lidocaine significantly retarded the fall in myocardial pH during ischemia and improved ATP recovery after reperfusion. There was a good correlation between suppression of HR x LVP observed before induction of ischemia and decreased drop in pH during the early phase of ischemia in the diltiazem-treated groups (r = -0.78, p less than 0.01), but not in the lidocaine-treated groups. These results indicate that the beneficial effects of diltiazem on the ischemic myocardium are due primarily to the cardio-depressant effects. The beneficial effects of lidocaine cannot, however, be explained solely on the basis of the depression of oxygen consumption.
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PMID:Effects of lidocaine on ischemic myocardial metabolism assessed by 31P-NMR in the isolated perfused rat heart. 195 18

The short-term effects of oral diltiazem on hemodynamics and distribution of cardiac output at rest and during semiupright bicycle exercise were evaluated in eight patients with stable effort angina on long-term beta 1-adrenergic blockade. Cardiac output and iliofemoral blood flow were measured using thermodilution. The patients were exercised to the same work load on a bicycle before and 2 h after oral diltiazem (60 mg in two patients and 120 mg in six). At maximal exercise, diltiazem reduced heart rate from 94 +/- 5 to 88 +/- 6 beats/min (p less than 0.01), mean arterial pressure from 139 +/- 5 to 127 +/- 4 mm Hg (p less than 0.01) and systemic vascular resistance from 9.7 +/- 0.7 to 8.4 +/- 0.4 x 10(2) dynes.s.cm-5 (p less than 0.05) compared with control. During exercise, cardiac output, iliofemoral blood flow, mean pulmonary wedge pressure and mean right atrial pressure were not altered, but stroke volume increased from 119 +/- 11 to 131 +/- 10 ml (p less than 0.05). Maximal ST segment depression during exercise was decreased and angina was less. Diltiazem does not alter the distribution of the cardiac output during exercise but improves ischemia.
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PMID:Effects of diltiazem and long-term beta 1-adrenergic blockade on hemodynamics and blood flow during exercise in patients with stable angina pectoris. 196 60

Diltiazem and Nifedipine could be synergic. The aim of this study was to investigate the benefits of their association. Eighteen patients, 15 men and 3 women, average age 61 +/- 6 years, with stable angina on effort, were studied. Eight patients had single vessel disease and 10 patients had multivessel disease. The patients underwent a randomised double-blind trial with 4 successive treatment periods each lasting one week: placebo; 360 mg/day of Diltiazem; 60 mg/day of Nifedipine; 180 mg/day of Diltiazem with 30 mg/day of Nifedipine. The benefits were evaluated clinically, by exercise stress testing and with drug plasma concentrations at the end of each sequence. The results at the end of the 3 treatment periods were significantly better than with placebo. Diltiazem was significantly better than Nifedipine with respect to the development of angina during exercise testing (1 patient compared with 7 patients) and to maximum load (118.3 +/- 33.3 watts compared with 105.9 +/- 35.4 watts) (p less than 0.05). The association of the two drugs did not give better results than Diltiazem alone. Compared with placebo, the total duration of exercise testing and the duration of 1 mm ST depression were significantly longer during the 3 treatment sequences but there were no significant differences between each of them. Secondary effects were significantly more common with Nifedipine (7 patients) and with the drug association (9 patients) than with Diltiazem alone (3 patients) or placebo (1 patient). Plasma concentrations of Diltiazem were 328 +/- 35 ng/l with the 360 mg/day dosage and 137 +/- 52 ng/l with the 180 mg/day dosage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of effects of diltiazem, nifedipine and their combination on exercise stable angina]. 202 Dec 84

Episodes of transient myocardial ischemia during ambulatory activities are common in patients with stable coronary artery disease and who are often asymptomatic. Selection of therapy for episodes of asymptomatic ischemia is limited by a lack of direct comparative studies. To determine the most effective monotherapy for patients with stable angina and a high frequency of asymptomatic ischemic episodes, propranolol-LA (mean daily dose, 293 mg), diltiazem-SR (mean daily dose, 350 mg), nifedipine (mean daily dose, 79 mg) were each compared with placebo, each for 2 weeks, in a randomized, double-blinded, crossover trial. Entry criteria were a positive exercise treadmill test during placebo therapy characterized by 1.0 mm or more ST segment depression and angina pectoris, and six or more episodes of transient ST segment depression of 1.0 mm or more on a 48-hour ambulatory electrocardiogram. One hundred ninety-four patients were screened, 63 were eligible and received randomized therapy, of which 56 patients completed at least two of the four treatment periods and were included in an intent-to-treat analysis. Fifty patients completed all four treatment phases and were included in the protocol-completed analysis. Anti-ischemia efficacy was assessed by 48-hour ambulatory electrocardiographic monitoring, exercise treadmill tests, and anginal diaries. Ninety-four percent of all episodes of ambulatory ischemia were asymptomatic. Compared with placebo, only propranolol was associated with a marked reduction in all manifestations of asymptomatic ischemia during ambulatory electrocardiographic monitoring (2.3 versus 1.0 episodes/24 hr; mean duration of ischemia per 24 hours, 43.6 versus 5.7 minutes; both p less than 0.0001). Diltiazem's reduction of the frequency of episodes compared with placebo (2.3 versus 1.9 episodes/24 hr) was associated with a trend (p = 0.08) in the protocol-completed analysis and with a significant reduction in the intent-to-treat analysis (p = 0.03). Nifedipine had no significant effect on any measured variable of ambulatory ischemia. The dosages of medication used may have been excessive for some patients, and a more beneficial effect may have been evident at a lower dose. In contrast to the marked effects of the active agents on ambulatory asymptomatic ischemia, the effects on exercise performance and angina pectoris were slight. The active agents modestly improved treadmill exercise duration time until 1 mm ST segment depression (3%), and only propranolol and diltiazem had significant effects. Only diltiazem significantly prolonged the total exercise time. Anginal frequency was significantly decreased by both propranolol and diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of propranolol, diltiazem, and nifedipine in the treatment of ambulatory ischemia in patients with stable angina. Differential effects on ambulatory ischemia, exercise performance, and anginal symptoms. The ASIS Study Group. 224 50

In a double blind crossed ten-week study with a randomized beginning the authors compared in 25 patients with chronic stable angina pectoris (II-III according to NYHA classification) and with normal blood pressure the effect of placebo, nifedipine, diltiazem and in 16 of the patients (who completed treatment with the combined drugs) also a combination of nifedipine and diltiazem. Nifedipine, 60 mg per day, and diltiazem, 270 mg per day, improved significantly the total amount of performed work as compared with placebo, they delayed significantly the onset of stenocardias and reduced the ST depression in lead V5 during ergometry, they reduced significantly the rate of stenocardias per day as well as the nitroglycerin consumption. Diltiazem, as compared with nifedipine, increased significantly the total volume of performed work and delayed the development of stenocardias during ergometry, the symptomatic improvement of the patients being similar. A combination of 30 mg nifedipine per day with 180 mg diltiazem per day did not lead to improvement, as compared with a higher dose of diltiazem alone, as compared with a higher dose of diltiazem alone. A combination of 60 mg nifedipine per day with 270 mg diltiazem per day did not improve the exercise tolerance, as compared with diltiazem alone, however, it reduced significantly the rate of stenocardias. However, the combination of the latter amounts was tolerated without side-effects only by 13% of the patients (2 of 15 patients), 53% (8 of 15 patients) terminated treatment prematurely because of several side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effectiveness of nifedipine, diltiazem and their combination in the treatment of chronic stable angina pectoris]. 220 31


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