Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional formulations of metoprolol have become well established in cardiovascular medicine and are particularly useful in the management of hypertension and ischaemic heart disease. Recently developed controlled release metoprolol delivery systems (metoprolol CR/ZOK and metoprolol OROS) were designed to overcome the drug delivery problems of matrix-based sustained release forms by releasing the drug at a relatively constant rate over a 24-hour period, and thus producing sustained and consistent metoprolol plasma concentrations and beta 1-blockade while retaining the convenience of once daily administration. Clinically and statistically significant reductions in blood pressure have been observed with metoprolol CR/ZOK and metoprolol OROS 24 hours after administration in mildly or moderately hypertensive patients. Studies in patients with mild to moderate hypertension have demonstrated that a similar or higher percentage of patients achieved a goal response with metoprolol CR/ZOK compared with matrix-based sustained release formulations of metoprolol, or conventional atenolol or bisoprolol, while metoprolol OROS achieved an equal or greater response rate compared with conventional or matrix-based sustained release metoprolol preparations. In patients with stable effort angina pectoris, once daily administration of metoprolol CR/ZOK provided at least equal antianginal efficacy as conventional metoprolol in divided doses, while metoprolol OROS reduced the mean number of anginal attacks by the same margin as atenolol. Controlled release metoprolol formulations have been well tolerated in clinical trials. Metoprolol CR/ZOK was associated with a similar or lesser degree of adverse effects related to the central nervous system compared with atenolol or long acting propranolol. Metoprolol CR/ZOK also demonstrated less pronounced beta 2-mediated bronchoconstrictor effects than atenolol in asthmatics, and less general fatigue and leg fatigue in healthy subjects. Metoprolol OROS produced less pronounced bronchoconstrictor effects than atenolol, matrix-based sustained release metoprolol or long acting propranolol in patients with asthma or obstructive airways disease, and healthy volunteers. These results are presumably due to the beta 1-selectivity of metoprolol in addition to the relatively low plasma concentrations maintained by metoprolol CR/ZOK and metoprolol OROS, and the avoidance of high peak plasma concentrations with these agents. Despite the relative safety of the controlled release forms of metoprolol, the use of all beta-adrenoceptor antagonists should be avoided in patients with a history of bronchospasm. Thus, controlled release metoprolol formulations offer the potential to maximise the confirmed benefits of this agent in the management of hypertension and angina, by maintaining clinically effective plasma concentrations within a narrow therapeutic range over a 24-hour dose interval.
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PMID:Controlled release metoprolol formulations. A review of their pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and ischaemic heart disease. 137 20

The objective of this study was to assess whether a 10-d treatment with oral theophylline improves the working capacity in patients with ischaemic heart disease, and to compare theophylline with conventional anti-anginal therapy. Twenty-four patients with stable effort-induced angina were included in the study. The patients received double-blind treatment in randomized order during 4 consecutive 10-d periods, separated by a 4-d wash-out period, with (a) metoprolol durules 200 mg once daily + theophylline durules 300 mg b.i.d., (b) theophylline + placebo, (c) metoprolol + placebo, and (d) placebo alone. At the end of each period a supine exercise stress test was performed. Maximal workload increased to 111 +/- 6 W during treatment with theophylline, compared to 106 +/- 6 W during placebo treatment (P = 0.01). Metoprolol increased the maximal workload to 117 +/- 6 W (P less than 0.001). The effects of metoprolol and theophylline were additive, and the working capacity increased to 123 +/- 7 W during combined therapy. Neither the degree of ST-depression nor the scoring of chest pain at maximal workload differed between the four treatment regimens. An improved working capacity was shown in patients with stable effort-induced angina pectoris during long-term theophylline treatment. The effect was additive to that of beta-blockade.
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PMID:Improved working capacity in patients with ischaemic heart disease during a 10-day treatment with oral theophylline. 164 Jan 92

Metoprolol and other beta-adrenergic blocking drugs are known to exert cardioprotective effects that include significant reduction in occurrence of ventricular fibrillation (VF) following myocardial ischemia and infarction. To help determine the mechanism of these cardioprotective effects, this study evaluated the effect of equipotent beta-blocking doses of metoprolol and three other beta-blockers with differing ancillary properties on ventricular fibrillation threshold (VFT) in the normal canine heart. Metoprolol tartrate (1.0 mg/kg i.v.), atenolol (0.3 mg/kg i.v.), propranolol hydrochloride (0.3 mg/kg i.v.), pindolol (0.03 mg/kg i.v.), or saline control (0.9% NaCl solution; vehicle) was given, alone and in combination with lidocaine (L), to groups of six pentobarbital (32.5 mg/kg i.v.) anesthetized mongrel dogs after control VFT and control isoproterenol-induced (ISO) positive chronotropic effects had been determined. The D- (membrane stabilizing, non-beta blocking) and L- (beta blocking) isomers of propranolol also were administered to separate groups of six anesthetized dogs in a dose of 0.3 mg/kg i.v. Blood samples (venous) were taken before drug or vehicle administration, 10 min after drug/vehicle administration and at half-hour intervals thereafter during experimentation. ISO responses and VFT were determined 5 and 15 min, respectively, after drug/vehicle administration and at half-hour intervals for a total experimental period of 165 min. VF was induced with a train of pulses (5 s, 100 Hz, 3-ms duration, 250-omega resistance) applied by bipolar platinum electrodes to a paced heart (200 beats/min). Voltage (V) was increased every 60 sec (0.25-V increments between 0-3.5 V and 0.5-V increments greater than 3.5 V) until VF occurred. Metoprolol increased VFT significantly (p less than 0.05) and maximally (max delta V = 2.3 +/- 0.7 V) at 135 min postdrug when the ISO-induced increase in heart rate was inhibited (%I ISO) by less than 53%. Max delta V was not significantly increased following i.v. administration of atenolol (0.8 +/- 0.6 V), pindolol (0.1 +/- 0.1 V), or saline (0.1 +/- 0.1 V). Max delta V was 0.5 +/- 0.2 in the D-propranolol-treated group and 0.5 +/- 0.3 in the L-propranolol-treated group. These values did not differ from max delta V obtained in the propranolol-treated group (0.6 +/- 0.4 V). Changes in VFT for all groups were, over time, negatively correlated with %I ISO and were not dependent on membrane stabilizing effect (metoprolol, propranolol (D,DL), pindolol), intrinsic sympathomimetic activity (pindolol), or cardioselectivity (metoprolol, atenolol).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of metoprolol, alone and in combination with lidocaine, on ventricular fibrillation threshold: comparison with atenolol, propranolol, and pindolol. 243 44

The acute hemodynamic responses to beta-adrenoceptor blockade with the beta 1-selective antagonist metoprolol, and to combined alpha/beta-receptor blockade with labetalol, were compared intraindividually in a randomized single-blind, cross-over study. Fourteen patients with proved ischemic heart disease, aged 52-64 years, were studied at rest (supine) and during ischemia-inducing exercise (in the seated posture) using invasive percutaneous techniques. Metoprolol reduced heart rates and cardiac output greatly (p less than 0.001) and systemic arterial pressures slightly (p less than 0.001) under all conditions. Left ventricular filling pressures increased. Labetalol induced a slight decrease in heart rates during exercise, while cardiac output was unchanged. Systemic arterial pressures and vascular resistances, pressures and resistances in the pulmonary circulation, and left ventricular filling pressures were distinctly lower. During ischemia-inducing exercise, the differences between the effects of labetalol and metoprolol on heart rate, cardiac output, systemic vascular resistance, and left ventricular filling pressures were highly significant. The effects on the rate X pressure product and on angina were similar. It is concluded that combined alpha/beta-blockade with labetalol offsets or attenuates the potential adverse hemodynamic effects of beta-receptor blockade alone without loss of symptomatic efficacy.
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PMID:Hemodynamic effects at rest and during exercise of combined alpha/beta-receptor blockade and of beta-receptor blockade alone in patients with ischemic heart disease. 244 2

The unpredictable effect of antihypertensive therapy on coronary risk resulting from changes in lipid levels is an increasingly recognized problem. Different drugs have been shown to exert varying effects on lipids. This problem is particularly evident in young hypertensive patients who may be candidates for lifelong therapy. The effects of chlorthalidone and metoprolol on fasting plasma lipids and lipoprotein levels were compared in two similar nonrandomized groups of patients with mild hypertension. Chlorthalidone therapy was associated with an increase in serum cholesterol of 8.1% (17 mg/dl), mainly reflecting an increase in low-density lipoprotein (LDL) cholesterol. Serum triglycerides increased by 16% (20 mg/dl) and high-density lipoprotein (HDL) cholesterol levels decreased by 10% (3 mg/dl, not significant). Metoprolol therapy induced no changes in total, low, very low, or high-density lipoprotein. Serum triglyceride concentration increased by 22% (28 mg/dl). Application of the Israel Ischemic Heart Disease Study data to these findings indicates a slight decrease at most in the 5-year estimated probability of myocardial infarction in the chlorthalidone-treated group, whereas a clearly favorable influence on the calculated risk of coronary heart disease was observed for those treated with metoprolol. These data suggest that the different forms of therapy for mild hypertension carry varying degrees of significance in terms of risk of coronary heart disease, which should be considered when choosing medication.
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PMID:Do beta-blockers alter lipids and what are the consequences? 248 Nov 77

The hemodynamic responses to 3 different therapeutical regimens: beta-adrenoceptor blockade, calcium inflow inhibition and combined alpha-beta-blockade were evaluated in 3 matched randomized groups of patients with ischemic heart disease and typical exercise-induced angina. The groups consisted of 22, 16 and 15 men, mean age 55-59 years. They were studied at rest and during ischemia-inducing exercise, before and after single oral doses of 100 mg metoprolol, 10 mg nifedipine and 200 mg labetalol. Pressures in the brachial artery and the pulmonary circulation were recorded by means of percutaneously introduced catheters. Cardiac output was determined according to the Fick principle. Metoprolol reduced mean arterial pressures, heart rate and cardiac output. Systemic vascular resistance and left ventricular filling pressure increased. Nifedipine resulted under all conditions in a distinct reduction of systemic vascular resistance and arterial pressures and a slight increase in heart rate and cardiac output. Left ventricular filling pressure was significantly lowered, the more the higher the initial level. The effect of labetalol was similar to that of nifedipine; however, cardiac output was unchanged and heart rate was slightly reduced. Left ventricular filling pressure was significantly lower. It is apparent that suppression of adrenergic stimulation by beta-receptor blockade alone may have adverse hemodynamic effects in ischemic heart disease and prompt further functional deterioration. Conversely, both calcium and combined alpha-beta-receptor blockade tend to improve left ventricular function by lowering both left ventricular preload and total systemic vascular resistance. The results strongly suggest that in patients in whom beta-receptor blockers appear indicated, their adverse hemodynamic effects can be offset by concomitant alpha1-receptor blockade or vasodilation without losing symptomatic efficacy. Combined alpha-beta-receptor blockade has the advantage over calcium antagonists alone to prevent any increase in adrenergic activity and related hyperkinetic response.
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PMID:Differential hemodynamic effects of beta-adrenoceptor blockers, Ca antagonists and combined alpha-beta-receptor blockade in ischemic heart disease. 286 48

This study investigates effects of beta-adrenergic blockade on total silent ischemic time assessed by ambulatory electrocardiographic monitoring and its relation to heart rate and time of day in ambulatory men with coronary artery disease. Metoprolol, when titrated to optimal dose in a controlled trial in 9 patients, reduced both total silent ischemic time (from 156 +/- 65 to 20 +/- 15 minutes, p = 0.04) and frequency of silent ischemic episodes (from 8 +/- 2 to 2 +/- 2 episodes, p = 0.03) compared with placebo. Mean daily heart rate was reduced, from 82 +/- 2 beats/min during placebo to 58 +/- 1 beats/min, as was heart rate at onset of 1 mm of ST-segment depression (106 +/- 2 to 74 +/- 4 beats/min, both p less than 0.001). Heart rate increased 10 +/- 1 beats/min during silent ischemia with placebo therapy, but increased only 4 +/- 1 beats/min during metoprolol treatment (p less than 0.03). During placebo administration the largest proportion of silent ischemic time occurred between 0600 and 1200 hours. Metoprolol attenuated this circadian variation in silent ischemia while reducing (p less than 0.05) total silent ischemic time in all periods. Thus, beta-adrenergic blockade reduces the frequency of silent myocardial ischemic episodes and total silent ischemic time, while mean daily heart rate and heart rate at onset of ischemia and maximal ischemia decrease. Metoprolol treatment also attenuates circadian variation of silent ischemia. These data may be interpreted to suggest that beta-adrenergic activation operates in the pathogenesis of silent myocardial ischemia and its circadian variation.
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PMID:Effects of titrated beta blockade (metoprolol) on silent myocardial ischemia in ambulatory patients with coronary artery disease. 363 Sep 34

The effects of chlorthalidone and metoprolol on fasting plasma lipids and lipoprotein levels were compared in two similar nonrandomized groups of patients with mild hypertension. Chlorthalidone therapy was associated with an increase in serum cholesterol of 8.1% (17 mg/dl), mainly reflecting an increase in low-density lipoprotein (LDL)-cholesterol. High-density lipoproteins (HDL)-cholesterol decreased, but the difference between pre- and posttreatment levels did not reach statistical significance. Serum triglyceride (TG) concentration increased by 16% (20 mg/dl). Metoprolol therapy was not associated with changes in total, very low-density lipoprotein (VLDL)-, LDL- and HDL-cholesterol levels. Serum TG concentration increased by 22% (28 mg/dl), mainly due to an increase in VLDL-TG. Application of the Israel Ischemic Heart Disease Study data to these findings could predict only a very slight decrease in the 5-year estimated probability of myocardial infarction in the chlorthalidone-treated group. Metoprolol therapy has, theoretically, a more favorable influence on coronary heart disease risk status. These data suggest that the different forms of therapy for mild hypertension have a different effect on the theoretical coronary heart disease risk status, a fact that should be taken into consideration in the choice of medication.
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PMID:Different effects of metoprolol and chlorthalidone on serum lipoprotein levels in mild hypertension. Possible implications for coronary heart disease risk status. 651 49

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

Recent studies strongly support the prognostic importance of transient silent ischemia. Because patients with silent ischemia are at higher risk of a cardiac event, they are likely to benefit not only from control of symptoms, but also from treatment directed at prevention of ischemia. The efficacy of controlled-release metoprolol 200 mg once daily and diltiazem 60 mg 4 times daily was assessed in a randomized, double-blind, crossover study in 32 patients with proven coronary artery disease, predominantly asymptomatic myocardial ischemia, positive bicycle exercise test results, and > or = 5 minutes of asymptomatic ST-segment depression on a 24-hour screening ambulatory electrocardiogram (ECG). At the beginning and at the end of both 3-week treatment periods, an exercise test was performed and a 72-hour ambulatory ECG was recorded. Both active treatment periods were preceded by a 2-week placebo phase. Both treatments effectively reduced and postponed exercise-induced ST depression and reduced the total ischemic integral on the ambulatory ECG. Only metoprolol significantly reduced the mean number of ischemic episodes (54%, p = 0.0003, vs 31% for diltiazem, p = NS) and the mean duration of ischemia (51%, p = 0.012, vs 27% for diltiazem, p = NS) compared with baseline values. Metoprolol strongly blunted the morning and afternoon peak in the circadian distribution of ischemia, whereas diltiazem did not change the circadian distribution of ischemia at all.
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PMID:Efficacy of metoprolol and diltiazem in treating silent myocardial ischemia. 797 65


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