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)

The systemic and coronary haemodynamic effects of intravenous nicardipine were investigated in 10 patients with a more than 70 p. 100 stenosis of the left coronary artery. Two brief atrial pacing tests (ST1 and ST2) were performed. ST2 was performed 30 minutes after an intravenous injection of nicardipine 2.5 mg over 5 minutes. Nicardipine produced a 25 p. 100 decrease in ventricular systolic pressure and a substantial increase in cardiac index (from 2.74 +/- 0.48 to 3.46 +/- 0.35 l/min/m2, p less than 0.001). Measurement of the coronary flow rate by the thermodilution method showed a 40 p. 100 increase in sinus blood flow while coronary resistance decreased not only in territories with normal supply but also in myocardial territories distal to the coronary stenosis (from 2.76 +/- 2.3 to 1.83 +/- 1.5 mmHg/ml, p less than 0.02). With the same paced heart rate the ventricular function parameters were significantly improved during ST2 (cardiac index ST2 3.56 +/- 0.65 vs ST1 2.8 +/- 0.48, p less than 0.001; dp/dt max ST2 2143 +/- 369 vs ST1 1874 +/- 301 mmHg/sec, p less than 0.05), reflecting a lower degree of myocardial ischaemia. This was confirmed by the lower amplitude of electrocardiographic depression and by a higher lactate extraction coefficient (LE ST1 6 +/- 7 p. 100 vs LE ST2 12 +/- 12 p. 100, p less than 0.05). Mean arterial blood pressure and coronary sinus blood flow rate values were identical during the two atrial pacing tests.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Systemic and coronary hemodynamic effects of intravenous nicardipine at rest and in ischemia induced by rapid atrial stimulation]. 312 11

The two dihydropyridine calcium antagonists, nicardipine and nifedipine, were compared in 12 patients with both stable angina pectoris and systemic hypertension using a double-blind, crossover protocol. After a 2-week placebo run-in period, each patient was randomized to either nicardipine or nifedipine; each drug was titrated up to either blood pressure normalization, appearance of adverse effects, or maximal dosage (40 mg, three times a day with nicardipine and 30 mg, three times a day with nifedipine) and then administered for 4 weeks. Maximal symptom-limited exercise tests were performed at the end of the placebo run-in and each treatment period, 3 and 8 hours after drug administration. Nicardipine and nifedipine were used at the mean doses of 100 +/- 20 mg/day and 57 +/- 20 mg/day, respectively. Both drugs reduced, significantly and similarly, standing and supine blood pressure, frequency of anginal episodes, and nitroglycerin consumption. At 3 hours after drug administration, exercise duration and time to 1-mm ST depression increased significantly from 402 +/- 84 and 306 +/- 108 seconds, respectively, with placebo; to 533 +/- 135 and 442 +/- 138 seconds during nicardipine; and to 518 +/- 118 and 437 +/- 133 seconds during nifedipine, with a concomitant reduction of peak ST depression. Both submaximal and maximal exercise diastolic blood pressure were significantly reduced by the two calcium antagonists whereas systolic blood pressure was decreased only at submaximal but not at maximal exercise; the heart rate was not significantly modified by the two drugs at any exercise stage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A randomized double-blind crossover study of nicardipine and nifedipine in patients with angina pectoris and concomitant essential hypertension. 315 18

Nicardipine treatment has been evaluated in patients with chronic stable effort angina or with angina at rest due to coronary spasm. Acute studies in patients with effort angina suggest a very favorable hemodynamic profile characterized by coronary vasodilatation and reduction in determinants of myocardial oxygen demand. Both open and controlled trials in patients with effort angina show that long-term oral administration increases exercise time and time to onset of 1 mm ST-segment depression and decreases angina frequency. With treatment for up to 6 months, antiischemic effects were maintained without serious adverse reactions. Other studies indicate that nicardipine is generally comparable to propranolol and nifedipine in prolonging exercise time and time to onset of ST-segment depression. Nicardipine, however, does not depress heart rate at rest, and maximal exercise workload is higher with nicardipine than with either placebo or propranolol. In a controlled study of patients with angina at rest due to coronary spasm, nicardipine decreased angina frequency and nitroglycerin consumption by approximately 80%. Episodes of symptomatic and asymptomatic ST-segment shift, as recorded by ambulatory electrocardiographic monitoring, showed a trend to decrease in number. Nicardipine appeared similarly effective in patients with coronary spasm superimposed on significant coronary disease and with spasm in the absence of significant coronary disease. Nicardipine appears to be safe and effective in the management of patients with angina pectoris.
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PMID:Usefulness of nicardipine for angina pectoris. 330 Feb 37

The newer dihydropyridine calcium antagonists are structurally related to nifedipine, but may provide greater vascular selectivity and wider clinical utility. Five new dihydropyridines-nisoldipine, nicardipine, nimodipine, felodipine and nitrendipine-are reviewed with regard to their preclinical pharmacology, haemodynamic effects and clinical indications. Nisoldipine is a potent arterial vasodilator with minimal electrophysiological and negative inotropic effects. Although data are still preliminary, the drug has shown some efficacy in both exertional angina and essential hypertension. The dosing interval is not yet clearly established, but may be twice daily. Utility in congestive heart failure awaits confirmation, but preliminary studies are promising. Nicardipine is an especially potent peripheral, cerebral and coronary arterial vasodilator that causes 10-fold less myocardial depression in animals than nifedipine, and may provide important cardioprotective effects during ischaemia. Human haemodynamic studies have confirmed nicardipine's lack of negative inotropism, its ability to reduce coronary and peripheral vascular resistance, and its lack of effect on cardiac conduction. Several controlled trials have documented its efficacy in exertional angina, vasospastic angina, and essential hypertension. Nicardipine's potential as an antiatherosclerotic agent is currently under investigation. Nimodipine is undergoing a unique clinical development programme aimed at cerebrovascular disorders. In almost all species, nimodipine selectively increases cerebral blood flow and reverses cerebral artery spasm without altering cerebral oxidative metabolism or systemic blood pressure. In humans, a large, double-blind, placebo-controlled trial in subarachnoid haemorrhage showed that nimodipine significantly reduced the severity of neurological deficits associated with delayed cerebral vasospasm. Several uncontrolled trials with larger numbers of patients support these results. Nimodipine has also proved useful in reducing cerebral artery spasm during intracranial surgery, and in the prophylactic treatment of migraine headaches. A preliminary study of nimodipine in acute stroke showed promising results in limiting neurological disability. Felodipine is a very potent systemic arterial vasodilator with negligible myocardial depressant activity. It is also a renal artery vasodilator. Unlike the other new dihydropyridines, felodipine prolongs the A-H interval on electrophysiological testing, but only to about 50% of that observed with verapamil. Felodipine is undergoing clinical trials in essential hypertension.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:'Second generation' dihydropyridine calcium antagonists. Greater vascular selectivity and some unique applications. 331 91

The effects were studied of several calcium channel blocking agents on muscle twitch, and possible interactions between these drugs and pancuronium and suxamethonium, using a rat phrenic-hemidiaphragm preparation. Nicardipine, verapamil and diltiazem each caused a concentration-related depression of muscle response. Nicardipine had the most, and diltiazem the least, potent effect. Verapamil and diltiazem 5 and 10 mumol litre-1 caused a concentration-dependent enhancement of suxamethonium-induced neuromuscular blockade, but increased the effect of pancuronium only at 10 mumol litre-1. Nicardipine 10 mumol litre-1 significantly enhanced pancuronium-induced neuromuscular blockade, but not that produced by suxamethonium.
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PMID:Differential effects of calcium channel blocking agents on pancuronium- and suxamethonium-induced neuromuscular blockade. 337 24

In a double-blind, randomized, crossover clinical trial, a new calcium antagonist, nicardipine (90 mg/day in 3 divided doses), was compared with propranolol (120 mg/day in 3 divided doses) in 25 patients with chronic stable angina. The mean weekly frequency of angina episodes decreased from 7.8 +/- 1.2 (+/- standard error of the mean) with placebo to 3.8 +/- 1.2 with nicardipine treatment and 3.5 +/- 1 with propranolol treatment (p less than 0.001). With exercise testing, 5 patients receiving nicardipine and 3 receiving propranolol had no angina or ST-segment changes. Comparing paired samples of both drugs with placebo, significant improvement occurred in exercise duration (nicardipine, 1.3 +/- 0.3 minutes, p less than 0.001; propranolol, 1.0 +/- 0.4 minutes, p less than 0.01), time to onset of angina (nicardipine, 1.5 +/- 0.4 minutes, p less than 0.001; propranolol, 1.5 +/- 0.5 minutes, p less than 0.001), maximal ST-segment changes (nicardipine, 0.7 +/- 0.1 mm, p less than 0.01; propranolol, 0.06 +/- 0.1 mm, p less than 0.01) and time to 1 mm of ST depression (nicardipine, 2.5 +/- 0.4 minutes, p less than 0.01; propranolol, 2.0 +/- 0.3 minutes, p less than 0.01). One patient receiving propranolol and 2 receiving nicardipine withdrew from the study because of transient side effects. Mild side effects occurred in 10 patients receiving propranolol and 5 receiving nicardipine. Nicardipine proved to be safe and effective for patients with chronic stable angina; it had fewer side effects than propranolol in the doses used.
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PMID:Comparison of nicardipine and propranolol for chronic stable angina pectoris. 351 May 24

To define the effects of nicardipine, a new dihydropyridine calcium antagonist drug, on exercise- and pacing-induced myocardial ischemia, 15 men with coronary artery disease were studied during cardiac catheterization. Nicardipine was administered intravenously as a 2-mg bolus followed by an infusion titrated to maintain a 10- to 20-mm Hg decrease in systolic arterial pressure. At rest, nicardipine decreased systemic and coronary vascular resistances, left ventricular end-diastolic pressure and increased coronary blood flow, heart rate and myocardial oxygen consumption. During bicycle exercise-induced myocardial ischemia, nicardipine significantly prolonged exercise duration and time to 1 mm of ST-segment depression. These changes were associated with no alteration in the product of systolic pressure and heart rate, decreased left ventricular end-diastolic pressure, systemic and coronary vascular resistances and increased coronary blood flow, as well as myocardial oxygen consumption. During atrial pacing, the heart rate threshold for myocardial ischemia was not changed by nicardipine administration, despite improvement in the ratio of coronary blood flow to myocardial oxygen consumption and hemodynamic changes otherwise similar to those during exercise. Nicardipine favorably influenced myocardial metabolic state, as indexed by lactate extraction during pacing-induced ischemia. Nicardipine is a potent coronary and systemic vasodilating drug that improves exercise tolerance and myocardial metabolic response to pacing stress, the mechanism for which appears to be partially mediated through increased coronary blood flow.
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PMID:Effects of nicardipine on exercise- and pacing-induced myocardial ischemia in angina pectoris. 363 Sep 28

Experiments were designed to investigate the effect of two calcium antagonists, diltiazem and nicardipine (concentration range: 10(-7)-10(-4) M), on the contractile responses to transmural nerve stimulation, exogenous noradrenaline and tyramine in isolated canine saphenous vein rings. Both diltiazem and nicardipine inhibited the contractile response to transmural nerve stimulation in a non-competitive, concentration-dependent manner. At a concentration of 10(-4) M, diltiazem and nicardipine inhibited the maximum contractile response to transmural nerve stimulation to 0.8 +/- 0.8% and 20 +/- 10% of control respectively. Effects of diltiazem and nicardipine (up to 10(-4)M) on the contractile response to exogenous noradrenaline were minimal. The only significant difference observed was a 30% depression of the maximum contractile response with a shift in ED50 at high concentrations of nicardipine. Diltiazem (up to 10(-4) M) had no significant effect on concentration-effect curves for tyramine. Nicardipine inhibited the response to tyramine in a non-competitive manner with the maximum response depressed to 46% of control at 10(-4) M-nicardipine. Release of [3H]noradrenaline during transmural nerve stimulation was reduced by both calcium antagonists in a concentration-dependent manner. However, release of [3H]noradrenaline produced by the indirect sympathomimetic agent tyramine was not significantly inhibited by nicardipine. These experiments suggest that the calcium antagonists diltiazem and nicardipine inhibit the contractile response to transmural nerve stimulation in the canine saphenous vein predominantly by inhibiting the release of endogenous noradrenaline. However, nicardipine appears to have an additional post-synaptic inhibitory effect on the responses to exogenous as well as endogenous noradrenaline.
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PMID:Effect of calcium antagonists on adrenergic mechanisms in canine saphenous veins. 372 10

During repeat exercise testing in 10 patients with stable angina, individual optimal doses of nicardipine were determined. Hemodynamic values and cardiac metabolism were studied during 2 pacing periods carried out before and after this dose (mean 5.3 mg). Postpacing ST-segment depression diminished (1 mm) after nicardipine administration (p less than 0.05), whereas pacing time to onset of angina did not change. Nicardipine administration increased heart rate 16% (p less than 0.005) and reduced systolic (10%) and diastolic (8%) blood pressures (both p less than 0.005). Coronary blood flow increased 16% (p less than 0.05) and coronary vascular resistance decreased 24% (p less than 0.01). Myocardial oxygen consumption was unchanged despite an 11% decrease in rate-pressure product during pacing (p less than 0.02). In the control state before nicardipine administration, metabolic signs of ischemia included release of lactate across the heart in 7 patients, decreased mean free fatty acid and glutamate uptake and alanine release during pacing, together with increased glucose uptake and citrate release during recovery. After nicardipine lactate release decreased in 5 of the 7 patients, pacing no longer changed free fatty acid, glutamate and alanine uptake/release from the level at rest. During recovery glucose uptake was reduced and citrate release was unaffected. The hemodynamic data indicate that nicardipine is a systemic and coronary vasodilator, increasing oxygen supply to the ischemic myocardium. The metabolic results indicate a change in substrate utilization toward that of normal heart, suggesting improved aerobic energy supply.
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PMID:Metabolic and hemodynamic effects of nicardipine during pacing-induced angina pectoris. 381 68

Nicardipine, 30 and 40 mg thrice daily, was administered to 66 patients with stable angina pectoris in a multicentre, randomised, double-blind, cross-over trial. With nicardipine therapy, duration of exercise and cumulative oxygen consumption increased, while times to onset of angina and 1 mm ST segment depression were prolonged. Anginal frequency and nitroglycerin consumption declined with use of nicardipine, but this did not reach statistical significance. Resting heart rate increased slightly and resting blood pressure decreased. Two patients on nicardipine and one on placebo sustained acute infarction. Otherwise, side effects were generally mild and transient.
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PMID:Nicardipine for stable angina pectoris. 392 58


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