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)

L-propionylcarnitine, a naturally occurring derivative of L-carnitine, essential for mitochondrial fatty acid transport and high-energy phosphate exchange, acutely reduces myocardial ischaemia and improves ischaemia-induced cardiac dysfunction following intravenous administration. This randomized, crossover study was designed to compare the long-term anti-ischaemic effects of oral L-propionylcarnitine with diltiazem in patients with stable, exercise-induced angina. After a 2-week washout phase of anti-anginal medication and a 2-week single-blind placebo period, 46 patients were included in the study, 23 of whom received 1500 mg L-propionylcarnitine daily for 6 weeks, and 23 diltiazem (180 mg daily for 3 weeks, followed by 360 mg daily for 3 weeks), crossing over to the other treatment after a 1-week washout period. Three patients on L-propionylcarnitine and two on diltiazem discontinued. Both treatments resulted in comparable exercise duration (582 +/- 35 s and 588 +/- 33 s, mean +/- SEM), time to 0.1 mV ST depression (436 +/- 38 s and 465 +/- 36 s), and increase in time to 0.1 mV ST depression from baseline (20% and 28%), L-propionylcarnitine and diltiazem, respectively. Diltiazem decreased the rate-pressure product at rest and exercise, L-propionylcarnitine did not. Both compounds significantly reduced ST depression at maximal exercise [23% (L-propionylcarnitine) vs 35% (diltiazem), P < 0.05 diltiazem vs L-propionylcarnitine]. Diltiazem increased the time to onset of angina by 22%. In contrast, no significant changes occurred with L-propionylcarnitine. During the study, anginal attacks were reduced by 70% and 57%, and nitroglycerin consumption decreased by 57% and 70%, L-propionylcarnitine and diltiazem, respectively. Thus, both L-propionylcarnitine and (high-dose) diltiazem result in anti-ischaemic effects and decrease anginal attacks in daily life. Although the effect of diltiazem on exercise-induced ischaemia appears more pronounced than that of L-propionylcarnitine, this novel metabolic approach to ischaemia warrants further development.
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PMID:Anti-ischaemic efficacy of L-propionylcarnitine--a promising novel metabolic approach to ischaemia? 873 16

Ca++-antagonist is effective not only for variant angina but also for effort angina. The effects of sustained release diltiazem (diltiazem-R) and beta 1-blocker (atenolol) on exercise tolerance were studied in seven patients with stable effort angina in a cross over trial. Diltiazem-R (100mg) or atenolol (50mg) was given once a day, each treatment period lasting for two weeks after a two-week control period. The treadmill exercise test was performed on the last day of each protocol. Both diltiazem-R and atenolol decreased heart rate at rest and the decrease with atenolol was greater than that with diltiazem-R. The systolic blood pressure was unchanged at rest by both drugs. At maximal work levels, atenolol decreased the heart rate and pressure rate product significantly but diltiazem-R did not. Both diltiazem-R and atenolol significantly prolonged the exercise time (average 137 and 165 seconds respectively), time to onset of 1mm ST depression (240 and 288 seconds respectively). There was no significant difference in exercise tolerance between diltiazem-R and atenolol. These findings suggest that diltiazem-R, a sustained release Ca++-antagonist, provides beneficial effects in patients with stable effort angina.
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PMID:Effect of sustained release diltiazem (Diltiazem-R) in patients with stable effort angina. 883 Jun 46

In the 10 years since our previous review of this topic, the acute coronary syndromes (Q wave myocardial infarction [QMI], non-Q wave MI [NQMI], and unstable angina) have been more clearly categorized. Many of the differences delineated between QMI and NQMI still hold: a less extensive infarction and a lower in-hospital mortality, but a larger degree of jeopardized myocardium leading to a higher incidence of reinfarction and recurrent angina. The pathophysiology of NQMI appears to be similar to that of unstable angina except for the greater incidence and extent of thrombus formation and coronary artery occlusion with NQMI. Prognostic studies have shown that ST depression and anterior infarct location are associated with a greater risk for posthospital clinical events than the findings of ST elevation and other infarct locations. Symptom-limited stress testing using electrocardiogram and thallium-201 imaging are now recommended before discharge or in the early postdischarge period, with coronary arteriography recommended for evidence of residual ischemia. Aspirin and low dose heparin should be administered on admission after NQMI to decrease further thrombus formation, and aspirin continued in the posthospital period. Diltiazem administration is recommended in NQMI without evidence of pulmonary congestion to prevent recurrent nonfatal acute myocardial infarction. Percutaneous transluminal coronary angioplasty and surgical revascularization should be reserved for patients with NQMI with residual ischemia.
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PMID:The non-Q wave myocardial infarction revisited: 10 years later. 912 24

This paper was designed to evaluate the effectivity of several vasodilators, applied topically, to attenuate the hyperreactivity of radial arteries (RA) implanted as aorto-coronary bypass. Remnant segments of the RA were obtained from 20 operations, and each of the segments was divided into 4 rings. The rings were incubated for 30 minutes in control conditions (n = 20) or in presence of 30 microM of Diltiazem (DILT, n = 6), 30 microM of mibefradil (MIBE, n = 4) or a mixture of 30 microM of verapamil + 30 microM of nitroglycerin (VP-NTG, n = 6). A subsequent exposure to KCl 80 mM (in absence of vasodilators) evoked a sustained contraction in control rings, which was attenuated by 35 +/- 9% by DILT, 48 +/- 13% by VP-NTG and by 69 +/- 20% by MIBE (p < 0.05). Preincubation with vasodilators also attenuated the rate and intensity of rhythmic contractions of the RA. In rings that were cold-stored during 24 hs and then restimulated with KCl 80 mM the depressing effect was still evident: DILT 53 +/- 6%, VP-NTG 46 +/- 14% and MIBE 61 +/- 9% (p < 0.05). The effect of MIBE was more intense and persistent than that of DILT or VP-NTG, even at concentrations eliciting a similar initial depression of contraction. It is concluded that the exposure to vasodilators during a period equivalent to the duration of the surgical preparation of the RA produces an attenuation of the arterial reactivity that might provide an additional protection against RA spasm during the immediate postoperative period.
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PMID:[Vasodilators in isolated human radial arteries]. 1118 44

The objective of this study was to assess the safety and efficacy of long-acting preparations of two commonly used calcium antagonists with particular reference to their effects on heart rate. Twenty patients with chronic stable angina were recruited to a double-blind, double-dummy crossover study of controlled-release diltiazem (diltiazem CR) versus sustained-release nifedipine (nifedipine SR) and underwent clinical assessment, symptom and adverse event reporting, and repeated treadmill exercise tests over a 10- to 11-week period. The main outcome measures were heart rate at rest and exercise, incidence of angina and nitroglycerin use, treadmill exercise performance (duration, time to angina, time to 1-mm ST-segment depression, heart rate at equivalent maximal exercise, and maximal ST-segment depression), and adverse events. Diltiazem CR significantly reduced heart rate at rest and equivalent exercise and incidence of angina and nitroglycerin use compared with nifedipine SR. Exercise duration time to angina and time to 1-mm ST-segment depression (but not maximal ST-segment depression) were all significantly improved by diltiazem CR. Diltiazem CR also caused significantly fewer adverse events than nifedipine SR. Calcium antagonists with negative chronotropic effects (eg, diltiazem CR) are safer and more efficacious as monotherapy in chronic stable angina than dihydropyridines (eg, nifedipine SR) even when a long-acting formulation of the latter is used.
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PMID:Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect. 1131 69

A randomized, double-blind, parallel-group study comparing the efficacy and tolerability of once-daily diltiazem capsules with amlodipine tablets in patients with stable angina. After a run-in period of 1 to 3 weeks, 34 patients received once-daily diltiazem and 33 patients received amlodipine. Patients received either diltiazem, 240 mg/day, or amlodipine, 5 mg/day, for 2 weeks followed by diltiazem, 360 mg/day, or amlodipine, 10 mg/day, for 2 weeks. Standard treadmill exercise testing was the primary efficacy assessment. Patients also recorded incidence of angina attacks and use of glyceryl trinitrate spray. Both treatments gave significant improvement in time to onset of angina and time to maximal exercise. With the exception of amlodipine, 5 mg/day, both treatments gave significant increases in time to 1-mm ST segment depression. Diltiazem, 360 mg/day, gave a significant decrease in rate pressure product. There were no significant treatment differences in any of the exercise test parameters. Both treatments reduced incidence of angina attacks and use of glyceryl trinitrate spray. The incidence of edema was significantly less in patients receiving diltiazem. In conclusion, both treatments were effective in controlling patients' angina, but diltiazem was better tolerated, with a lower incidence of edema.
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PMID:A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina. 1148 40

A simple and novel method for the extraction and quantification of diltiazem hydrochloride was developed and applied to homogenization and stability studies. The method used solid phase extraction coupled with reversed-phase high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Validation showed inter-day recoveries ranging from 84.00 to 96.52% with relative standard deviations ranging from 12.01 to 15.94%. Intra-day recoveries ranged from 67.95 to 106.1% with relative standard deviations less than 5%. The method showed excellent linearity from 50 to 250 mg/ml in undiluted gel (R2 = 0.996). The homogenization study showed good homogenization using both 50 and 100 depression techniques. Diltiazem was stable at a concentration of 246 mg/ml for 30 days and at a concentration of 99.6 mg/ml for 60 days no matter the storage conditions explored in this study.
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PMID:Analysis of diltiazem in Lipoderm transdermal gel using reversed-phase high-performance liquid chromatography applied to homogenization and stability studies. 1590 20

Quinidine is effective for treatment of atrial fibrillation (AF) in horses, but often accelerates ventricular response rate. Diltiazem effectively controls heart rate response to AF in other species. This investigation determined the effects of diltiazem on cardiac rate and rhythm, left ventricular (LV) function, central hemodynamics, and peripheral blood flow in normal, standing, nonsedated horses. A dose-finding study was performed. Afterward, 8 healthy horses were treated with diltiazem IV every 30 minutes to achieve cumulative dosages of 0 (saline control), 1, 1.5, and 2 mg/kg. Plasma diltiazem concentration, heart rate and rhythm (by electrocardiography), LV function and central hemodynamics (by cardiac catheterization), LV dimensions (by echocardiography), and forelimb blood flow (by Doppler sonography) were determined during each treatment period. Diltiazem plasma concentrations between 390 and 910 ng/mL were achieved, with considerable variation among horses. Cardiac effects of diltiazem included intermittent depression of the sinus and atrioventricular (AV) nodes and mild impairment of systolic and diastolic LV function. Vascular effects of diltiazem included arterial vasodilatation, increased limb blood flow, and decreased systemic vascular resistance. Baroreceptor reflex-mediated sympathetic activation increased sinus node rate and presumably blunted the depressive effects of diltiazem on myocardial and nodal tissues. Two horses developed transient high-grade sinus arrest with severe systemic hypotension. Diltiazem appears relatively safe in healthy horses, but dosage may be limited by hypotension from vasodilatation and direct suppression of sinus node discharge. Because of its inhibitory effects on AV nodal conduction, diltiazem may prove useful for heart rate control in horses with AF.
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PMID:Effects of diltiazem on hemodynamic variables and ventricular function in healthy horses. 1623 15


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