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

A double-blind crossover study, with placebo periods preceding each active treatment, was carried out in 29 patients with ischaemic heart disease to compare the clinical efficacy of isosorbide 5-mononitrate 40 mg twice daily and the same regimen of sustained-release isosorbide dinitrate. Assessment was by bicycle ergometry, symptomatology and blood nitrate level measurements. After 2-weeks' therapy with isosorbide 5-mononitrate, mean ST segment depression at the highest comparable exercise level for each patient was reduced by 32.5% (p less than 0.01), the mean maximum exercise level was increased from 87 to 102 Watts (17.8%, p less than 0.01), and mean work capacity was increased from 581 Watts-minutes to 783 Watts-minutes (34.6%, p less than 0.01). With sustained-release isosorbide dinitrate, ST segment depression was reduced by 16.5% (p less than 0.05); maximum exercise level showed only a small non-significant increase, from 89 to 97 Watts (8.6%), but work capacity increased (p less than 0.05) from 593 Watts-minutes to 705 Watts-minutes (18.9%). There was no significant difference between drugs as regards ST segment reduction but a slight difference in favour of isosorbide 5-mononitrate (p less than 0.05) in terms of maximal exercise level and work capacity. Both drugs resulted in very small reductions in blood pressure (p less than 0.001 for systolic with isosorbide 5-mononitrate; p less than 0.01 for systolic and p less than 0.05 for diastolic with sustained-release isosorbide dinitrate). Heart rate and rate-pressure product changed little with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparative clinical trial of isosorbide 5-mononitrate and sustained-release isosorbide dinitrate in ischaemic heart disease. 308 99

The effects of transdermal nitrate (TN) (Transiderm-Nitro TTS, Geigy Pharmaceuticals, one 10 cm2 patch daily) and oral isosorbide dinitrate (ISDN) (Sorbitrate, Stuart Pharmaceuticals, 10 mg three times daily) were compared in a group of 20 patients with chronic stable angina pectoris. Treadmill exercise duration was prolonged from a median time of 365 s to 428 s after ISDN (P less than 0.05), but was unchanged after TN. The difference between the active treatments was not significant. Weekly consumption of glyceryl trinitrate (GTN) increased during treatment with TN from a median value of 5.5 to 6.3 (P less than 0.05). A decrease was observed after ISDN (7.8 to 3.9, P = NS), and the difference between the drugs was significant (P less than 0.01). Systolic arterial pressure was significantly lower during the ISDN than during the TN treatment period in both the supine (135 +/- 5 vs 128 +/- 5 mm Hg; P less than 0.05) and standing positions (134 +/- 5 vs 122 +/- 5 mm Hg; P less than 0.05). No change in weekly attack rate, the degree of ST depression at angina on treadmill testing, or the number of episodes of ST depression recorded during a 24 h period by Holter monitoring was observed after either drug. In this study, an antianginal effect was demonstrated for ISDN but not for TN. It is suggested that the dose of TN may have been inadequate to demonstrate such an effect, and further studies using a higher dose schedule will be required.
 ...
PMID:Comparison of transdermal nitrate and isosorbide dinitrate in chronic stable angina. 309 Oct 55

Continuous application of transdermal nitroglycerin appears to result in tolerance to the antianginal effect. In a double-blind study the effects of continuous (24 h/day) and intermittent (16 h/day) application of transdermal nitroglycerin in a dosage of 10 mg/day were compared with the effects of placebo in 12 patients with chronic stable angina receiving treatment with beta-adrenergic blocking or calcium channel blocking agents. Exercise performance was assessed 2 to 4 hours after initial application and after 1 week of each treatment given in random order with a 3 day interval between treatments. Exercise time to onset of angina, total exercise duration and time to 1 mm ST segment depression were all significantly increased after initial application during the continuous and intermittent treatment periods. These increases were maintained after 1 week of intermittent but not continuous treatment. Thus the benefit of initial application of transdermal nitroglycerin is maintained with intermittent treatment and a daily nitrate-free interval, whereas tolerance to antianginal effect occurs with continuous treatment.
 ...
PMID:Transdermal nitroglycerin in angina pectoris: efficacy of intermittent application. 311 51

Two single-blind placebo-controlled studies were consecutively performed with nitroglycerin (NTG) (5 and 10 mg/24 hours) patches in 24 patients with stable angina pectoris. The relation of NTG patch efficacy with dosage and different subsets of patients during acute and chronic patch therapy was analyzed. NTG patch effects were assessed by multistage treadmill exercise test at 5, 16, 20 and 24 hours after patch application, during single patch administration and after 3 months of continuous therapy, with washout phases as well as with 1- and 7-day placebo patch periods. The analysis of differences between NTG and placebo patch demonstrated significant improvement of exercise capacity in the total group of 24 patients. A taxonomy analysis revealed 2 different subsets in the sample of 24 patients, having similar exercise ST depression but different exercise walking times in the washout period. Group I (15 patients), with an initial 68% of maximal predicted time, showed moderate increases in magnitude of exercise efficacy during the acute and chronic period, with low decrease of effects over 24 hours. Efficacy was greater during the chronic phase, with evident dose relation of all changes. Group II (9 patients), with 40% of maximal predicted time, demonstrated an increased efficacy during acute and chronic therapy, with a steep decrease of all values over 24 hours and significant improvement of exercise tolerance during chronic therapy; these changes were not mainly dose-related. These differences in the magnitude and in the pattern of exercise efficacy over 24 hours, during acute and chronic NTG patch therapy, could probably be attributed to different nitrate mechanisms of action, depending on the pathophysiologic characteristics of stable angina pectoris in 2 subsets of patients. The controversies about NTG patch efficacy have been discussed with regard to relation between multiple modes of nitrate action and the subsets of patients with different prevailing mechanisms of stable angina pectoris.
 ...
PMID:Relation of transdermal nitroglycerin efficacy with dosage in different subsets of patients. 312 37

The efficacy of a 2.5 mg sustained-release buccal nitroglycerin preparation given 8-hourly in effort-induced stable angina pectoris was investigated by means of graded exercise testing in 15 patients. An initial double-blind crossover study, compared with a placebo (duration six days) was followed by a further 15-day open treatment period on the active drug. Exercise testing was carried out 2 and 7 h after tablet administration at the conclusion of active treatment in the double-blind phase, and 2 h after tablet administration at the conclusion of the open treatment phase. Workload and exercise duration were significantly increased and mean electrocardiographic ST segment depression and ST segment recovery time significantly reduced by buccal nitroglycerin in the initial phase of the study, and these improvements were maintained over the subsequent 15-day assessment period. Systolic blood pressure at rest was significantly decreased by active treatment; other haemodynamic parameters remained unchanged. The study demonstrated the efficacy of sustained-release buccal nitroglycerin in effort-induced stable angina pectoris, and an absence of (+) tolerance to the therapeutic effects of this mode of nitrate administration.
 ...
PMID:Evaluation of a sustained-release buccal nitroglycerin preparation in stable angina pectoris. 313 28

The aim of this study was to investigate whether, and to which extent, sustained treatment with transdermal nitroglycerin plasters may lead to the development of tolerance in patients with effort-induced angina pectoris. Ten patients, all men, mean age 62.7 years, took part in a double-blind, cross-over, acute study, comparing the transdermal therapeutic system of nitroglycerin 10 mg/24 hours with placebo. Patients were then treated for 1 month with the active drug in single-blind condition, and finally they took part in a further acute study identical to the first. Cycloergometric exercise tests were carried out 4 hours after dosing. In comparison with placebo, the active drug significantly (P less than 0.01) increased ischaemic threshold (ST depression = 1 mm) after both acute (from 299 +- 92 to 413 +- 120 sec) and chronic treatment (416 +- 107 sec). The same results were obtained for exercise duration to peak exercise (acute study: from 336 +- 65 to 482 +- 90 sec; chronic treatment: 466 +- 118 sec). The final acute study confirmed the stability of angina, showing that the improvement in exercise tolerance after chronic treatment was entirely due to the pharmacological effect of the drug. In terms of single patient response to the active treatment, 7 of the 10 patients showed an improvement in exercise tolerance after both acute and chronic treatment, while in 3 patients no antianginal effect was observed. These results suggest that nitrate tolerance cannot be considered an inevitable finding in patients chronically treated with transdermal patches.
 ...
PMID:Individual responses to transdermal nitrates after chronic administration in angina pectoris. 314 53

The relation between the duration of ischemic ST-segment depression (1 mm or more 60 ms after the J point) and the clinical awareness of chest pain was studied in 31 patients (aged 39-73 years) undergoing symptom-limited, graded treadmill exercise testing. The response of these patients to nitrate therapy (spray or sublingual tablet) given immediately on cessation of exercise was also studied. During exercise, angina pectoris appeared at an estimated workload of 4.6 +/- 2.2 metabolic equivalents (METS) (mean +/- SD), and pathological ST-segment depression at 4.9 +/- 1.9 METS (p = NS.) On cessation of exercise, angina disappeared after 3.0 +/- 1.9 min, but ST-segment depression persisted for more than twice as long (6.6 +/- 4.1 min) (p less than 0.0001). The ratio of time to ST-segment recovery/time to relief of pain (a quantitative measure of silent ischemia during recovery) increased with age (r = 0.49, p = 0.002), and in 16 patients over 60 years of age was higher than in 15 younger patients (3.6 +/- 2.5 vs. 2.1 +/- 1.4) (p less than 0.04). The silent ischemia ratio after exercise tended to decrease, although not significantly so (p = 0.2), in patients who received oral nitrates; there was no difference in the response to spray or tablet in this regard. We conclude that ST-segment depression frequently persists after relief of exercise-induced angina pectoris and more so in elderly patients.
 ...
PMID:Persistent painless ST-segment depression after exercise testing and the effect of age. 329 58

We studied 14 patients, 9 males and 5 females, with an average age of 53.6 +/- 9.2 years, having been suffering from effort angina for over 6 months, with positive ergometer test for angina and ST-segment depression greater than 1 mm. All the patients performed a washout period of 7 days at the end of which, before and after acute administration (90 min) of isosorbide 5-mononitrate or placebo some echocardiographic parameters were controlled according to a double-blind, randomized, crossover design. Moreover, after 2 months of open treatment with isosorbide 5-mononitrate (20 mg three times daily), echocardiographic parameters were investigated again. Continuous ECG monitoring (24 h) was performed after the washout period and after 2 months of treatment. After acute administration of isosorbide 5-mononitrate, we observed a reduction in pre- and afterload, whereas after 2 months of treatment the reduction in preload seems to play a more important role. Together with other mechanisms these haemodynamic changes are responsible for the substantial diminution of myocardial oxygen consumption, and consequently for the reduction of transient ischaemic episodes, both symptomatic and asymptomatic with heart rate increase. These results suggest that isosorbide 5-mononitrate exhibits a definite nitrate-typical vascular activity that is evident both after single administration and after 2 months of treatment.
 ...
PMID:An evaluation of the effects of isosorbide 5-mononitrate in patients with angina on effort using dynamic electrocardiography and echocardiography. 330 Sep 74

One of the most promising concepts in nitrate therapy is interval therapy, a dosage scheme with marked changes of nitrate concentrations in the 24-h interval. In a single-blind, placebo-controlled study in patients with coronary heart disease we investigated the circadian anti-ischaemia and haemodynamic response to interval therapy with isosorbide dinitrate (120 mg sustained release 1 X 1). 10 male patients (46-75 years, mean 60 years) with chronic stable angina and ST-segment depression during exercise entered the trial. At the end of a 10-day placebo period (medication at 8 am) three exercise tests were performed (10 am, 2 pm, 6 pm), recording ST-segment changes, pulmonary capillary wedge pressure (PCP) and cardiac index (CI). Spontaneous ischaemic events were detected by Holter monitoring until 8 am the next day. After three weeks of therapy with isosorbide dinitrate, the protocol was repeated (statistics: paired t-test, *P less than 0.05). PCP was reduced by 8.3 mmHg* at 10 am, 8.0 mmHg at 2 pm, 2.9 mmHg (NS) at 6 pm with a concomitant increase of cardiac index (+0.8,* +0.7*, +0.3 NS l min-1 m-2). While the haemodynamic improvement was maximal in the morning the anti-ischaemia effect (reduction of ST-depression) was constant during the active day (-0.40*, -0.50*, -0.43* mm). Four transient ischaemia episdodes at night were recorded under placebo, none under isosorbide dinitrate. In conclusion, all parameters studied demonstrate the effectiveness of chronic interval therapy with isosorbide dinitrate.
 ...
PMID:Circadian investigation of interval therapy with isosorbide dinitrate in coronary heart disease. 340 8

Little information has been published regarding the nitrate-induced changes of left ventricular volumes at rest and during exercise in relation to the degree of the anti-ischaemic response. Therefore we assessed the electrocardiographically defined nitrate response to a single tablet of 80 mg isosorbide dinitrate s.r. and compared it to the changes in end-diastolic volumes at rest and during exercise, as determined by radionuclide ventriculography. Thirty-four of the 63 patients were classified as good nitrate responders, whereas 29 patients showed insufficient nitrate response with regard to the reduction of exercise-induced ST-segment depression. The baseline characteristics were quite comparable. At rest the ISDN-induced decrease of the end-diastolic count rate was significantly less (-17%) in patients with insufficient ST-segment response when compared to patients with good ST-segment response (-25%). During exercise, in patients with good ST-segment response, ISDN reduced the end-diastolic volume significantly (-19%), whereas in patients with insufficient ST-segment response the end-diastolic volume remained unchanged. In this special subset of patients with insufficient nitrate response we further evaluated the effects of additional beta or/and calcium blockade. The benefits from verapamil were equivalent to propranolol. However, a considerable part of the patients investigated needed the combination of verapamil and propranolol for an optimal anti-ischaemic drug treatment. Thus, our data support the concept that preload reduction plays a major role for the anti-ischaemic effects of ISDN in patients with exercise-dependent ischaemia. Since, a suboptimal therapeutic effect must be considered, objective control of the nitrate therapy (usually by exercise- and Holter-ECG) must be regarded as obligatory for each individual patient if optimal results are to be expected.
 ...
PMID:The insufficient nitrate response: patients' characterization and response to beta and calcium blockade. 340 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>