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)

ISDN (standard release formulation) 40 mg administered 6 times daily (= 240 mg) remained effective during a 4-week treatment of patients with stable angina in terms of decreasing anginal attacks and reducing ischemic ST segment depression at stress testing in the upright position (step climbing test). The sustained antianginal activity is explained by fluctuating plasma levels, provided by rapid drug release from the standard formulation, short administration intervals and an 7-hour-night pause. When comparing acute and chronic antianginal activity of ISDN (40 mg) administered 4 times daily with regard to the type of stress testing it became evident that a marked attenuation of antiischemic activity (-35%; p less than 0.01) occurred in the supine (bicycle ergometry) but not in the upright (step climbing test) position. The most probable explanation for the significant attenuation of efficacy in the supine position is marked blood redistribution into central compartments with increase of cardiac filling pressures during chronic therapy. Rapid development of tolerance both to the hemodynamic and antiischemic effects of glycerol trinitrate within 24 hours could be shown during intravenous administration (3 mg/h) in patients with stable angina. It is concluded that the antiischemic effects of oral ISDN (standard release formulation) administered 4-6 times daily is preserved during long-term therapy due to fluctuating plasma levels. Nitrate therapy providing constant doses over time (e.g. I.V. nitroglycerin) leads to a rapid attenuation of efficacy most probably due to counter regulatory mechanisms.
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PMID:[Long-term effect of organic nitrates in angina pectoris: dependence on the form of administration and mode of stress]. 253 10

In the treatment of myocardial ischemia in hypertensive patients, nitrates as the basic compound have to be combined with another substance in order to achieve a maximum effect and a 24-h-protection. As these patients often show an impaired left ventricular function because of arterial hypertension or previous myocardial infarction, a further deterioration of the left ventricular ejection fraction (EF) has to be avoided. We therefore investigated in a pilot study. EF, blood pressure, and ST-segment depression under isosorbide dinitrate 120 mg s.r. alone, and in combination with verapamil 120 mg s.r. in 14 male patients with angiographically proven coronary artery disease and arterial hypertension. EF at rest ranged from 29% to 76%. Radionuclide ventriculography was performed at rest and simultaneously with the ECG during exercise before medication, 2 h after ISDN and 4 h after the additional intake of verapamil. The systolic blood pressure at rest fell from 159 +/- 14 to 132 +/- 10 (p less than 0.001) after 2 h and to 132 +/- 16 mmHg after 6 h (p less than 0.01). During exercise there was a decrease from 196 +/- 21 to 174 +/- 21 (p less than 0.01) and to 178 +/- 22 mmHg (p less than 0.001), respectively. The ST-segment depression was reduced from 2.2 +/- 1.1 to 0.8 +/- 0.6 (p less than 0.01) and to 0.9 +/- 0.5 mm (p less than 0.001). EF at rest improved from 53 +/- 14% to 57 +/- 14% after ISDN alone and to 58 +/- 15% after ISDN + verapamil (p less than 0.01), and during exercise from 57 +/- 20% to 62 +/- 19% (p less than 0.05) and to 61 +/- 17% (n.s.). Even in the subgroup of patients with impaired LV-EF (8 at rest and 7 pts during exercise) there was a significant improvement (p less than 0.05) as well after ISDN alone, as there was with combination therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Combination therapy with isosorbide dinitrate and verapamil in patients with coronary heart disease and hypertension: effect on blood pressure, ischemia and left ventricular function]. 258 61

In a group of 17 men and women aged 38-65 years (means = 51.1) three months after the first myocardial infarction we studied changes in silent ischemic ST segment depression by using Holter monitoring and exercise stress testing before and after 120 mg/daily of oral isosorbide dinitrate (Isoket). Repeated ECG monitoring and exercise stress test were performed after two weeks. It was found that before isosorbide dinitrate therapy 16 out of 17 patients had 56 episodes of ST segment depression of 1-5 mm including 6 (37.5%) symptomatic episodes and 10 (62.5%) asymptomatic episodes. The number of asymptomatic episodes after isosorbide dinitrate therapy decreased more than five times (p less than 0.001), their duration was three times shorter (p less than 0.01). ST segment depressions were also significantly smaller. During isosorbide dinitrate therapy the duration of stress test was almost doubled and the achievable heart rate increased (p less than 0.02; p less than 0.05). The magnitude of ST segment depression during exercise testing also decreased significantly (p less than 0.01) and at heart rate below 100 beats/min ischemic ST segment depression were not observed, in contrast to pre-treatment period. Thus it may be concluded that silent myocardial ischemia is a frequent event in patients after the first myocardial infarction and isosorbide dinitrate significantly decreases the number of symptomatic and asymptomatic episodes detected by Holter monitoring.
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PMID:[Isosorbide dinitrate treatment of silent myocardial ischemia in patients after myocardial infarction]. 267 15

In this randomised, double-blind placebo-controlled crossover study we investigated the efficacy of 120 mg isosorbide dinitrate s.r. 12 h after application in comparison to 2 and 6 h in 18 patients with angiographically proven coronary artery disease, stable exercise-induced angina and reproducible ST-segment depression. Bicycle ergometry was performed before, 2, 6 and 12 h after medication and nitrate plasma levels were drawn before each exercise test. After 2 h, the exercise-induced ST-segment depression in comparison to placebo was reduced from 2.3 mm +/- 0.8 to 0.7 +/- 0.5, after 6 h to 1.0 mm +/- 0.8) and after 12 h to 1.9 mm +/- 0.8 (p less than 0.01). 82% of the patients suffering from angina on the control exercise test before medication were free of symptoms 2 and 6 h after ISDN 120 mg s. r., but showed angina again after 12 h. In comparison to the plasma levels 2 h after ingestion, the concentrations in plasma after 12 h were much lower for ISDN, equal for IS-2-MN, and more than double for IS-5-MN. Thus, 12 h after ingestion of 120 mg ISDN s.r. there is still a significant reduction of ST-segment depression. This 12-h benefit is 40% od the maximum effect.
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PMID:[Extent of therapeutic effect and duration of 1 capsule of 120 mg isosorbide dinitrate in a slow release form]. 267 52

In 11 patients (2 female, 9 male) suffering from angiographically proven CHD (age 45-60 years; 54.3 years on an average) the efficacy of a once-daily oral medication with 120 mg ISDN/50 mg ISMN and diltiazem (D) each in a long-acting preparation was examined in a placebo-controlled study. Each period lasted for 3 days; 2 capsules were given at 0700 a.m. one capsule at 5 p.m. Long-term ECG-recordings for 24 hrs (Tracker recorder, Pathfinder III) were performed twice under placebo and once during the third day of ISDN or ISMN, ISDN/ISMN + D in the morning and JSDN or ISMN in the morning and D in the afternoon. The rate of ischemic events declined from 10.4 to 4.7, 3.3 and 2.2; the duration of ischemia in 24 hours declined from 128 min to 43 min, 44 min and 34 min. The product of ST-depression (mV) and time of duration (min) showed an equivalent course. A more than 80% reduction of ischemia (duration and frequency) was achieved by a combination therapy in 72% of the patients. Minimal increase of heart rate at the beginning of ST-depression increased significantly during all periods of therapy, maximal increase of heart rate at that time showed a decrease only during combination therapy with D, the mean value did not change significantly. The once-daily application of ISDN/ISMN (50 mg) in a long-acting preparation (120 mg) led to a significant reduction of silent myocardial ischemia. The efficacy of ISDN/ISMN can be improved by D (120 mg, long acting preparation) up to a greater than 80% reduction in frequency and duration of ischemic events.
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PMID:[Combination therapy with slow release isosorbide nitrate and diltiazem in silent myocardial ischemia]. 268 57

The effects of isosorbide dinitrate single dose 120 mg daily and nifedipine 20 mg twice daily were studied in 17 patients with variant angina pectoris due to coronary artery spasm. After a placebo phase the patients were randomized to treatment with either isosorbide dinitrate or nifedipine. After six weeks the patients were crossovered for another six weeks period of treatment. There was significant decrease of number of angina attacks during both treatment regimens. Using 24 hours Holter monitoring we also proved significant decrease of number of ST segment elevation or depression, either symptomatic or asymptomatic. There was increase of performed work during exercise tests after both treatment periods. The efficacy of Isoket 120 mg and Adalat Retard 2 x 20 mg daily in the treatment of patients with active variant angina pectoris was comparable in our study. 3 patients suffered untolerable headache during isosorbide dinitrate phase and had to terminate treatment after first day only.
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PMID:[Comparison of isosorbide dinitrate and nifedipine in the treatment of variant angina pectoris. Randomized study]. 280 34

The study aimed at evaluating an effect of a single dose of isosorbide dinitrate (Sorbonit) on the exercise reaction in the patients with coronary disease of various degree and in healthy individuals. The study involved 20 male patients of mean age 54.0 +/- 4.5 years with history of myocardial infarction and 12 healthy males of mean age 45.6 +/- 5.0 years. Ergometric test has been performed twice: prior to and 15 minutes after sublingual administration of isosorbide dinitrate in the dose of 10-15 mg. The first test has been interrupted when horizontal ST load exceeded 1 mm or contractions rate was 60% of the maximum value. Similar loads have been used after the administration of Sorbonit. The following parameters have been evaluated: heart rate (HR), systolic blood pressure (BPS), HR x BPS, lactate level (LA), and cardiac index. The value of the load has been measured with the aid of oxygen consumption (VO2). Significant depression of ST segment (less than 3 mm) in the exercise ECG has been noted in 8 patients following isosorbide dinitrate. Exercise tolerance has increased in these patients - CI increased during exercise following drug administration (VO2 the same as prior to the drug administration), and VO2/CI has became closer - physiological.
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PMID:[Effect of isosorbide dinitrate (sorbonit) on the exercise reaction in patients with coronary disease and in healthy individuals]. 281 70

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.
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PMID:Comparison of transdermal nitrate and isosorbide dinitrate in chronic stable angina. 309 Oct 55

Fourteen male patients with exertion-related angina pectoris and reproducible ST-segment depression on stress testing were each treated with isosorbide dinitrate (ISDN) 40 mg three times daily, verapamil 120 mg three times daily and placebo three times daily for two weeks according to a double-blind cross-over protocol. The mean improvement of exercise-induced ST-segment depression amounted to 73% on the first day of ISDN treatment (P less than 0.001) and to 54% following acute administration of verapamil (P less than 0.001). On the last day of continuous treatment, the antianginal efficacy of ISDN was somewhat mitigated (reduction of ST-segment depression: 54%; P less than 0.001), while the effect of verapamil remained unchanged (55%, P less than 0.001). The double product (heart rate x systolic blood pressure) at the end of stress testing decreased most pronouncedly on day 1 of ISDN treatment (-21%; P less than 0.01). On chronic testing, both drugs similarly influenced this parameter: 10-11% (P less than 0.05). The mean global ejection fraction (EF) assessed by gated blood pool scintigraphy on day 13 showed a stress-induced fall from 49 to 44% (P less than 0.05) after the administration of placebo. The respective values with ISDN were 53% at rest and 52% on exercise (n.s.), and after giving verapamil 50% and 47% (n.s.). Thus, ISDN 40 mg and verapamil 120 mg displayed beneficial anti-ischaemic effects in patients with stable exertion-related angina pectoris after acute and chronic administration. The efficacy of ISDN declined somewhat in the course of the two-week treatment, whereas that of verapamil remained unchanged. Beneficial effects of both drugs were also demonstrated with regard to the rate-pressure product. Isosorbide dinitrate 40 mg and verapamil 120 mg administered three times daily can be recommended for the acute and chronic therapy of patients with stable angina.
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PMID:Comparison of the antianginal efficacy of isosorbide dinitrate (ISDN) 40 mg and verapamil 120 mg three times daily in the acute trial and following two-week treatment. 328 Mar 17

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.
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PMID:The insufficient nitrate response: patients' characterization and response to beta and calcium blockade. 340 9


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