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)

A single-blind study (n = 59) was performed to assess the effect of long-term (4 week) orally administered molsidomine (2 mg 4 X daily), isosorbide dinitrate (10 mg 4 X daily), and placebo on exercise tolerance performed on the bicycle ergometer by patients with stable angina on effort and with significant coronary artery disease. Isosorbide dinitrate had similar effects to placebo, both failed to modify the pressure-rate product, the sustained work load, and the ST segment depression, but slightly decreased, although not significantly, the incidence of angina. Although not affecting the pressure-rate product and the mean blood pressure, molsidomine decreased significantly the ST segment depression (p less than .05). In conclusion, by markedly reducing preload and because of its long-lasting effect (up to 6 h), the new vasodilator drug molsidomine plays a useful role in the long-term management of stable angina on effort.
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PMID:Effects of long-term molsidomine treatment versus isosorbide dinitrate and placebo on exercise tolerance in stable angina. 643 Aug 11

Nine men with angiographically proven coronary sclerosis and a reproducible ischemic response on the exercise ECG were treated for 9 weeks with a dose of 180-240 mg isosorbide dinitrate slow release (ISDN sr) daily. In the week before the beginning of the treatment (week 1) and in the week after its conclusion (week 10), exercise tests were carried out before and 1 and 3 h after administration of 60 mg ISDN sr or placebo. This part of the investigation was double-blind, cross-over and randomized. In an open study carried out during the 2nd-9th weeks, exercise tests were carried out weekly before and 1 and 3 h after the usual morning dose of 60 mg ISDN sr. The interval between the morning exercise and the last evening dose was 8-10 h. Exercise duration and required level of exertion remained constant during the entire study. The sum of ischemic ST-segment depression during and after exercise, heart rate (ECG) and blood pressure (RR) were all measured. Both before and after the period of treatment 60 mg ISDN sr produced a significant reduction in ST-segment depression after 1 and 3 h. During the treatment phase no significant improvement in comparison to controls could be observed from the 7th week onward. However, even in controls the ST-segment depression was less in the 8th and 9th weeks than during the first few weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic treatment and tolerance with high doses of isosorbide dinitrate in a slow release form in patients with angina pectoris. 666 22

The purpose of this study was to investigate whether the anti-ischemic effects of a single 80-mg tablet of isosorbide dinitrate in sustained-release form are attenuated after 2 weeks of twice-daily administration. In order to follow a double-blind protocol with respect to the 12-h interval, we also evaluated, in randomized order, another group of patients receiving the tablets once daily. Parameters for assessment of the anti-ischemic effects were changes in exercise-induced ST-segment depression and the simultaneously recorded left ventricular ejection fraction, as determined by radionuclide ventriculography. The ST-segment depression was measured completely blind; the left ventricular ejection fraction was calculated automatically with a clinically validated software. In the group that received the tablets once daily (n = 10) none of the patients showed any signs of attenuation of the beneficial anti-ischemic effects. However, seven of the 12 patients who received the tablets twice daily demonstrated significant attenuation. Thus, based on analysis of the presently available studies, in order to guarantee maintenance of the anti-ischemic benefits, a once-daily high dose of ISDN in sustained-release form (80 mg or even higher) is recommended.
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PMID:Anti-ischemic effects of an 80-mg tablet of isosorbide dinitrate in sustained-release form before and after 2 weeks treatment with 80 mg once daily or twice daily. 666 24

Hemodynamic measurements were carried out during exercise testing with floating catheterization in 12 male patients with multiple-vessel disease and stable angina pectoris after placebo, after acute treatment with 60 mg ISDN, and after 4 weeks treatment with 4 X 60 mg ISDN. The acute effects of ISDN at the maximal comparable workload were a 32% decrease in PAd, a 41% decrease in ST-segment depression, and a 35% increase in maximal workload. After 4 weeks therapy we found an attenuation of the efficacy of ISDN, with only a 12% decrease in PAd, a 33% decrease in ST-segment depression, and an 18% increase in maximal workload.
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PMID:Hemodynamic measurements and exercise testing to assess the development of tolerance against slow-release isosorbide dinitrate. 666 26

Forty patients suffering from angiographically proven coronary artery disease with stable angina pectoris were subjected to a randomized, double-blind, placebo-controlled study. The patients were divided into three groups who for 28 days running were given 20, 40, or 60 mg ISDN respectively, in sustained-release form, three times a day, and one group which received a placebo. A bicycle exercise test was performed prior to and 1, 3, 5, and 8 h following drug administration. The acute study was repeated at 14 and 28 days after drug administration. Following acute administration of 20, 40, or 60 mg ISDN SR a significant reduction in ST-segment depression was observed; between the ISDN-treated groups and the placebo group the difference was significant. After 4 weeks of treatment the mean reduction in ST-segment depression was unchanged. There was a significant improvement in the frequency of anginal attacks in all the ISDN-treated groups after 4 weeks of treatment, but not change in the placebo group. Thus, no attenuation of the anti-ischemic and antianginal effect could be recorded. During acute administration there was a significant dose-dependent reduction in blood pressure at rest in the ISDN-treated groups as compared with the placebo group. After 4 weeks of treatment a considerable attenuation of the blood pressure reduction was noted in all the ISDN-treated groups. Heart rate and pressure-rate product did not reflect any uniform trend.
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PMID:Antianginal efficacy of long-term nitrate therapy. 666 27

Ten patients with angiographically proven coronary heart disease, stable exercise-induced angina pectoris, and reproducible ST-segment depression were treated with ISDN tablets in daily doses of 240 mg (6 X 40 mg) and placebo for 28 days each on the basis of a randomized double-blind protocol with intraindividual crossover. On the 1st, 7th and 28th days of each treatment cycle an exercise stress test was performed 1 h after the second dose of the day. ISDN treatment resulted in a sustained reduction of anginal attacks, with a weekly rate ranging from 1.4 to 3.9 (mean values) as compared to 10.5 to 11.7 attacks during placebo treatment (2 p less than 0.001). Exercise-induced ST-segment depression during ISDN-therapy (constant work-load) was found to be significantly improved as compared to placebo: day 1, ISDN: 5.3 +/- 1.5 mm vs. placebo: 12.1 +/- 2.2 mm (2p less than 0.01); day 7, ISDN: 7.6 +/- 2.0 mm vs. placebo: 10.8 +/- 2.1 mm (2p less than 0.05); day 28, ISDN: 5.7 +/- 1.2 mm vs. placebo: 11.2 +/- 2.1 mm (2p less than 0.01). Heart rate in the upright position (tilting table) was significantly different between ISDN and placebo on day 7: ISDN 92 +/- 3 bpm vs. placebo 85 +/- 4 bpm (2p less than 0.001), but not on day . 28.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sustained antianginal efficacy of oral high-dose isosorbide dinitrate in patients with coronary heart disease. 666 31

The clinical manifestations of symptomatic coronary arterial spasm were analyzed in 30 patients whose coronary arteriograms demonstrated no fixed severe obstructions. The study group consisted of 14 men and 16 women (average age, 47 years). Angina at rest was invariable and it was usually typical in quality, location, duration and response to nitroglycerin. Exertional angina occurred in 23 percent and syncope with angina in 33 percent. Spontaneous remission of angina for at least 1 month occurred in 57 percent of patients. Prinzmetal's variant angina occurred in 77 percent of patients and only S-T segment depression or T wave changes during angina occurred in 23 percent. Major arrhythmias during ischemia developed in 47 percent. Exericse tests were positive in 24 percent. Myocardial infarction, probably due to coronary spasm, occurred in 7 percent of patients. Isosorbide dinitrate and propranolol were effective therapy in only 39 percent and 6 percent of patients, respectively. Nifedipine, a calcium flux antagonist, was effective in 80 percent of patients. Patients with normal coronary arteriograms who have clinical features suggestive of coronary arterial spasm should be considered for further investigation, including long-term electrocardiographic monitoring and provocative testing for spasm.
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PMID:Syndrome of symptomatic coronary arterial spasm with nearly normal coronary arteriograms. 698 57

In a double-blind study 40 patients with coronary heart disease, who all complained of typical exertion-dependent angina pectoris symptoms and showed ECG changes after work in conformity with a myocardiac hypoxia, were examined in ergometric exertion tests before as well as immediately and 60 minutes after a single dose of 3.75 mg of Isoket-spray or Placebo-spray respectively. The Isoket-spray group was compared with the placebo group, furthermore, within the Isoket-spray group, the original ergometry (without medication) and the subsequent ergometries. The ST-depression, the time until reattainment of the original electrocardiographical situation after cessation of exertion and the subjective complaints showed highly significant improvements after use of the Isoket-spray in both repeated ergometries. Rapid and long-term relief after application of Isoket-spray were thus impressively shown in this double-blind study.
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PMID:[Ergometric double-blind study, Isoket-spray versus placebo-spray, in patients with coronary heart disease (author's transl)]. 746 71

Exercise echocardiography and exercise electrocardiography were performed to test the anti-ischemic effects of isosorbide dinitrates (2 x 40 mg) und nisoldipine (2 x 10 mg) using a randomized, double-blind, placebo-controlled crossover trial. A total of 24 patients with symptomatic coronary artery disease and exercise-induced ST segment depression underwent 144 investigations (6 in each patient) at the first placebo treatment, 1st and 8th day during treatment with the first drug and the second placebo treatment 1st and 8th day during treatment with the second drug. A wall motion score (sum of 14 segments; wall motion grading: normal = 1, hypokinetic = 2, akinetic = 3, dyskinetic = 4) and ST depression at the exercise were used to assess the anti-ischemic effects. Both drugs reduced the number of exercise-induced wall motion abnormalities on the maximal comparable exercise level in comparison to placebo treatment. The wall motion score on the maximal comparable exercise level during placebo treatment was 25.5 +/- 6.9, during isosorbide dinitrate treatment (1 day) 23.5 +/- 7.2 and 23 +/- 6.7 (8th day; for both treatment days, p < or = 0.001 vs. placebo treatment), and during nisoldipine treatment (1st day) 23.6 +/- 5.9 and 23 +/- 6.8 (8th day; p < or = 0.001). ST segment depression changed at exercise during first placebo treatment to 0.153 +/- 0.068 mV, during ISDN treatment to 0.102 +/- 0.055 (1st day, p < 0.001) and to 0.117 +/- 0.056 (8th day, p < 0.001). ST segment depression during nisoldipine treatment was 0.121 +/- 0.075 mV on the 1st day (p < or = 0.002) and 0.120 +/- 0.071 mV on the 8th day (p < 0.001). Exercise echocardiography can be used to test anti-ischemic drug effects. There were no differences in the reduction of exercise-induced ischemia between the two drugs.
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PMID:[Stress echocardiography--a new test for evaluating the anti-ischemic effect of medication]. 757 69

In a double-blind, cross-over study the acute clinical efficacy and pharmacokinetic profile of a newly developed isosorbide dinitrate extended-release (ISDN-ER) formulation (10 mg immediate release and 60 mg slow release) were examined in eight angina patients. Exercise tests were done 1 h before and 1, 6 and 10 h after acute ISDN or placebo; similar testing was repeated after 14 days of open-labelled treatment. At 1, 6 and 10 h after administration, ISDN-ER significantly reduced the mean ST depression at highest comparable workload (HCWL) by 0.8, 0.6, and 0.6 mm, respectively. Total exercise duration increased significantly by 46, 42 and 72 s. The rate-pressure product at HCWL was not reduced significantly at any time, while digital plethysmography demonstrated a significant effect on arterial pulse curves throughout the 10 h. After 14 days of once-daily treatment, similar or somewhat attenuated clinical effects were observed. Pharmacokinetic measurements showed a first peak of ISDN at 1-2 h and a second peak at 4-5 h. The 5-isosorbide mononitrate (5-ISMN) metabolite peaked at 5-8 h and remained high at 10 h. After 14 days of treatment, the mean plasma concentrations of ISDN and 5-ISMN before drug were 0 and 69 ng.ml-1, respectively. Thus, satisfactory acute clinical efficacy and low nitrate levels during the night were observed. However, long-term clinical efficacy needs to be established in larger, placebo-controlled trials.
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PMID:A new isosorbide dinitrate extended-release formulation: pharmacokinetic and clinical parameters in patients with stable angina pectoris. 787 87


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