Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 results of a randomized double-blind study with two comparable treatment groups are reported. In the course of treatment the frequency of angina pectoris during exercise as measured by a 4-point rating scale of symptom intensity decreased significantly for both groups. In comparison to the base line data the mean total workload increased significantly in both treatment groups (Molsidomin from 379 to 526 watt min; ISDN from 382 to 524 watt min-1). The product of systolic blood pressure and heart rate (BP X HR) under maximal workload increased significantly in both groups (Molsidomin from 17.5 to 20.9 mmHg min-1 1000(-1); ISDN from 17.7 to 20.2 mmHg min-1 1000(-1). The decrease in the ischaemic ST-segment depression on the level of maximal workload of the base line test was significant for both groups for all measures (Molsidomin from 0.27 to 0.08 mV; ISDN from 0.28 to 0.07 mV). The decrease of the ST-segment depression on the individual maximal workload level was significant for all measures in the Molsidomin group, but only on the first day of treatment in the ISDN group.
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PMID:Comparative study of long-term effects of Molsidomin 8 mg (slow release form) and ISDN 40 mg (slow release form) on angina pectoris and ischaemic ST-segment depression during maximal bicycle-ergometry in patients with coronary insufficiency. 344 28

Although nitrates are among the oldest drugs in cardiology the problem of tolerance is a scientific challenge of today. We examined and compared the effects of initial and chronic therapy (4 weeks) with 1 X 1 ISDN 120 mg sustained release in 9 patients with coronary heart disease and impaired left ventricular function. At intraindividually identical workloads (average 50 +/- 12 watt) there was a reduction of PCWPm from 32.5 +/- 9.5 to 19.7 +/- 9.8 mm Hg. This reduction of PCWPm during bicycle ergometry was fully achieved in long-term therapy. With the first dose of ISDN cardiac index (CI) at maximum workload increased from 6.0 +/- 1.2 to 6.8 +/- 1.3 l/min/m2; during chronic therapy cardiac index improved from 5.3 +/- 1.3 to 6.6 +/- 1.1 l/min/m2. Exercise capacity during bicycle ergometry in the sitting position increased concomitantly from 414 to 686 watt X min. In long-term therapy there was a further significant improvement to 772 watt X min. ST-segment depression, measured as sum of ST-depression in all 12 standard ECG leads decreased from 0.63 mV before medication to 0.11 mV after the first dose and to 0.16 mV in long-term therapy. The investigation of ventricular function during ventriculography and the investigation of coronary vasomotion during coronary angiography after ergonovine maleate i.v. and ISDN s.l. also demonstrated the full nitrate effect in long-term therapy.
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PMID:[Hemodynamics and coronary dynamics under ISDN long-term therapy]. 379 97

Thirty-two hospitalized patients with angiographically-documented coronary artery disease and stable angina pectoris (NYHA class III) were randomly assigned to one of four treatment groups. After a one-week washout period, baseline examinations (systolic time intervals, blood pressure and exercise ECG) were performed. The patients were then treated with either 20 mg isosorbide dinitrate in sustained-release form (sustained-release ISDN), 20 mg isosorbide 5-mononitrate (IS 5-MN), 2.5 mg buccal nitroglycerin in sustained-release form (NTGB) or 6.5 mg oral nitroglycerin in sustained-release form (NTGO) and one hour thereafter, the heart rate, blood pressure and systolic time intervals were determined. Subsequently, the patients were treated with the respective nitrates four times daily for two weeks. On the seventh and 14th days, the heart rate, blood pressure and systolic time intervals were again determined before and after the first dose of the day. Additionally, after the first dose on the 14th day, an exercise ECG was performed. The effect of the nitrates on the venous capacitance system is reflected by the increase in the PEP/LVET ratio where NTGO and NTGB elicited marked actions and those of sustained-release ISDN and IS 5-MN were of a lesser extent. An effect on systolic and diastolic blood pressure at rest and during exercise could be documented only after administration of NTGB. The anti-ischemic effect of the nitrates was based on the reduction of ST-segment depression during exercise; after two weeks of treatment, sustained-release ISDN and IS 5-MN were associated with complete tolerance development while NTGO continued to exert a slight, and NTGB a clear reduction in ST-segment depression. Personal protocols documented that nitrate consumption and rate of anginal attacks during longterm treatment were unaffected by sustained-release ISDN, IS 5-MN and NTGO, but were reduced by 50% while on treatment with NTGB.
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PMID:[4 different nitrate preparations with regard to the possible development of tolerance in long-term treatment]. 392 14

A new compound, Isosorbide-5-mononitrate (IS-5-MN; 40 mg orally), was compared with sustained-release Isosorbide dinitrate (SRDI; 40 mg orally) in 18 patients with chronic exercise-induced angina pectoris. The patients were studied in a randomized placebo-controlled single-blind trial. Multistage bicycle test with computer-assisted electrocardiographic analysis was performed before, 60-90, 240 and 360 minutes after treatment administration. Both drugs significantly and comparably prolonged exercise time (p less than 0.01) and time to development of 1 mm ST-segment depression (p less than 0.01) at the 3 times of study. At the highest common level of work, ST-segment depression and its integral were significantly reduced by both IS-5-MN and SRDI compared to placebo (p less than 0.01); conversely, the peak ST-segment depression was unaffected. Compared to placebo, a significant increment in maximal heart rate/systolic blood pressure was observed after drug administration. It is concluded that 40 mg of orally administered IS-5-MN is effective during at least 6 hours and that its therapeutic action is comparable to that of SRDI.
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PMID:[Efficacy and duration of action of isosorbide-5-mononitrate in the treatment of stable angina of effort. Comparison with sustained-release isosorbide dinitrate]. 401 70

To explore beneficial and harmful effects of various combinations of antianginal drugs, we compared antianginal and cardiorespiratory effects of nifedipine and isosorbide dinitrate in low and high doses in combination with nadolol, a long acting beta-adrenoceptor blocker in a double-blind study in 19 patients with stable angina pectoris. Nadolol alone and in combination with the other two drugs reduced anginal attack rate and glyceryl trinitrate consumption; the high dose isosorbide dinitrate showed a further significant (P less than 0.05) reduction in both but the high dose nifedipine did not show such a trend. sigma ST depression (all leads) was significantly (P less than 0.05) more reduced by the high dose nifedipine than by the same dose of isosorbide dinitrate in combination with nadolol. Nadolol reduced forced expiratory volume in one sec (FEV1) slightly and this effect was reversed both by isosorbide and nifedipine. Isosorbide dinitrate in combination with nadolol reduced the basal and post-exercise arterial oxygen saturation (SaO2) whereas nifedipine did not reduce the mean SaO2 below the pre-trial level. A significantly greater sigma ST depression was associated with a lower post-exercise SaO2 (less than or equal to 92%) during all treatment periods but the fall of SaO2 occurred more often during isosorbide than during nifedipine treatment periods. These studies show that both isosorbide dinitrate and nifedipine enhance antianginal efficacy of nadolol. Isosorbide dinitrate, unlike nifedipine, reduces SaO2 which is associated with a greater sigma ST depression.
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PMID:A comparison of nifedipine and isosorbide dinitrate in angina pectoris with particular reference to arterial oxygen saturation. 613 59

Isosorbide dinitrate (ISDN) and its two mononitrate metabolites were studied for their effects on the force-frequency relationship of isolated rabbit left atrial preparations. ISDN (4.9 and 15 microgram/ml) (50-150 times maximum therapeutic plasma concentrations) produced no significant effect on the frequency-dependent changes in contractile force. A concentration of 90 micrograms/ml (approximately 900 times therapeutic concentrations) produced a depression of contractility normally observed at frequencies of 80-400 beats/min. The two mononitrate metabolites of ISDN (endo- and exo-nitratoisosorbide) (90 micrograms/ml and 450 micrograms/ml) failed to alter the normal-force-frequency relationship over the range of 10-400 beats/min. These concentrations are several thousand times greater than plasma levels achieved in man with therapeutic dosing of ISDN. The basic lack of effect of ISDN and its metabolites on this fundamental property of myocardial contractility under the test conditions suggests that their therapeutic action is not mediated through direct effects on myocardial excitation-contraction coupling mechanisms.
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PMID:Effect of isosorbide dinitrate and its metabolites on rabbit atrial myocardial force-frequency relationships in vitro. 619 Apr 55

A number of carefully controlled studies in recent years have unequivocally documented evidence of tolerance development with respect to anti-ischemic effects during longterm treatment with nitrates [1, 3, 4, 5, 7, 8]. To determine to what extent tolerance development can be circumvented through an interval regimen, a study was performed in ten patients with stable angina pectoris and reproducible ST-segment depression according to a randomized, double-blind, cross-over, placebo-controlled protocol. Analysis of the anti-ischemic effect of 20 mg ISDN was carried out after acute administration and during chronic treatment on an interval regimen with the administration of 20 mg ISDN in the morning (at 8 a.m.) and at midday (1 p.m.) (Figure 1). On acute administration, 20 mg ISDN led to a reduction in ST-segment depression from 2.15 to 0.40 mm (p less than 0.01) and during longterm treatment from 2.25 to 0.40 mm (p less than 0.01) (Figure 2, Table 1). After acute administration the plasma concentration of ISDN was 9 ng/ml, 2-ISMN 34 ng/ml and 5-ISMN 149 ng/ml (Figure 5, Table 2). Of the control values during longterm treatment, a detectable level was found only for 5-ISMN with a concentration of 36 ng/ml while that of both 2-ISMN and ISDN was 0 ng/ml. On renewed administration, there was an increase of ISDN to 9 ng/ml, 2-ISMN to 37 ng/ml and 5-ISMN to 208 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Prevention of the development of tolerance to isosorbide dinitrate in interval therapy]. 637 43

The antianginal action of a fixed combination of pindolol (7.5 mg) and isosorbide dinitrate (ISDN, 30 mg slow release) was compared with placebo in sixteen patients with stable, exercise-induced angina pectoris. Exercise tests were performed on a bicycle ergometer before and 90 min after the oral application of active drug or placebo. All patients showed an ischemia-induced ST-depression in the ECG during and shortly after exercise. There was no effect of placebo on blood pressure, heart rate, ST-segment depression or work tolerance. The combination of pindolol and ISDN significantly reduced systolic blood pressure and heart rate at rest and during exercise. ST-segment depression was reduced (2 p less than or equal to 0.001), when compared with placebo at the same workload. Mean total work was higher (2 p less than or equal to 0.001) after active drug, leading to an improved exercise-tolerance in 11 out of 16 patients.
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PMID:Effect of a combination of pindolol and isosorbide dinitrate on ischemic ST-segment depression and exercise ability in angina pectoris. 638 4

Based on studies carried out according to randomized, double-blind, crossover, placebo-controlled protocols, analysis was performed to assess the antiischemic effects of (a) 40 mg ISDN, both after acute administration and during long-term treatment with four doses daily, (b) treatment with 20 mg ISDN twice daily (at 8 a.m. and 1 p.m.), and (c) 0.8 mg sublingually administered NTG during treatment with 40 mg ISDN four times daily. After acute administration of 40 mg ISDN there was a reduction in ST-segment depression from 2.05 to 0.18 mm (p less than 0.01). During chronic treatment, statistically-significant changes were no longer detectable. Sublingual administration of 0.8 mg NTG led to a reduction of ST-segment depression during the acute phase of ISDN from 1.20 to 0.15 mm (-87%; p less than 0.01) and during chronic treatment from 1.90 to 0.90 mm (-53%; p less than 0.01). Accordingly, as compared with changes induced in the acute and placebo phases, the effectiveness of NTG during chronic ISDN treatment was diminished. After acute administration of 20 mg ISDN, ST-segment depression was reduced from 2.15 to 0.40 mm (p less than 0.01) and to a comparable degree during long-term twice-daily treatment, from 2.25 to 0.40 mm (p less than 0.01). There was a significant reduction in the rate of anginal attacks and nitrate consumption. Thus, with respect to the anti-ischemic effectiveness of ISDN, tolerance development is incurred during repeated administration. Concomitantly, the effectiveness of NTG is not essentially negated, but rather diminished.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tolerance development during isosorbide dinitrate treatment: can it be circumvented? 642 Oct 9

Nitrates are effective in the management of exertional angina pectoris primarily due to their peripheral effects i.e. venodilation and arterial dilation, and thereby reduction in myocardial oxygen demand. These drugs also improve collateral blood flow in ischemic areas and in some patients may increase coronary blood flow by modifying tonus in the conductive or conduit coronary vessels. Sublingual nitroglycerin is the most effective antianginal agent but its prophylactic use is limited by its short duration of action. Until recently, the efficacy of long-acting oral nitrates was seriously questioned. However, recent data suggests that when given acutely in adequate doses, oral nitrates, transcutaneous and buccal preparations of nitroglycerin all exert prolonged hemodynamic and antianginal effects. Development of tolerance to the circulatory and antianginal effects during chronic therapy, however, remains a concern. Published literature suggests that tolerance to the circulatory effects and to headaches develops rapidly during sustained therapy with long-acting nitrates. However, reports regarding the development of tolerance to the antianginal effects and reduction of ST segment depression remain conflicting. Partial tolerance to the antianginal effects has been well-documented during chronic therapy with isosorbide dinitrate. Duration of improvement in exercise tolerance during four times daily therapy with isosorbide dinitrate has been shown to be shortened compared to prolonged effects following acute therapy. Recent data suggests that given in high doses, beneficial effects of ST segment depression during exercise may also diminish during chronic therapy with long acting nitrates. Tolerance to antianginal and circulatory effects can be reversed by withholding long-acting nitrates for 24 to 36 hours. Furthermore, initial studies suggest that tolerance to antianginal effects during sustained therapy can be avoided by giving smaller but effective doses of ISDN (20 to 40 mg) twice a day rather than prescribing larger doses more frequently.
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PMID:Nitrates for angina pectoris. A critical review of therapeutic efficacy and tolerance. 643 Jul 66


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