Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitrates are well established in the treatment of angina pectoris and the presence of sulfhydryl groups seems to be fundamental to nitrate-induced vasodilatation. The present study was performed to elucidate if large oral doses of N-acetylcysteine (NAC, 2,400 mg X 2), a donor of sulfhydryl groups, given together with a single oral dose of the long-acting nitrate, isosorbide-5-mononitrate (5-ISMN, 60 mg), would modify the nitrate effect evaluated by exercise testing before and after additional sublingual doses of nitroglycerin (NTG). Ten patients with angina pectoris and angiographically proven significant coronary artery disease were included. All patients received a baseline therapy with beta blockers. None of the patients had developed nitrate tolerance at inclusion. NAC/5-ISMN treatment significantly prolonged the total exercise time as compared with placebo/5-ISMN (7.7 +/- 2.1 min vs. 6.8 +/- 1.7 min, p less than 0.05). This increase was of such magnitude that no further effect was obtained after additional NTG doses. This study demonstrated that increased availability of sulfhydryl groups can increase the exercise capacity in angina pectoris patients treated with 5-ISMN without nitrate tolerance.
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PMID:N-acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing. 246 64

Twenty-four patients with severe stable angina pectoris were included in a randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of a controlled-release preparation of isosorbide-5-mononitrate (ISMN-CR) 60 mg once daily or twice daily as adjunctive treatment to a beta blocker. In bicycle ergometer exercise tests performed 4 h after study drug intake, total exercise time and time until 1-mm ST-depression increased significantly during both regimens as compared with placebo (p less than 0.05). However, only the 60-mg once-daily regimen was significantly better than placebo with regard to time until angina pectoris. The results indicate that ISMN-CR 60 mg once daily is effective as adjunctive to beta-blocker treatment, and nitrate tolerance appeared to develop during the twice-daily regimen. In 10 of the patients, the effect of additional sublingual nitroglycerin (NTG) was studied. Exercise time after NTG remained remarkably constant throughout all study periods. Exercise time was significantly prolonged after additional NTG and independent of the dose level of ISMN-CR. This indicates that cross-tolerance to NTG was not induced during sustained treatment with ISMN-CR.
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PMID:Efficacy of controlled-release isosorbide-5-mononitrate as adjunctive treatment to beta-blocking agents in patients with stable angina pectoris. 247 13

Nitrates are beneficial in post-myocardial infarction patients with stable, unstable, and Prinzmetal's variant angina and as adjunctive therapy in congestive heart failure. They are available in multiple formulations that differ in chemical structure, pharmacokinetics, onset and duration of activity, and peak effect; all of these variables may condition the choice of nitrate preparation and routes of administration. Other conditions, such as different types of angina, intensity of symptomatology, psychological attitude, patient's compliance, and cost of treatment, have to be taken into account. The potential problem of nitrate tolerance requires further evaluation and can be prevented or reversed with intermittent-dosing regimens. Up-to-date nitrates continue to be a mainstay in the treatment of patients with myocardial infarction, especially if complicated by painful or silent ischemia.
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PMID:Chronic treatment after acute myocardial infarction: which drug for which patient? Nitrates. 248 40

To investigate the antiischemic efficacy and development of tolerance to transdermal nitroglycerin, 14 patients with chronic, stable angina pectoris were studied using continuous ambulatory electrocardiographic monitoring. Patients demonstrated initial hemodynamic responsiveness to sublingual nitroglycerin and were titrated to a maximally tolerated dose of 30 to 60 mg/24 hours (52 +/- 5 mg). Two crossover phases were use in a randomized, double-blind, placebo-controlled manner: continuous nitroglycerin therapy (patches containing active drug worn for 24 hours) and intermittent nitroglycerin therapy (12-hour active drug followed by a 12-hour nitrate-free period). There were no differences in frequency or duration of ischemic episodes between the placebo days of each phase. A significant effect in frequency of episodes was observed between placebo and treatment days of continuous therapy (p less than 0.05). Nonsignificant reductions in frequency and duration of ischemic episodes also occurred during intermittent therapy. The major antiischemic effect of transdermal nitroglycerin therapy occurred during the first day of treatment but was lost by 48 hours. Reductions in frequency and duration of ischemic episodes (p less than 0.05) were present on day 1 of continuous therapy but ischemic episodes returned to placebo levels by day 2, suggesting the development of tolerance. Intermittent therapy did not prevent the development of tolerance on day 2 of treatment. The results demonstrate that the use of high doses of transdermal nitroglycerin in patients with chronic, stable coronary artery disease produced a beneficial reduction in the frequency and duration of ischemia. However, the antiischemic benefit was lost between 24 nd 48 hours after the onset of continuous and intermittent therapy, presumably due to tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin. 210 35

The transdermal nitroglycerin patches have been very successful nitrate formulations since their introduction in 1982. Nevertheless, considerable controversy regarding efficacy and tolerance has arisen. Nitroglycerin has multiple mechanisms of action in angina pectoris. Transdermal nitroglycerin in ointment formulation has been known to be effective in angina. The patches, when used in a dose of greater than or equal to 10 mg (24 h)-1, provide classic nitrate NTG effects in angina patients. However, the problem of nitrate tolerance is significant; in acute dosing, the transdermal patches lose their efficacy by 24 h and, with chronic dosing, appear usually to have little advantage over placebo in improvement of angina. An intermittent or interval approach to transdermal patch delivery appears to be the best method of avoiding nitrate tolerance. Current data suggest using the patches for 12 or 14 h consecutively and then removing them for 10-12 h. Such dosing strategies appear to eliminate or markedly reduce the problem of nitrate tolerance.
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PMID:Transdermal nitroglycerin in angina pectoris. 250 Oct 90

A newly developed glyceryl trinitrate (GTN) patch with biphasic release (7.5 mg GTN (24h)-1) was compared with placebo in 40 patients with stable angina pectoris, in a double-blind randomized crossover study. Exercise tests employing a bicycle ergometer were carried out 2 and 10h after application of the patch on the first day and after 7 days of continuous therapy and 2h after patch reapplication at the end of a 3-month period of once daily therapy. In comparison with placebo, 2h after acute dosing, ST-segment depression was decreased from 0.15 mV to 0.07 mV (P less than 0.001), the time to 0.1 mV ST-segment depression was increased from 3.6 to 5.0 min (P less than 0.001) and work capacity was increased from 280 W min-1 to 446 W min-1 (P less than 0.001). After 1 week of daily GTN therapy the effects at 2h were somewhat greater than in the acute test. Compared with the values 2h after GTN patch application, the effects after 10h, both on the first day and 7th day, were substantially lower. During long-term therapy, the effects observed after 1 week of GTN therapy were maintained. The decrease in effects between 2 and 10h probably represent partial nitrate tolerance but the similar effects on the first and 7th day indicate no change during sustained therapy.
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PMID:Antiischaemic effects of phasic release nitroglycerin system during acute and sustained therapy. 250 Oct 93

Sixteen patients with chronic, stable exercise-induced angina pectoris were studied during acute and sustained therapy with a new nitroglycerin (GTN) patch*. This patch provides a biphasic GTN release profile with therapeutic GTN plasma concentrations developing soon after application and persisting for 12h, but with low plasma concentrations during the remainder of the 24h period. This profile of GTN release was designed to avoid nitrate tolerance by providing a low nitrate period for substantial periods during each 24-h application period. In a placebo-controlled double-blind study, two GTN patches each releasing 7.5 mg GTN were applied. The active patches induced a significant decrease in systolic blood pressure and an increase in heart rate during initial application. Exercise duration to the end-point of moderate angina (P2) was increased at 4 and 8h during acute therapy and the changes during sustained therapy were similar. Thus, the Biophase GTN patch has been shown to improve exercise performance during acute therapy and, more importantly, to maintain this effect during sustained once-daily therapy.
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PMID:Antianginal efficacy of a new nitroglycerin patch. 250 Oct 94

The effect of isosorbide dinitrate (ISDN) in patients with stable angina pectoris consists of an effect on the capacity vessels, of an increase in the arterial compliance (wind kessel function), a dilation of reactive stenoses in the coronary system, an improvement in the collateral function and a direct myocardial effect. In practice isosorbide dinitrate should be given preferably in single doses of 20 mg or more in a non-depot form for maintenance therapy; oral administration three or four times a day is appropriate. The dose effect relation justifies a dose increase in individual cases. Taking the galenics and therapy intervals into consideration, an anti-anginal effect can be seen in acute as well as chronic treatment. With chronic administration of the substance a weakening of the haemodynamic effects occurs. This does not necessarily interfere with the anti-ischemic effect. This weakening can best be explained by counter-regulatory processes. With the usual nitrate doses a tolerance on the vasculary level is not reached, i.e. an alteration in molecular processes. On the other hand, under conditions, under which the weakening of haemodynamic effects becomes fully visible, as for example in ergometric exercise with elevated legs, a decrease in the antianginal efficacy can be observed during a maintenance therapy with isosorbide dinitrate.
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PMID:[Dose-response behavior and long-term effect of organic nitrates. Experimental and clinical studies]. 250 32

NAC has been thought to reverse nitrate tolerance by replenishing depleted intracellular sulfhydryl groups, however data on interactions between N-acetylcysteine and nitrates in patients with stable angina are controversial and disappointing. Therefore, we studied the effect of NAC on nitrate responsiveness of epicardial arteries and of the venous system (assessed as changes in effective vascular compliance) in dogs (n = 12) during long-term nitroglycerine (GTN)-treatment (1.5 micrograms/kg/min for 5 to 6 days). In dogs with GTN-specific tolerance (shift of venous or epicardial artery dilation with 15- to 17-fold higher dosages), NAC (100 mg/kg i.v.) had no dilator effect and did not alter the dose response relations of nitroglycerin. However, in nontolerant dogs (n = 7) NAC augmented (1.5- to 2-fold) the reduction of peripheral vascular resistance induced by 0.5-1.5 microgram/kg/min GTN. In vitro, the augmentation of purified guanylate cyclase activity by GTN (100 microM) was potentiated by NAC (0.01-1.0 mM) in saline or in canine plasma, whereas NAC alone was ineffective. Therefore, NAC does not restore GTN-responsiveness in epicardial arteries or veins in vivo and a small, tolerance-independent augmentation of GTN-induced dilation may result from NAC-induced extracellular formation of a stimulant of guanylate cyclase from GTN.
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PMID:Failure of the sulfhydryl donor N-acetylcysteine (NAC) to reverse nitrate tolerance in large epicardial arteries and the venous capacitance system of the dog. 251 88

In 24 patients (pts) with proven coronary artery disease, stable angina pectoris (AP) and elevated pulmonary artery pressure (PAP) during bicycle exercise, the acute and chronic (4 and 8 months) effects of several long-acting nitrates in different dosages: 50-300 mg pentaerythrityltetranitrate (PETN) or 40-120 mg isosorbide dinitrate (ISDN) were evaluated in comparison to sublingual nitroglycerin. Nitroglycerin was about 30%-40% more effective than PETN and ISDN with regard to pulmonary artery pressure at exercise. Beneficial effects of both long-acting nitrates were shown with regard to the number of anginal attacks, nitroglycerin consumption, and ST-segment depression both during short- and long-term treatment. Both nitrates decreased exercise pulmonary artery pressure by 15%-20%, at acute testing and during chronic therapy. There was no difference with respect to the long-term effects of both long-acting nitrates. However, more side-effects were observed during ISDN treatment. There were no signs of nitrate tolerance development with the therapy schedules under investigation.
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PMID:[Long-term effect of various nitrates in ischemic heart disease and latent heart failure]. 251 96


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