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At least 145 records · Page 8Linked to original sources
PubMed1994

The utility of Nitroderm TTS in angina pectoris: long-term treatment after switching from long-acting oral isosorbide dinitrate.

Long-acting oral isosorbide dinitrate (ISDN) was replaced by Nitroderm TTS, and the utility of this drug in long-term treatment was assessed in 69 patients with angina pectoris. The frequency of attacks (p < 0.001) and the consumption of sublingual nitrate tablets (p < 0.01) were found to be significantly lower at 2 weeks to 6 months than in the observation period in patients who experienced attacks or received sublingual tablets during the observation period. On the other hand, no significant time-lapse changes from the observation period were noted in patients who experienced no attacks or received no sublingual tablets during the observation period. The symptoms of adverse effects were mild. The improvement rates (improved) of subjective symptoms and electrocardiogram (ECG) in Group A were about 50% after 6 months. On the other hand, the improvement rates (not aggravated) of subjective symptoms and ECG in Group B were more than 90%. Nitroderm TTS is considered a useful plaster preparation which can be used for sufficiently extended periods of time because its efficacy was as high as, or higher than, that of oral ISDN when this drug was administered over a long period of time after a switch from long-acting oral ISDN in angina pectoris patients.

Administration, Cutaneous↗
PubMed1997

[Inhibitory effect of isosorbide dinitrate on whole blood aggregation].

Isosorbide dinitrate (ISDN) has an inhibitory effect on platelet aggregation through the generation of nitric oxide (NO). We examined the effect of ISDN on whole blood aggregation using an impedance aggregometer. Blood samples were obtained from 16 patients with acute myocardial infarction and 4 patients with angina pectoris before and after an intravenous administration of ISDN during coronary arteriography. Whole blood obtained from normal healthy donors was used for an in vitro study. Whole blood aggregation after administration of ISDN was significantly inhibited compared to that before administration (36.1 +/- 8.3 vs 43.7 +/- 8.4 omega, p < 0.001), and cyclic guanine monophosphate (c-GMP) concentration increased (5.56 +/- 2.0 vs 5.14 +/- 1.86 p mol/ml, p < 0.05). The inhibitory effect of ISDN was also observed in the in vitro study, in which the effective concentration of ISDN corresponded to the blood level of ISDN (> or = 10(-7) mol) in the clinical setting. The inhibitory effect of ISDN was diminished by the addition of methylene blue or NG-monomethyl-L-arginine monoacetate in the exo vivo and in vitro studies. The concentration of c-GMP was increased by the addition of ISDN to platelets and white blood cell suspended plasma compared to the control (1.93 +/- 0.50 vs 1.77 +/- 0.42 p mol/ml, p < 0.05), but there was no significant difference when ISDN was added to platelet-rich plasma. These results suggest that ISDN inhibits whole blood aggregation through NO generation and white blood cells are important in the mechanism of ISDN action.

Angina Pectoris↗
PubMed1990

Effects of isosorbide dinitrate on exercise capacity in cardiac patients--relationship between oxygen uptake responses and hemodynamic effects.

Acute effects of oral isosorbide dinitrate on exercise capacity were evaluated in 14 patients with chronic heart disease measuring the anaerobic threshold and left ventricular function during exercise. A symptom-limited exercise test was performed on a bicycle ergometer with work rates increased by 1W every 6 seconds. Left ventricular function was continuously monitored with a computerized cadmium telluride detector following the intravenous injection of technetium-labeled red blood cells. Thirty minutes after the control exercise test, patients were given isosorbide dinitrate, 5 mg orally. The second exercise test was performed 30 min later. Isosorbide dinitrate improved the anaerobic threshold from 715.4 +/- 172.9 to 774.9 +/- 173.5 ml/min (p less than 0.01) and ejection fraction at peak exercise from 36.7 +/- 11.6 to 39.9 +/- 12.3% (p less than 0.05). However, there was no significant change in maximum work rate or peak oxygen uptake. Those patients for whom isosorbide dinitrate resulted in a 10% or greater improvement in the anaerobic threshold had both higher pre-treatment ejection fractions and greater increases in peak exercise ejection fraction following isosorbide dinitrate. Measurements of the anaerobic threshold and left ventricular function during exercise may be useful in the evaluation of the efficacy of vasodilators in cardiac patients.

Anaerobiosis↗
PubMed1979

Effect of isosorbide dinitrate on response to submaximal and maximal exercise in patients with congestive heart failure.

Isosorbide dinitrate is an effective vasodilator that improves resting left ventricular performance in patients with congestive heart failure, but little is known of the effect of the drug on the response to exercise. Bicycle exercise to symptomatic maximum was performed by 18 patients with class II to IV congestive heart failure before and 90 minutes after administration of isosorbide dinitrate, 40 mg orally. Although resting pulmonary wedge pressure and systemic vascular resistance were significantly reduced after isosorbide dinitrate, exercise duration was not altered and maximal oxygen consumption was not significantly changed (13.6 +/- 1.3 [SEM] standard error of the mean versus 13.8 +/- 1.2 ml/kg per min). At peak exercise pulmonary wedge pressure of 37.1 +/- 1.7 mm Hg, cardiac index of 4.19 +/- 0.35 liters/min per m2, and systemic vascular resistance of 14.7 +/- 1.3 units were not significantly different after nitrate administration. However, at submaximal loads, pulmonary wedge pressure was reduced from 33.6 +/- 1.7 to 27.9 +/- 1.8 mm Hg (P less than 0.01), and systemic resistance from 16.5 +/- 1.5 to 13.7 +/- 1.0 units (P less than 0.01) after administration of isosorbide dinitrate. Thus, short-term administration of nitrates does not improve maximal exercise capacity or left ventricular performance at maximal exercise in patients with congestive heart failure, but it does appear to improve pump function at submaximal work loads and may therefore enable patients to perform limited exercise more comfortably.

Administration, Oral↗
PubMedDate not supplied

Pharmacokinetics of isosorbide dinitrate after intravenous infusion in human subjects.

Plasma concentrations of isosorbide dinitrate have been measured after intravenous infusion of drug at a rate of 5.0 mg h-1 for 150 min and after single equal oral doses of 12.5 mg of drug in solution to two normal human subjects. During the infusion, uneven plateau concentrations were approached after 30 min. The calculated average steady-state plasma levels were 258 ng ml-1 and 514 ng ml-1 in the two subjects respectively. The half-life of elimination of isosorbide dinitrate after termination of the infusion was 9--10 min. After oral doses, peak plasma levels of 26.6 ng ml-1 and 12.7 ng ml-1 occurred at 10 min and 20 min in the two subjects respectively. The terminal half-life of drug after the oral doses was much longer than the elimination half-life (about 10 min), and was associated with the absorption phase. Fairly good agreement was obtained between the observed concentrations and those predicted by a one-compartment open model. The systemic availability of isosorbide dinitrate after the oral doses was up to only 3 per cent of the equal doses infused, indicating that presystemic elimination processes accounted for very large proportions of the oral doses. The systemic clearances of drug after infusion of 0.32 l min-1 and 0.16 l min-1 were unexpectedly low for a drug of reported high liver extraction ratio.

Adult↗
PubMed1985

[Transcutaneous application of nitroglycerin and isosorbide dinitrate versus placebo: effect in myocardial ischemia].

The effect of nitroglycerin ointment (30 mg) and isosorbide dinitrate ointment (100 mg) versus placebo on exercise capacity has been investigated in 12 patients. All had angina pectoris and coronary artery disease documented by coronary angiography. Nitroglycerin and isosorbide dinitrate ointment produced a significant increase in exercise capacity, without any significant difference in the beneficial effect of the two. Stress-induced changes of the ST-segment in the electrocardiogram decreased by 65% after nitroglycerin ointment and by 41% after isosorbide dinitrate ointment, compared to placebo. These results indicate that nitroglycerin and isosorbide dinitrate ointment reduce stress-induced myocardial ischemia at similar work loads.

Administration, Topical↗
PubMed1981

Availability of isosorbide dinitrate, diazepam and chlormethiazole, from i.v. delivery systems.

The loss of isosorbide dinitrate from aqueous solutions stored in plastic infusion bags and/or infused through plastic giving sets was investigated. During simulated infusions, the loss of isosorbide dinitrate was found to be flow-rate dependent. The clinical and pharmacokinetic significance of this loss is discussed. Infusion o isosorbide dinitrate from a glass syringe through high density polyethylene tubing overcame the loss associated with its administration via plastic infusion bags and intravenous giving sets. This method was also applied successfully to minimise the previously reported loss of diazepam and chlormethiazole during infusions.

Adsorption↗
PubMed1991

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.

BACKGROUND: To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS: Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS: The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Adolescent↗
PubMed1992

Bioavailability and metabolism of isosorbide dinitrate from a transdermal spray.

The plasma pharmacokinetics of isosorbide dinitrate (ISDN), isosorbide-2-nitrate (IS-2-N) and isosorbide-5-nitrate (IS-5-N) were investigated in 12 healthy volunteers after a single cutaneous administration of 60 mg ISDN (CAS 87-33-2) in the form of a solution sprayed onto the skin (TD Spray Iso Mack), in comparison with an intravenous infusion of 5 mg ISDN. After the intravenous dose, the apparent steady state volume of ISDN distribution came to 179.9 l, total body clearance was 3.14 l min-1, and terminal half-life was 79 min, on average. The transdermal absorption resulted in an average peak plasma concentration of 6.9 ng ISDN ml-1 at 5 h after the administration. ISDN concentrations between 1 and 5 ng ml-1 were maintained over at least 15 h. On average, 16.5% of the topically applied ISDN reached the systemic circulation. Total variations in Cmax (CV = 47.9%) and AUC (CV = 36.0%) of transdermal ISDN were similar to those usually observed after oral ISDN.

Administration, Cutaneous↗
PubMed1993

Propranolol compared with propranolol plus isosorbide dinitrate in portal-hypertensive patients: long-term hemodynamic and renal effects.

The long-term hemodynamic and renal effects of propranolol were compared with those of propranolol plus isosorbide dinitrate in 44 portal-hypertensive alcoholic cirrhotic patients. Eight control patients, 8 patients receiving propranolol and 14 patients receiving propranolol plus isosorbide dinitrate were hemodynamically evaluated. Renal function was studied in a fourth group of 14 patients receiving propranolol plus isosorbide dinitrate. Portal pressure decreased more (p < 0.05) with combined therapy (-21.6%, from 19.5 +/- 4.8 to 15.4 +/- 4.3 mm Hg) than with propranolol alone (-12.5%, from 19.9 +/- 1.2 to 17.4 +/- 1.8 mm Hg). Serum urea and creatinine levels, plasma sodium concentration, urine volume and urinary sodium excretion showed nonsignificant changes in all groups studied. Combined therapy induced a significant (p < 0.05) decrease in plasma renin activity (from 4.42 +/- 4.7 to 1.59 +/- 1.9 ng/ml/hr) and nonsignificant reductions in plasma aldosterone concentration and creatinine clearance. None of the eight patients with ascites or history of ascites not receiving isosorbide dinitrate showed evidence of impairment in renal sodium metabolism during the study period. In contrast, 8 of the 14 patients (57%) with ascites or history of ascites receiving isosorbide dinitrate showed impairment in renal sodium metabolism (p < 0.01), as reflected by the development or worsening of ascites and the need of higher diuretic requirements. Long-term combined administration of propranolol plus isosorbide dinitrate is superior to propranolol alone in the pharmacological treatment of portal hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1983

High-dosage isosorbide dinitrate therapy for angina.

We investigated the possibility that high dosages (480 mg/d) of isosorbide dinitrate might reduce the frequency of angina attacks in selected patients who had not responded to low dosages of the drug (40 mg/d), and that the patients could tolerate the high levels of medication and maintain their responsiveness over the long term. In the single-blind phases of this trial 24 patients with grade 3 stable angina pectoris were given a placebo for 4 weeks and then increasing doses of isosorbide dinitrate for a further 6 weeks. The 19 patients who both responded to and tolerated high doses of the drug kept taking 480 mg/d for an average of 1 year. The average weekly rate of angina attacks fell by 74%, from 6.05 in the placebo phase to 1.6 during long-term active treatment (p less than 0.01). Nitroglycerin consumption decreased accordingly. The patients' assessments of their levels of activity and well-being and their angina thresholds showed improvement among most of them. The trend of angina frequency was stable in 12 cases, downward in 6 and upward in only 1 case. Exercise performance as evaluated by a graded treadmill test showed a small but nonsignificant improvement of 18%. It was concluded that some patients who do not respond to the antianginal action of low-dosage isosorbide dinitrate and cannot be given beta-blockers may respond to high dosages and tolerate them for over a year. Isosorbide dinitrate may be clinically useful in patients with coronary heart disease even though their exercise performance is not significantly improved.

Adult↗
PubMed1991

Controlled release isosorbide-5-mononitrate in angina pectoris: a comparison with standard formulation isosorbide dinitrate.

In a randomized, double-blind, placebo controlled, crossover study, the antianginal and anti-ischemic effects of a controlled release formulation of isosorbide-5-mononitrate 60 mg once daily and of a standard formulation of isosorbide dinitrate 30 mg qid, were assessed during the first day of treatment and after seven days of sustained therapy. In comparison to placebo, the acute administration of isosorbide-5-mononitrate increased treadmill walking time at 4 and 8 h, and isosorbide dinitrate prolonged treadmill walking time when tested at 4 h after each of the first three doses. During sustained therapy, isosorbide dinitrate produced no significant changes over placebo values. Isosorbide-5-mononitrate prolonged treadmill walking time 4, 8 and 12 h after morning dosing by 54, 41 and 52 s, but these changes were not significant compared to placebo. Treadmill walking time was, however, significantly greater at 4 and 12 h during isosorbide-5-mononitrate therapy compared with isosorbide dinitrate. There was no significant difference in treadmill walking time during acute and sustained therapy with isosorbide-5-mononitrate indicating a lack of tolerance; there was a complete loss of effect during sustained qid therapy with isosorbide dinitrate.

Angina Pectoris↗
PubMed1975

Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects.

An oral dose of 5 mg of 14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.

Biotransformation↗
PubMed1984

Concomitant calcium antagonist plus isosorbide dinitrate therapy for markedly active variant angina.

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 +/- 9 [mean +/- standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 +/- 63 mg per day) alone, (2) verapamil (453 +/- 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 +/- 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 +/- 37.3 chest pains per week, consumed 24.4 +/- 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 +/- 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 +/- 3.6 chest pains per week and 3.5 +/- 2.6 ST segment deviations per week, p less than 0.05; nifedipine/isosorbide dinitrate, 3.1 +/- 4.0 chest pains per week and 5.5 +/- 6.6 ST segment deviations per week, p less than 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Effects of isosorbide dinitrate and hydralazine on regional metabolic responses to arm exercise in patients with heart failure.

The reduced exercise capacity of patients with heart failure is thought to be due in part to impaired skeletal muscle oxygen delivery. To determine if hydralazine and isosorbide dinitrate improve skeletal muscle oxygen delivery in such patients, the effects of these agents on regional metabolic responses to forearm exercise were examined in 16 patients with heart failure. Arm oxygen extraction and branchial venous lactate concentration were measured at rest and during 3 minutes of rhythmic handgrip and then remeasured after administration of oral hydralazine (nine patients) or sublingual isosorbide dinitrate (nine patients). Hydralazine increased mean (+/- standard deviation) cardiac output at rest from 3.5 +/- 0.5 to 4.9 +/- 1.0 liters/min (p less than 0.01) and decreased arm oxygen extraction from 39 +/- 8 to 33 +/- 10 percent (probability [p] less than 0.01), suggesting improved resting limb oxygen delivery. However, hydralazine did not reduce arm oxygen extraction during exercise (control 63 +/- 4, hydralazine 60 +/- 12 percent; p = not significant [NS]) or venous lactate during exercise (control 16.6 +/- 7.8, hydralazine 17.1 +/- 4.8 mg/100 ml; p = NS). Isosorbide dinitrate increased the cardiac output from 3.6 +/- 0.7 to 4.5 +/- 0.7 liters/min (p less than 0.01) but had no effect on arm oxygen extraction at rest (control 40 +/- 11, isosorbide dinitrate 38 +/- 11 percent; p = NS) and during exercise (control 66 +/- 5, isosorbide dinitrate 64 +/- 8 percent; p = NS) or on venous lactate during exercise (control 17.9 +/- 6.4, isosorbide dinitrate 17.1 +/- 3.9 mg/100 ml; p = NS). These data suggest that hydralazine and isosorbide dinitrate do not improve skeletal muscle oxygen delivery during exercise in patients with heart failure.

Adult↗
PubMed1978

Improvement in exercise haemodynamics by isosorbide dinitrate in patients with severe congestive cardiac failure secondary to ischaemic heart disease.

Seven patients with severe chronic congestive cardiac failure secondary to ischaemic heart disease performed submaximal supine exercise before and after 5 mg sublingual isosorbide dinitrate at the time of cardiac catheterisation. Exercise before isosorbide dinitrate produced a poor response in left ventricular performance. After isosorbide dinitrate this response was significantly improved. Compared with the control exercise period, cardiac index increased from mean 2.6 to 3.1 1/min per m2 (P less than 0.0025), stroke volume index from mean 22 to 27 ml/m2 (P less than 0.0025), and left ventricular stroke work index from mean 21 to 30 g m/m2 (P less than 0.01). Mean left ventricular filling pressure fell from 37 to 26 mmHg (P less than 0.01). Although isosorbide dinitrate reduced left ventricular filling pressure at rest from mean 26 to 17 mmHg (P less than 0.005), there was no significant change in mean cardiac index or stroke volume index, while left ventricular stroke work index decreased from mean 29 to 22 g m/m2 (P less than 0.05). Isosorbide dinitrate effectively reduces left ventricular filling pressure in the resting patient with congestive cardiac failure but produces a more comprehensive improvement in left ventricular performance during exercise.

Aged↗
PubMed1991

Influence of standard and nicotine-reduced cigarette smoke on plasma concentrations of isosorbide dinitrate and its metabolites in rats.

Rats dosed orally with isosorbide dinitrate (1 mg kg-1) were exposed to smoke from standard and nicotine-reduced cigarettes for 8 min using a smoking machine. Plasma concentrations of isosorbide dinitrate and 5-isosorbide mononitrate, one of its major metabolites were approximately equal in the exposed groups, but were lower than in the non-smoking control group. The 2-isosorbide mononitrate concentration was also lower in the group exposed to smoke from standard cigarettes. Since the pharmacokinetics were influenced by smoke from both types of cigarette smoke, the effect may be attributed in large part to non-nicotine components of the smoke.

Animals↗
PubMed1992

Short report: comparison of the effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying in patients with Chagasic achalasia.

The effects of sublingual nifedipine and isosorbide dinitrate on oesophageal emptying were compared in 11 patients with Chagasic achalasia. The oesophageal emptying of a radiolabelled test meal was assessed three times in each patient by a scintigraphic technique. No treatment preceded one of the studies (basal study). Nifedipine (20 mg) by the sublingual route 30 min before the meal, preceded one study. Isosorbide dinitrate, 5 mg by the sublingual route 5 min before the meal, preceded the third study. The order of the studies was allocated randomly for each patient. Oesophageal retention at the completion of the meal was significantly less (P less than 0.01) after isosorbide dinitrate (median: 54%, range: 5-87%) than after sublingual nifedipine (median: 78%, range: 7-99%) or after the control study (median: 83%, range: 5-100%). This difference persisted up to 20 min after the meal. Values measured in the control study and after sublingual nifedipine were not different (P greater than 0.10). These results show that isosorbide dinitrate, but not sublingual nifedipine, enhances oesophageal emptying in Chagasic achalasia.

Administration, Sublingual↗