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At least 343 records · Page 19Linked to original sources
PubMed1981

Sublingual isosorbide dinitrate in severe congestive heart failure.

Sublingual isosorbide dinitrate was administered to 17 patients with severe congestive heart failure to characterize the hemodynamic action of the drug. Isosorbide dinitrate effect was maximal 30-60 min after administration. The most striking effect was a marked fall of the mean pulmonary capillary wedge pressure which dropped from 28 to 20 mm Hg (p less than 0.01). Pulmonary artery systolic pressure dropped from 55 to 43 mm Hg (p less than 0.01) and right atrial pressure from 11 to 8 mm Hg (p less than 0.01). Arterial blood pressure fell slightly whereas no significant change in heart rate or cardiac index was noted. 8 of the 17 patients showed a marked and sustained reduction of their pulmonary capillary wedge pressure. The hemodynamic response was moderate in 2 patients whereas 6 patients showed no appreciable improvement. A symptomatic but transient reduction in arterial blood pressure occurred in the last patient. Patients responding favorably to the drug had significantly higher initial systolic blood pressure that nonresponders (133 vs. 102 mm Hg, p less than 0.01). However, there was no reliable clinical parameter to predict which of the subjects will respond favorably to the administration of isosorbide dinitrate.

Blood Pressure↗
PubMed1987

Dose-effect relationship amongst three different sustained-release forms of isosorbide 5-mononitrate in patients with coronary artery disease.

Fifteen patients with coronary artery disease and stable angina pectoris were included in a double-blind, randomized, cross-over study. The patients received 25, 50 and 100 mg isosorbide 5-mononitrate, as well as a placebo, for subsequent 1-week periods. On the 7th day of each treatment period, 8 h after medication application, an exercise test was performed. A highly significant (p less than 0.001) and dose-dependent reduction of the sum of the ST-segment depression was observed at similar workloads: 28.6, 46 and 63.5% decreases occurred at the 25, 50 and 100 mg isosorbide 5-mononitrate doses, respectively. Compared to placebo, the frequency of anginal attacks and the consumption of nitroglycerin likewise decreased highly significantly (p less than 0.001) with all three doses. Isosorbide 5-mononitrate plasma levels (8 h post-application) increased linearly with the dose; amounting to 228 +/- 53, 485 +/- 93 and 991 +/- 177 ng/ml at the 25, 50 and 100 mg doses of the sustained release medication forms, respectively.

Aged↗
PubMed1989

Comparison of relaxation induced by glyceryl trinitrate, isosorbide dinitrate, and sodium nitroprusside in bovine airways.

Nitrates are generally regarded as bronchial smooth muscle relaxants. However, reports about the clinical efficacy of the nitrates in the treatment of asthma are conflicting. In the present study, the relaxant effects of glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, and isoproterenol were measured and compared in vitro in airway preparations isolated from variously sized airways in bovine lung. Strips of trachealis from cervical and thoracic ends of the trachea and rings of intrapulmonary bronchi of various diameters (14 to 1 mm outer diameters) were mounted for recording of isometric tension. Submaximal tone was induced using 10(-6) M carbachol, and responses to cumulatively increasing concentrations of glyceryl trinitrate, isosorbide dinitrate, sodium nitroprusside, or isoproterenol were measured. Isoproterenol (10(-8) to 10(-4) M) was equiactive as a relaxant in all preparations. Glyceryl trinitrate (10(-7) to 10(-5) M) relaxed trachealis, but was progressively and significantly less effective as a relaxant as the diameters of the bronchial rings decreased. Although less potent than isoproterenol, sodium nitroprusside (10(-6) to 10(-4) M) was effective in relaxing all the airway preparations. Similar to glyceryl trinitrate, sodium nitroprusside was less effective in small than in large airways. However, the relationship between relaxant responses to sodium nitroprusside and airway size was not as marked as for glyceryl trinitrate. Isosorbide dinitrate at concentrations as great as 10(-5) M did not relax carbachol-induced tone in any of the bronchial rings and only induced a small amount of relaxation in trachealis at 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Comparison between isosorbide dinitrate in aerosol and in tablets for the treatment of hypertensive emergencies.

Sixty patients with a hypertensive emergency (mean arterial pressure >130 mm Hg and evidence of target organ damage) were randomly divided into two groups of 30 patients each. Group A received 1.25 mg of isosorbide dinitrate aerosol upon arrival and a second dose 15 minutes later when the mean arterial pressure reduction was < 15%. Group B received a single 5 mg tablet of sublingual isosorbide dinitrate. Electrocardiography was performed in both groups prior to and 30 minutes after the medication. Blood pressure was monitored for 6 hours. Blood pressure in Group A patients decreased in an average time of 10 minutes from 191 +/- 12/122.3 +/- 5 to 151.5 +/- 9.2/93 +/- 4 mm Hg, p < 0.005. Mean arterial pressure decreased by 22.8%: 145 +/- 7 to 112 +/- 7.5 mm Hg, p < 0.005. No adverse effects occurred. Five patients in Group B did not respond; in the rest of the group blood pressure decreased 45 minutes after receiving the medication from 194 +/- 8/125 +/- 5.5 to 160 +/- 11/98 +/- 6 mm Hg; p < 0.005. Mean arterial pressure decreased by 20.1%: 148.3 +/- 12 to 118.6 +/- 9 mm Hg, p < 0.002; ten patients suffered headache. Three patients in Group A had a subepicardial lesion in the first electrocardiograph, which disappeared with the use of the aerosol. In Group B, electrocardiography results were normal. These results seem to indicate that isosorbide dinitrate aerosol is better than tablets for the treatment of patients with a hypertensive emergencies.

Administration, Inhalation↗
PubMed1986

Antianginal effect of isosorbide dinitrate spray in patients with exercise-induced stable angina.

Ten patients with stable exercise-induced angina took part in this study. Isosorbide dinitrate and placebo sprays were administered in a double-blind, randomized crossover study. The dose of isosorbide dinitrate given was two squirts (= 2.5 mg) 2 min before testing. When taken before exercise it significantly improved (p less than 0.014) exercise tolerance. Significant (p less than 0.0005) ischaemic changes in the electrocardiogram also occurred. These effects occurred later than with placebo. Exercise time was prolonged with the active drug. The results of this study show that isosorbide dinitrate spray improves the exercise tolerance of patients with ischaemic heart disease.

Administration, Oral↗
PubMedDate not supplied

A multicentre open comparison of isosorbide-5-mononitrate and nifedipine given prophylactically to general practice patients with chronic stable angina pectoris.

A total of 126 patients from general practice with chronic stable angina pectoris entered the treatment phase of this open, randomized, crossover comparison of 20 mg isosorbide-5-mononitrate, and 20 mg nifedipine. Both treatments were given orally, three times daily, for 4 weeks and sublingual administration of glyceryl trinitrate was allowed throughout. Over the whole treatment period, there was no statistically significant difference between treatments for anginal attacks. However, significantly fewer glyceryl trinitrate tablets were required by patients receiving prophylaxis with nifedipine, although this difference was too small to be of clinical significance. No statistical difference existed between treatments in respect of scores for 'overall intensity of pain', 'physical exercise ability' and 'general well-being'. Of those patients who expressed a preference, the majority preferred the second treatment with no statistically significant difference between isosorbide-5-mononitrate and nifedipine. Both treatments showed similar levels of adverse events, the major difference (not significant) being for flushing of the skin which occurred in five patients given nifedipine compared with one patient given isosorbide-5-mononitrate. It is concluded that, in clinical terms, the two treatments were similar. Headache and dizziness/giddiness were the most frequently recorded adverse events.

Angina Pectoris↗
PubMedDate not supplied

Effect of peroral administration of isosorbide dinitrate on portal pressure and blood flow in patients with cirrhosis of the liver.

The effect of slow-release isosorbide dinitrate, given orally four times daily for 14 days, on the portal circulation was studied in 10 patients with liver cirrhosis and oesophageal varices. Mean arterial pressure and heart rate were not influenced significantly by isosorbide dinitrate. Statistically significant dilation of the portal vein by 11.9% and an increase in blood flow velocity by 35.4% and in portal blood flow rate by 54.3% were observed at the end of therapy. The average wedged hepatic vein pressure was 32.9 mmHg before therapy and after therapy it was decreased to 60.5%. The slight decrease observed in free hepatic vein pressure was not statistically significant. Before treatment the portohepatic gradient was four times above normal and after therapy it fell to 9.5 mmHg. The results indicate that, in patients with portal hypertension, an improvement in haemodynamics can be achieved by the use of isosorbide dinitrate. This improvement may lead to the prevention of bleeding from oesophageal varices.

Administration, Oral↗
PubMedDate not supplied

Patient compliance with once-daily and twice-daily oral formulations of 5-isosorbide mononitrate: a comparative study.

This study compares patient compliance with once- and twice-daily formulations of 5-isosorbide mononitrate. A total of 31 patients (20 men and 11 women) with stable angina pectoris were randomized to receive either 60 mg 5-isosorbide mononitrate in a controlled release formulation once daily, or 20 mg 5-isosorbide mononitrate twice daily. The results indicated that compliance assessed using the electronic Medication Event Monitoring System (MEMS) was better with the once-daily than with the twice-daily formulation; patients on the once-daily regimen performed better with respect to the total number of bottle openings, the number of openings per day, the timing of openings and the intervals between openings. The apparently superior compliance with the once-daily regimen appeared to be reflected in better efficacy; patients on the once-daily regimen experienced fewer angina attacks (a mean of 1.7 per 7 days, compared with 3.3 per 7 days for patients on the twice-daily regimen) and used fewer nitroglycerin tablets than those on the twice-daily regimen.

Aged↗
PubMed1989

Influence of electric foot shock on pharmacokinetics of isosorbide dinitrate orally administered to rats.

The influence of emotional stress on the pharmacokinetics of isosorbide dinitrate (ISDN) was studied in rats. Plasma levels of orally administered ISDN and metabolites (5-isosorbide mononitrate and 2-isosorbide mononitrate) were lower in rats emotionally stressed by foot shock than in non-stressed control rats. The decrease in the ISDN levels may be mainly due to the delay of drug absorption from the gastrointestinal tract.

Administration, Oral↗
PubMed1989

Influence of electric foot shock on pharmacokinetics of isosorbide dinitrate subcutaneously administered to rats.

The influence of emotional stress on the pharmacokinetics of isosorbide dinitrate (ISDN) administered s.c. to rats was studied. The plasma level of ISDN in emotionally stressed (ES) rats was the same as that in non-stressed control rats. However, the levels of its metabolites, 5-isosorbide mononitrate (5-ISMN) and 2-isosorbide mononitrate (2-ISMN), were markedly lower in ES rats than in the control rats. On the other hand, urine ISDN and 2-ISMN excretion rates were lower in ES rats than in the control rats. These observations suggest that the pharmacokinetics of ISDN administered s.c. is influenced by emotional stress such as foot shock.

Animals↗
PubMed1979

Comparison of placebo, nitroglycerin, and isosorbide dinitrate for effectiveness of relief of angina and duration of action.

Each of 13 patients with angina had either chewable isosorbide dinitrate, nitroglycerin (sublingual therapy), or placebo administered on each of three different days when mild anginal pain had been induced by walking on a treadmill. Both therapy with isosorbide dinitrate and therapy with nitroglycerin were effective in bringing about complete relief of the angina in less than ten minutes of uninterrupted continuous walking on the treadmill in 11 of the 13 subjects, while administration of placebo afforded complete relief in none. The duration of action of the drug was determined by following the first effort (during which the tested drug was given) by successive ten-minute walks at the same workload that first induced anginal pain. Half-hour resting periods separated the repeated periods of exercise, and the duration of action was taken to be the time from administration of the agent to the return of angina on one of the repetitive efforts. No prolonged protection was afforded by administration of the placebo. Nitroglycerin protected for slightly longer than one hour, while isosorbide dinitrate protected for 2 1/2 to 3 hours.

Aged↗
PubMed1990

Influence of emotional stress on pharmacokinetics of isosorbide dinitrate intraperitoneally administered to rats.

The plasma level of isosorbide dinitrate intraperitoneally administered to rats stressed by foot-shock was almost the same as that in non-stressed control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2-isosorbide mononitrate, were lower in stressed rats than in non-stressed rats, suggesting that stress may influence the metabolism and/or excretion of the metabolites.

Animals↗
PubMed1987

Experience of long term treatment and different dosage regimens of isosorbide 5-mononitrate.

The results of 2 clinical studies of controlled-release isosorbide 5-mononitrate (Imdur) in patients with angina pectoris are presented. In an open study in 106 patients the antianginal efficacy of controlled-release isosorbide 5-mononitrate 60 mg once daily was demonstrated by a progressive reduction in the use of short-acting glyceryl trinitrate and in the number of anginal attacks over 6 months. The only significant side effect was headache, which generally disappeared rapidly (after an average of 5 to 6 days). 30 patients were treated in a 1-week single-blind crossover study comparing controlled-release isosorbide 60 mg once daily with a conventional formulation of the drug 20 mg 3 times daily. Both regimens produced similar antianginal and anti-ischaemic effects when the patients were tested by standard ergometry, and the only significant side effect (transient headache) was equally frequent with both regimens.

Adult↗
PubMed1987

Long term efficacy of a controlled-release formulation of isosorbide 5-mononitrate (Imdur) in angina patients receiving beta-blockers.

In a multicentre double-blind crossover study the clinical efficacy and tolerability of a controlled-release formulation, Durules, of isosorbide 5-mononitrate (Imdur) 60mg once daily was compared with placebo over 2 weeks in 70 patients with stable exercise-induced angina pectoris who were receiving concomitant long term beta-blockade. Isosorbide 5-mononitrate significantly improved exercise capacity and signs of myocardial ischaemia, while reducing the number of anginal attacks and consumption of short-acting glyceryl trinitrate tablets compared with beta-blocker therapy alone. During an open follow-up period of 1 year, there was no attenuation of the antianginal efficacy of isosorbide 5-mononitrate. The drug was well tolerated during both phases of the study, and the only significant adverse effect was headache, which rapidly disappeared during continued treatment.

Adrenergic beta-Antagonists↗
PubMed2001

Relative bioavailability of two isosorbide dinitrate sublingual tablet formulations administered as single doses in healthy subjects.

OBJECTIVE: The purpose of this study was to evaluate the relative bioavailability and bioequivalence of a test and a reference sublingual tablet each containing 5 mg of isosorbide dinitrate in healthy volunteers. METHODS: The study was conducted as an open-label, randomized, single-dose, two-period crossover design in 20 healthy volunteers with a washout period of 7 days, under fasting conditions. Plasma concentrations of the major active metabolite isosorbide 5-mononitrate were quantified, using a validated capillary gas chromatographic assay, with electron-capture detection. The pharmacokinetic parameters used to assess the bioequivalence of the two preparations were AUC(0-infinity) and AUC(0-infinity) for the extent of absorption and Cmax and tmax for the rate of absorption. RESULTS: The calculated 90% confidence intervals of the geometric mean values of the test/reference ratios were 98.2% to 103.2% (point estimate; 100.7%) for AUC(0-infinity) 96.9% to 103.8% (point estimate; 100.3%) for AUC(0-infinity), and 87.9% to 98.2% (point estimate; 92.9%) for Cmax. No statistically significant difference was found for tmax and elimination half-life (t 1/2) values. CONCLUSION: From the results of the present study, it is concluded that the test and reference isosorbide dinitrate sublingual preparations are bioequivalent in both extent and rate of absorption and it can be assumed that they are therapeutically equivalent and exchangeable in clinical practice.

Administration, Sublingual↗
PubMed1994

Lack of pharmacologic tolerance and rebound angina pectoris during twice-daily therapy with isosorbide-5-mononitrate.

OBJECTIVE: To determine whether isosorbide-5-mononitrate (IS-5-MN), an active metabolite of isosorbide dinitrate, when given twice daily (in the morning and 7 hours later), prevents development of tolerance and reduction in exercise performance or is associated with a rebound increase in anginal attacks in patients with stable angina pectoris. DESIGN: Multicenter, placebo-controlled, parallel-group, double-blind, randomized study. SETTING: Four university teaching hospitals and five private cardiology outpatient clinics. PATIENTS: 116 patients with stable exertional angina who stopped treadmill exercise because of angina pectoris. INTERVENTION: After stopping all antianginal drugs with the exception of beta-blockers, patients received single-blind placebo for 1 week followed by either 20 mg of IS-5-MN (n = 60 patients) or placebo (n = 62 patients) twice daily at 0800 hours and 1500 hours for 2 weeks. MEASUREMENTS: Serial symptom-limited exercise tests and patients' diaries recording activity and date, time, and severity of anginal attacks. RESULTS: Compared with placebo recipients, patients receiving IS-5-MN walked significantly longer at 2, 5, and 7 hours after the 0800-hour dose (P < 0.01) and at 2 and 5 hours after the 1500-hour dose (P < 0.01). Before the morning (0800-hour) dose, exercise duration increased by 0.53 minutes in placebo recipients and by 0.85 minutes in those receiving IS-5-MN therapy (P = 0.10). Neither nocturnal nor early-morning anginal attacks increased during IS-5-MN therapy compared with placebo. Headaches occurred in 19 (32%) patients in the IS-5-MN group and in 9 (15%) patients in the placebo group but necessitated discontinuation of treatment in only 2 (3%) patients in the IS-5-MN group. CONCLUSION: Isosorbide-5-mononitrate, 20 mg twice daily given 7 hours apart, was well tolerated and improved exercise performance for 7 hours after the morning dose and for 5 hours after the afternoon dose without evidence of development of pharmacologic tolerance. No rebound increase in anginal attacks was found.

Adult↗
PubMed1993

Duplex Doppler ultrasonographic comparison of the effects of propranolol and isosorbide-5-mononitrate on portal hemodynamics.

Eighteen cirrhotic patients with esophageal varices at risk for bleeding took part in a double-blind study. The variations in PFV induced by either 40 mg of propranolol or 60 mg of sustained-release isosorbide-5-mononitrate on two consecutive days were evaluated with a duplex Doppler device. Both drugs caused a significant decrease in maximum (propranolol, P = 0.002; isosorbide-5-mononitrate, P = 0.021). Four patients responded to propranolol, three to isosorbide-5-mononitrate, and eight to both drugs; three did not show any change. Duplex Doppler sonography may be of use in the selection of the right pharmacologic treatment for the individual patient for the prevention of a bleeding esophageal varix.

Delayed-Action Preparations↗
PubMed2002

[The influence of isosorbide mononitrate on skin blood flow in patients with Raynaud's syndrome].

The influence of isosorbide mononitrate on skin blood flow in the pulp of finger by means of laser-Doppler flowmetry was evaluated in 19 women with Raynaud's syndrome. Skin blood flow changes were measured after cooling the hand. Isosorbide mononitrate decreased the influence of cooling on skin blood flow in the pulp of finger. This finding supports the theory that endothelial dysfunction is one of the reasons of Raynaud's syndrome. We suppose that application of isosorbide mononitrate should be useful in prevention and the treatment of Raynaud's phenomenon attacks.

Female↗