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At least 217 records · Page 12Linked to original sources
PubMed2003

[Favorable results of conservative treatment with isosorbide dinitrate in 25 patients with fourth-degree hemorrhoids: a pilot study].

OBJECTIVE: To evaluate application of isosorbide dinitrate 1% ointment in the treatment of fourth-degree haemorrhoids. DESIGN: Prospective pilot study. METHOD: Twenty-five consecutive patients, 12 men and 13 women, with a median age of 48 years (range: 30-78), presenting in the period October 1999-December 2001 with fourth-degree haemorrhoids, were treated with isosorbide dinitrate 1% ointment. RESULTS: In 24 out of 25 patients (96%) the objective, reduction of the stangulated haemorrhoids and relief of pain, was achieved. In one patient the haemorrhoids were not reduced. This patient was cured after classic haemorrhoidectomy. Two patients interrupted the treatment because of severe headache, but after renewed instructions they continued the therapy and were cured. CONCLUSION: Isosorbide dinitrate 1% ointment gave good results in the treatment of fourth-degree haemorrhoids, with only few side effects.

Administration, Topical↗
PubMed1984

Regional myocardial dysfunction in patients with angina at rest and response to isosorbide dinitrate assessed by phase analysis of radionuclide ventriculograms.

Left and right ventricular synchrony was assessed in 15 patients with angina at rest but no previous infarction by phase analysis of equilibrium radionuclide ventriculograms. Transient thallium-201 perfusion defects were noted in all during angina at rest and coronary vasospasm was documented in nine of the patients. Radionuclide ventriculograms were performed at control, during the ischemic episodes and after intravenous isosorbide dinitrate. Left and right ventricular phase histograms were quantified by the standard deviation from the mean of the peak (SD). Left ventricular ejection fraction averaged 65 +/- 11% (mean +/- standard deviation) at control, decreased in all patients during angina at rest to 49 +/- 14% (p less than 0.01) and increased in all patients after isosorbide dinitrate to 66 +/- 12%. However, ejection fraction during ischemia was abnormal in only nine patients and changed in two by less than 5% from the control value. Regional wall motion abnormalities were noted in all patients during the ischemic episodes but resolved after isosorbide dinitrate administration. Control left ventricular SD was 14.5 +/- 4 degrees, increased in all patients to 22.8 +/- 5 degrees during angina at rest (p less than 0.01) and returned to control values after isosorbide dinitrate administration (14.2 +/- 4 degrees). In contrast, right ventricular SD did not significantly change during ischemia as compared with control and isosorbide dinitrate. It is concluded that in angina at rest, a normal left ventricular ejection fraction does not exclude severe regional dysfunction; separate left and right ventricular SD is a sensitive index in detecting transient left ventricular dysfunction, and relief of ischemia is associated with rapid normalization of regional left ventricular function.

Adult↗
PubMed1998

Head-up tilt testing potentiated with low-dose sublingual isosorbide dinitrate: a simplified time-saving approach for the evaluation of unexplained syncope.

BACKGROUND: Head-up tilt testing is widely used in the clinical assessment of patients with unexplained syncope. However, the lack of a standard methodology and the conflicting results concerning sensitivity and specificity of the procedure have prompted further studies to define a more cost-effective approach for tilt testing. OBJECTIVES: Our clinical investigation was undertaken to assess the diagnostic value in unexplained syncope of a simple and time-saving protocol for head-up tilt testing, including low-dose sublingual isosorbide dinitrate administration. PATIENTS AND METHODS: A group of 73 consecutive patients (43 women and 30 men, mean age 39.6+/-21.8 years) with unexplained syncope despite conventional clinical cardiovascular and neurologic assessment and 10 asymptomatic control subjects underwent head-up tilt testing with isosorbide dinitrate challenge. Participants were tilted at 60 degrees for 30 minutes without medication; if no symptoms occurred, 1.25 mg of isosorbide dinitrate was administered sublingually and tilting was continued for an additional 15 minutes. RESULTS: During the drug-free phase of the test 14 (19.2%) patients had syncope. After isosorbide dinitrate administration syncope occurred in another 28 patients (38.3%); minor symptoms in association with hypotension developed in 10 (13.7%) patients. The test result was negative in all control subjects. The positive rate and specificity of head-up tilt testing with isosorbide dinitrate provocation were 57.5% and 100%, respectively. CONCLUSIONS: This new practical diagnostic procedure was found to be fairly sensitive and clearly specific in inducing a vasovagal reflex in patients with syncope of uncertain origin. Consequently, such approach could give a significant contribution in the diagnostic workup of these patients.

Administration, Sublingual↗
PubMedDate not supplied

[Effect of isosorbide dinitrate on the lower esophageal sphincter pressure in patients with Chagas' disease].

The effect of 5 mg of sublingual isosorbide dinitrate on the lower esophageal sphincter pressure of 28 chagasic patients with esophageal involvement, was studied by continuous perfusion manometry. The pressure was measured at 5 minute intervals for 60 minutes after drug administration. Isosorbide dinitrate reduced sphincter pressure from 5 to 60 minutes (p less than 0.01). Only two patients hadn't sphincter pressure reduced lower than 50% of initial value at 20 minutes after drug administration. These results indicate that isosorbide dinitrate may be useful to reduce lower esophageal sphincter pressure in chagasic megaesophagus.

Adult↗
PubMed1976

Isosorbide dinitrate for the relief of severe heart failure after myocardial infarction.

Severe congestive heart failure secondary to myocardial infarction remains a difficult management problem. Although intravenous vasodilators and mechanical assist devices have been reported to improve the depressed hemodynamic function, these interventions are limited to the intensive care unit and cannot be used for long-term management. This study evaluates the hemodynamic and symptomatic response to sublingual administration to isosorbide dinitrate (5 to 10 mg) in seven consecutive patients with severe congestive heart failure after anterior wall myocardial infarction. Serial measurements of mean right atrial and pulmonary arterial end-diastolic pressure, mean blood pressure, heart rate and cardiac output were obtained during the control period and during the 4 hours after administration of isosorbide dinitrate. The peak response occurred approximately 30 minutes after drug administration with an 83 percent reduction in mean right atrial pressure (from 6 to 1 mm Hg, P less than 0.02), a 36 percent reduction in pulmonary arterial end-diastolic pressure (from 25 to 16 mm Hg, P less than 0.0001) and a 6 percent reduction in mean blood pressure (from 94 to 88 mm Hg (P less than 0.05). There were small but statistically not significant increases in cardiac index (from 2.3 to 2.6 liters/min per m2 and stroke work index (from 26 to 32 gm/beat per m2). The total systemic vascular resistance was reduced by 5 percent from 1,605 to 1,518 dynes sec cm-5 (P less than 0.10). The baseline heart rate of 105 beats/min was not significantly changed. The reduction in pulmonary arterial end-diastolic pressure became statistically significant (P less than 0.05) between 15 and 30 minutes after administration of isosorbide dinitrate and remained significant for 3 to 4 hours. This reduction of pulmonary arterial end-diastolic pressure to less than 22 mm Hg was associated with relief of the patients' pulmonary symptoms. The response to nitroglycerin (0.4 mg) was similar in magnitude but of much shorter duration (approximately 15 minutes for nitroglycerin versus 4 hours for isosorbide dinitrate in patients with and without congestive heart failure. The slope (calculated by dividing the change in cardiac index or stroke work index by the change in pulmonary arterial end-diastolic pressure) was significantly (P less than 0.05) depressed in the patients with congestive heart failure. These data demonstrate that the symptomatic pulmonary venous hypertension can be effectively relieved by isosorbide dinitrate without further compromising left ventricular function.

Blood Pressure↗
PubMed1985

Isosorbide dinitrate sublingual therapy for inferior myocardial infarction: randomized trial to assess infarct size limitation.

To assess the potential of isosorbide dinitrate sublingual therapy for limiting myocardial infarct size, 41 patients with inferior acute myocardial infarction (AMI) were studied. Twenty patients were randomly assigned to the control group and 21 to the treatment group. Patients in the treatment group received 10 mg of isosorbide dinitrate every 2 hours for 72 hours. To estimate infarct size, QRS scoring, peak creatine kinase (CK) serum levels and CK curves were used. There were no significant differences between the 2 groups in maximal or cumulative activity of CK or QRS score (percent of left ventricle infarcted: 16% in the control group, 17% in the treatment group). In both groups the QRS score increased significantly by 13 hours after AMI, and the increase was highly significant by 19 to 23 hours. Thus, sublingual isosorbide dinitrate at the dosage given did not reduce infarct size in patients with inferior AMI.

Administration, Oral↗
PubMed1991

[Bioavailability and bioequivalence of organic nitrates. Isosorbide dinitrate--a study of sustained-release preparations].

Assessment of Bioavailability of Organic Nitrates/Comparative bioavailability study of sustained-release isosorbide dinitrate preparations. Relative bioavailabilities of isosorbide dinitrate (ISDN, CAS 87-33-2) and the metabolite isosorbide-5-mononitrate (IS-5-MN, CAS 16051-77-7) were studied after application of Maycor retard 40 (sustained-release capsules, multiple unit formulation, test preparation) in comparison to sustained-release tablets (single unit formulation, reference preparation) with 16 healthy male volunteers in a two-way crossover design. Test and reference formulations were previously characterised in vitro by dissolution tests. ISDN, IS-5-MN (IS-2-MN) plasma concentrations were determined using a selective and sensitive GLC-method with ECD-detection. As pharmacokinetic parameters AUC, Cmax and half value duration (HVD) were evaluated. Bioequivalence was assessed by calculating 90%-confidence intervals (ANOVA, ANOVAlog, Mann-Whitney-test) for ISDN and IS-5-MN. Bioequivalence was accepted if due to the inclusion rule one of the calculated intervals fulfill the requirements of 80 and 120% (AUC) or 70 and 130% (Cmax, HVD), respectively. Relative bioavailability of the test formulation was calculated as 94% (ISDN) and 96% (IS-5-MN). Maximum plasma concentrations of ISDN (IS-5-MN) were determined for the test preparation as 14.3 +/- 3.1 ng/ml (265 +/- 45 45 ng/ml) and as 22.8 +/- 12.6 ng/ml (287 +/- 59 ng/ml) for the reference product. HVD-values were for the test preparation 4.5 +/- 1.3 h (ISDN) and 8.5 +/- 1.3 h (IS-5-MN) and for the reference formulation 3.1 +/- 1.2 h (ISDN) and 8.1 +/- 1.4 (IS-5-MN).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1988

The effects of an intravenous infusion of isosorbide dinitrate during open heart surgery.

Recent awareness of right ventricular dysfunction during open heart surgery has focused attention upon the importance of protection of the right ventricle and control of right ventricular afterload for the maintenance of the cardiac output. Conventional doses of systemic vasodilators, when used to reduce pulmonary vascular resistance, may produce systemic hypotension, reduce coronary arterial perfusion and even lower the cardiac output. A study of the effects of bolus intravenous isosorbide dinitrate during open heart surgery showed that following cardiopulmonary bypass intravenous isosorbide dinitrate produced highly significant falls in pulmonary artery pressure and induced active pulmonary vasodilatation without systemic side-effects or reduced atrial filling procedures. Treatment with intravenous isosorbide dinitrate by low-dose infusion during and after open heart surgery significantly lowered mean pulmonary artery pressure and pulmonary vascular resistance (P less than 0.001) in patients receiving no sympathomimetic drug support. The results suggest that possibly the effect of low-dose isosorbide dinitrate following cardiopulmonary by-pass is exerted predominantly on the right ventricular afterload if systemic arterial pressure is not elevated. This may have applications in the management of pulmonary hypertension and of acute right heart failure following cardiac surgery.

Adult↗
PubMed1998

Vasodilator therapy of hypertensive acute left ventricular failure: comparison of captopril-prazosin with hydralazine-isosorbide dinitrate.

A prospective study to evaluate and compare the cardiorespiratory effects and clinical efficacy of the Neurohormonal inhibitors (Captopril 50 mg+prazosin 1 mg only) and direct arteriolar and venular dilators (Intravenous hydralazine 30 mg+oral isosorbide dinitrate 30 mg) used as vasodilator therapy, was undertaken in a randomized, single blind study in 17 Nigerian patients with hypertensive acute left ventricular failure. Both vasodilator regimes separately and significantly reduced the systolic and diastolic blood pressures (P<0.001 ANOVA), heart rate (P<0.001 ANOVA), and the respiratory rate (P<0.05 ANOVA), the double product, but increased the peak expiratory flow rate (P<0.05 ANOVA). However, the neurohormonal antagonists, captopril and prazosin (n=9) caused a statistically significantly greater reduction in heart rate (P<0.05 ANOVA) respiratory rate (P<0.05 ANOVA) and induced a significantly greater increase in the self-paced exercise capacity, 24 h after initiation of treatment, (P<0.02) compared to the hydralazine and isosorbide dinitrate combination (n=8). Five of the nine patients on the neurohormonal antagonist therapy were ambulant at 24 h, compared to none of the eight patients receiving conventional venular and arteriolar dilators hydralazine and isosorbide dinitrate (chi2=5.84 dfi P<0.05). There was a significant inverse correlation between the systolic blood pressure heart rate product, and the distance covered during symptom limited self paced exercise capacity (r=-0.58, P=0.0146 ANOVA). One of eight patients in the hydralazine+isosorbide nitrate combination died, but there was no mortality in the captopril+prazosin group. These findings collectively suggest that captopril+prazosin combination may be a superior vasodilator therapy compared to hydralazine-isosorbide dinitrate, in hypertensive acute pulmonary oedema.

Adult↗
PubMed1985

[Comparative study of the bioavailability and pharmacokinetics of isosorbide dinitrate formulations in retard form and in standard preparations by determination of isosorbide-5-mononitrate].

The aim of the study was to determine the relative bioavailability and the pharmacokinetic parameters following administration of a slow-release formulation of isosorbide dinitrate (ISDN, Isdin) capsules (20, 40 and 60 mg). A gas chromatographic method was used to determine the plasma concentrations of ISDN and isosorbide-5-mononitrate (IS-5-MN). All of the required pharmacokinetic parameters were ascertained. The study was performed on 12 healthy volunteers in a steady-state crossover design. A comparison of the areas under the plasma concentration/time curves of the test preparations and the commercial preparations showed higher values for the test preparations in all of the investigations. However, these values were only statistically significant for the 40 and 60 mg formulations ISDN and the 60 mg formulation IS-5-MN.

Biological Availability↗
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↗
PubMed1992

Reduction of portal pressure by chronic administration of isosorbide dinitrate in patients with cirrhosis: effects on systemic and splanchnic hemodynamics and liver function.

We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis.

Adult↗
PubMed1983

Bioavailability of isosorbide dinitrate and its two mononitrate metabolites from sustained-release formulations.

Plasma concentrations and bioavailability of isosorbide dinitrate (ISDN) and its active metabolites isosorbide 2-mononitrate (2-ISMN) and isosorbide 5-mononitrate (5-ISMN) from two sustained-release formulations and one standard-release formulation of isosorbide dinitrate were compared. Means of peak drug concentrations of ISDN, 2-ISMN, and 5-ISMN after administration of the 20-mg sustained-release formulation were 5.5, 24.4, and 129.1 ng/ml, respectively, at 3.1, 4.2, and 4.5 h; after the 40-mg sustained-release formulation, they were 10.9, 44.0, and 214.5 ng/ml, respectively, at 4.2, 6.3, and 6.7 h; and after the 20-mg standard formulation, they were 19.1, 34.7, and 159.2 ng/ml, respectively, at 0.5, 1.0, and 1.5 h. As might be expected, peak concentrations and their times of occurrence were statistically significantly different when results from the sustained-release formulation were compared to those from the standard formulation. Plasma drug concentrations were detectable for longer after administration of the sustained-release formulations. The extent of bioavailability of ISDN, 2-ISMN, and 5-ISMN from the three formulations as estimated from the areas under the plasma drug concentration - time curves were not statistically significantly different (p greater than 0.05). The ratios for relative drug bioavailability from the respective formulations were similar whether ISDN, 2-ISMN, or 5-ISMN data were used for calculation. Reasons are discussed for the biphasic decline of plasma ISDN concentrations (half-lives 26 min and 5.1 h) obtained after administration of the standard-release formulation.

Adolescent↗
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↗
PubMed1986

Effects of isosorbide dinitrate on rheumatic and non-rheumatic mitral regurgitation.

Isosorbide dinitrate was given to seven patients with isolated mitral regurgitation (three cases of rheumatic origin, four non-rheumatic) to assess its hemodynamic effects. The pulmonary capillary pressure, left ventricular end-diastolic pressure, left ventricular end-diastolic volume index, and the aortic pressure were all significantly reduced. The heart rate was significantly increased, while the systemic vascular resistance and the left ventricular contractility index were unchanged. The regurgitant flow increased by an average of 72.2% in the rheumatic group, but decreased by an average of 4.8% in the non-rheumatic group (p < 0.05). The forward cardiac output decreased slightly in both groups, but the difference was not significant (NS). It appears that isosorbide dinitrate has a more detrimental effect on cases of mitral regurgitation of rheumatic origin than on those of non-rheumatic origin. We suggest the difference in the responses is a consequence of the dynamic nature of the regurgitant orifice in the non-rheumatic group and the static nature of the orifice in the rheumatic group.

Journal Article↗
PubMed1996

The effect of isosorbide dinitrate on uterine artery and umbilical artery flow velocity waveforms at mid-pregnancy.

OBJECTIVE: To study the effect of isosorbide dinitrate, a nitric oxide donor, on the maternal cardiovascular system and on uterine and umbilical artery blood flow velocities in mid-pregnancy. METHODS: Eighteen women with low-risk pregnancy at 17-24 weeks' gestation were given a single 5-mg dose of sublingual isosorbide dinitrate, a nitrovasodilator. Blood flow velocity waveforms in the ascending uterine artery and in the umbilical artery were measured by an image-directed, pulsed color Doppler ultrasound scan before and after the medication was administered. Maternal blood pressure (BP) and heart rate were also obtained. RESULTS: The mean arterial BP decreased from 86 mmHg (95% confidence interval [CI] 72-99) to a nadir of 73 mmHg at 6 minutes (95% CI 61-85, P < .04). Mean maternal heart rate increased from 85 beats per minute (95% CI 80-90) to 96 beats per minute at 6 minutes (95% CI 87-105, P < .01). Mean systolic-diastolic flow velocity ratio (S/D) in the umbilical artery rapidly declined from 4.18 (95% CI 3.80-4.56), reaching a nadir of 3.12 at 6 minutes (95% CI 2.65-3.84, P < .001). The S/D in the uterine artery decreased from 4.83 (95% CI 3.99-5.56) to a nadir of 4.02 at 10 minutes (95% CI 3.41-4.63, P < .001). CONCLUSION: Isosorbide dinitrate, a donor of nitric acid, lowers mean maternal BP and reduces the Doppler impedance in the umbilical and uterine arteries. This drug could prove to be beneficial when endothelial cell dysfunction leads to insufficient synthesis and release of endothelium-derived relaxing factor, resulting in generalized vasoconstriction and increased resistance to flow in the uteroplacental circulation.

Adolescent↗
PubMed1990

Altered hemodynamic response to isosorbide dinitrate in essential hypertension.

Relaxation produced by nitrates on venous, arteriolar, and large arterial vessels is well known but has never been studied in human hypertensive aortas studied in vivo. In this investigation, the effects of acute oral administration of 20 mg of isosorbide dinitrate were evaluated in 12 patients with sustained essential hypertension and nine normotensives of the same age. Noninvasive measurements of systolic, diastolic, and mean arterial pressure, carotid-femoral pulse wave velocity and aortic-arch diastolic diameter using suprasternal echocardiography were determined before and 3 hours after drug administration. In normal subjects, isosorbid dinitrate significantly decreased systolic blood pressure and pulse pressure but did not affect diastolic and mean arterial pressure. In contrast, in hypertensives, the same dosage of isosorbid dinitrate decreased together systolic, diastolic mean, and pulse pressure. In both populations, pulse wave velocity decreased significantly whereas aortic arch diastolic diameter increased markedly. The increase was observed mainly in normal subjects. The study provided evidence that (1) both in normal subjects and hypertensives, isosorbide dinitrate caused an increase in aortic diameter together with an increase in arterial distensibility; and (2) the changes in mean arterial pressure were significant only in hypertensives, indicating that the altered vasodilator response in essential hypertension is not endothelium-mediated.

Administration, Oral↗