Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Isosorbide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed1994

Acute effect of ibopamine and isosorbide mononitrate on blood volume distribution in congestive heart failure.

In order to compare ibopamine (IBO), a dopamine congener, with isosorbide mononitrate (ISMN) and to study their interaction in effects on the capacitance vasculature in congestive heart failure (CHF), a prospective, randomized, placebo-controlled, double-blind clinical trial was performed in 32 patients with New York Heart Association class II-IV CHF, randomly assigned to receive single oral doses of placebo, 200 mg IBO, 20 mg ISMN, or both IBO and ISMN. After labelling of red cells with 99mTc, changes in regional radioactivity, indicative of changes in blood volume, were recorded using a gamma-camera before and at 30, 60 and 120 min after drug administration. At 30 and 60 min, arterial systolic and pulse pressures were higher with IBO than with ISMN and placebo (for pulse pressure by mean 13.7 mmHg, 95% confidence interval 4.5-23.0 mmHg, at 30 min), probably reflecting an IBO-induced rise in stroke volume at unchanged heart rate and mean arterial pressure. IBO did not change regional radioactivity except for a transient increase of 4.4% (0.5-7.6%) in the thorax at 30 min. This was attenuated by concomitant ISMN treatment since, starting at 30 min, the drug increased radioactivity in the legs, compared with patients not receiving the drug, by 8.0% (95% confidence interval 0.2-15.8%), leading to a fall in thoracic and left ventricular radioactivity at 30 min of 3.4% (0.3-7.0%) and 6.4% (0.8-11.9%), respectively, and a fall of 5.5% (0.5-10.5%) in hepatic radioactivity at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Differential effects of the novel NO-donating drug pirsidomine and isosorbide dinitrate on the venous vascular bed.

Sixteen healthy male subjects were investigated on four occasions when they received either placebo, 10 mg isosorbide dinitrate (ISDN), or 2.5 or 10 mg pirsidomine, a novel NO-donating drug. A constant-rate iv. infusion of a subsystemic dose (average 42 ng.min-1, SD 20.5) of noradrenaline in a dorsal hand vein was begun 1 h before drug treatment. It did not cause systemic changes but reduced the venous hand vein diameter by about 50%. This venoconstrictor response was approximately halved by 10 mg ISDN. Pirsidomine, in contrast, did not affect the in situ venoconstrictor responses to noradrenaline. ISDN and pirsidomine reduced systemic resting blood pressure. ISDN and 10 mg pirsidomine were approximately equipotent in reducing systolic blood pressure, both in terms of the duration and the extent of the effect (maximum average reduction of ISDN -6.7, 95% CI -10.3 to -3.0; and 10 mg pirsidomine -7.6, 95% CI -11.3 to -4.0 mmHg, respectively); 2.5 mg pirsidomine was less effective (-4.1, 95% CI -7.8 to -0.5). ISDN and 10 mg pirsidomine were also similarly effective in reducing diastolic blood pressure (ISDN -8.4 mmHg, 95% CI -10.5 to -6.2; 10 mg pirsidomine -6.0 mmHg, 95% CI -8.2 to -3.9; 2.5 mg pirsidomine -2.8 mmHg, 95% CI -5.0 to -0.6) but the effects of ISDN were longer lasting. Although similar with regard to their putative mechanism(s) of action and likely arterial/arteriolar effects, pirsidomine and ISDN seem to affect the venous vascular bed in distinctly different ways.

Adult↗
PubMed1995

Influence and interference of isosorbide dinitrate and food intake on superior mesenteric artery impedance in humans.

The influence of isosorbide dinitrate (ISDN) and food ingestion on superior mesenteric artery impedance was investigated in 24 healthy volunteers (age 40 +/- 2.7 years). Superior mesenteric artery circulation was assessed by duplex ultrasound. Pulsatility index (PI) was considered as a parameter of vascular resistance and was calculated as the peak-to-peak amplitude of the waveform divided by the mean amplitude. The subjects were randomly allocated to four groups (ISDN, meal, ISDN + meal, meal + ISDN). PI measurements were performed in resting and fasting conditions and serially for 1 h after sublingual 5 mg ISDN, ingestion of a 300-kcal, 300-ml mixed liquid meal; sublingual 5 mg ISDN followed 10 min later by the test meal; and ingestion of the test meal followed 5 min later by sublingual 5 mg ISDN. Five minutes after 5 mg sublingual ISDN, PI had increased from 6.8 to 12.4, while after intake of a meal PI had decreased from 7.6 to 4.9. Separate effects of 5 mg ISDN and meal intake lasted for at least 1 h. The reflex vasoconstrictive effect of 5 mg ISDN on the superior mesenteric artery circulation was counterbalanced by ingestion of a meal in healthy volunteers.

Adult↗
PubMed1992

Investigation of a possible pharmacokinetic interaction between ibopamine and isosorbide-5-mononitrate.

The possibility of a pharmacokinetic interaction between isosorbide-5-mononitrate (5-ISMN) and epinine, the active metabolite of ibopamine, has been investigated in 8 healthy male subjects given single doses of 200 mg ibopamine and 20 mg 5-ISMN, separately and together. The plasma 5-ISMN concentration-time profile was the same whether 5-ISMN was administered concomitantly with ibopamine or alone [AUC(o-t): 2.24 micrograms.ml-1.h after 5-ISMN alone, 2.16 micrograms.ml-1.h after 5-ISMN+ibopamine]. The plasma concentrations of total and free epinine and the urinary recovery of total epinine, homovanillic acid and dihydroxyphenylacetic acid, too, were not different when ibopamine was administered alone or concomitantly with 5-ISMN. The intake of ibopamine did not change the blood pressure and heart rate. The decrease in diastolic blood pressure induced by 5-ISMN was not influenced by concomitant intake of ibopamine. The observations suggest that in healthy volunteers there is no pharmacokinetic interaction between 5-ISMN and ibopamine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate.

The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale. A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery. It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.

Adult↗
PubMed1991

Clinical chronopharmacology of oral sustained-release isosorbide-5-mononitrate in healthy subjects.

In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in relation to the individual circadian control values. The pharmacokinetic parameters (Cmax, tmax, AUC, t 1/2) did not differ after morning and after evening dosing, tmax being 5.2 h and 4.9 h, respectively. In contrast, the cardiovascular effects of IS-5-MN were clearly circadian phase-dependent. The maximum decrease in blood pressure decrease and increase in heart rate occurred significantly earlier after the evening (BPsys 2.8 h; BPdia 2.9 h; HR 3.8 h) than after the morning dose (BPsys 5.0 h; BPdia 6.0 h; HR 5.2 h). Thus, the peak haemodynamic effects coincided with the peak drug concentration after the morning dose, whereas the peak effect was in advance of the peak drug concentration after the evening dose of IS-5-MN. The data provide evidence of circadian phase-dependency in the dose-response relationship of oral IS-5-MN.

Administration, Oral↗
PubMed1985

Effectiveness of nicorandil in the preservation of myocardium stressed by transient ischemia and its influence on cardiac metabolism during coronary artery occlusion with subsequent reperfusion: a comparison with isosorbide dinitrate.

This study was designed to investigate the effects of nicorandil in comparison to isosorbide dinitrate (ISDN) on hemodynamics, on myocardial metabolism and on effectiveness in the preservation of ischemically stressed myocardium. Repeated ischemia (3 min) was produced in anaesthetized open-chest mongrel dogs by proximal, intermittent left anterior descending artery occlusion with subsequent reperfusion. In each experiment 2--3 control occlusions were compared to 2--3 occlusions under nicorandil or ISDN. Application of both nicorandil (0.64 mumol X kg-1 body weight, i.v.) and ISDN (1.27 mumol X kg-1 body weight, i.v.) led to a significant afterload reduction and to a decrease of the coronary vascular resistance. The efficiency of the compounds in the protection of ischemic myocardium was examined by quantification of oxygen-debt and oxygen-repayment in the occlusion and reperfusion periods. Compared to control, premedication with nicorandil led to a significant increase of oxygen-debt, whereas ISDN reduced it significantly. Oxygen-repayment remained unchanged. The influence of the drugs on the metabolism of glucose, lactate and free fatty acids (FFA) was examined under basic conditions, in ischemia and during reperfusion. For all substrates, extraction, extraction ratio and oxygen extraction ratio were calculated. Under basic conditions, glucose metabolism was significantly enhanced in both groups but FFA metabolism was inhibited only by ISDN. In ischemia, FFA metabolism was enhanced by nicorandil and depressed by ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Regional differences in the actions of verapamil and isosorbide dinitrate on rabbit and dog vascular smooth muscle.

The effects of verapamil and isosorbide dinitrate (ISDN) alone or together on mechanical responses of the rabbit coronary artery and mesenteric vein, and the dog coronary artery have been investigated. Verapamil, in concentrations exceeding 10 nM consistently inhibited and at 10 microM, blocked the contraction evoked by excess concentrations of K in these tissues, but agonist-induced contraction was not modified by the presence or absence of Ca. In concentrations greater than 1 microM, verapamil depolarized the membrane by inhibiting the K-conductance of the membrane. ISDN had little effect on the rabbit coronary artery in concentrations below 10 microM. In contrast, in the rabbit mesenteric vein and dog coronary artery, ISDN in concentrations over 1 microM inhibited the contraction evoked by excess concentrations of K or by agonists. Species differences were apparent in the actions of ISDN on vascular tissues. When verapamil and ISDN were simultaneously applied to the rabbit mesenteric vein and dog coronary artery, the K-induced contraction was markedly inhibited by an amount exceeding that produced by the sum of the contractions evoked by the individual application of both agents. An enhanced vasodilating action induced by simultaneous applications of both agents indicates a possible clinical benefit for anti-anginal treatment.

Animals↗
PubMed1986

Pharmacokinetics of isosorbide-5-nitrate in renal failure.

The pharmacokinetics of the antianginal drug isosorbide-5-nitrate (IS-5-N) was studied in 20 patients with varying degrees of chronic renal failure after repeated oral doses of standard 20 mg tablets t.d.s. Blood samples were taken in the steady state on the 2nd and 28th days, and the plasma level was assayed by HPLC. There was no statistically significant difference in Cssmax, t1/2 and AUCss0-8 between the 2nd and 28th days, nor was a difference found between patients with mild and severe renal failure.

Aged↗
PubMed1984

Controlled comparison of the pharmacodynamic effects of nicorandil (SG-75) and isosorbide dinitrate in man.

Nicorandil (SG-75) is a long acting mononitrate. A randomized, double-blind, crossover study in 10 healthy subjects has compared the haemodynamic actions of single sublingual doses of nicorandil 15, 30 and 60 mg with Isosorbide dinitrate (ISDN) 5 mg and placebo. Heart rate, blood pressure, systolic time intervals (STI) and left ventricular echocardiograms were used to assess haemodynamics over a 6 h period. Within 15 min of nicorandil administration, heart rate increased and peripheral resistance decreased (dose-dependent); the preejection period (corrected; PEPc) and the ratio of PEP to left ventricular ejection time (LVET) - PEP/LVET - were shortened by the 60 mg dose; the heart rate corrected electromechanical systole (QS2c) was almost unchanged; left ventricular end diastolic and systolic diameters (EDD and ESD) were diminished. The effects on certain parameters had not completely disappeared after 6 h. ISDN produced a similar pattern with somewhat less intense effects; although PEPc and PEP/LVET were prolonged. The effects of both drugs can be attributed to vasodilatation on both the arteriolar and venous sides. The predominant action of ISDN was to reduce preload and thereby to lengthen PEPc and PEP/LVET; in addition, it lessened afterload. Although nicorandil caused a distinct reduction in preload, as shown by the smaller EDD, the effects of afterload reduction were predominant at the high dose induced shortening of PEPc and PEP/LVET. The profile of action of nicorandil should encourage clinical testing to evaluate its ability to induce ventricular unloading.

Adult↗
PubMed1983

Haemodynamic and clinical effects of isosorbide-dinitrate in patients with severe effort angina on beta-blocking treatment.

The effect of isosorbide-dinitrate (ISDN) 20 mg 4 times daily against placebo has been tested in 12 patients with stable effort induced angina pectoris receiving prophylactic treatment with metoprolol. ISDN did not decrease the attack rate or nitroglycerine consumption, nor was exercise tolerance increased after it. Left ventricular function, assessed by radionuclide ventriculography, increased in 6 out of 8 patients (p less than 0.1). It is concluded that ISDN has no place in the treatment of haemodynamically intact patients with severe angina pectoris in spite of beta-blocking treatment, but that it may be of value in the treatment of patients with left ventricular failure, including those whose left ventricular failure has been brought about by beta-blocking treatment necessitated by angina pectoris.

Adult↗
PubMed1986

Effect of sublingual isosorbide dinitrate on sputum volume and viscoelasticity in chronic obstructive lung disease.

The effect of isosorbide dinitrate (ISDN) on sputum volume and sputum viscoelasticity in 12 patients with chronic obstructive lung diseases (COLD) was investigated by the double-blind randomized cross-over method with matched placebo. Each patient was given either sublingual ISDN 5 mg or placebo at 9 a.m. and sputum was collected for 3 h before and after 9 a.m. The dynamic viscoelasticity of the sputum was measured using a coaxial cylinder rheometer at an angular frequency of 0.1 rad/s. ISDN significantly increased sputum volume, and it caused a significant decrease in dynamic viscosity and in dynamic elasticity compared to placebo. The findings suggest that ISDN might be useful as an expectorant in the treatment of COLD when abundant and viscous sputum is present.

Adult↗
PubMed1986

Isosorbide dinitrate in plasma and dialysate during haemodialysis.

In 10 patients with end stage renal disease on regular haemodialysis the plasma concentrations and dialyzer clearance of isosorbide dinitrate (ISDN) were determined after an oral dose of a retarded release formulation of 60 mg ISDN. The maximal plasma concentration of ISDN 2-7 h after oral administration was higher (14 ng/ml) than has been reported in healthy volunteers. The haemodialyzer clearance of ISDN was 92.4 ml/min at a blood flow of 200 ml/min and dialysate flow of 500 ml/min. During a 5-h haemodialysis an average of 0.3 mg ISDN was removed from the patient's circulation, representing about 0.5% of the administered dose and about 3% of the available drug in the circulation. No influence of haemodialysis on the plasma level of ISDN was found.

Aged↗
PubMed1986

Isosorbide-5-mononitrate in the treatment of acute left ventricular failure following acute myocardial infarction.

Eleven patients with acute left ventricular failure following acute myocardial infarction (mean pulmonary capillary wedge pressure [PCW] greater than 20 mmHg) were entered into an open, haemodynamic study of oral isosorbide-5-mononitrate (ISMN). Left ventricular failure was resistant to intravenous diuretic therapy. No patient received concurrent cardioactive drugs nor further diuretic therapy during the study period. Haemodynamic data were acquired via a flow-directed thermodilution catheter placed in the pulmonary artery. Baseline data were acquired prior to the intravenous administration of an ISMN challenge. Thereafter, oral ISMN (20 mg, 8 hourly) was administered over 48 h. Following intravenous ISMN challenge, mean PCW fell from 26.2 to 17.5 mmHg. Cardiac index fell from 2.4 to 2.3 l/min/m2 due to a fall in heart rate (103 to 96.8 beats/min) as stroke volume and blood pressure were unchanged. At 8 h following ISMN, two patients were withdrawn due to hypotension (systolic pressure less than 85 mmHg). In the remainder, PCW remained acceptable throughout 48 h (13.1 mmHg at 48 h), cardiac output, systemic blood pressure and heart rate showed no further significant change. These data suggest that ISMN is effective in the treatment of acute left ventricular failure following acute myocardial infarction.

Adult↗
PubMed1984

Bronchodilator effect of sublingual isosorbide dinitrate in asthma.

The bronchodilating effect of 5 mg sublingual isosorbide dinitrate (ISDN) was studied in 10 patients with bronchial asthma, using the double-blind randomised cross-over method with matched placebo. In a further 20 asthmatics the effect of sublingual ISDN was compared with that of metaproterenol given by a metered dose inhaler to a total dose of 2.25 mg, again using the cross-over method. The forced oscillation method was used to measure respiratory resistance (Rrs) and spirometry was used to measure vital capacity (VC) and forced expiratory volume in one second (FEV1). 5 minutes after administration of ISDN Rrs had decreased (p less than 0.05) and VC (p less than 0.01) and FEV1 (p less than 0.01) were significantly increased. The changes were still present after 15, 30 and 60 min. The placebo had no significant effect. ISDN increased FEV1 less than metaproterenol, and the difference between them was statistically significant (p less than 0.05). However, there was no significant difference between ISDN and metaproterenol in the improvement in Rrs and VC. Of the total of 30 patients, 11 experienced headache and 4 had transient hypotension after ISDN administration. These side effects subsided spontaneously. It was concluded that sublingual ISDN had a bronchodilating effect in stable asthmatics.

Adult↗
PubMed1987

Pharmacokinetics of isosorbide-5-nitrate during haemodialysis and peritoneal dialysis.

The pharmacokinetics of isosorbide-5-nitrate (IS-5-N) was studied in ten patients on haemodialysis (HD) after a single oral dose of 20 mg IS-5-N, and in six patients on continuous ambulatory peritoneal dialysis (CAPD) after repeated oral doses of 3 X 20 mg IS-5-N. There was significant removal of IS-5-N from blood during HD; Cmax decreased by about 20%, AUC(0-8 h) by 30% and t1/2 by about 20% from 4.3 to 3.4 h, and plasma clearance was increased by 81 ml/min. No important loss of IS-5-N was observed in patients on CAPD.

Adult↗
PubMed1989

Effects of diltiazem and isosorbide-5-mononitrate, alone and in combination, on patients with stable angina pectoris.

The anti-anginal effect of sustained release diltiazem, isosorbide-5-mononitrate (IS-5-MN) and their combination has been evaluated in 25 patients in 4 blinded treatment periods of 2 weeks each. The number of anginal attacks during each treatment period was reduced from a mean of 23 during placebo to 15 during diltiazem and 15 during combination therapy, but it was not significantly changed after IS-5-MN-20. A similar pattern was seen for nitroglycerin consumption and number of angina-free days. Maximal exercise capacity was also significantly improved following diltiazem and the drug combination, and it was not changed after IS-5-MN. ST segment depression was less pronounced after diltiazem and the combination compared to IS-5-MN. There was no difference in exercise capacity or ST segment change between diltiazem and the combination. The PR interval was slightly prolonged after diltiazem, but this was of no clinical importance. Adverse effects of diltiazem treatment were rare. Headache was common following IS-5-MN (13 patients) and the combination (11 patients). Thus, sustained-release diltiazem was of value in the treatment of chronic stable angina pectoris, whereas IS-5-MN was not effective, either as a single therapy or in combination with diltiazem. The reason for the inefficacy of IS-5-MN is not known, but the development of tolerance and an inadequate dose are possible explanations.

Adult↗
PubMed1993

Influence of isosorbide dinitrate on superior mesenteric artery impedance in humans.

In a randomized, double-blind, placebo-controlled crossover study the acute effect of isosorbide dinitrate (ISDN) on the superior mesenteric artery velocity waveform was studied in 10 healthy subjects (mean age 48.2 years) over a 10-minute period. The superior mesenteric artery pulsatility index (PI), which quantifies the blood velocity waveform, increased from the second minute following sublingual administration of 5 mg ISDN (basal PI 4.88 +/- 0.32) and reached its upper level (8.22 +/- 1.38) from the fourth minute on. In comparison with placebo, the significant rise of PI (second minute) occurred before the significant decrease of systolic blood pressure (ninth minute) and before the significant increase in the heart rate (fourth minute). Diastolic and mean arterial blood pressures remained unchanged. These observations suggest an immediate vasoconstrictive effect of ISDN on the resistance vessels of the vascular bed of the superior mesenteric artery.

Aged↗