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PubMed1992

Isosorbide dinitrate spray. Attenuation of cardiovascular responses to laryngoscopy and intubation.

We evaluated the efficacy of isosorbide dinitrate buccal spray (Isomack) in attenuating the cardiovascular response to laryngoscopy and tracheal intubation in 60 patients undergoing elective surgery under general anaesthesia. Patients were allocated to one of three groups of 20 patients each. Group 1 patients were administered placebo buccal spray 90 s before induction of anaesthesia. Groups 2 and 3 had isosorbide dinitrate spray 30 and 90 s before induction of anaesthesia. Systolic, diastolic and mean arterial pressures and heart rate were monitored. After the spray, group 3 patients had a significant decrease in systolic arterial pressure (p less than 0.01). At 1 min after intubation, systolic, diastolic and mean arterial pressures showed a significant increase in group 1 patients (24.9 mmHg, 14.2 mmHg and 18.7 mmHg respectively). In contrast, groups 2 and 3 showed a significant decrease in these parameters (p less than 0.01). Although significant tachycardia was present following intubation in all the three groups, the degree of tachycardia was greater in groups 2 and 3 (p less than 0.01).

Adolescent↗
PubMed1990

Lack of effect of verapamil and isosorbide dinitrate on the hepatic clearance of indocyanine green in cirrhosis.

1. Vasodilators are currently under investigation as possible therapeutic agents in the treatment of portal hypertension. Among them calcium-channel antagonists and organic nitrates have been of particular interest. Few and conflicting data, however, have been reported on their effect on liver function. 2. Twenty patients with biopsy-proven alcoholic cirrhosis were studied before and 25-35 min following the acute administration of 5 mg verapamil i.v. (eight patients) or 5 mg isosorbide dinitrate sublingually (12 patients). The plasma clearance of indocyanine green (ICG) and its intrinsic hepatic clearance were used as indices of liver function. Seven further patients were investigated before and after a placebo infusion according to the same methodology. 3. No significant change in ICG kinetics was found after verapamil or isosorbide dinitrate.

Adult↗
PubMed1983

Analysis and microbiological stability of an isosorbide 50% mixture.

Isosorbide mixture containing 50% w/v isosorbide and 5% w/v sorbitol is used in the treatment of hydrocephalus. The G.L.C. analysis of the mixture is described and its antimicrobial properties investigated. Results for the determination of lead in the mixture are given and the significance of the levels discussed with relevance to the treatment of infants.

Bacteria↗
PubMed1983

Isosorbide in the management of infantile hydrocephalus.

Experience with 101 hydrocephalic infants treated primarily with isosorbide is reported. For those with moderate hydrocephalus the aim was to avoid shunt surgery, and this was achieved in 31 of the 43 infants. In cases with severe hydrocephalus or when the cerebrospinal fluid was abnormal the aim was to delay shunt surgery until the optimum time, with a lower risk of complications. Five of 48 such infants avoided shunts and 30 achieved a worthwhile delay. Nine other children were treated with isosorbide following shunt complications. Toxic effects were infrequent, not severe, and reversible on stopping treatment or reducing dosage. 63 infants eventually had shunts inserted.

Cerebrospinal Fluid Shunts↗
PubMed1984

Hypotensive effects and biotransformation of nicorandil, a new antianginal agent, administered to rats by different routes: comparison with nitroglycerin and isosorbide dinitrate.

The effects of nicorandil, N-(2-hydroxyethyl)nicotinamide nitrate (ester), in reducing systemic blood pressure (SBP) in rats were studied in comparison with isosorbide dinitrate and nitroglycerin. The drugs were administered to pentobarbitone-anaesthetized rats by jugular vein (i.v.), portal vein (p.v.), intrajejunal (i.j.), intraperitoneal (i.p.) and subcutaneous (s.c.) routes. Nicorandil was absorbed rapidly through all routes, and caused marked hypotension dose-dependently. With isosorbide dinitrate and nitroglycerin, unlike nicorandil, the p.v. dose required to induce a vasodepressor response was significantly greater than that required to cause a comparable response after i.v. administration. In non-recirculating rat liver perfusion experiments, nicorandil was reduced only 5-10% during a single passage through the liver, while nitroglycerin was reduced over 95%. In recirculating liver perfusion experiments, the progressive decrease of nicorandil in the blood recirculated was accompanied by a corresponding increase of SG-86, a dinitrate compound of nicorandil (its main metabolite). Sixty min after dosing, nicorandil was decreased by approximately 73% of the initial nicorandil blood concentration and SG-86 was increased by approximately 70%. The extent of degradation of nicorandil in liver homogenates, examined by thin-layer chromatography, was in the following order: rat = guinea-pig greater than dog = monkey greater than pig. In these species a close inverse relationship is apparent between the rate of liver nicorandil degradation and hypotensive effects of nicorandil.

Animals↗
PubMed1975

Isosorbide in treatment of infantile hydrocephalus.

This paper reports the experiences of the second clinical trial in the use of isosorbide in the treatment of 34 selected cases of infantile hydrocephalus of all types. Subject to careful biochemical monitoring of serum electrolyte, urea, and acid-base balance, treatment with 2 g/kg body weight 6-hourly is safe. Side effects are immediately eliminated by interrupting therapy. With lower dosage, prolonged maintenance therapy was possible, for as long as 11 months, without side effects and with need for much less frequent biochemical monitoring. Isosorbide effectively prevented the need for shunt therapy in 10 of 34 patients, including 3 infants with uncomplicated congenital hydrocephalus of moderate degree and infants whose hydrocephalus was associated with spina bifida and whose cerebral mantle was between 20 to 25 mm. In posthaemorrhagic and postmeningitic hydrocephalus valuable time was gained before shunt therapy until the infant and his CSF were fit for operation.

Adolescent↗
PubMed1999

Effect of isosorbide mononitrate on the human optic nerve and choroidal circulations.

AIMS: To assess the effects of the nitric oxide donor 5-isosorbide mononitrate (ISMO) on blood flow in the optic nerve head (ON flow) and choroid (Ch flow). METHODS: Laser Doppler flowmetry was used to measure ON flow and Ch flow in 12 normal subjects by aiming the laser beam at the fovea and at the temporal rim, respectively. In a double masked, randomised, crossover design, each subject received orally on separate days either 20 mg of 5-isosorbide mononitrate (ISMO) or placebo. Ch flow and ON flow were determined monocularly at baseline and 1 hour after dosing. In the last six subjects, additional measurements were obtained at 3 hours. Mean arterial blood pressure (BPm), heart rate, and intraocular pressure (IOP) were monitored, and ocular perfusion pressure (PP) was estimated. RESULTS: No significant changes in ON flow, PP, IOP, or BPm were observed following placebo. Following ISMO, ON flow increased from baseline by 19.8% (SEM 9.3%) at 1 hour (paired t test, p = 0.058) and by 33.1% (7.5%) at 3 hours (p = 0.007). Compared with the changes following placebo, statistically significant increases in ON flow were observed both at 1 (p = 0.050) and 3 hours (p = 0.041) after ISMO treatment. Compared with placebo, PP decreased significantly 1 hour after ISMO dosing (p = 0.039), mainly as a function of reduced BPm. A significant inverse correlation (R = -0.618; p = 0.032) was observed between the percentage changes in PP and ON flow 1 hour following ISMO administration, but not after placebo. No significant change in foveal Ch flow was documented. CONCLUSIONS: These results suggest that, in normal subjects, ISMO increases significantly ON flow but not Ch flow. The inverse correlation observed between PP and ON flow suggests that the same mechanism(s) responsible for systemic vasodilatation and blood pressure decrease may also cause the ON flow increase.

Adult↗
PubMed1973

Double-blind evaluation of verapamil, propranolol, and isosorbide dinitrate against a placebo in the treatment of angina pectoris.

In the treatment of angina pectoris a double-blind evaluation of verapamil (Cordilox) at two dose levels-namely, 80 mg thrice daily and 120 mg thrice daily-propranolol (Inderal) 100 mg thrice daily, and isosorbide dinitrate (Vascardin) 20 mg thrice daily has been made against a placebo. The assessment was based on relief from daily attacks of angina on effort and the response to a whole-body exercise test. We can find no statistically significant difference between the effects of verapamil (120 mg three times a day) and propranolol (100 mg three times a day) in the treatment of angina of effort. Both of these preparations are more effective than a placebo both in the reduction of daily attacks (P < 0.01) and in the prolongation of exercise test (P < 0.05). Isosorbide dinitrate (20 mg three times a day) appears to be no more effective than a placebo in the treatment of angina on effort, but 14 out of 32 patients experienced headache of such severity that even when the dose was reduced to 10 mg thrice daily this drug therapy had to be withdrawn. Both propranolol (100 mg three times a day) and verapamil (120 mg three times a day) had a significant lowering effect on the diastolic blood pressure as measured with the patient standing (P < 0.01).

Adult↗
PubMed1985

Assessment of dermal glyceryl trinitrate and isosorbide dinitrate for patients with angina pectoris.

Dermal nitrate preparations are claimed to be useful in the treatment of angina, as their slow absorption by-passing the liver leads to a sustained action. Ten patients with angina were exercised on a treadmill after dermal application of 16.64 mg glyceryl trinitrate or 100 mg isosorbide dinitrate or placebo. Exercise duration was significantly increased at one and three hours for both nitrate preparations but not at six hours after application. The calculated workload achieved was significantly increased (p less than 0.01) at one and three hours for both preparations and at six hours (p less than 0.05) for isosorbide dinitrate. Headaches were common with glyceryl trinitrate cream. The dermal nitrate preparations studied had a duration of antianginal action similar to that of oral nitrate tablets. Aside from their value when the oral route cannot be used or absorption may be delayed, dermal nitrate preparations have no advantage over oral preparations for angina pectoris.

Administration, Topical↗
PubMed1996

Topical treatment of erectile dysfunction: randomised double blind placebo controlled trial of cream containing aminophylline, isosorbide dinitrate, and co-dergocrine mesylate.

OBJECTIVE: To examine the effectiveness in treating impotence to topically applied cream containing three vasodilators--aminophylline, isosorbide dinitrate, and co-dergocrine mesylate--which act by different mechanisms. DESIGN: Randomised double blinded placebo controlled crossover trial over two weeks. SUBJECTS: 36 men with erectile dysfunction randomly allocated to two equal groups. INTERVENTIONS: Active cream containing aminophylline 3%, isosorbide dinitrate 0.25%, and co-dergocrine mesylate 0.05% for one week and placebo for another. MAIN OUTCOME MEASURES: Patients' reported experience of penile responses and side effects of treatment in questionnaires. Penile tumescence and arterial flow in the laboratory. RESULTS: 21 patients reported full erection and satisfactory intercourse with the active cream. Three men reported full erection and satisfactory intercourse with either cream. The active cream was more effective in psychogenic than organic impotence (eight out of nine men with psychogenic impotence achieved a full erection upsilon four out of eight with neurogenic impotence and two out of seven with arterial insufficiency). No major side effects were reported. In the laboratory the active cream increased penile arterial flow (0.19 (SD 0.08) m/s upsilon 0.02 (0.15) m/s with placebo) and induced tumescence in 24 patients. CONCLUSIONS: Topical treatment with a cream containing three different vasodilators might be considered before intracavernous injection of vasoactive agents, particularly in psychogenic impotence.

Administration, Topical↗
PubMed1985

Endoscopic variceal pressure measurements: response to isosorbide dinitrate.

An endoscopic pressure sensor has been evaluated in the measurement of oesophageal variceal pressure and its response to drug ingestion. The variceal pressure showed a highly significant correlation with the splenic pulp pressure (r = 0.97) in six patients with liver disease of diverse aetiology and with hepatic venous wedge pressure (r = 0.92) in eight alcoholic cirrhotic men. Intraduodenal infusion of isosorbide dinitrate in the cirrhotics produced no change in wedge pressure or endoscopic variceal pressure despite profound falls in arterial systolic pressure. Thus isosorbide dinitrate appears to be of no value in treating portal hypertension. This study establishes the endoscopic pressure sensor as a valuable tool in screening drugs in this condition.

Adult↗
PubMed1977

Vasodilator therapy in acute myocardial infarction. Use of sublingual isosorbide dinitrate.

The haemodynamic effect of a long-acting vasodilator isosorbide dinitrate has been studied in 10 patients after an acute myocardial infarct, all of whom had evidence of left ventricular failure. Left ventricular filling pressure measured as the mean pulmonary artery wedge pressure was raised in all patients and fell significantly from 20+/-6 to 13+/-5 mmHg (P less than 0-001) within 10 minutes of sublingual isosorbide dinitrate. This 35 per cent fall in left ventricular preload was accompanied by significant fall in mean pulmonary artery pressure from 30+/-7 to 20+/-4 mmHg (P +less than 0-001) and mean right atrial pressure from 11+/-3 to 6+/-2 mmHg but cardiac output measured by thermodilution was unchanged. Mean systemic blood pressure was also significantly reduced. This improvement in left ventricular performance resulting from a reduction in left ventricular filling pressure and systemic blood pressure indicates that there may be a place for long-acting vasodilator in the treatment of acute myocardial infarction.

Aged↗
PubMed1989

Biotransformation of glyceryl trinitrate and isosorbide dinitrate in vascular smooth muscle made tolerant to organic nitrates.

It has been proposed that organic nitrates are prodrugs and biotransformation to a pharmacologically active metabolite (i.e., nitric oxide) must occur before the onset of vasodilation. If this postulated mechanism is correct, tolerance to organic nitrate-induced vasodilation might involve decreased biotransformation of organic nitrates by vascular smooth muscle. In this study, biotransformation of isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN) was estimated by measuring isosorbide mononitrate (ISMN) and glyceryl dinitrate (GDN), respectively, rather than the nitrate anion, because of a more sensitive method for measurement of ISMN and GDN. To test this hypothesis, isolated rabbit aortic strips (RAS) were made tolerant in vitro by incubation with 500 microM GTN or ISDN for 1 h. After a washout period and submaximal contraction with phenylephrine, the tissues were incubated with either 2.0 microM [14C]ISDN or 0.5 microM [14C]GTN for 2 min. ISDN- or GTN-induced relaxation of RAS was monitored and tissue parent drug and metabolite contents were determined by thin-layer chromatography and liquid scintillation spectrometry. ISDN- and GTN-induced relaxation of RAS and the metabolite concentrations were significantly less for both GTN- and ISDN-tolerant tissue compared with nontolerant tissue. These results are consistent with the hypothesis that organic nitrate biotransformation is required for organic nitrate-induced vasodilation.

Animals↗
PubMed2006

Antidiuretic hormone and osmolality in isosorbide therapy and glycerol test.

Changes in plasma antidiuretic hormone (p-ADH) and plasma osmolality (p-Osm) levels were studied in 63 patients with Ménière's disease before and after isosorbide administration and a glycerol test. Increments in both p-ADH and p-Osm levels were observed after isosorbide administration and the glycerol test. The p-ADH secretion appeared to be secondarily stimulated by an increase in the p-Osm level. This p-ADH level increase affects cochlear fluid homeostasis. Based on these results, we must consider both the p-Osm and p-ADH levels when treating patients with Ménière's disease by osmotic diuretics.

Audiometry, Pure-Tone↗
PubMed1981

Polarcardiographic (triaxicardiometric) study on the effect of isosorbide dinitrate on exercise-induced myocardial ischemia.

30 patients suffering from stable angina pectoris were studied by triaxicardiometric (polarcardiographic) method. Triaxicardiometry including the X, Y, Z Frank leads, azimuth (H degrees), elevation (V degrees) angle derivations and spatial magnitude (M) tracings were taken at rest and after submaximal bicycle ergometer exercise. After receiving 30 mg/day isosorbide dinitrate for a minimum of 5 days the whole procedure was repeated, stored by an analogue tape recorder and evaluated by a TPA/i computer. It has been stated that the method of triaxicardiometry has an excess sensitivity on the demonstration of ischemic alteration of anterior and posterobasal left ventricular wall compared to the traditional X, Y, Z leads. According to the pre- and post-exercise bicycle ergometer testing estimated by triaxicardiometry, isosorbide dinitrate caused a significant reduction of subendocardial myocardial ischemia.

Angina Pectoris↗
PubMed1987

Controlled study of the haemodynamic effects of isosorbide 5-mononitrate in acute myocardial infarction.

In view of the favourable results of the short-term therapy of acute myocardial infarction (AMI) with glyceryl-trinitrate (GTN) infusion, we undertook a randomized study to test the hypothesis whether the administration of a single dose of isosorbide 5-mononitrate (IS 5-MN) given orally would have the same favourable haemodynamic effect as observed with GTN infusion. For this purpose we evaluated the haemodynamic effects of IS 5-MN compared to isosorbide dinitrate (ISDN), observed in the same group of patients. 10 patients (8 males, 2 females) aged 50-76 years (mean 63) with AMI (7 anterior, 3 inferior) admitted to the coronary care unit within 48 h from onset of symptoms were entered into this single-blind randomized study; at the time of study entry, 8 patients were in Killip class I, and 2 patients in Killip class II. All drugs with haemodynamic effects were withdrawn 12 h before the study started. Both the haemodynamic profile and the clinical status were stable in all patients. Haemodynamic parameters were recorded with a Swan-Ganz thermodilution catheter, cardiac output was measured by the thermodilution method, and the left ventricular ejection time was calculated according to the Weissler method. The echo left ventricular end-diastolic diameter was measured by evaluation of the M-mode echocardiographic recording.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1987

Calcium channel blocker and isosorbide 5-mononitrate in the management of chronic cardiac failure.

In the management of the patient with chronic cardiac failure, the combination of an arteriolar vasodilator and venodilator should be beneficial. 8 patients with NYHA grade III-IV chronic cardiac failure were studied following placebo, after 4 weeks' therapy with the arteriolar vasodilator felodipine, and with the combination of felodipine and oral isosorbide 5-mononitrate. Haemodynamic measurements were made at rest and during dynamic exercise at an individual, fixed, near maximal workload. Ejection fraction (EF) was obtained by gated radionuclide ventriculography. At rest, heart rate was unchanged 73 +/- 6 at control, 72 +/- 4 with felodipine and 74 +/- 4 beats/min with the addition of isosorbide 5-mononitrate. Mean arterial pressure fell from 98 +/- 5 to 84 +/- 4 (p less than 0.02) and 84 +/- 3 mm Hg (p less than 0.02) with nitrate. Cardiac index increased from 2.2 +/- 0.1 to 2.5 +/- 0.2 litres/min/m2 with felodipine and further to 2.6 +/- 0.2 litres/min/m2 (p less than 0.02) with nitrate. Exercise tachycardia and mean arterial pressure were not significantly affected by therapy. Cardiac index increased on exercise from 4.4 +/- 0.3 to 4.8 +/- 0.3 litres/min/m2 with felodipine and 4.9 +/- 0.3 litres/min/m2 (p less than 0.05) with the addition of nitrate. Stroke volume index increased from 35.4 +/- 4 to 40.8 +/- 4 beats/min/m2 and further to 41.0 +/- 4 beats/min/m2 (p less than 0.05) and EF from 14 +/- 3 to 18 +/- 3% with nitrate. In conclusion, in patients with chronic cardiac failure, treatment with a calcium channel blocker produced sustained haemodynamic improvement, particularly on exercise, and combination with nitrate produced further benefit.

Chronic Disease↗
PubMed1994

Doppler diastolic transmitral flow patterns in severe heart failure: response to controlled changes in filling pressure using intravenous isosorbide dinitrate.

Serial Doppler diastolic transmitral flow patterns were compared with simultaneous hemodynamic measurements in a homogeneous group of patients with severe (New York Heart Association class 4) heart failure who were receiving high dose (508 +/- 271 micrograms/min) intravenous isosorbide dinitrate. The Doppler tracing uniformly showed a severe restrictive pattern, with tall peak early diastolic filling (E) wave (84 +/- 12 cm/s), small late filling (A) wave (28 +/- 8 cm/s) and very high E/A ratio (3.2 +/- 0.8). Isosorbide dinitrate decreased wedge pressure and systemic vascular resistance by a third and increased cardiac index by more than 40%. Transmitral Doppler E/A ratio changed directly in relation to the changes in pulmonary capillary wedge (r = 0.85, p = 0.03) and right atrial pressure (r = 0.84, p = 0.03), indicating preload dependence of transmitral flow velocity, even in severe heart failure.

Aged↗