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At least 505 records · Page 28Linked to original sources
PubMed2006

[Favourable results with local injections of botulinum-A toxin in patients with chronic isosorbide dinitrate ointment-resistant anal fissures].

OBJECTIVE: To determine the effectiveness of injection of botulinum-A toxin in the internal anal sphincter as a treatment for chronic therapy-resistant anal fissures. DESIGN: Prospective. METHODS: In the period October 2002-February 2005, 32 consecutive patients (15 men and 17 women), with a median age of 44 years (range: 23-78 years) and suffering from chronic isosorbide dinitrate ointment-resistant anal fissures, were treated with an injection of 40 IU botulinum-A toxin (Dysport, Ipsen, The Netherlands) in the ventral side of the internal anal sphincter. The injection was given as an outpatient procedure under general or spinal anaesthesia. RESULTS: After a median follow-up of 14 months (range: 2-28 months), the chronic anal fissures were cured in 24 ofthe 32 patients (75%). Twenty-two patients were given a second or a third injection. A fissure recurred in one of the cured patients (4%), and one patient suffered from temporary flatus incontinence. CONCLUSION: Botulinum-A toxin injections were effective in 75% of patients with isosorbide dinitrate ointment-resistant chronic anal fissures. This is a simple technique with fewer side effects than local application of NO donors and fewer complications and less morbidity than surgical sphincterotomy.

Adult↗
PubMedDate not supplied

[Isosorbide dinitrate tolerance in the treatment of patients with angina pectoris and the effect of addition of captopril on therapeutic results].

The authors investigated in patients with stable angina the influence of a single dose and of long-term administration of isosorbide dinitrate alone and combined with captopril. Administration of 40 mg Iso-Mack ret. every 8 hours for four weeks did not lead to the development of tolerance. However, captopril added to isosorbide dinitrate tends to improve the investigated indicators after a single dose as well as after long-term treatment. It is probable that concurrent administration of the two drugs causes addition of their vasodilatating action and thus the vascular resistance declines, as well as the cardiac pre-load and after-load and the oxygen consumption of the heart muscle. The authors discuss possible mechanisms of the increased vasodilatation after addition of captopril.

Adult↗
PubMedDate not supplied

[New drug forms of isosorbide dinitrate: the problem of an objective evaluation in patients with ischemic heart disease].

In 7 patients with ischemic heart disease and stable angina pectoris the efficacy of three oral isosorbide dinitrate (ID) formulations, nitrosorbide, isodinite and isodinite-retard, was compared. The antianginal and anti-ischemic effects were assessed in terms of exercise treadmill tests performed prior to and repeatedly after (2, 5 and 7 hours) single-dose administration (in comparison with placebo). The efficacy of isodinite-retard only slightly differed from that of placebo. Isodinite had a more pronounced effect than nitrosorbide, although the duration of isodinite effect was shorter than that of nitrosorbide. Plasma ID and its metabolite, isosorbide-5-mononitrate concentrations mirrored exercise duration changes. ID content in the tablets of all formulations studied corresponded to those indicated by the manufacturer. The differences in the efficacy of ID formulations can be attributed to the differences in their bioavailability. Thus, the method used permitted to reveal significant distinctions in the efficacy of different ID formulations. These distinctions must be taken into account in clinical practice.

Angina Pectoris↗
PubMed1990

[A new antianginal preparation: isosorbide-5-mononitrate].

Repeated treadmill exercise tests were used in 20 patients with stable exercise-induced angina in order to comparatively examine various dosage forms of isosorbide-5-mononitrate (IMN) and isosorbide dinitrate (ID) during their single administration. The antianginal effect of conventional IMN tablets (Monisid, Bulgaria) lasted about 5 hours and 1-2 hours longer than that shown by long-acting tablets (Olicard, FRG) and lasted on an average of 12 hours. There was a correlation between the antianginal effect of IMN and its blood concentration. A significant individual variability was observed in the potency of all the dosage forms of IMN and ID under study. The dosage form of IMN had antianginal effects that were similar and even superior to those exhibited by ID.

Angina Pectoris↗
PubMed1990

Long-term effect of isosorbide dinitrate and nifedipine, singly and in association, in patients with chronic heart failure.

The effect of 2-month treatment with isosorbide dinitrate (120 mg day-1), nifedipine (2 x 20 mg day-1) and their combination has been assessed in 16 patients with mild to moderate chronic cardiac failure. Isosorbide dinitrate decreased right atrial (-23%), pulmonary wedge (-20%) and pulmonary arterial (-17%) pressures but did not significantly change either cardiac output or systemic and pulmonary vascular resistance. Nifedipine increased cardiac output (+13%) and decreased systemic and pulmonary vascular resistance (both -17%) with no change of pressures. Combined therapy with both drugs decreased ventricular filling pressures (-8% and -15%), systemic (-20%) and pulmonary (-13%) arterial pressures, increased cardiac output (+26%) and decreased both systemic (-29%) and pulmonary (-29%) vascular resistances. Changes during exercise were almost the same as at rest. The effect of both drugs was more pronounced in patients with more severely pathological haemodynamic measurements before treatment. We conclude that combined treatment with both preload- and afterload-reducing agents can preserve or even potentiate a favourable haemodynamic effect of individual drugs.

Blood Pressure↗
PubMed1990

Effect of sublingual isosorbide dinitrate in portal hypertension.

Nitrates decrease portal pressure by decreasing portal venous inflow and resistance. We studied over 20 minutes the effect of 10 mg isosorbide dinitrate sublingual on intrasplenic pulp pressure, mean arterial pressure and heart rate, in 13 patients with cirrhotic or non-cirrhotic portal hypertension. The pulp pressure fell progressively over 20 minutes, from mean 43.6 +/- 2.4 (SEM) to 35.6 +/- 1.8 cm H2O (p less than 0.001). This was accompanied initially by a significant fall in mean arterial pressure (85.8 +/- 1.9 to 80.4 +/- 2.7 mmHg at 4 minutes; p less than 0.01) and rise in heart rate (92.5 +/- 5.0 to 102.6 +/- 5.9 per minute at 6 minutes; p less than 0.02), following which these parameters remained stable. One patient developed giddiness due to hypotension at 15 minutes. We conclude that sublingual isosorbide dinitrate decreases pulp pressure in cirrhotic and non-cirrhotic portal hypertensives, but this is initially accompanied by significant hemodynamic changes.

Administration, Sublingual↗
PubMed1975

[Treatment of ischemic heart disease with beta-receptor blockers and isosorbide dinitrate (author's transl)].

The effects of a beta-receptor blocker (Betadrenol), an isosorbide dinitrate preparation (Isoket) and the combination of the two substances (Betaket) were compared with a placebo in a controlled double blind trial in 20 patients with confirmed attacks of angina pectoris and/or ischemic changes in the ECG on ergometer exercise. Important assessment criteria of the efficacy were regression of ischemic ECG changes on standardized ergometer exercise, increase in load resistance and the nitroglycerine requirement. Treatment with the combination of betablocker and isosorbide dinitrate (Betaket) was more effective in comparison to treatment with the individual substances.

Adrenergic beta-Antagonists↗
PubMed1989

Correlation between isosorbide dinitrate plasma levels and coronary vasodilation after chewing capsules.

In 10 patients with coronary artery disease coronary angiograms were performed in identical projections before and 5, 10 and 15 min after sublingual administration of two chewing capsules with 5 mg of isosorbide dinitrate (ISDN) each. Simultaneously, blood samples were taken for gas-chromatographical determination of nitrate plasma levels. The average ISDN plasma levels amounted to 138 +/- 73 ng/ml, 102 +/- 76 ng/ml and 62 +/- 34 ng/ml in the fifth, tenth and fifteenth min, resp. In the fifteenth min significant isosorbide mononitrate plasma levels (greater than 70 ng/ml) were found only in three patients. Mean diameters of angiographically normal coronary segments were measured with the automatic edge detection system CAAS; they increased by an average of 20 +/- 10%, 26 +/- 11%, and 27 +/- 13% (p less than 0.001) in the fifth, tenth and fifteenth min, resp. Due to hysteresis of the coronary dilation in relation to ISDN plasma levels no significant correlation was found between these parameters. The minimal diameters of seven of 10 coronary stenoses analyzed in seven patients reacted with a maximal increase of 23%-98%. Thus, ISDN chewing capsules may be preferable for rapid and prolonged relief of anginal attacks as well as for potent dilation of epicardial coronary arteries as desired during angiography.

Administration, Sublingual↗
PubMed1989

[Use of isosorbide-5-mononitrate in acute myocardial infarction].

Isosorbide mononitrate in a dose of 20 mg t.i.d. was used in 25 patients admitted few hours after acute myocardial infarction. The following parameters were analysed: systolic and diastolic blood pressure, heart rate, clinical features, and laboratory data. Heart rate and diastolic blood pressure remained unchanged, however systolic blood pressure was slightly reduced (p less than 0.01). There was a reduction in the angina episodes post-AMI. None of the patients included in the study had clinical deterioration or showed infarction extension. There were no changes in laboratory data. After the interruption of the drug, one patient died on the 6th day with acute mitral insufficiency. In conclusion, isosorbide mononitrate can be safely used during an uncomplicated acute myocardial infarction, without the risk of haemodynamic deterioration, and helps to prevent post-infarction angina.

Adult↗
PubMed1989

[Bioavailability of sustained-release and nonsustained-release isosorbide-5-mononitrate].

Bioavailability of Sustained Release and Non Sustained Release Isosorbide-5-Mononitrate. In a randomized, open cross-over study in 18 healthy subjects plasma concentration of isosorbide-5-mononitrate (IS-5-MN) after oral administration was determined over 24 h by gas chromatography. A single dose of three sustained release and two standard preparations was given: (A) a capsule (Elantan), 50 mg; (B) a development tablet, 50 mg and (C) a development capsule, 100 mg; furthermore (D) and (E) non sustained release tablets, 40 and 2 x 20 mg, of two different producers. (D) was considered as reference preparation. Standard preparations (D) and (E) were bioequivalent. But maximum plasma concentrations (cmax) of all sustained release preparations were significantly lower from 13% (C) to 53% (A). Also the moment of maximum plasma concentrations (tmax) occurred significantly later between 2 h 40 min and 3 h 50 min. A significant loss in relative bioavailability was observed for (A) with 82.5% and for (C) with 81.4%. (B) achieved the highest relative bioavailability (93.9%) of the sustained release preparations (n.s.). "Therapeutic concentrations" above 100 ng/ml over 24 h were maintained only by (C). Terminal elimination half-lives were calculated between 5.5 and 6.5 h (mean). Plasma concentration-time curves were simulated in steady state.

Biological Availability↗
PubMed1989

Drug plasma levels and coronary vasodilation after isosorbide dinitrate chewing capsules.

Five, ten and fifteen min after sublingual administration of 10mg isosorbide dinitrate (ISDN) in chewing capsules, in 10 patients with coronary artery disease, ISDN plasma levels were correlated with the dilation of epicardial coronary arteries as well as with changes in aortic blood pressure and heart rate. Due to the rapid and extensive drug absorption, maximal ISDN plasma levels averaged 138 +/- 73 ng ml-1 and were already obtained after 5 min; they declined to 102 +/- 76 and 62 +/- 34 ng ml-1 in the 10th and 15th min respectively. In 7 patients isosorbide mononitrate plasma levels were still negligibly low (less than 30 ng ml-1). Mean diameters of 'normal' coronary segments increased by an average of 20 +/- 10%, 26 +/- 11% and 27 +/- 13% (P less than 0.001) at 5, 10 and 15 min respectively compared to control. The maximal drop in systolic aortic pressure (147 +/- 19 to 115 +/- 15 mmHg; P less than 0.01) as well as the maximal increase in heart rate (66 +/- 4 to 80 +/- 11 beats min-1; P less than 0.01) were observed in the 15th min; diastolic aortic pressure and double product remained constant. Due to the long persistence of coronary dilation and haemodynamic changes, none of these drug effects correlated significantly with the ISDN plasma levels. In addition, the minimal diameters of 10 coronary stenoses were measured in 7 patients; with ISDN 7 stenoses showed dilation ranging from 23% to 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Sublingual↗
PubMed1989

[Effect of isosorbide dinitrate on neutrophil migration in vivo].

The influence of isosorbide dinitrate on polymorphonuclear neutrophils migration into a sterile inflammatory focus was evaluated in 12 patients with ischemic heart disease. The number of neutrophils migrated into the "skin window" increased significantly during treatment with isosorbide. Also granulocyte clearance increased in comparison with control investigation. Possible clinical implications of this phenomenon are discussed.

Adult↗
PubMed1989

[Effects of isosorbide-5-mononitrate on exercise capacity, prostacyclin synthesis, the renin-aldosterone axis and catecholamines in patients with cardiac insufficiency].

Isosorbide-5-mononitrate (IS-5-MN) is an active metabolite of isosorbide dinitrate with a longer plasma half life. Aim of the study was the evaluation of the effects of 40 mg/day of IS-5-MN on exercise capacity in patients with heart failure NYHA class II. After 1 week of wash-out, 10 patients with heart failure NYHA Class II, assumed 20 mg bid for 3 weeks. Bicycle ergometer tests were performed before (A), at the end of therapy (B), and 1 week later (C); in phase B the stress test was performed after 6 hours from the last assumption of IS-5-MN. We measured 24 hour urinary 6K-PGF1 alpha, the stable metabolite of prostacyclin, basal plasma renin activity (PRA) and plasma aldosterone, exercise-release of epinephrine and norepinephrine at the end of each phase of the study. The treatment with IS-5-MN improved the exercise capacity sigma (Watt.min), A less than (B = C), (p less than 0.01), while delta of heart rate (HR) during exercise (basal HR - maximal exercise HR)/(Watt.min), decreased, A greater than (B = C), (p less than 0.008). Basal BP and HR did not change. This fact seems consistent with the hypothesis of a combined effect of nitrates on both the venular and the arteriolar districts. Basal PRA and aldosterone, and catecholamine release during exercise after IS-5-MN did not change, while only norepinephrine increased 1 week after the end of the therapy, (A = B) less than C, (p less than 0.05): 24 hour urinary 6-K-PGF1 alpha increased after IS-5-MN A less than (B = C), (p less than 0.05). The results indicate that medium-term IS-5-MN treatment increases exercise capacity in patients with heart failure NYHA class II and that the effect lasts for 1 week after nitrate withdrawal at least. Prostacyclin is probably involved in medium-term clinical effect of IS-5-MN.

Aged↗
PubMed1989

Bioavailability of isosorbide dinitrate from an oral therapeutic system and from tablet Sorbonit Prolongatum 20,0 in human volunteers.

The bioavailability of isosorbide dinitrate from an oral therapeutic system (OTS) and from tablet Sorbonit Prolongatum 20,0 mg in 6 volunteers employing a crossover method was studied. Concentrations of isosorbide dinitrate (1),2-mononitrate (2) and 5-mononitrate (3) are plotted as mean concentrations for all volunteers. As evident, the concentration-time curves are similar after administration of both OTS and tablet Sorbonit Prolongatum. Concentration of the nitrates in the serum is close to the maximum level starting 2 h after the drugs were administered. Such concentration is nearly constant for 7 h in the case of nonmetabolized 1 and for 9 h for its metabolites. 24 h after administration metabolites 2 and 3 were found in the serum of 5 subjects. Based on the experimental data, we calculated the areas under curves (AUC). The observed differences in AUC appeared statistically insignificant at the 95% confidence level for the two preparations studied in the case both 1 and its metabolites.

Administration, Oral↗
PubMed1989

New isosorbide 5-mononitrate derivative with hypotensive activity.

Synthesis and pharmacological properties of the 5-fluoro-nicotinic ester with isosorbide-5-mononitrate 3 are reported. The new compound shows an in vitro activity on rabbit aortic helical strips five times higher than isosorbide-5-mononitrate. The hypotensive activity in guinea-pigs of 3 is markedly superior to that of 5-ISMN. In the rat 3 shows a bioavailability and an acute toxicity inferior to those of 5-ISMN after oral administration.

Animals↗
PubMed1988

[Hemodynamic action of isosorbide-5-mononitrate during rapid venous administration in patients with acute myocardial infarct].

20 patients with acute myocardial infarction were catheterized with a balloon thermodilution catheter and the hemodynamic changes following a rapid i.v. administration of 10 mg of isosorbide-5-mononitrate were studied up to the 4th hour. The drug causes a fall of the left ventricular filling pressure with 20%, of the arterial pressure with 5%, of the cardiac index with 9%, of the stroke index and of the stroke driving index and a slight increase of the systemic arterial vascular resistance without influencing the cardiac rate and the total pulmonary-vascular resistance. The drug action begins immediately, it is best expressed between the 3d and 30th minute and lasts 1-2 h. The hemodynamic changes are unidirectional in patients with left ventricular filling pressure below and above 1.9 kPa. The i.v. administration of isosorbide-5-mononitrate is indicated in the treatment of acute left cardiac failure in patients with acute myocardial infarction for the rapid reduction of pulmonary congestion and is suited for patients with a tendency toward arterial hypotension.

Adult↗
PubMed1987

Oral isosorbide-5-mononitrate: pharmacokinetics and clinical efficacy.

Isosorbide-5-mononitrate is a longer acting active metabolite than the parent drug, isosorbide dinitrate (ISDN), with a half-life of around 4 hours. In coronary heart disease, myocardial infarction and in heart failure it causes a typical nitrate action on the central hemodynamics, but due to a complete systemic availability with high and predictable systemic drug levels, a drug action with a lower interindividual variability than with ISDN is to be expected. There is a close correlation between serum level and effect. The antianginal exercise tolerance increasing and unwanted effects as well as the development of tolerance to the drug action are comparable with those of ISDN. This naturally long-acting metabolite in ISDN works usually with a standard dosage of 20 mg twice daily.

Administration, Oral↗
PubMed1987

Effects of isosorbide on perilymphatic pressure and oxygenation.

Using a servocontrolled micropipet pressure measuring system, the effect of intravenous and oral administration of isosorbide, a hyperosmolar agent that is an anhydrate of sorbitol, was examined in 11 fasting cats. Following intravenous administration of 2 g/kg of the agent, perilymphatic pressure has shown, on the average, a significant reduction of 136% of the initial value (3.6 +/- 0.3 mm Hg). A strong rebound phenomenon, however, with a 61% rise to the initial value, was noted, and this did not come down in 3 hours. On the contrary, no rebound phenomenon was noted after oral administration, which caused a significant 60% drop in perilymphatic pressure for more than 90 minutes. Using polarographic technique, perilymphatic oxygen tension was measured and showed a maximal increase of 145% to the initial value. The time it took to reach the maximal PO2 tension was equal to the time it took to come down to the minimal perilymphatic pressure. This is a strong indication that isosorbide improves perfusion and increases blood flow of the inner ear vessels.

Administration, Oral↗