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PubMed1999

Long-acting isosorbide mononitrate.

Elantan long (EL) is the only long-acting isosorbide mononitrate formulation based on a controlled membrane principle. 30% of the dose is available for immediate release and the remaining 70% is gradually released over time. After oral administration, isosorbide mononitrate EL has a quick onset of action (30 minutes) and effects are evident for up to 17 hours. The antianginal effects of once-daily isosorbide mononitrate EL 50 to 100mg were generally similar to those of conventional isosorbide mononitrate or isosorbide dinitrate 10 to 20mg twice or 3 times daily, or sustained-release nifedipine 20mg twice or 3 times daily. Patients tended to show a better response with once-daily isosorbide mononitrate EL 50mg than with bupranolol 100mg. Patients showed significantly greater improvement in some quality-of-life indices with once-daily isosorbide mononitrate EL than with twice or 3 times daily regimens of conventional isosorbide mononitrate or isosorbide dinitrate. Tolerance did not develop after 13 months of once-daily administration of isosorbide mononitrate EL. No rebound increase in incidence of ischaemic episodes was observed after discontinuation of the drug.

Angina Pectoris↗

PubMed1989

Lack of effect of asymmetrical dosage timing of isosorbide-5-mononitrate on nitrate tolerance during long-term administration.

Isosorbide 5-mononitrate is an active metabolite of isosorbide dinitrate and possesses many theoretical advantages over its parent drug. However, the development of partial tolerance has been demonstrated when the drug is given 12 hourly or 8 hourly. We have therefore evaluated the acute and sustained (2 weeks) effects of isosorbide-5-mononitrate 40 mg given twice daily (08.00 h and 14.00 h, allowing an 18-h dose-free period) in 19 patients with stable chronic angina, using computerized exercise testing and a placebo-controlled, double-blind, randomized trial protocol. There were two phases of 2 weeks each in which patients received placebo or active isosorbide-5-mononitrate. Acute testing was performed 2 h after the first dose and chronic testing 2 h after the morning dose on Day 14. Acute testing showed an increase in exercise time from a mean (SD) of 6.7 (2.2) min to 10.1 (2.95) min (P less than 0.01) after a single dose of isosorbide-5-mononitrate 40 mg. The time to 1 mm of ST depression, and rest and peak exercise heart rates increased significantly during acute testing with isosorbide-5-mononitrate; resting and peak exercise systolic blood pressures fell significantly. Due to drop outs cross-over analysis was performed on 11 patients who completed both chronic phases and 13 patients were assessed for the comparison of acute isosorbide-5-mononitrate with chronic isosorbide-5-mononitrate. After 2 weeks of therapy exercise time did not show a sustained increase 8.01 (2.14) min chronic placebo to 8.58 (1.93) min chronic isosorbide-5-mononitrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1982

Randomized double-blind comparison of nifedipine and isosorbide dinitrate in patients with coronary arterial spasm.

The effects of nifedinpine and isosorbide dinitrate on the frequency of angina and consumption of nitroglycerin were studied in 19 patients with coronary arterial spasm. After a lead-in phase, the patients were randomized to treatment with either nifedipine or isosorbide dinitrate. After dose titration (40 to 120 mg/day) and evaluation, they were given the alternate therapy. During the initial segment of the double-blind phase, one patient died suddenly (nifedipine phase), one dropped out of the study (nifedipine phase) and another was unable to tolerate therapy (isosorbide dinitrate phase). In the other 16 patients, the mean frequency of angina was less during therapy with both nifedipine (0.69 episode/day, p less than 0.05) and isosorbide dinitrate (0.77 episode/day, p less than 0.05) phases than during the lead-in phase (1.71 episodes/day). The mean frequency of angina was similar in the nifedipine and isosorbide dinitrate phases. A 50 percent or greater decrease in frequency of angina compared with lead-in phase values occurred in 13 of 18 patients during treatment with nifedipine and in 10 of 16 during treatment with isosorbide dinitrate. Of the 16 patients who completed both double-blind phases, 7 showed greater improvement (that is, a 50 percent or greater decrease in frequency of angina) with nifedipine than with isosorbide dinitrate); 6 others showed greater improvement with isosorbide dinitrate, and the other 3 had a less than 50 percent difference in frequency of angina with the two drugs. These findings in a limited number of patients suggest that both nifedipine and isosorbide dinitrate are effective in certain patients with coronary spasm but that neither drug is clearly superior.

Adult↗

PubMed1998

Vascular hyporeactivity persists despite increased contractility after long-term administration of isosorbide dinitrate in portal hypertensive rats.

BACKGROUND/AIMS: Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamics. Isosorbide dinitrate is an effective portal hypotensive drug. The present study aimed to investigate whether chronic administration of isosorbide dinitrate could affect vascular responsiveness in portal hypertensive rats. METHODS: Portal hypertension was induced by partial portal vein ligation. Sham-operated (Sham) rats served as controls. There were four animal groups for this study: portal vein ligation-isosorbide dinitrate group, portal vein ligation-vehicle (Veh) group, Sham-isosorbide dinitrate group and Sham-Veh group. Isosorbide dinitrate (5 mg x kg(-1) x 12 h(-1) was given by gavage for 8 days starting 1 day before ligation and continuing thereafter. Mesenteric arteries were removed for contractile study after hemodynamic measurement. RESULTS: Contractile responses to KCI (15-90 mM) and phenylephrine (10(-9)-10(-4) M) were recorded. Both vascular reactivity and sensitivity were significantly reduced in portal vein ligation rats as compared to Sham rats. Chronic isosorbide dinitrate treatment reduced portal venous pressure in portal vein ligation rats. Moreover, the maximal contractile responses to KCl and phenylephrine were significantly enhanced in both portal vein ligation and Sham rats after isosorbide dinitrate treatment, but relative hyporeactivity persisted in portal vein ligation rats. In contrast, a single dose of isosorbide dinitrate did not alter the contractile sensitivity or reactivity to KCl or phenylephrine in either portal vein ligation or Sham rats. CONCLUSION: Our results show that long-term administration of isosorbide dinitrate enhanced vascular contractility in both portal vein ligation and Sham rats, but relative hyporeactivity persisted in portal vein ligation rats.

Administration, Oral↗

PubMed1997

Gastric emptying of semisolid meal unaltered by 3 days' administration of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate.

BACKGROUND: Evidence has accumulated that nitric oxide is involved in the regulation of gastrointestinal motor activity. We investigated whether nitric oxide derived from a sustained-release isosorbide dinitrate (Cedocard retard) had an effect on gastric emptying and on subjective feelings. METHODS: Twelve healthy males aged 23-32 years received at weekly intervals, for 3 days twice daily, either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate, or placebo, under random double-blind conditions. After a further dose on day 4, subjects ate a 1168 kJ semisolid meal, the emptying of which was recorded scintigraphically for 50 min. RESULTS: Neither dosage of isosorbide dinitrate had an effect on emptying which differed from the effect of placebo and the effects of the two dosages were the same. The radioactivity remaining in the stomach 50 min postprandially was 68.5% +/- 4.5 S.E.M. after placebo, 65.4 +/- 5.6% after 20 mg isosorbide dinitrate and 66.1 +/- 4.4% after 40 mg isosorbide dinitrate. With 40 mg isosorbide dinitrate, all 12 subjects complained of persistent headache, whereas only slight headache was reported by 7 subjects on 20 mg isosorbide dinitrate and by 1 subject on placebo. CONCLUSION: Twenty and 40 mg doses of sustained-release isosorbide dinitrate twice daily had no effect on the gastric emptying of a semisolid meal, but dose-dependently induced headaches.

Adult↗

PubMed1985

Randomized crossover trial of isosorbide mononitrate (Elantan 20) and slow-release glyceryl trinitrate in the treatment of angina pectoris.

An open, randomized, comparative crossover clinical trial was carried out to compare the clinical efficacy of 20 mg isosorbide mononitrate 3-times daily and 6.4 mg sustained-release glyceryl trinitrate 3-times daily in the treatment of angina pectoris. Fifty patients entered the trial and 48 patients completed. Each treatment was given for 12 weeks followed by crossover to the alternative drug. Both treatments resulted in marked significant improvements relative to the pre-trial baseline, but isosorbide mononitrate was shown to be significantly (p less than 0.001) more efficacious than sustained-release glyceryl trinitrate in the reduction of the number of angina attacks and sub-lingual glyceryl trinitrate consumption. Angina frequency was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 33 (69%) of the patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 3 (6%) patients (p less than 0.001). Sub-lingual glyceryl trinitrate consumption was lower with isosorbide mononitrate than with sustained-release glyceryl trinitrate in 36 (75%) patients, but lower with sustained-release glyceryl trinitrate than with isosorbide mononitrate in only 5 (10%) patients. Examination of the effect of changing from isosorbide mononitrate to sustained-release glyceryl trinitrate therapy or vice versa confirmed the clinical superiority of isosorbide mononitrate. Physical exercise capacity was reported as improved in 20 (60%) patients with isosorbide mononitrate but in only 12 (25%) patients with sustained-release glyceryl trinitrate (p less than 0.02). Neither treatment showed any tendency for a reduction in effect during 12-weeks' continuous therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

[Effects of intravenous infusion of isosorbide dinitrate on hemodynamics during anesthesia and surgery].

Ninety nine patients with ischemic changes of the heart on preoperative and intraoperative ECG tracings were studied to evaluate effects of intravenous infusion of isosorbide dinitrate on hemodynamics during anesthesia and surgery. These patients ranging in ages from 24 to 80 years were administered intravenous isosorbide dinitrate at a rate of either 0.5 or 1 microgram.kg-1 x min-1 during anesthesia and surgery. Arterial blood pressure was not influenced with intravenous isosorbide dinitrate at the speed of 0.5 microgram.kg-1 x min-1 during anesthesia and surgery. The arterial pressure of the patients decreased slightly but significantly 30 min after the start of 1 microgram.kg-1 x min-1 of isosorbide dinitrate infusion, but it recovered to the control level at the end of administration of isosorbide dinitrate. Heart rate was unchanged with intravenous isosorbide dinitrate during anesthesia and surgery in both groups, except a mild increase at the end of isosorbide dinitrate infusion of 1 microgram.kg-1 x min-1. Arterial blood oxygen tension showed no decrease during the administration of isosorbide dinitrate and no adverse reactions associated with administration of the drug was detected in this study. Significant improvement of ischemic changes on ECG tracings were observed in about 25% of the patients who received 1 micrograms.kg-1 x min-1 of intravenous isosorbide dinitrate.

Adult↗

PubMed1983

Use of isosorbide dinitrate saliva concentrations for biopharmaceutical investigations.

The concentration of isosorbide dinitrate in paired samples of plasma and mixed saliva was monitored for up to 24 hr after oral administration of 60 mg of sustained-release isosorbide dinitrate to eight healthy volunteers. Measured isosorbide dinitrate plasma concentrations were mainly in the range of 0.1-10 ng/ml. Isosorbide dinitrate was excreted into saliva resulting in a mean (+/- SD) saliva-plasma concentration ratio of 0.68 +/- 0.37. A significant correlation between concentrations of isosorbide dinitrate in saliva and plasma was found (p less than 0.01). The sustained-release properties of the administered formulation were confirmed from the concentrations of isosorbide dinitrate found in both saliva and plasma. Saliva-plasma ratios were independent of the absolute concentrations of isosorbide dinitrate but showed a slight tendency to decrease with time. The principal factor relating saliva and plasma isosorbide dinitrate concentrations appeared to be the degree of plasma protein binding of the drug.

Adolescent↗

PubMedDate not supplied

Haemodynamic interactions between the novel calcium sensitiser levosimendan and isosorbide-5-mononitrate in healthy subjects.

OBJECTIVE: The new calcium sensitiser levosimendan also possesses vasodilatory effects due to potassium-channel opening. The aim of the present study was to assess the possible haemodynamic interactions between levosimendan and isosorbide-5-mononitrate in young healthy men. METHODS: The study was crossover, placebo controlled, double blind, randomised, and it comprised of four study days with one medication--levosimendan, isosorbide-5-mononitrate, levosimendan plus isosorbide-5-mononitrate or placebo--given on each. Levosimendan was administered i.v. as an initial bolus dose of 12 microg/kg over 10 min, followed by a continuous infusion of 0.2 microg/kg/min for a total time of 2 h. Isosorbide-5-mononitrate (20 mg) was given orally as a single dose. Leg blood flow and venous capacity (venous occlusion plethysmography), cardiac output (impedance cardiography), skin blood flow (laser-Doppler flowmetry), blood pressure and heart rate were recorded at baseline, and 20 min, 1 h, 2 h, 4 h and 6 h after the start of the infusion. An orthostatic test was performed at baseline and at 2 h 15 min. Twelve healthy, male subjects were included. Their mean age was 24 years (range 20-34 years). RESULTS: Levosimendan increased leg blood flow by 32%, and no additive effect of the combination of levosimendan and isosorbide-5-mononitrate was observed. The effects of levosimendan on heart rate and blood pressure were minimal and in close conformity with previous studies. In general, there were no additive effects of the combination compared with each drug alone at rest. The only additive effect was seen in the orthostatic response. Heart rate increased by 40 beats min(-1) with the combination (95% confidence interval compared with placebo 11-24 beats min(-1)), by 30 beats min(-1) with levosimendan (2-15 beats min(-1)), by 28 beats min(-1) with isosorbide-5-mononitrate (1-15 beats min(-1)), and by 22 beats min(-1) with placebo. Furthermore, three subjects were unable to stand upright for the stipulated time with the combination, and the orthostatic test had to be discontinued prematurely. There were no changes in the conduction intervals in the electrocardiogram on any of the treatments. The combination had no influence on the occurrence of headache compared with isosorbide-5-mononitrate alone. CONCLUSION: No major additive haemodynamic effects of the combination of levosimendan and isosorbide-5-mononitrate compared with each drug alone could be observed at rest. However, during an orthostatic test, the circulatory response was significantly potentiated with the combination, and three of the subjects were unable to stand upright for the stipulated time.

Adult↗

PubMed1987

Hemodynamic evaluation of isosorbide dinitrate in alcoholic cirrhosis. Pharmacokinetic-hemodynamic interactions.

Isosorbide dinitrate, a long-acting organic nitrate, has been shown to decrease portal pressure in the experimental animal and humans. We conducted a double-blind randomized hemodynamic evaluation of the effects of placebo and 10 mg and 20 mg isosorbide dinitrate in stable individuals with alcoholic cirrhosis. Baseline values for all three groups were similar. Isosorbide dinitrate resulted in a peak reduction of the hepatic venous gradient of 24.7% +/- 3.0%, with significantly decreased values 4 h after the administration of the 20-mg dose. A reduction of arterial pressure and cardiac index (peak decrease of 25.7% +/- 1.5%) was well tolerated by 13 of 15 patients. Changes in mean arterial pressure were not predictive of modifications in the hepatic vein wedge pressure. There was no relation between the area under the plasma isosorbide dinitrate concentration curve and hemodynamic changes. Levels of isosorbide-5-mononitrate, a vasoactive metabolite, were detectable for an 8-h period. Isosorbide dinitrate significantly reduced portal pressure in stable cirrhotics, in association with systemic hemodynamic changes. Thus, titration of isosorbide dinitrate is required to maximize hemodynamic benefits in individual patients. As the decrease in portal pressure is more predictable than the effect of previously tested pharmacologic agents, isosorbide dinitrate should be evaluated for its efficacy in the management of portal hypertension.

Blood Pressure↗

PubMed2006

The "PRIM" study: a randomized comparison of prostaglandin E2 gel with the nitric oxide donor isosorbide mononitrate for cervical ripening before the induction of labor at term.

OBJECTIVE: The purpose of this study was to compare the efficacy and safety profile of prostaglandin E2 with isosorbide mononitrate for cervical ripening before the induction of labor at term. STUDY DESIGN: Primigravid women were assigned randomly to receive either 40 mg of isosorbide mononitrate or 2 mg of prostaglandin E2. Efficacy outcomes were the cervical ripening effect of each agent and the time from treatment initiation to delivery. Safety outcomes were the incidence and frequency of maternal side effects and events that would be potentially hazardous for mother and baby during outpatient cervical ripening. RESULTS: Prostaglandin E2 was more effective than isosorbide mononitrate in inducing a change in modified Bishop score. Mean duration from treatment initiation to delivery was greater for isosorbide mononitrate than prostaglandin E2. There were no adverse events in the isosorbide mononitrate group that would contraindicate outpatient treatment. However, in the prostaglandin E2 group, 7% of the pregnancies had abnormal fetal heart rate patterns (P = .0002). Maternal satisfaction was significantly higher in the isosorbide mononitrate group. CONCLUSION: Although isosorbide mononitrate was less effective, maternal satisfaction was significantly greater. The safety profile of each agent was such that it would be reasonable to give isosorbide mononitrate, but not prostaglandin E2, on an outpatient basis.

Adult↗

PubMed1996

Effects of isosorbide-5-mononitrate on variceal pressure and systemic and splanchnic haemodynamics in patients with cirrhosis.

BACKGROUND: Isosorbide-5-mononitrate is a long-acting nitrovasodilator which was introduced for the treatment of portal hypertension because of its capacity to reduce portal pressure. In contrast to vasoconstrictors, isosorbide-5-mononitrate acts primarily by decreasing portal-collateral resistance without deleterious effects on liver function, although at high doses, a reflex splanchnic vasoconstriction elicited by the fall in arterial pressure may further decrease portal pressure. However, there is no information on the effects of isosorbide-5-mononitrate on variceal pressure, which is thought to be a major determinant of variceal haemorrhage. METHODS: We investigated the effects of isosorbide-5-mononitrate (40 mg, orally; n = 12) or placebo (n = 10) on variceal pressure (non-invasive endoscopic gauge) and hepatic haemodynamics in 22 patients with cirrhosis. RESULTS: Placebo administration had no significant effects. In contrast, isosorbide-5-mononitrate significantly reduced variceal pressure (from 13.5 +/- 3.6 to 9.8 +/- 3.2 mmHg, p < 0.005). This was associated with a fall in wedged hepatic venous pressure (from 28 +/- 5.8 to 25.9 +/- 6.2 mmHg, p < 0.005), hepatic venous pressure gradient (from 20 +/- 4 to 18 +/- 4.7 mmHg, p < 0.005) and azygos blood flow (from 668 +/- 197 to 597 +/- 160 ml/min, p < 0.05), suggesting that the decrease in variceal pressure caused by isosorbide-5-mononitrate could be caused by both reductions in collateral resistance and collateral blood flow. Isosorbide-5-mononitrate moderately reduced mean arterial pressure (-13 +/- 16%; p < 0.005), its fall being directly related to the fall in hepatic venous pressure gradient (r = 0.6, p < 0.01). CONCLUSIONS: The results of this study show that isosorbide-5-mononitrate markedly and significantly reduces variceal pressure in patients with cirrhosis and provide further support for its clinical use in the pharmacological treatment of portal hypertension.

Aged↗

PubMed1990

The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate.

Three times daily administration of isosorbide dinitrate may avoid much of the tolerance seen with more frequent dosing. To determine the daylong pattern of the antianginal effect of three times daily isosorbide dinitrate, eight men with stable exertional angina and a positive exercise test were studied. The subjects had demonstrated increased exercise duration in response to oral isosorbide dinitrate therapy and absence of complete tolerance to long-term three times daily isosorbide dinitrate. Treadmill exercise to onset of angina was performed over 2 days at 8 AM, 9 AM, 11 AM, 1 PM, 2 PM, 4 PM, 6 PM and 7 PM. On one day each patient received isosorbide dinitrate at 8 AM, 1 PM and 6 PM in a previously titrated dose (mean 27.5 mg), which had been taken three times daily for at least 2 weeks. On the other day at the same hours each patient received double blind a placebo identical in appearance to isosorbide dinitrate. One hour after the 8 AM dose of isosorbide dinitrate, mean systolic blood pressure at rest had fallen by 19 mm Hg and mean exercise time to angina increased by 200 s. However, by 11 AM exercise time had returned to control level. One hour after the 1 PM dose of isosorbide dinitrate, exercise time increased by a mean of 150 s but was again at control level 2 h later.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed2001

Vaginal application of the nitric oxide donor isosorbide mononitrate for preinduction cervical ripening: a randomized controlled trial to determine effects on maternal and fetal hemodynamics.

OBJECTIVE: Our aim was to assess the effects of vaginally administered isosorbide mononitrate (a nitric oxide donor) on maternal and fetal hemodynamics in pregnant women at term. STUDY DESIGN: We conducted a randomized controlled trial. Women were randomly selected to receive vaginally administered isosorbide mononitrate, 20 mg (n = 13) or 40 mg (n = 11), or to undergo a vaginal examination only (n = 12). Maternal pulse, blood pressure, and fetal heart rate were recorded at baseline and then every 30 minutes until 360 minutes. Umbilical artery resistance index and pulsatility index measurements were performed at 0, 180, and 330 minutes. RESULTS: Maternal pulse rate was greater after the administration of isosorbide mononitrate, 20 or 40 mg, compared with the pulse rate in the vaginal examination-only group (greatest difference in means, 21 beats/min; P <.01). Maternal systolic and diastolic blood pressures were greater in the 20-mg and 40-mg isosorbide mononitrate groups than in the vaginal examination-only group (greatest difference in mean systolic and diastolic blood pressure, 15 and 16 mm Hg, respectively; P <.02 and P <.001, respectively). Fetal heart rate was greater in the 40-mg isosorbide mononitrate group than in either the 20-mg isosorbide mononitrate group or the vaginal examination-only group (difference in mean, 15 beats/min; P <.05). No woman required treatment for maternal or fetal tachycardia or maternal hypotension. Neither dose of isosorbide mononitrate had a significant effect on umbilical artery resistance or pulsatility index. CONCLUSIONS: Vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women at term has an effect on both maternal and fetal hemodynamics, but this effect is not clinically significant.

Adolescent↗

PubMed1996

Role of pentobarbitone anaesthesia and sympathetic tone in the haemodynamic effects of isosorbide dinitrate in rats with cirrhosis.

The haemodynamic effects of nitrovasodilators and their mechanisms of action on portal hypertension remain unclear. The splanchnic and systemic haemodynamic response to the infusion of isosorbide dinitrate (100 micrograms/kg per min), a nitrovasodilator, was investigated in cirrhotic rats. The role of the conscious state in the haemodynamic response to isosorbide dinitrate was examined using rats that were anaesthetized with pentobarbitone. The role of sympathetic tone in the haemodynamic response to isosorbide dinitrate was examined using rats pretreated with the ganglion blocker hexamethonium. Isosorbide dinitrate had no haemodynamic effects in conscious, unblocked normal and cirrhotic rats. Isosorbide dinitrate had no haemodynamic effects in normal and cirrhotic rats treated with hexamethonium. In normal anaesthetized rats, isosorbide dinitrate significantly decreased systemic vascular resistance (414 +/- 25 vs 290 +/- 26 dyn.s/cm-5 per 100 g). In cirrhotic anaesthetized rats, isosorbide dinitrate significantly decreased mean arterial pressure (98 +/- 6 vs 79 +/- 7 mmHg), systemic vascular resistance (318 +/- 30 vs 207 +/- 10 dyn.s/cm-5 per 100 g), portal pressure (14.0 +/- 1.0 vs 11.3 +/- 0.9 mmHg) and portal territory vascular resistance (1362 +/- 163 vs 1031 +/- 182 dyn.s/cm5 per 100 g). In conclusion, this study shows that the portal hypotensive effects of isosorbide dinitrate depend upon the alterations of vascular tone by pentobarbitone.

Adjuvants, Anesthesia↗

PubMed2005

Intracervical application of the nitric oxide donor isosorbide dinitrate for induction of cervical ripening: a randomised controlled trial to determine clinical efficacy and safety prior to first trimester surgical evacuation of retained products of conception.

OBJECTIVE: To determine the therapeutic efficacy and safety of a nitric oxide (NO) isosorbide dinitrate donor to induce cervical ripening of women with missed abortions before surgical evacuation of the uterus. DESIGN: A prospective, randomised, double-blind controlled trial. SETTING: Tertiary referral maternity teaching hospital. Population Sixty women with missed abortions and no cervical dilation. METHODS: Women requesting surgical evacuation of the uterus were randomly selected to receive endocervical 80 mg/1.5 mL isosorbide dinitrate gel solution (n= 30) or 400 mug/1.5 mL misoprostol gel solution (n= 30) every 3 hours to a maximum of four doses or until reaching cervical ripening. Vital signs and symptoms were recorded at baseline and then every 3 hours until finishing therapy. Adverse events, such as headache, abdominal pain, pelvic pain, backache, nausea and vomiting, were evaluated. MAIN OUTCOME MEASURES: Probability of reaching cervical ripening >8 mm Hegar dilator; evaluated at 3, 6, 9 and 12 hours after application of isosorbide dinitrate or misoprostol. RESULTS: The probabilities of induction of cervical ripening by isosorbide dinitrate and misoprostol after four repeated doses at 3-hour intervals were significantly different (P<0.001). Efficacy of therapy after 12 hours was 97% for the isosorbide dinitrate group and 70% for the misoprostol group. Systolic and diastolic blood pressures were lower after administration of isosorbide dinitrate than prostaglandin analogues. The difference in the mean systolic and diastolic blood pressure between treatment groups was greatest at 3 hours, with a difference of 7.7 mmHg (P<0.001) and 5.9 mmHg (P<0.003), respectively. The most frequent side effect associated with isosorbide dinitrate administration was headache, which occurred in 18 out of 30 patients, compared with only 5 out of 30 women in the misoprostol group [relative risk (RR) 2.41, 95% confidence interval (CI) 1.45-4.03, P<0.001). Women treated with misoprostol reported mainly pelvic pain (RR 3.24, 95% CI 1.99-5.27, P<0.001). CONCLUSIONS: Intracervical administration of 80 mg isosorbide dinitrate in women with missed abortions appears to be effective for cervical ripening prior to surgical evacuation of the uterus. Differences in the incidence of non-serious adverse events are not likely to be clinically significant.

Abortion, Induced↗

PubMed1994

The interaction of alpha-human atrial natriuretic peptide (ANP) with salbutamol, sodium nitroprusside and isosorbide dinitrate in human bronchial smooth muscle.

1. Contractions in human bronchial rings evoked by methacholine (10(-6) M) were reversed by single contractions of alpha-human atrial natriuretic peptide (10(-6) M), salbutamol (10(-6) M), sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M) and the extent of the relaxations compared. The activity of combinations of ANP with salbutamol, sodium nitroprusside and isosorbide dinitrate were compared with those for each agonist alone. 2. ANP and salbutamol were equipotent in reversing methacholine-evoked contraction and, in combination these agonists evoked an additive response. ANP and sodium nitroprusside also evoked similar degrees of relaxation and were additive, as were ANP and isosorbide dinitrate; however, with isosorbide dinitrate a higher concentration was required to evoke the same degree of relaxation as ANP, sodium nitroprusside or salbutamol. 3. Cumulative concentration-response curves to methacholine (10(-9)-3 x 10(-4) M) were examined in the presence and absence of the above bronchodilator substances, alone and in combination allowing their abilities to protect against contraction to be compared. ANP (10(-6) M) and salbutamol (10(-6) M) each attenuated subsequent contractions evoked by methacholine, an ability not shared with sodium nitroprusside (10(-6) M) or isosorbide dinitrate (4.2 x 10(-5) M). Indeed at lower concentrations of methacholine (< 3 x 10(-7) M), sodium nitroprusside evoked a paradoxical enhancement of methacholine-evoked contractions. 4. In combination, ANP and salbutamol attenuated contractions evoked by methacholine to a significantly greater degree than that seen with either agonist alone, whilst a combination of ANP and sodium nitroprusside evoked no greater effect than that seen with ANP alone. By contrast, isosorbide dinitrate and ANP together evoked a greater inhibition than ANP alone.5 These results suggest that a combination of agents such as ANP and salbutamol evokes a greater effect than either alone, both in reversing and protecting against methacholine-evoked contractions.Such combinations may be of benefit in the treatment of patients, allowing lower doses of drug to be used. Combinations of ANP and isosorbide dinitrate may likewise be of interest; however, the mechanism underlying the enhancement of ANP responses by isosorbide dinitrate requires further study.

Albuterol↗

PubMed2004

Acute administration of carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of portal pressure in patients with viral cirrhosis.

OBJECTIVE: Propranolol is known to decrease portal pressure in cirrhotic patients with portal hypertension; however, a substantial number of patients do not respond to propranolol administration. The addition of isosorbide-5-mononitrate may enhance portal pressure reduction in patients receiving propranolol. Carvedilol is a nonselective beta-blocker with alpha(1)-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. Additionally, carvedilol has a greater portal hypotensive effect than propranolol alone in patients with cirrhosis. The current study is aimed at comparing the acute hemodynamic effects of carvedilol with the effects of propranolol plus isosorbide-5-mononitrate in patients with viral cirrhosis. METHODS: Patients with viral cirrhosis were randomly assigned to receive an oral administration of carvedilol of 25 mg (n = 11) or an oral administration of propranolol 40 mg plus isosorbide-5-mononitrate 20 mg (n = 11). Hemodynamic values were measured at basal and 90 min after drugs administration. RESULTS: Both carvedilol and propranolol plus isosorbide-5-mononitrate significantly decreased cardiac index, heart rate, and HVPG. The magnitude of changes in HVPG observed between the basal and after drugs administration was greater in patients receiving carvedilol than in those receiving propranolol plus isosorbide-5-mononitrate (-18.6 +/- 3.6%vs-10.1 +/- 3.6%, p < 0.05). Hepatic blood flow increased following carvedilol administration but remained unchanged in patients receiving propranolol plus isosorbide-5-mononitrate. The magnitude of decrease in mean arterial pressure (MAP) did not differ between the two groups of patients. CONCLUSION: In our patients with viral cirrhosis, carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of HVPG. Carvedilol administration causes an increase in hepatic blood flow, but its systemic effects were similar to those of propranolol plus isosorbide-5-mononitrate.

Antihypertensive Agents↗