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PubMed2001

A comparison of isosorbide mononitrate, misoprostol and combination therapy for first trimester pre-operative cervical ripening: a randomised controlled trial.

OBJECTIVE: To determine whether a combined therapy with isosorbide mononitrate (40mg) and misoprostol (400 microg) for pre-operative cervical ripening in the first trimester would result in improved clinical effectiveness, and fewer side effects compared with each agent used alone. DESIGN: Randomised controlled trial. SETTING: Glasgow Royal Infirmary. POPULATION: Sixty-six primigravid women scheduled for suction termination of pregnancy. METHODS: Women were randomly assigned to receive before surgery, per vaginam, isosorbide mononitrate 40 mg (n = 22), misoprostol 400 microg (n = 22) or both agents together [isosorbide mononitrate 40 mg and misoprostol 400 microg] (n = 22). MAIN OUTCOME MEASURES: 1. To assess the cumulative force required to dilate the cervix to 8 mm; 2. the onset of new symptoms before termination of pregnancy. RESULTS: The cervical resistance following combination therapy with isosorbide mononitrate and misoprostol was not significantly different than following misoprostol alone [24.5N vs 18.5N; median difference (95% CI) 19N (-22 to 49)]. Pre-treatment with misoprostol used alone resulted in a lower cervical resistance than isosorbide mononitrate alone (18.5N vs 39N, P = 0.04, Mann-Whitney U test). There was no difference in the number of women remaining asymptomatic following either isosorbide mononitrate or misoprostol or combination therapy [14/22 (64%) vs 11/21 (52%) vs 11/22 (50%), Fisher's exact test]. CONCLUSIONS: We have not shown any advantage of combining misoprostol with the nitric oxide donor isosorbide mononitrate compared with misoprostol alone for pre-operative cervical ripening in the first trimester.

Abortifacient Agents, Nonsteroidal↗
PubMed1980

Haemodynamic effects of oral salbutamol alone and in combination with sublingual isosorbide dinitrate in patients with severe congestive cardiac failure.

To examine possible augmentation of the effects of isosorbide dinitrate by salbutamol, haemodynamic measurements were made in 10 patients with severe chronic congestive cardiac failure who received isosorbide dinitrate 2.5 to 25 mg sublingually and salbutamol 4 to 12 mg orally, alone and in combination. Isosorbide dinitrate reduced mean left ventricular filling pressure from 29 to 18 mmHg and increased mean cardiac index from 1.7 to 2.0 1/min per m2, with no significant change in mean heart rate. Systemic arterial mean pressure fell from 85 to 72 mmHg. Salbutamol increased cardiac index from 1.8 to 2.2 1/min per m2. There was no significant change in left ventricular filling pressure, heart rate, or systemic arterial pressure. Compared with control, combined isosorbide dinitrate and salbutamol reduced left ventricular filling pressure from 27 to 19 mmHg and increased cardiac index from 1.8 to 2.7 1/min per m2, with no significant change in heart rate. Systemic arterial pressure fell from 82 to 75 mmHg. The reduction in left ventricular filling pressure by combined treatment was similar to that produced by isosorbide dinitrate alone, but the increase in cardiac index was significantly greater than that produced either by isosorbide dinitrate alone or salbutamol alone. Combined sublingual isosorbide dinitrate and oral salbutamol have an additive effect in improving left ventricular performance in patients with severe chronic congestive cardiac failure.

Aged↗
PubMed2006

[Usefulness of sublingual isosorbide to assess the reversibility of pulmonary hypertension in cardiac transplant candidates].

BACKGROUND: Continuous infusion of short life vasodilators are employed to test reversibility of pulmonary hypertension in cardiac transplant candidates. Sublingual isosorbide administration has not been described in the literature and it might be a simpler alternative. AIM: To evaluate sublingual isosorbide administration as a test of reversibility of pulmonary hypertension in heart failure. PATIENTS AND METHODS: Prospective evaluation of patients referred for cardiac transplant evaluation. Patients underwent right catheterization for hemodynamic measurements at baseline and after repeated doses of 5 mg sublingual isosorbide every 5 minutes until observing a decrease in pulmonary vascular resistance decrease or symptomatic hypotension. RESULTS: Twenty one patients, 18 men, age 49+/-15 years, were studied. Fourteen (66%) were transplanted. The mean sublingual isosorbide dose was 15+/-5 mg. After isosorbide administration, there was a significant decrease in mean arterial pressure (80+/-8.5 to 71+/-6.6 mmHg, p <0.0001), mean pulmonary artery pressure (38+/-11 to 26+/-7.8 mmHg, p <0.0001), systemic vascular resistance (1540+/-376 to 1277+/-332 dyn*s/cm5 p <0.001), pulmonary vascular resistance (3.5+/-2.2 to 2,5+/-1.6 Wood Units, p <0.05) and transpulmonary gradient (13+/-7 a 10+/-4 mmHg, p <0.004). The cardiac output increased from 3.96+/-0.7 to 4.38+/-0.9 L/min, p=0.05. The relation between pulmonary and systemic vascular resistance before and after isosorbide was 0.17 and 0.15, respectively (p=0.04). One transplanted patient with partial reversibility of pulmonary hypertension developed acute right heart failure. CONCLUSIONS: Sublingual isosorbide administration is useful and well tolerated to evaluate the reversibility of pulmonary hypertension prior cardiac transplant.

Administration, Sublingual↗
PubMed1989

[Evaluation using serial exercise tests of verapamil alone and combined with isosorbide dinitrate in exertional angina].

The response to verapamil alone and combined with isosorbide dinitrate in a group of 12 patients with severe ischemic heart disease and stable effort angina was assessed by means of serial treadmill testing. The study was randomized, of a square latin design and double-blind. The tested drugs and dosages were 120 mg of verapamil, 120 mg of verapamil plus 20 mg of isosorbide dinitrate and placebo. Patients were serially tested (Bruce protocol) over three consecutive days at 8-9-12 and 16 hours. A significative improvement was observed in several ischemic parameters both with verapamil alone and combined with isosorbide dinitrate, but this improvement was remarkably enhanced with the combination of drugs. The mean exercise time to produce angina improved from 268 +/- 18 sec (basal) to 379 +/- 19 sec (verapamil plus isosorbide dinitrate) and the time for 1 mm ST segment depression from 163 +/- 22 sec (basal) to 257 +/- 19 sec (verapamil plus isosorbide dinitrate) when measured at the last daily test (8 hours after drug administration). It is concluded that both verapamil alone and combined with isosorbide dinitrate at the chosen doses are clinically efficient, significantly improving the ischemic parameters. The combination of verapamil and isosorbide dinitrate resulted in a remarkably better improvement in this group of patients with stable effort angina.

Adult↗
PubMed1982

Isosorbide dinitrate and nifedipine treatment of achalasia: a clinical, manometric and radionuclide evaluation.

The effects of sublingual isosorbide dinitrate (5 mg) and nifedipine (20 mg) were compared in 15 patients with achalasia. The parameters examined included the manometric measurement of the lower esophageal sphincter pressure, the radionuclide assessment of esophageal emptying and the clinical response. The mean basal lower esophageal sphincter pressure fell significantly after both drugs (p less than 0.01), with a maximum fall of 63.5% 10 min after receiving isosorbide dinitrate, but by only 46.7% 30 min after nifedipine. The esophageal radionuclide test meal retention was significantly less (p less than 0.01) only after receiving isosorbide dinitrate. The drug improved initial esophageal emptying by its effect on the lower esophageal sphincter and by relieving the test meal hold-up noted to occur at the junction of the upper and midesophagus. Eight patients cleared their test meal within 10 min after isosorbide dinitrate administration while only two did so after nifedipine. Subjectively, 13 patients had their dysphagia relieved by isosorbide dinitrate and 8 by nifedipine. However, this relief was not confirmed in 4 patients by the radionuclide study and they, as well as the other 3 patients who did not respond to therapy, were referred to pneumatic dilatation. Side effects were more prominent after nitrates. Three of the patients are currently receiving nifedipine and 5 patients received isosorbide dinitrate therapy for 8-14 mo. The radionuclide test meal is currently the best way of objectively evaluating drug therapy in patients with achalasia. Isosorbide dinitrate is more effective than nifedipine in relieving their symptoms.

Adolescent↗
PubMed1994

Inactivation of human aldehyde dehydrogenase by isosorbide dinitrate.

Isosorbide dinitrate inactivated E1 and E2 isozymes of human aldehyde dehydrogenase (EC 1.2.1.3), abolishing both dehydrogenase and esterase activities. NAD promoted, whereas chloral and NAD protected the enzyme from inactivation. The inactivation was irreversible upon dialysis and occurred without incorporation of the 14C-labeled isosorbide dinitrate. Inactivation was associated with formation of products, isosorbide-2-mononitrate and isosorbide-5-mononitrate. At 25 degrees C there were two pathways of product formation: a fast pathway, sensitive to aldehyde dehydrogenase inhibitors, and a slower pathway insensitive to inhibitors. The fast product formation and inactivation occurred simultaneously, and both were inhibited by chloral and by the irreversible active site-directed inhibitor bromoacetophenone. At 0 degree C the slow product formation was abolished, allowing study of the enzyme catalyzed reaction. The inactivation of the E1 isozyme at 0 degree C occurred in a single turnover that accounted for 80% of catalytic activity loss with isosorbide-2-mononitrate being the major product. No nitrate was ever detected; at 25 degrees C, nitrite was detected but in less than stoichiometric amounts. The mononitrates were also substrates and inactivators of aldehyde dehydrogenase. Isosorbide-2-mononitrate had the lowest K(i) and k3 values for the E1 isozyme when compared with that of the other two nitrate esters of isosorbide. Reversibility of inactivation by 2-mercaptoethanol suggested involvement of enzyme sulfhydryls. The inactivation appears to be mechanism-based and involves the esterase function of aldehyde dehydrogenase.

Aldehyde Dehydrogenase↗
PubMed1975

Isosorbide dinitrate. Effect on the vasodilator response to nitroglycerin.

To evaluate whether there is cross-tolerance to the circulatory effects of isosorbide dinitrate and nitroglycerin, six subjects were given 120 mg/day of sustained-action isosorbide dinitrate in three divided doses for six to eight weeks. Prior to and during the last week of long-term isosorbide dinitrate administration, the effects of sublingually given nitroglycerin (0.9 mg) on plethysmographically measured calf blood flow and venous volume at 30 mm Hg (VV[30]) were measured on three occasions and averaged. Although the arteriolar dilation produced by nitroglycerin was unaltered by isosorbide dinitrate, the venodilation was significantly attenuated. The VV[30] increased from 3.00 to 3.28 ml/100 ml (P less than .02) with nitroglycerin prior to isosorbide dinitrate administration, but failed to increase with nitroglycerin during the long-term administration of isosorbide dinitrate (2.95 to 2.95 ml/100 ml, P greater than .5).

Administration, Oral↗
PubMedDate not supplied

Isosorbide 5-mononitrate pharmacokinetics in humans.

When isosorbide 5-mononitrate was intravenously infused at a rate of 4 mg h-1 for 2.5 h to five human subjects, its concentrations in plasma increased slowly to 185 ng ml-1 +/- 5 per cent C.V. at 2.5 h and a steady-state plasma level was not reached during the infusion. When the infusion was discontinued, plasma drug concentrations declined with an elimination half-life of 4.2 h +/- 6 per cent C.V. The systemic clearance after the infusion doses was 132 ml min-1 +/- 18 per cent C.V. and the volume of distribution was 48.4 +/- 16 per cent C.V. After equal oral doses of 10 mg, the peak plasma isosorbide 5-mononitrate concentration of 191 ng ml-1 +/- 16 per cent C.V. was reached at 1.1 h +/- 30 per cent C.V., and plasma levels declined with a terminal half-life of 4.9 h. The complete systemic availability of isosorbide 5-mononitrate indicated that pre-systemic elimination after the oral doses was negligible. A one-compartment open model appeared adequate to describe the plasma level data after intravenous infusion and oral dose. After single oral doses of 10 mg isosorbide dinitrate, the peak plasma concentration of the 5-mononitrate metabolite of 72 ng ml-1 +/- 27 per cent C. V. occurred at 1.7 h +/- 41 per cent C.V. Approximately 50 per cent (range 22--68 per cent) of the oral dose of isosorbide dinitrate circulated in plasma as the 5-mononitrate metabolite. The pharmacokinetics of isosorbide mononitrates are markedly different to those of the parent dinitrate and these differences follow from the greater systemic availability and volume of distribution of the mononitrates.

Adult↗
PubMed1977

Quantitative determination of isosorbide dinitrate and two metabolites in plasma.

A GLC method for the determination of plasma isosorbide dinitrate and two metabolites, isosorbide 2-mononitrate and isosorbide 5-mononitrate, is described. The three substances are extracted from alkalinized plasma with ether. Quantitation is effected by electron-capture detection after GLC separation with a 30% SE-30 column. The unusually heavy liquid phase loading is necessary to eliminate irreversible adsorption on the solid support. The electron-capture detector provides excellent sensitivity and specificity because of the electronegative nature of the nitric ester. The method was used to study the blood levels of isosorbide dinitrate and two metabolites in four beagle dogs after single oral doses of 40 mg of isosorbide dinitrate and in two human volunteers after a sublingual dose of 10 mg of isosorbide dinitrate.

Administration, Oral↗
PubMed1975

Concentrations of the vasodilator isosorbide dinitrate and its metabolites in the blood of human subjects.

An oral dose of 5 mg of 14C-isosorbide dinitrate was rapidly absorbed, biotransformed and excreted by human subjects. Peak whole blood concentrations of radioactivity were reached after 1.5 to 2 hours and declined relatively slowly. The radioactivity in whole blood mainly represented metabolites, isosorbide mononitrates. The peak concentrations found were 4.5, 11.7 and 34.3 ng/ml of isosorbide dinitrate, isosorbide 2-mononitrate and isosorbide 5-mononitrate, respectively, in the blood of one subject and 5.9, 15 and 61.3 ng/ml, respectively, in the blood of another subject. However, concentrations of the metabolites declined relatively slowly during 6 h after the oral urine of the first day (ca. 78%). The results showed that isosorbide mononitrates were available to contribute to the pharmacological action.

Biotransformation↗
PubMed1995

Effect of isosorbide dinitrate on gastroesophageal reflux in healthy volunteers and patients with Chagas' disease.

The effect of isosorbide dinitrate (ISD) on gastroesophageal reflux and gastric emptying during the 24-min period following a liquid meal was studied in healthy volunteers, Chagas' disease patients with normal esophageal motility (CD-1 group), and Chagas' disease patients with esophageal dysmotility (CD-2 group) with dynamic scintigraphy. At random, on two separate days, the subjects received 5 mg isosorbide dinitrate or an identical-appearing placebo tablet, by the sublingual route, and ingested a liquid test meal containing [99mTc]phytate colloid before scintigraphic studies were performed. Gastroesophageal reflux episodes were more frequent (P = 0.016) and gastroesophageal reflux indexes were greater (P < 0.010) after isosorbide dinitrate than after placebo in CD-2 group (N = 15) but not in healthy volunteers (N = 14) or CD-1 group (N = 9); six of seven CD-2 patients presenting with gastroesophageal reflux after isosorbide dinitrate had abnormal clearance of refluxate. Gastric emptying was similar in healthy volunteers (N = 13), CD-1 patients (N = 6), and CD-2 patients (N = 13), and no effect of isosorbide dinitrate on it was detected in any of the groups. In separate studies, 5 mg isosorbide dinitrate reduced the lower esophageal pressure (P < 0.01) in seven CD-2 patients. These results indicate that ISD increases the tendency towards GER in CD-2 patients, but not in healthy volunteers or CD-1 patients. This effect is probably related to an exceedingly intense relaxation of the LES caused by ISD in CD-2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris.

The efficacy and safety of extended-release isosorbide mononitrate tablets were evaluated in patients with stable effort angina. In a double-blind study, 313 patients with stable effort-induced angina were randomized to receive placebo or extended-release isosorbide mononitrate: 30, 60, 120 or 240 mg once daily in the morning. Serial exercise testing was performed using the standard Bruce treadmill protocol on days 1, 7, 14, 28 and 42 immediately before morning drug administration, and 4 and 12 hours after administration. After initial dosing, all groups that received extended-release isosorbide mononitrate had significant (p < 0.01) increases in mean total exercise time of approximately 30 to 50 seconds in relation to placebo 4 and 12 hours after administration. On day 42, mean changes from baseline in total exercise time of patients who received 120 or 240 mg of extended-release isosorbide mononitrate exceeded placebo by approximately 50 to 60 seconds 4 hours after dosing (p < 0.01), and by 30 to 35 seconds 12 hours after dosing (p < or = 0.05). No significant difference was detected between responses to extended-release isosorbide mononitrate and placebo 24 hours after administration (i.e., immediately before the next dose). Thus, there was neither significant activity nor demonstrable rebound of effort-induced angina (zero-hour effect) at the end of the dosing interval. Transient headache was the most prevalent adverse experience. Extended-release isosorbide mononitrate (120 and 240 mg administered orally once daily) significantly prolonged exercise time to development of moderate effort-induced angina 4 and 12 hours after dosing during long-term therapy, without development of nitrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Circulatory improvement after hydralazine or isosorbide dinitrate administration in patients with heart failure. Effect on metabolic responses to submaximal exercise.

Hydralazine and isosorbide dinitrate can increase the cardiac output during submaximal exercise in patients with heart failure but whether this increase improves oxygen delivery to underperfused exercising muscle is uncertain. To investigate this question, we measured three systemic markers of skeletal muscle oxygen availability--exercise VO2, mixed venous lactate concentration and oxygen debt--during submaximal exercise in 15 patients with heart failure both before after hydralazine (nine patients) or isosorbide dinitrate (eight patients) administration. Hydralazine increased the cardiac output during exercise from 4.9 +/- 1.2 liter/min to 6.5 +/- 1.8 liter/min (p less than 0.01) but had no effect on exercise VO2 (control, 531 +/- 135 ml/min; hydralazine, 489 +/- 102 ml/min), peak lactate concentration (control, 18.3 +/- 4.2 mg/dl; hydralazine, 17.9 +/- 3.6 mg/dl) or oxygen debt (control, 474 +/- 213 ml; hydralazine, 465 +/- 170 ml) (all p greater than 0.10). Isosorbide dinitrate increased the cardiac output during exercise from 4.6 +/- 0.9 liter/min to 5.3 +/- 0.8 liter/min (p less than 0.01) but also did not change exercise VO2 (control, 488 +/- 62 ml/min; isosorbide, 473 +/- 44 ml/min), peak lactate concentration (control, 19.2 +/- 6.0 mg/dl; isosorbide, 21.4 +/- 8.2 mg/dl) or oxygen debt (control, 522 +/- 154 ml; isosorbide, 445 +/- 147 ml) (all p less than 0.10). We conclude that short-term administration of hydralazine or nitrates to patients with heart failure can substantially improve circulatory function during exercise but that this improvement probably does not enhance skeletal muscle nutritional flow.

Adult↗
PubMed1993

Isosorbide-5-mononitrate versus propranolol in the prevention of first bleeding in cirrhosis.

BACKGROUND: Hemodynamic studies have shown the efficacy of nitrates in reducing portal pressure in cirrhosis. We therefore studied the efficacy of isosorbide-5-mononitrate vs. propranolol in the prevention of first bleeding within a prospective controlled trial. METHODS: One hundred eighteen cirrhotics with esophageal varices were blindly randomized to receive 20 mg of isosorbide-5-mononitrate three times a day (n = 57) or propranolol (n = 61) up to the maximum tolerated dose. Both groups also received ranitidine (150 mg/day). RESULTS: The median follow-up was 29 months. Twenty-six patients dropped out (13 in the isosorbide group) because of poor compliance or complications unrelated to treatment. Eighteen patients died (9 in the isosorbide-treated group), 6 due to bleeding. The 1- and 2-year actuarial percentages of patients free of bleeding was 90.8% and 82.2% in the isosorbide-5-mononitrate--and 93.9% and 85.8% in the propranolol-treated groups, respectively (P = NS). These values are higher than those expected from the North Italian Endoscopic Club predicting scores. There were few major side effects in either group. The 2-year survival rate did not differ between the two groups (82.2% vs. 85.4%). CONCLUSIONS: Isosorbide-5-mononitrate administered orally is a safe and effective alternative to propranolol in the prophylaxis of bleeding in cirrhosis.

Aged↗
PubMed2004

Different haemodynamic effects of a single dose of long-acting isosorbide-5-mononitrate in healthy subjects and patients with cirrhotic portal hypertension.

BACKGROUND: The action pathways of nitrates are hypothesised to be deranged in cirrhosis. AIM: In order to confirm it, the acute haemodynamic effects of isosorbide-5-mononitrate in cirrhotic patients and controls was investigated. PATIENT: Nine cirrhotics and nine healthy controls. METHODS: Evaluation in the fasting state, 90 min after isosorbide-5-mononitrate or placebo (double-blind on two different days) and then 30 and 120 min after eating a standard meal. Various systemic and splanchnic haemodynamic parameters, including arterial impedance, assessed as Doppler pulsatility index, were measured. RESULTS: isosorbide-5-mononitrate reduced arterial pressure and increased heart rate and mesenteric pulsatility index both in controls and in cirrhotics, whereas the following parameters behaved differently in the two groups (P < 0.05): hepatic pulsatility index decreased (-9%) and the portal velocity increased (+13%) in controls, whereas hepatic pulsatility increased (+18%) and portal velocity decreased (-18%) in cirrhotics. The two groups presented a similar pattern of changes in most variables under placebo after a meal. In controls, the administration of isosorbide-5-mononitrate blunted the postprandial mesenteric vasodilation and related changes in splanchnic and systemic circulation, expected at 30 min, in comparison to those observed under placebo. In cirrhotics, instead, the postprandial pattern was similar under placebo and isosorbide-5-mononitrate. CONCLUSIONS: The acute administration of isosorbide-5-mononitrate produces different haemodynamic effects in healthy and diseased livers, both in the fasting state and after a meal, consistent with the hypothesis of a deranged response of the intrahepatic microcirculation to nitrates in cirrhosis.

Aged↗
PubMed1999

Value of sublingual isosorbide dinitrate before isoproterenol tilt test for diagnosis of neurally mediated syncope.

Head-up tilt-table test is valuable in diagnosing type of syncope. Sensitivity varies in reports and is mostly poor. Isoproterenol or nitroglycerin is regularly used to increase head-up tilt-table test sensitivity. The aim of this study was to assess the value of sublingual isosorbide dinitrate administration before isoproterenol tilt test as a simple, practical test for diagnosis of neurally mediated syncope. Ninety-six patients (45 men and 51 women, mean age 42.5 years) with recurrent (median 4 times) loss of consciousness that remained unexplained after clinical and noninvasive assessment and 72 healthy volunteers (36 men and 36 women, mean age 40.1 years) were randomly divided into groups: isosorbide-isoproterenol test and isoproterenol test. During isosorbide-isoproterenol test, a positive response (syncope in association with sudden hypotension or bradycardia) occurred in 35 patients (72.9%) with unexplained syncope, an exaggerated response (minor symptoms in association with slowly increasing hypotension alone) occurred in 7 (14.6%), a negative response in 2 (4.2%), and drug intolerance in 4 (8.3%). During isoproterenol testing, these percentages were 52.1%, 16.7%, 25.0%, and 6.2%, respectively. Only 3 control volunteers (8.3%) had a positive response to isosorbide-isoproterenol test and 2 (5.6%) to isoproterenol test. The duration of the test and the time for syncope induction in the isosorbide-isoproterenol test were shorter than those in the isoproterenol test (24.84 +/- 5.15 vs 35.70 +/- 6.28 minutes [p <0.01]; 4.53 +/- 2.86 vs 6.27 +/- 4.11 minutes [p <0.05]). This study concluded that isosorbide-isoproterenol test could be valuable in diagnosing unexplained syncope for its high sensitivity, powerful specificity, and short duration.

Administration, Sublingual↗
PubMed2002

[Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers].

The extended use of interventional surgery of revascularisation has modified the prognosis and the evolution of ischaemic heart diseases. However, both coronary artery bypass graft and percutaneous transluminal coronary angioplasty failed to make the symptomatic or subclinical ischaemic manifestations of chronic coronary insufficiency disappear. The interest of using betablockers as a first-line therapy was widely demonstrated. However, their combination with another efficient molecule is often necessary. The aim of this trial has been to appreciate the efficiency of the association of a betablocker with either trimetazidine or with isosorbide monoitrate. Hundred and eighty five patients retaining a positive effort test despite 100 mg of atenolol, received in addition, either 60 mg of trimetazidine (93 cases) of 60 mg of isosorbide mononitrate (92 cases) for a two-month period and are then re-evaluated at the end of this period. The ischaemic threshold is delayed in a significant way in both groups (p < 0.0001; trimetazidine +7%, isosorbide mononitrate +10.7%). Twenty-three percent of the exercise tests under trimetzidine and 19% under isosorbide mononitrate become negative after two months of the therapeutic combination. The clinical improvement is even clearer with the disappearance of the angina crisis during the week before the second exercise test in 63% of the cases under trimetazidine and 54% of the cases under isosorbide mononitrate, among the patients who had kept it under atenolol at the inclusion. In conclusion, the combination of a second efficient molecule, trimetazidine or isosorbide mononitrate, brings a functional and objective improvement to patients with insufficient chronic coronary disease not totally controlled using a betablocker, even with high dosage. One should notice two important advantages in favour of the trimetazidine: one is practical due to a better tolerance (lack of cephalalgia), the other is conceptual (use of the complementary metabolic approach of cellular oxygenation rather than the haemodynamic approach of nitrate compounds which are already in concurrency with all other anti-ischaemic molecules).

Adrenergic beta-Antagonists↗
PubMed2003

A comparison of isosorbide mononitrate and misoprostol cervical ripening before suction evacuation.

OBJECTIVE: To compare the efficacy of a nitric oxide donor (isosorbide mononitrate) and a prostaglandin E1 analogue (misoprostol) for cervical priming before suction termination of pregnancy. METHODS: This was a randomized, double blind, placebo-controlled trial. One hundred twenty-six healthy women requesting termination of pregnancy between 9 and 12 weeks' gestation were recruited. Women were randomized into three groups: control, isosorbide mononitrate, and misoprostol. All women were given moistened intravaginal study drugs (placebo, 40 mg of isosorbide mononitrate, or 400 microg of misoprostol) 4-6 hours before suction evacuation. Side effects were assessed 3 hours after drug administration. The cervical dilatation and the cumulative force required to dilate the cervix to 8 mm were measured by a cervical tonometer before suction evacuation. Operative blood loss was measured after sieving off the products of gestation. RESULTS: There were no differences in the baseline cervical dilatation, cumulative force, and operative blood loss between the isosorbide mononitrate and placebo groups. However, women in the misoprostol group had a significantly greater cervical dilatation, required less cumulative force, and had less blood loss than women in the isosorbide mononitrate or control group. The majority (more than 80%) of women in all three groups found their cervical priming agents acceptable. CONCLUSION: Intravaginal isosorbide mononitrate was less effective than misoprostol in cervical ripening before suction termination of pregnancy.

Abortion, Induced↗