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At least 19 recordsLinked to original sources

A prospective randomised trial of atosiban versus hexoprenaline for acute tocolysis and intrauterine resuscitation.

OBJECTIVE: The aim of this study was to compare the efficacy and side effect profile of atosiban with hexoprenaline when used for intrauterine resuscitation of intrapartum fetal distress. STUDY DESIGN: Women in labour with acute intrapartum fetal distress detected by cardiotocography were randomly assigned to receive intravenous atosiban or hexoprenaline. SETTING: Department of Obstetrics and Gynecology, Karl Franzens University of Graz and General Hospital Graz, Austria. POPULATION OR SAMPLE: One thousand and four hundred and thirty-one women with singleton pregnancy at term and cephalic presentation were enrolled in the study during October 2000 and May 2001. METHODS: A prospective, randomised, pilot study with no a priori sample size calculation. MAIN OUTCOME MEASURE: Efficacy of treatment for stopping uterine contractions and the resumption of contractions determined by fetal heart rate monitoring. RESULTS: Tocolysis was achieved in 92% (12/13) of the women receiving atosiban and 100% (13/13) of those receiving hexoprenaline. Maternal tachycardia developed in 1/13 women, receiving atosiban and 10/13 women hexoprenaline. Hypertension occurred in 1/13 on atosiban and 3/13 women on hexoprenaline. Palpitations were only reported by 10/13 women receiving hexoprenaline. Uterine contractions resumed after 8 minutes (+/-3) in the atosiban group and 14 minutes (+/-4) in the hexoprenaline group (P < 0.001). CONCLUSION: Atosiban and hexoprenaline were similarly effective for stopping uterine contractions. Women receiving atosiban had significantly fewer adverse events than those receiving hexoprenaline. Uterine contractions resumed more promptly in the atosiban group. Considering the low incidence of mild maternal adverse events, atosiban may be an option for acute intrapartum tocolysis for fetal distress.

Adult↗

Indices of cardiac function during treatment with betamimetic drugs (fenoterol and hexoprenaline).

The limiting factor in the treatment of preterm labor by betamimetics is the effect of these drugs on heart rate and cardiac action. In this paper we compare these effects produced by hexoprenaline and fenoterol, which are both beta-sympathomimetic drugs now in clinical use. As indices of cardiac action we measured the pre-ejection period (PEP), the left ventricular ejection time (LVET) and their sum, namely total electromechanical systole (QS2) by thoracic impedance cardiography. In 20 individual tests, seven subjects were given both hexoprenaline and fenoterol on separate occasions in a dose relationship of 1 : 12.5. We found a relation between PEP/LVET on the one hand and the Heather-index (an impedance specific parameter of response to stress) on the other. Both parameters represent inotropic effects in cardiac action. With increasing betamimetic stimulation there was a decrease of PEP/LVET (-23% for hexoprenaline and -29% for fenoterol) and an increase in the Heather-index (+98% for hexoprenaline and +117% for fenoterol). These results are not statistically significantly different and so we cannot agree with Lipshitz [19 ]who reported less beta 1-stimulation with hexoprenaline.

Adult↗

The extrapulmonary effects of inhaled hexoprenaline and salbutamol in healthy individuals.

We have investigated the cardiovascular and metabolic effects of multiple inhaled doses of salbutamol and hexoprenaline in 12 healthy volunteers. They inhaled 200 micrograms of salbutamol or hexoprenaline at 15 min intervals for 60 min from a metered dose inhaler (total dose 1000 micrograms). We measured heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval on the ECG, and plasma potassium at baseline, 10 min after each inhalation, and 30 and 60 min after the last inhalation. There was no difference in the effects of the two drugs on blood pressure, total electromechanical systole, or QTc interval. Salbutamol significantly increased heart rate compared with hexoprenaline. Hexoprenaline caused a significantly greater fall in plasma potassium compared with salbutamol.

Administration, Inhalation↗

Hexoprenaline activates potassium channels of human myometrial myocytes.

Hexoprenaline is a beta-adrenergic agent used for tocolysis after the 26th week of pregnancy. The purpose of the present study was to demonstrate the site of action of hexoprenaline on the membrane of single isolated smooth muscle cells. The main action of beta-mimetics on the cell is hyperpolarization of the cellular membrane, i.e. beta-mimetics have similar effects as K(+)-ions (Standen et al., 1989). Our results indicate a prolonged and significantly enhanced activity of K(+)-channels in the cell membrane, as may also be demonstrated by the use of the K(+)-channel activator Calcitonin-gene related peptide (CGRP). In control experiments under physiological conditions, we observed a large conductance K(+)-channel with 158 pS. The channel was voltage dependent and Ca++ sensitive indicating that it belongs to the class of big conductance Ca(++)-activated K(+)-channels (BKCa). Hexoprenaline and CGRP both increased the open probability (P(o)) of the channel measured with the patch clamp system in the cell attached configuration. Hexoprenaline was also an activator of the BKCa in the presence of Nitrendipine, indicating that the activation of the Ca++ sensitive channel is not an indirect effect of Ca++ currents via L-type Ca++ channels.

Adult↗

Effects of hexoprenaline on the lecithin/sphingomyelin ratio and pressure-volume relationships in fetal rabbits.

A placebo-controlled, double-blind trial was carried out on 74 New Zealand White rabbit fetuses from 15 does to assess the effect of a fetal injection of hexoprenaline on surfactant release. After the uterus was exposed, half the fetuses received 0.1 ml (0.25 microgram) of hexoprenaline injected intraperitoneally through the intact uterine wall; the other half received an equivalent volume of placebo. After 3 hours, the abdomen was reopened, and the fetuses were surgically delivered and killed before breathing. The lecithin/sphingomyelin (L/S) ratios, obtained from lung washings, revealed a mean of 1.59:1 for the placebo group and 1.92:1 for the hexoprenaline group (p less than 0.001). Pressure/volume curves were generated from the lungs of 24 fetuses from 10 does, and the volume of air in the lungs for each pressure was analyzed in four ways: total volume, volume per gram of fetal body weight, volume per gram of dry lung weight, and as a percentage of total lung capacity at a pressure of 40 cm H2O. A first and second inflation-deflation curve was obtained for each experiment. The lungs from the hexoprenaline-treated group retained significantly more air than those from the placebo group. The most significant comparison was obtained when lung volume was expressed per gram of dry lung weight. The possibility of administering a beta 2-sympathomimetic drug to the mother in advanced preterm labor, specifically to release surfactant in the fetal lung, is suggested.

Amniotic Fluid↗

[Tocolysis with hexoprenalin and salbutamol in a clinical comparison].

140 patients with a threatening premature birth at the greater than or equal to 24-less than 37 week of gestation were in this study randomly treated with hexoprenalin or salbutamol. In 77% in the hexoprenalin and in 74% in the salbutamol group the weight of the newborn was greater than or equal to 2500 g. In 66% in both study groups the birth occurred after the completed 37 weeks of gestation. During infusion of hexoprenalin tachycardia in mothers occurred statistically highly significantly less than during salbutamol. 11% of the mothers in the hexoprenalin group had side-effects during infusion compared to 30% in the salbutamol group. The correlation between the tocolysis-index (Baumgarten) and the prolongation-index (Richter) given by the regression lines facilitates in some measure the comparison of different tocolytic drugs concerning its tocolytic effect.

Albuterol↗

[Hexoprenalin as a tocolytic drug (author's transl)].

Hexoprenalin, a betasympathomimetic drug, was tested with respect to tocolytic effect and cardiovascular side effects. The dosage varied according to the obstetrical situation and the resultant indication for tocolysis. "Long-term tocolysis" in the prophylaxis of premature labour was indicated when more or less rhythmical uterine contractions were present without any effect, as yet, on the cervix. The dosage was 0.075 microgram/min hexoprenalin intravenously as long-term infusion using a motor pump. In a collective of 20 patients in the last trimester of pregnancy the tocolytic effect was satisfactory, the mean rise in fetal heart rate being 2.43% and the mean rise in maternal heart rate 4.13%. Massive tocolysis to inhibit effective premature labour was indicated when rhythmical uterine contractions had already exerted an effect on the cervix. The dosage was 0.33 microgram/min hexoprenalin intravenously in form of a long-term infusion using a motor pump. In a collective of 20 patients in the last trimester of pregnancy the tocolytic effect was satisfactory, the mean rise in maternal heart rate being 33% and the mean rise in fetal heart rate 3%. Acute tocolysis to inhibit labour during parturition was indicated when ominous signs of fetal distress were present, or as premedication before surgical intervention. The dosage was 1.0 microgram/min hexoprenalin as an intravenous bolus over a period of 5 min. In a collective of 10 patients the tocolytic effect was adequate. Evaluation of the rise in maternal and fetal heart rate does not appear to be useful.

Female↗

The role of hexoprenaline in suprapubic amniocentesis during late pregnancy. A pilot study.

Suprapubic amniocentesis is often complicated by the fetal head being fixed in the pelvis, oligohydramnios or a hyperirritable myometrium. These factors limit the success rate associated with the procedure. If the myometrium is relaxed with a beta 2-stimulant, a higher success rate may be achieved. This was investigated in a randomized, prospective, double-blind pilot study using hexoprenaline. When four- or five-fifths of the fetal head was palpable above the pelvis, hexoprenaline (17 amniocenteses) showed no advantage over a placebo (16 amniocenteses). However, when three-fifths or less of the fetal head was palpable above the brim, 4 dry taps were obtained in the control group using a placebo (17 amniocenteses), while none occurred in the study group (19 amniocenteses) (P less than 0,05). Elevation of the fetal head was less difficult in the study group, but this difference was not statistically significant. These results suggest that hexoprenaline is not indicated for routine use during amniocentesis. When a dry tap is obtained or when marked difficulty is encountered in lifting the fetal head from the pelvis, 10 micrograms hexoprenaline administered intravenously 5 minutes before amniocentesis appears to facilitate successful completion of the procedure. However, a larger series is necessary to confirm this observation.

Adolescent↗

[Hemodynamic changes during tocolysis with hexoprenaline and fenoterol].

The authors examined two groups of 50 patients each who had been given an average dose of 0.24 microgram/min Hexoprenaline or respectively 1.8 micrograms/min Fenoterol as beta-mimetics for premature labor. The patients who received Fenoterol were also given Verapamil as additional medication in a ratio of 1 : 40. In addition to blood pressure, heart rate, urine elimination and serum or urine osmolarity, the hemodynamic parameters stroke volume, cardiac output and total peripheral resistance were investigated. Stroke volume was measured by means of impedance cardiography. Giving equipotent doses, Hexoprenaline/Fenoterol dose ratio of 1 : 8, there was a slower and smaller increase in heart rate over 24 hours with Hexoprenaline, with identical suppression of uterine contractility (external tocography). This was also reflected in the cardiac output, while there were no differences in the stroke volumes. Inhibition of diuresis was lower with Hexoprenaline. This might be due to the fact that since there is no organ specificity for beta-1 or respectively beta-2 receptors and the patterns of distribution differ, Hexoprenaline has a somewhat less pronounced action on beta-1 receptors than Fenoterol, though the same beta-2 action.

Drug Therapy, Combination↗

Placental transfer of 14C-hexoprenaline.

The placental transfer of a single intravenous injection of 14C-hexoprenaline was studied in eight pregnant New Zealand white rabbits. Maternal and fetal blood was sampled intermittently for 60 minutes after the injection. An initial rapid decrease in the levels of 14C-hexoprenaline in maternal blood was followed by a second slower phase, whereas fetal levels remained insignificant. The conclusion, therefore, is that the rapid improvement in fetal heart rate after the administration of a single maternal intravenous injection of hexoprenaline in the treatment of fetal distress is due to the action on the uterus and/or on maternal cardiovascular function, and not to direct stimulation of the fetus.

Animals↗

Hexoprenaline: beta-adrenoreceptor selectivity in isolated tissues from the guinea-pig.

1. A catecholamine beta-adrenoreceptor agonist, hexoprenaline, was examined in vitro on five guinea-pig tissues and its potency relative to isoprenaline (as 100) obtained. 2. Hexoprenaline clearly delineated between those tissues classified as containing beta2-adrenoreceptors (trachea, hind limb blood vessels and uterus; relative potencies 219, 110 and 76 respectively) and those classified as containing beta1-adrenoreceptors (atria and ileum; relative potencies 3.3 and 1.0 respectively). 3. Hexoprenaline differed from some previously studied noncatecholamine beta-adrenoreceptor agonists in being only two-fold less potent, relative to isoprenaline, as a vasodilator in perfused hind limb than as a tracheal relaxant.

Animals↗

An evaluation of oral hexoprenaline sulphate (Ipradol) in exercise-induced asthma.

The effect of hexoprenaline sulphate (1 mg) administered orally on the fall in peak expiratory flow rate (PEFR) after exercise was investigated in 20 asthmatic patients. Compared with placebo, the fall in PEFR expressed as a percentage of the resting value (measured immediately before exercise) was less in 16 of the 20 patients in the presence of hexoprenaline sulphate. This consistent amelioration of exercise-induced asthma has not been observed in this laboratory with similar drugs (such as salbutamol and terbutaline). While eight patients were afforded significant protection by the hexoprenaline sulphate, a fall in PEFR after exercise was within the normal range (less than 10% of the resting value) in only four patients.

Adolescent↗

Bronchodilator effect of hexoprenaline aerosol in bronchial asthma and chronic bronchitis.

The bronchodilator effects of aerosols of hexoprenaline (200 microgram and 400 microgram), and salbutamol (200 microgram) were compared in 15 patients with asthma, and nine patients with chronic bronchitis. In both groups of patients, hexoprenaline and salbutamol produced a similar increase in the forced expiratory volume in one second (FEV1), and mean percentage increase in FEV1. Neither drug caused tachycardia or arrhythmia. It was concluded that hexoprenaline aerosol was a safe and effective bronchodilator.

Adult↗

A comparison of the uterine beta2-adrenoreceptor selectivity of fenoterol, hexoprenaline, ritodrine and salbutamol.

A study was undertaken to compare the uterine beta2-adrenoreceptor selectivity of fenoterol, hexoprenaline, ritodrine and salbutamol. The drugs in doses having an equivalent effect on uterine activity, were randomly administered as an intravenous bolus to 10 patients who had been induced at term. The cardiovascular and uterine effects of the drugs were recorded. The rise in maternal pulse rate was significantly less (P less than 0,001) after the administration of hexoprenaline when it was compared with fenoterol, ritodrine, and salbutamol. Hexoprenaline proved to be the most chronotropically beta2-selective drug, having the least effect on the beta1-adrenoreceptors of the heart, for an equivalent effect on the uterus. Blood pressure changes were less significantly different between the drugs. The clinical use in obstetrics of a highly beta2-selective sympathomimetic drug is discussed.

Albuterol↗

[Hexoprenaline--a new tocolytic for treatment of premature labor].

Hexoprenaline is a selective beta 2-mimetic drug used in tocology for the prevention of premature labor and immature birth. From clinical application of the drug in bronchospasm therapy its selectivity, which is due to the elongated nitrogen substituent, is well-known. Because of the relatively small stimulation of cardiac beta 1-receptors the side-effects related therewith are less pronounced than with other beta-mimetics. The extent of tachycardia depends on the initial sympathomimetic condition of the patients. The success rate for hexoprenaline tocolyses is 34-78%, dependent on the initial tocological condition. The advantage of hexoprenaline compared with other tocolytics on the basis of experience made so far seems to relate to the smaller increase in chronotropy and the better tolerability.

Female↗

Comparison of carbuterol and hexoprenaline aerosol in bronchial asthma.

A new beta 2-adrenergic bronchodilator, carbuterol, was compared with hexoprenaline and placebo, by double-blind crossover technique in 10 adult asthmatic patients. Carbuterol 200 microgram was compared with hexoprenaline 200 microgram, corresponding to 2 inhalations from a standard aerosol in each case. The carbuterol effect, in terms of vital capacity and forced expiratory volume in 1 second (FEV1) was significantly longer than that of hexoprenaline. Its effect on airways resistance also appeared to be longer, although this difference was not statistically significant. The difference in duration of action may be due to greater potency of carbuterol, or to a longer elimination half-life of carbuterol. No significant effects on heart rate or blood pressure were noted with either drug.

Adolescent↗

Hexoprenaline and terbutaline administered by inhalation. A comparison between two beta2-adrenoreceptor agonists with respect to effect on bronchial obstruction, heart rate, blood pressure and muscle tremor.

In a controlled double-blind cross-over study in 15 patients with reversible bronchial obstruction hexoprenaline (Ipradol, 0.20 mg/puff) and terbutaline (Bricanyl, 0.25 mg/puff) when administered as metered aerosol in a dosage of one puff followed by two puffs 30 min later produced the same maximum improvement of ventilatory function. However, after inhalation of terbutaline a more sustained broncholytic effect was obtained than after hexoprenaline. Similar results were obtained in six patients after doubling the dose of each agent. The influence on pulse rate and blood pressure was negligible with either agent. The amplitude of finger tremor was measured after 2 + 4 puffs. No significant changes in mean values occurred after either of the two agents although after hexoprenaline an increase in amplitude of more than 100% was recorded in two out of six patients 30 min after the second dose.

Aerosols↗

A comparative assessment of carbuterol, fenoterol and hexoprenaline in allergic asthma.

Carbuterol tablets (2,0 mg) were compared with the tablets of fenoterol (2,5 mg) and hexoprenaline (1 mg). The three drugs were shown to be equally effective for a period of 4 hours, but carbuterol and fenoterol exerted a statistically significant bronchodilating action for 7 and 8 hours respectively, while the action of hexoprenaline lasted for 4 hours in the majority of patients. The aerosols of carbuterol (200 mg) and fenoterol (400 mg) appeared to be similar in inhibiting exercise-induced asthma, whereas hexoprenaline (200 mg) did not appear to be as effective.

Adolescent↗