[Maternal and fetal hemodynamics under simultaneous beta stimulation and beta1 blockade in a tocolysis model. Considerations on status of the neonatal beta receptor and transplacental passage of metoprolol]. / Maternale und fetale Hämodynamik unter gleichzeitiger beta-Stimulation und beta1-Blockade am Tokolysemodell. Berücksichtigung des neonatalen beta-Rezeptorenstatus und der transplazentaren Metoprolol-Passage).

This report summarizes the clinical experiences in the treatment of preterm labor using the combination of hexoprenaline and the beta 1-antagonist metoprolol. We found a dose dependency in the antagonism of positive inotropic effects primarily induced by the beta-stimulator hexoprenaline. To verify the pharmacological properties of metoprolol in transplacental passage we evaluated the plasma concentration of metoprolol in umbilical cord blood. There is quite a low concentration of the beta-blocker nearly 24 h after the last course of administration. The beta 2-receptor density--determined by (+/-)-125-iodocyanopindolol (ICYP) binding--and beta 2-receptor responsiveness--assessed by cyclic AMP response to isoprenaline stimulation--in lymphocytes derived from neonatal blood were also investigated. These results were compared with identical investigations in adult lymphocytes. The results indicate that in neonates beta 2-receptor density and responsiveness is significantly diminished in comparison to the adult controls. The present investigations induce a new concept for the estimation of concomitant fetal cardiovascular reactions under maternal beta-blockade.

Transplacental transfer of beta-adrenergic drugs studied by an in vitro perfusion method of an isolated human placental lobule.

A study was made of the transfer across an in vitro perfused human placenta of four beta-mimetics commonly used in obstetric practice. Between 2% and 3% of fenoterol, ritodrine, and salbutamol appeared on the fetal side after bolus injection into the maternal circulation. For hexoprenaline, the transfer (1%) was significantly lower than that observed with other beta-mimetics studied. With constant infusion of fenoterol into the maternal circulation and recycling of a small volume of perfusate on the fetal side, a fairly rapid rise in the concentration was seen. Some sulfate conjugation of fenoterol during its diffusion from the maternal to the fetal side of the placenta could be seen. In the in vitro perfused human placental lobule there is no apparent effect of synthetic beta-mimetics on the transfer of antipyrine or glucose and no stimulation of the production of lactate and pyruvate.

Hexoprenaline pharmacokinetics in pregnant and nonpregnant sheep.

Hexoprenaline, a beta 2-sympathomimetic agent, is used to suppress uterine contractions in the treatment of premature labor. However, little is known regarding the potential of this drug to undergo placental transfer or whether the pregnant state alters any of the pharmacokinetic parameters. Using sheep as a model, intravenous doses of 14C-hexoprenaline were administered to pregnant and non-pregnant animals. Measurable levels of radioactivity did not appear in fetal blood samples. After intravenous bolus administration, blood concentrations in the ewe could be fitted by a triexponential curve characteristic of a three-compartment pharmacokinetic model. Following intravenous infusion, a biexponential curve described the decline in blood concentrations. Mean terminal half lives for total radioactivity ranged from 2.5 to 4.2 hours. The pregnant animals tended to exhibit smaller apparent volumes of distribution and lower values for total body clearance, normalized to body weight, compared to non-pregnant sheep.

Hexoprenaline: a review of its pharmacological properties and therapeutic efficacy with particular reference to asthma.

Hexoprenaline1, N,N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl] hexamethyl-enediamine, sulphate is a selective beta2-adrenoreceptor agonist which is active in man as a bronchodilator by the oral or intravenous routes and by inhalation. It is indicated for use in the treatment of bronchospasm associated with obstructive airways diseases, including asthma, bronchitis and emphysema. Clinical experience and double-blind studies have established that hexoprenaline is an effective bronchodilator. It major advantage over many other many other brochodilators of equal efficacy is its generally low production of side-effects, particularly tremor, palptitations, and tachycardia. In comparative trials, it has generally been rated as superior to orciprenaline or trimetoquinol, but comparisons with salbutamol have provided equivocal results. Oral hexoprenaline was superior to fenoterol as long-term maintenance therapy is asthma, principally because its somewhat lesser bronchodilatory effects were more than compensated for by a lesser incidence of side-effects.