Betamimetic Drugs Research Articles

Effects of D2343, a new beta-mimetic drug, and terbutaline on spontaneous term labor.

The effects of an intravenous bolus injection of D2343 (0.75 or 1 mg) or terbutaline (0.25 mg) on spontaneous term labor were studied. The uterine activity was recorded by a transducer-tipped intrauterine catheter and calculated electronically by an uterine activity integrator module built in a conventional fetal monitor. After drug administration the uterine activity was reduced to a similar extent with D2343 and terbutaline but the contractions were abolished for a longer time with terbutaline injection (mean of 9.3-9.8 min compared with 17.0 min). Maternal blood pressure was unaffected in both groups but the increase in pulse rate was slightly higher in the D2343 groups. D2343 seems to have an effect ratio between uterine inhibitory capacity and cardiovascular side effects similar to terbutaline.

A study of maternal ECG characteristics before and during intravenous tocolysis with beta-sympathicomimetics. Effects of i.v. tocolysis on maternal ECG characteristics.

Severe maternal complications during beta-mimetic therapy have been reported. In a study of maternal complications related to intravenous tocolysis, which covering a period of 2 years, we paid special attention to the maternal ECG before and during treatment. There was a high prevalence of pretreatment ECG changes: tachycardia (23.6%), disorders of impulse conduction (43.6%), ST-depression (14.5%) and disorders of repolarization (43.6%). During intravenous beta-mimetic therapy there was an increase in the prevalence of tachycardia, prolonged QT-time and disorders of repolarization. We also studied the course in time of the different ECG characteristics during treatment. With regard to the ST-depression, a possible physiological adaptation to the beta-mimetic drug is described. We could not find this possible adaptation with regard to the other ECG characteristics. None of the women in the studied group showed clinical signs of myocardial ischemia, notwithstanding the high prevalence of ECG changes. We conclude that the ECG criteria for discontinuation of tocolytic therapy need re-evaluation.

Complications of beta-mimetic therapy in preterm labour.

Selective beta-mimetic drugs are the most frequently used agents for arresting preterm labour. For this purpose these drugs have to be given in high doses for several hours and since they act on several organ systems, side-effects, some of which are potentially dangerous, appear. These hazards, which involve chiefly the cardiovascular and metabolic areas, have been examined in the light of available experience with these drugs. This review considers the possible mechanisms for the side-effects and offers suggestions on how the dangers in the use of beta-mimetic drugs in preterm labour might be avoided.

The effects of α- and β-adrenergic stimulation on contractility and prostaglandin (prostaglandins E2 and F2α and 6-keto-prostaglandin F1α) production of pregnant human myometrial strips

The effects of catecholamines and alpha- and beta-adrenergic agonists and antagonists on the spontaneous contractility of superfused pregnant human myometrial strips are reported. Prostaglandins (prostaglandins E2 and F2 alpha and 6-keto-prostaglandin F1 alpha) were analyzed in the effluent of the superfusion medium by specific radioimmunoassays. Both epinephrine and norepinephrine dose-dependently (10 ng/ml to 1 microgram/ml) stimulated the contractility of the myometrial strips and significantly increased the synthesis of all prostaglandins assayed. alpha-Adrenergic blockers inhibited the catecholamine-induced increase in contractility. This was associated with decreased prostaglandins F2 alpha and E2 concentrations and a further increase in 6-keto-prostaglandin F1 alpha levels. Exclusive beta-adrenergic stimulation with beta-mimetic drugs had the same effect. Conversely, epinephrine stimulation together with beta-blockers resulted in a further increase in the prostaglandins F2 alpha and E2 release of the myometrial strips. This effect was even more pronounced with specific alpha-adrenergic stimulant drugs. Our results demonstrate the interrelationship of alpha- and beta-adrenergic stimulation and the prostaglandin system. alpha-Adrenergic stimulation increases myometrial contractility and the synthesis of prostaglandins F2 alpha and E2. beta-Adrenergic stimulation reduces contractility by further enhancing 6-keto-prostaglandin F1 alpha production.

Obstetrical attitudes to glucocorticoid treatment for fetal lung maturation: time for a change?

A questionnaire survey was conducted among 1004 specialist and trainee obstetricians in the Netherlands and northern Belgium (i.e., Flanders). Glucocorticoids would be used by 85% in Belgium and 74% in the Netherlands, while 59% in both countries would combine them with betamimetic drugs in preterm labor. The more frequently respondents relied on glucocorticoids, the more likely they were to use them at more advanced gestational ages, to combine them with betamimetic drugs and to use that combination beyond 34 wk. Of those using glucocorticoids, only 11% would not do so after 32 wk, while 37% would use them after 34 wk and 5% even beyond 36 wk of gestation. Gestational age limits did not differ for glucocorticoids with or without betamimetic drugs. The findings indicate that the encouraging results of the early trials have lead to widespread inappropriate use of prenatal glucocorticoid therapy. Substantial overuse was more frequent than rejection of its use.

Betamimetic drugs in the prophylaxis of preterm labour: extent and rationale of their use.

A questionnaire survey among 1004 specialist and trainee obstetricians in The Netherlands and northern Belgium (Flanders), revealed that 45% of the 521 (52%) respondents would use prophylactic betamimetics to prevent preterm labour. A further 33% would only use them as maintenance therapy after an acute episode of preterm labour. Only 22% would use neither form of prophylaxis, 23% would not prescribe oral betamimetics for out-patients, and a mere 12% would use neither prophylaxis nor out-patient treatment. Nevertheless, only 4% of those using betamimetics either prophylactically or as maintenance therapy said that they were very effective. The data indicate that a large body of obstetricians will resort to dubious treatments with poor effectiveness and unknown risks in an attempt to avoid the known risks of a condition for which aetiological insight and effective therapy are lacking.

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.

Cardiovascular effects of terbutalin in pregnant women.

Terbutalin, a beta-mimetic drug, appears to have a favorable beta 2:beta 1 ratio. It is suitable for uterine relaxation. Ten normotensive pregnant women with imminent premature labor were studied during intravenous infusion of terbutalin with the non-invasive method of quantitative sphygmometry. Cardiac output increased and total peripheral resistance decreased. As there was only slight variation in the arterial blood pressure, terbutalin is indicated especially in cases with hypotension.

The influence of long term beta-mimetic drug administration during pregnancy on blood loss postpartum

Early blood loss after delivery was measured in all prematurely ending singleton pregnancies (amenorrhea 29–38 wk) during which the patients had been treated with betamimetics (ritodrine or fenoterol) for the prevention of premature labor, during a 4 yr study period (1975–1978) ( n = 129). For comparison, postpartum blood loss was measured in the same way in all other (not treated) patients who delivered with the same gestational ages during the first 2 yr of the investigation ( n = 176). Only vaginal deliveries were included and some patient categories were excluded. Placental weight and episiotomy status were found to effect the amount of early postpartum blood loss at a significant level. Blood loss after delivery was found not to be increased by chronic beta-mimetic treatment, even when this treatment ended less than 24 h before delivery. Moreover, when the treatment—delivery interval exceeded 24 h, the average amount of blood loss by treated patients was less than that of the untreated patients in some comparison categories. No difference in the amount of blood loss was found according to the specific drug that had been used.

The effect of the beta-mimetic drug clenbuterol on maternal and fetal behaviour.

The effect of the beta-mimetic compound clenbuterol on maternal and fetal behaviour was studied in 12 normal primigravidae between 35 and 38 wk of gestation. None of the subjects exhibited any signs of uterine activity. Following a control period of 60 min, oral intake of 100 micrograms of clenbuterol resulted in a maximum increase in maternal and fetal heart rate of 13 and 7%, respectively. Maternal systolic blood pressure showed a rise of 6%, whereas diastolic blood pressure demonstrated a drop of 8%. The percentage incidence of fetal breathing and trunk movements did not show any significant change following oral clenbuterol administration, indicating the absence of any major effect of this drug on the fetal central nervous system. Maternal blood glucose levels demonstrated a fairly constant pattern during the entire study period.

Prolactin, estradiol, and thyroid hormones in umbilical cord blood of neonates with and without hyaline membrane disease: A study of 405 neonates from midpregnancy to term

Concentrations of prolactin (PRL), estradiol (E2), thyroxine (T4), triiodothyronine (T3), and reverse T3 in umbilical cord blood were measured by radioimmunoassay in neonates with (n = 60) and in a control group without (n = 345) hyaline membrane disease. Mean levels of all hormones assayed were not significantly different between the two groups at various stages of gestation. In the control group, gestational age correlated positively with PRL and inversely with reverse T3, whereas birth weight correlated positively with PRL, T4, and T3, but inversely with reverse T3 levels. Thus, larger, more mature neonates tended to have higher cord levels of PRL, T4, T3 and lower concentrations of reverse T3. The data also suggest that, in the premature neonate, various obstetric complications and exposure in utero to beta-mimetic drugs and glucocorticoids may be important determinants of the concentrations of E2 and thyroid hormone in cord blood.

Renin activity, aldosterone levels and urinary sodium and potassium excretion under tocolytic therapy with salbutamol

The effects of long-term therapy with salbutamol on renin activity, aldosterone levels and urinary sodium and potassium excretion in pregnant women are studied. Salbutamol was given intravenously in a first group of 18 patients in preterm labor, orally in a second group of 9 patients, whereas a third group of 17 patients was taken as control. No significant changes were observed in renin activity and aldosterone levels between the first and the fifth day of intravenous or oral therapy and in 24-h sodium urinary excretion. Only potassium excretion showed a significant decrease ( P < 0.01) within 24 h from the start of the intravenous therapy, returning to control levels after 48 h. From these results, no replacement of potassium seems to be necessary in patients undergoing tocolytic therapy with betamimetic drugs.

Maternal placental blood flow in hypertensive pregnancy and the effect of beta-mimetic drugs on it.

Maternal placental blood flow in hypertensive pregnancy and the effect of beta-mimetic drugs on it.

Randomized trial of two Beta-Mimetic drugs (Ritodrine and Fenoterol) in acute intra-Parum tocolysis

Randomized trial of two Beta-Mimetic drugs (Ritodrine and Fenoterol) in acute intra-Parum tocolysis

Clinical study of the labour inhibiting effects an side effects of acetylsalicylic acid (ASA) (author's transl)

In 37 pregnancy women preterm labour was inhibited with intravenous administration of ASA. 20 patients (Group I) had a combined treatment of ASA and Fenoterol. 7 pregnant women (Group II) without successful labour inhibition under Fenoterol were treated with ASA subsequently. In a third group of 10 women we administered ASA alone. The treatment was considered as successful if signs of preterm labour stopped and pregnancy maintained for 7 days or more. In the first group 16, in the second group all patients had been treated successfully. In group III we succeeded in labour inhibiting for more than 7 days in 6 cases. An initial loading dose of 5.5 to 7.0 mn/min ASA had been infused for 24 hours. If preterm labour was stopped, the dosage had been reduced. In all patients dose related but reversible symptoms of vertigo, tinnitus, headache and hyperventilation were seen. Furthermore we found a non-dose-dependent prolongation ( by 30% or normal) of bleeding time. In the fetus respectively the newborn an affection by this ASA treatment could be excluded. We propose inhibition of preterm labour by i.v. ASA administration in all pregnant women if beta-mimetic drugs are not successful or an intolerance is diagnosed. Contraindications for ASA therapy are mentioned.

The autonomic nervous system and perinatal metabolism.

The development of the autonomic nervous system in relation to perinatal metabolism is reviewed with particular attention given to the adipocyte, hepatocyte and the A and B cells of the islets of Langerhans. Adrenergic receptors develop in the B cell independently of normal innervation and by the time of birth, in most species studied, the pancreas, liver and adipose tissue respond appropriately to autonomic signals. Birth is associated with a huge surge in circulating catecholamines which is probably responsible for the early postnatal rise in free fatty acids and glucagon concentrations in plasma. beta-Blocking drugs such as propranolol have an adverse effect on fetal growth and neonatal metabolism, being responsible for hypoglycemia and for impairing the thermogenic response to cold exposure. beta-Mimetic drugs are commonly used to prevent premature labour and may help the fetus in other ways, for example, by improving the placental blood supply and the delivery of nutrients by increasing maternal fat and carbohydrate mobilization.

Neonatal respiratory distress syndrome (RDS) in cases of premature labor treated by betamimetic drugs

In 87 premature labors, 31 were treated with betamimetic drugs. The incidence of RDS in the treated group has been lower than in the non-treated group, especially when gestational age was shorter than 35 wk and when newborn's weight was lower than 2000 g.

A betamimetic drug and human fetal lung maturation

In a double-blind and randomized study the administration of a betamimetic drug to the mother from week 33 to 35 produces a significant increase in amniotic fluid palmitic acid levels. We suggest that the administration of a betamimetic drug during pregnancy to the mother can be useful in producing an acceleration of the fetal lung maturation.

Stimulation of the Alpha- and Beta-Adrenergic Receptors in Human Ovarian Vasculature &lt;i&gt;in vitro&lt;/i&gt;

The effect of fenoterol and norepinephrine was studied on the vascular resistance of in vitro perfused human ovary. It was found that the beta-adrenergic stimulant fenoterol causes vasodilatation, whereas the alpha-adrenergic stimulant norepinephrine elicits vasoconstriction in the arterial vascular bed of the ovary showing the role of adrenergic mechanism in the regulation of ovarian blood flow. It was supposed that therapeutical administration of beta-mimetic drugs leads to the elevation of ovarian blood flow, which may have special importance in the case of corpus luteum insufficiency.

Management of acute puerperal inversion of the uterus with beta-mimetic drugs and prostaglandins

Abstract The sequential administration of a β 2 -mimetic and a prostaglandin were found to be a most useful approach to the first-aid management of acute inversion of the puerperal uterus.