Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo

Abstract

Introduction Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β2‐mimetic terbutaline and magnesium sulfate (MgSO4) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia‐inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents. Material and methods In the isolated organ bath studies, rhythmic contractions of 22‐day‐ pregnant Sprague–Dawley rats were stimulated with KCl, and cumulative dose–response curves were constructed in the presence of MgSO4 or terbutaline. The uterus‐relaxing effects of terbutaline were also investigated in the presence of MgSO4 in both normal buffer and Ca2+‐poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO4 or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate. Results Both MgSO4 and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO4 significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca2+‐poor environment, MgSO4 was not able to increase the effect of terbutaline, indicating the role of MgSO4 as a Ca2+ channel blocker. In the cardiovascular studies, MgSO4 significantly decreased the tachycardia‐inducing effect of terbutaline in late pregnant rats. Conclusions The combined application of MgSO4 and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO4 could substantially reduce the tachycardia‐inducing side effect of terbutaline.

The combined uterorelaxant effect of sildenafil and terbutalin in the rat: The potential benefit of co-administration of low doses

“…In isolated organ bath studies we also investigated the uterus relaxant effect of co-administered sildenafil and terbutaline. As in our previous study [ 12 ], terbutaline elicited a significant uterine relaxing effect in 22-day pregnant rats. When terbutaline was added in a single and low concentration with cumulatively administered sildenafil, we observed a significant potentiating effect at lower concentrations of sildenafil, but the maximal inhibitory effect of sildenafil did not increase.…”

“…Following this, the animals were treated with sildenafil and terbutaline alone in a cumulative way every 15 min. The effect of co-administered sildenafil and terbutaline was also monitored as the animals were treated with repeated i. v. Single doses of terbutaline (0.15 μg/kg) along with increasing doses of sildenafil (from 0.42 μg/kg to 4.2 mg/kg, sequential additions of 0.42 μg/kg, 1.26 μg/kg, 4.2 μg/kg, 12.6 μg/kg, 42 μg/kg, 0.126 mg/kg, 0.42 mg/kg, 1.26 mg/kg, 4.2 mg/kg) (The concentration of terbutaline was determined based on previous literature data [ 12 , 16 ], while the concentration of sildenafil was determined by our preliminary, unpublished pilot study.) every 15 min in a cumulative manner.…”

“…Some evidence exists for synergistic effects with sildenafil and nifedipine [ 4 ]. Additionally, we have previously demonstrated in the pregnant rat, that synergistic tocolytic effects are found when combining terbutaline and magnesium sulfate or terbutaline and nifedipine [ 12 , 13 ]. Based on these, the importance of terbutaline in combination therapy is confirmed.…”

A Case Study of an Adverse Reaction to Inhaled Terbutaline-Causing Tremor in Both Hands

“…The patient is a chronic obstructive pulmonary disease, bronchial asthma patients, inhaled glucocorticoids are the most effective drugs for the treatment of asthma, regardless of the severity of the disease, they are the first line of treatment for all patients with persistent disease, fluticasone propionate is a relatively new inhaled glucocorticoid, which has better efficacy on the lung function of patients with chronic stabilized bronchial asthma, and tiotropium bromide is a new long-acting anti-choline Tiotropium bromide is a new type of long-acting anticholinergic, and its bronchodilator effect is better than ipratropium bromide, which is currently used as the first-line drug for the treatment of COPD in the clinic, and has been recommended by the Global Initiative for the Prevention and Control of COPD as the basic drug for stable COPD [15,16]. The patient's lung function: severe mixed pulmonary ventilation dysfunction, and the doctor has given him budesofrine inhalation aerosol, which contains the β2 agonist formoterol, and if it is intolerable, the literature suggests that AZD3101 can be used [17].…”