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Miscellaneous Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Atosiban, unavailable in the United States, inhibits oxytocin-induced uterine contractions by competing with oxytocin for myometrial binding (Shubert, 1995). Atosiban is a nonapeptide oxytocin analog with competitive oxytocin antagonist action. Consistent reduction in uterine activity during the infusion of atosiban has been observed (Goodwin et al., 1995). No systematic studies regarding the safety of this agent are published.
Preterm Labor
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Evidence for effectiveness (Table 19.5): Compared with placebo, atosiban does not reduce the incidence of PTB or improve neonatal outcome [58]. In one trial, atosiban was associated with an increase in extreme PTB <28 weeks and infant deaths at 12 months of age compared with placebo [58]. However, this trial randomized significantly more women to atosiban before 26 weeks’ gestation. Compared with betamimetics, atosiban is associated with similar incidences of PTB and perinatal morbidity/mortality and with fewer maternal drug reactions requiring treatment cessation [58]. Recent data comparing atosiban and nifedipine for tocolysis found no difference in pregnancy prolongation or perinatal outcome but fewer maternal side effects associated with atosiban [59, 60]. However, nifedipine was more cost-effective than atosiban [61]. There is insufficient evidence to assess the effectiveness of a different ORA, barusiban, as only one RCT has tested it against placebo at 34–35 weeks, with no changes in recorded outcomes [62]. Therefore, as per magnesium, the only evidence supporting the use of ORAs for primary tocolysis is that they have fewer side effects than the (effective) betamimetics.
The diagnosis and management of preterm labor with intact membranes
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Roberto Romero, Tinnakorn Chaiworapongsa, Francesca Gotsch, Lami Yeo, Ichchha Madan, Sonia S. Hassan
A large randomized clinical trial in which patients in preterm labor were allocated to either atosiban- or placebo-initiated treatment showed that atosiban-treated patients were significantly less likely to deliver within 24 hours, 48 hours, and 7 days than patients with placebo-initiated treatment (342). There was no difference in the interval from enrollment to delivery between the two groups. In this study, the rate of fetal/infant death was greater in patients allocated to atosiban than placebo. This was attributed to an excess number of patients with gestational ages less than 24 weeks allocated to the atosiban arm compared with the placebo-initiated treatment. Similarly, there was an excess of infection-associated preterm labor and delivery in patients allocated to atosiban. This concern for safety was probably the reason the FDA did not approve atosiban in the United States. Another randomized clinical trial in which patients with an episode of preterm labor were treated with atosiban and subsequently randomized to either maintenance therapy with atosiban (subcutaneous pump) or placebo showed that maintenance therapy was not associated with a reduction in the rate of preterm delivery (343). However, in this trial, prolonged exposure to atosiban did not result in an excess of fetal or infant death. This finding, coupled with the extensive experience in Europe with atosiban, makes it unlikely that there is a toxic effect of atosiban on the fetus.
Phloroglucinol inhibits oxytocin-induced contraction in rat gastric circular muscle and uterine smooth muscle
Published in Journal of Obstetrics and Gynaecology, 2023
Wenhui Yang, Hua Guo, Jinbo Niu, Junya Liu, Ran Su, Yingde Bai, Shuang Zhang, Qian Liu, Nan Sun
We evaluated whether phloroglucinol exerts the inhibitory effect on the contraction of gastric circular muscle and uterine smooth muscle induced by OT. It was found that the phloroglucinol, atropine and atosiban have no obvious effect on gastric circular muscle strips when OT was at 10−9 mol/L (Figure 2(A)). However, atropine and atosiban showed significant inhibitory effects when OT was at 10−8, 10−7 and 10−6 mol/L. Phloroglucinol remarkably inhibited the contraction of gastric circular muscle when OT was at 10−6 mol/L. In addition, atropine and atosiban significantly inhibited the contraction of uterine smooth muscle induced by OT, while phloroglucinol only dramatically inhibited the contraction of uterine smooth muscle when OT was at 10−6 mol/L (Figure 2(B)). These results suggested that phloroglucinol suppressed the OT-induced contraction of gastric circular muscle and uterine smooth muscle.
Oxytocin modulates steroidogenesis-associated genes and estradiol levels in the placenta
Published in Systems Biology in Reproductive Medicine, 2023
Sung-Min An, Min Jae Kim, Jea Sic Jeong, So Young Kim, Da Som Kim, Beum-Soo An, Seung Chul Kim
Additionally, we examined the synthesis of steroid hormones in the groups treated with atosiban, which inhibits OXT signaling. We evaluated the concentration of steroid hormones, including P5, P4, DHEA, T, and E2 (Table 1). Following treatment with atosiban at a dose of 0.6 mg/kg/day, the concentration of P5 in plasma was significantly increased (p < 0.05), while the concentration of other steroid hormones was not altered. A high dose of atosiban (1.2 mg/kg/day) significantly decreased the concentration of E2 (p < 0.05). However, the plasma concentration of other hormones, including P4, DHEA, and T, did not show significant changes in the high-dose atosiban group. These results suggest that changes in OXT signaling during pregnancy affect the production of steroid hormones.
In vitro contractile responses of human detrusor smooth muscle to oxytocin: does it really have effect?
Published in The Aging Male, 2020
Fatih Tarhan, Nesrin Çağlayan Duman, Songül Özkula, Atila Karaalp, Önder Cangüven
Carbachol, the muscarinic receptor agonist contracted all human bladder smooth muscle strips in a final concentration of 10−5 M for the functionality test (Figure 1(C)) whereas OT in any concentrations between 10−9 M to 10−5 M did not produce significant contraction on all human urinary bladder smooth muscle strips (Figure 1(A)). In only one bladder strip (male 60 years old) and in a very high (3 × 10−6 M) concentration slight contraction was recorded (Figure 1(B)). Moreover no contractile response was recorded in any OT concentrations between 10−9 M to 10−5 M in the presence of atosiban, the OT receptor antagonist (Figure 1(D)). As no responses to OT in all human bladder smooth muscle strips were recorded we decided to test whether OT is active or not. For this purpose OT was tested in rat uterine smooth muscle at in vitro organ bath. The rat uterine smooth muscle strips responded to OT in a dose dependent manner (concentrations between 10−9 M to 10−5 M) (Figure 2). Atosiban, the OT receptor antagonist diminished totally those contractile responses in a concentration of 10−5 M (data not given) in rat uterine smooth muscle strips. (Figures 1 and 2).