Management of preterm labor: atosiban or nifedipine?

Heus, Roel de; Mulder, E.J.H.; Visser, Gerard H.A.

doi:10.2147/ijwh.s7219

Cited by 20 publications

(13 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This limited evidence suggests no essential differences in the tocolytic efficacy of these two drugs. The oral administration, the lower costs and the possibly lower level of neonatal morbidity favour the use of nifedipine [ 42 , 43 ].…”

Section: The Efficacy Of Ccbs Against Ptbmentioning

confidence: 99%

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Gáspár

Hajagos-Tóth

2013

Pharmaceuticals

View full text Add to dashboard Cite

Dihydropyridine Ca2+ channel blockers (CCBs) are widely accepted in the treatment of premature labour. Their mechanism of action in tocolysis involves the blockade of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. In clinical practice, most experience has been gained with the use of nifedipine, whose efficacy is superior or comparable to those of β-agonists and oxytocin antagonists. Additionally, it has a favourable adverse effect profile as compared with the majority of other tocolytics. The most frequent and well-tolerated side-effects of CCBs are tachycardia, headache and hypotension. In tocolytic therapy efforts are currently being made to find combinations of tocolytic agents that yield better therapeutic action. The available human and animal studies suggest that the combination of CCBs with β-AR agonists is beneficial, although such combinations can pose risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular diseases. Preclinical data indicate the potential benefit of combinations of CCBs and oxytocin antagonists. However, the combinations of CCBs with progesterone or cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to remain one of the most important groups of drugs for the rapid inhibition of premature uterine contractions. Their significance may be magnified by further clinical studies on their combined use for tocolysis.

show abstract

Section: The Efficacy Of Ccbs Against Ptbmentioning

confidence: 99%

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Gáspár

Hajagos-Tóth

2013

Pharmaceuticals

View full text Add to dashboard Cite

show abstract

“…In addition, this preparation has a direct effect on vascular structure and acts on receptors throughout the body, so that nifedipine can decrease UA PI. 32 An umbilical arterial blood ow Doppler examination is one indicator of fetal blood ow that can provide an overview of intrauterine fetal conditions. Disrupted UA blood ow can cause fetal hypoxia and a unfavorable outcome on intrauterine fetal development.…”

Section: Nomentioning

confidence: 99%

The Impact of Nifedipine on Maternal and Fetal Blood Stream on the Threat of Preterm Labor: an Experimental Study

Anwar

Tiara

Anggraeni

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Preterm birth is a significant cause of perinatal morbidity and mortality and that becomes a major challenge in perinatal health care. Various pharmacological agents that inhibit uterine contractions are used in clinical practice to prevent preterm delivery. The maternal and fetal side-effect profiles of tocolytic agents are becoming an important consideration in selecting the drug of choice. Nifedipine, a dihydropyridine calcium entry blocker, is an effective tocolytic agent with low toxicity and teratogenicity, while carrying potential maternal as well as fetal vascular side effects due to its action on vascular smooth muscle. This study was performed to asses nifedipine use as tocolytic agent in preventing preterm birth, and assesing maternal as well as fetal vascular side effects.Methods: This experimental study with one-group pretest-posttest design was performed in 30 pregnant women undergoing nifedipine as tocolytic. Doppler assessment of uterine, umbilical and fetal middle cerebral arteries, ductus venosus, and cerebroplacental ratio was performed before and 48 hours after nifedipine therapy. Wilcoxon's signed ranks test was used to analyze the difference between the two variables. A P-value of < 0.05 was considered significant.Results: The result of the study showed nifedipine was associated with a significant decreased of pulsatility index uterine artery (p = 0.016; p-value<0.05) and umbilical artery (p = 0.037; p-value<0.05) after 48 hours therapy, while pulsatility index of fetal middle cerebral arteries, ductus venosus, and cerebroplacental ratio did not change significantly.Conclusion: The study concluded that nifedipine as tocolytic increased blood flow of uterine artery and umbilical artery after 48 hours therapy.

show abstract

“…Specifically, these drugs are known to cause either maternal cardiovascular effects, in utero constriction of the fetal ductus arteriosus (DA) or fetal tachycardia [5][6][7]. Atosiban (oxytocin receptor antagonist) is a safe tocolytic without serious side-effects but has not been granted FDA-approval due a lack of clinical efficacy [8,9]. Thus, novel safe and effective tocolytic agents are urgently needed for management of preterm labor.…”

Section: Introductionmentioning

confidence: 99%

Identification of mundulone and mundulone acetate as natural products with tocolytic efficacy in mono- and combination-therapy with current tocolytics

Siricilla

et al. 2021

Preprint

View full text Add to dashboard Cite

Currently, there are a lack of FDA-approved tocolytics for the management of preterm labor. We previously observed that the isoflavones mundulone and mundulone acetate (MA) inhibit intracellular Ca2+-regulated myometrial contractility. Here, we further probed the potential of these natural products to be small molecule leads for discovery of novel tocolytics by: (1) examining uterine-selectivity by comparing concentration-response between human primary myometrial cells and a major off-target site, aortic vascular smooth muscle cells (VSMCs), (2) identifying synergistic combinations with current clinical tocolytics to increase efficacy or and reduce off-target side effects, (3) determining cytotoxic effects and (4) investigating the efficacy, potency and tissue-selectivity between myometrial contractility and constriction of fetal ductus arteriosus (DA), a major off-target of current tocolytics. Mundulone displayed significantly greater efficacy (Emax = 80.5% vs. 44.5%, p=0.0005) and potency (IC50 = 27 μM and 14 μM, p=0.007) compared to MA in the inhibition of intracellular-Ca2+ from myometrial cells. MA showed greater uterine-selectivity, compared to mundulone, based on greater differences in the IC50 (4.3 vs. 2.3 fold) and Emax (70% vs. 0%) between myometrial cells compared to aorta VSMCs. Moreover, MA demonstrated a favorable in vitro therapeutic index of 8.8, compared to TI = 0.8 of mundulone, due to its significantly (p<0.0005) smaller effect on the viability of myometrial (hTERT-HM), liver (HepG2) and kidney (RPTEC) cells. However, mundulone exhibited synergism with two current tocolytics (atosiban and nifedipine), while MA only displayed synergistic efficacy with only nifedipine. Of these synergistic combinations, only mundulone + atosiban demonstrated a favorable TI = 10 compared to TI=0.8 for mundulone alone. While only mundulone showed concentration-dependent inhibition of ex vivo mouse myometrial contractions, neither mundulone or MA affected mouse fetal DA vasoreactivity. The combination of mundulone and atosiban yielded greater tocolytic efficacy and potency on term pregnant mouse and human myometrial tissue compared to single-drugs. Collectively, these data highlight the difference in uterine‐selectivity of Ca2+‐mobilization, effects on cell viability and tocolytic efficacy between mundulone and MA. These natural products could benefit from medicinal chemistry efforts to study the structural activity relationship for further development into a promising single- and/or combination-tocolytic therapy for management of preterm labor.

show abstract

Management of preterm labor: atosiban or nifedipine?

Cited by 20 publications

References 58 publications

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

The Impact of Nifedipine on Maternal and Fetal Blood Stream on the Threat of Preterm Labor: an Experimental Study

Identification of mundulone and mundulone acetate as natural products with tocolytic efficacy in mono- and combination-therapy with current tocolytics

Contact Info

Product

Resources

About