Prematurity prevention: the role of acute tocolysis

Blumenfeld, Yair J.; Lyell, Deirdre J.

doi:10.1097/gco.0b013e3283292455

Cited by 14 publications

(7 citation statements)

References 55 publications

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“…The most frequent maternal side-effect is headache which is associated with the transient hypotension caused by the loading doses [48]. Maternal tachycardia is the second most frequently reported adverse events following nifedipine therapy.…”

Section: Side-effects Of Ccbs During Tocolysismentioning

confidence: 99%

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

Gáspár

Hajagos-Tóth

2013

Pharmaceuticals

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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.

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Section: Side-effects Of Ccbs During Tocolysismentioning

confidence: 99%

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

Gáspár

Hajagos-Tóth

2013

Pharmaceuticals

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“…None is evidence-based and there is a controversy in the findings. Uterine contractions can be suppressed by tocolytic drugs but only for a very limited time and all compounds have considerable side-effects 31, 32…”

Section: Introductionmentioning

confidence: 99%

A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor

Kuon

Shi

Maul

et al. 2011

American Journal of Obstetrics and Gynecology

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Objectives To determine if optical methods can estimate cervix function during pregnancy and if progestins modify this process. Study Design Photos of the external cervix of timed-pregnant rats were taken every other day from day 13 (d13) until pp5 (postpartum day 5) following daily treatments with vehicle (controls) or progestin treatments (progesterone, P4 s.c., or vaginally; 17-alpha-hydroxyprogesterone caproate, 17P s.c. and RU-486 s.c., once on d16). Surface area (SA) of the cervix was estimated from photos. Results The SA of cervix increases throughout pregnancy and reverses pp in controls. In P4 s.c. or 17P s.c. groups, increases in SA are lower (17P group until day 19 only) (P<.05). Vaginal P4 does not prevent SA increases. Only the P4 s.c. blocked delivery. RU-486 increases SA of the cervix (P<.05) during preterm delivery. Conclusions An optical method is useful for quantitative assessment of the cervix and evaluation of agents that modify cervical function.

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“…Indeed, inhibition of VGCCs using dihydropyridines, such as nifedipine, is a mainstay of current clinical intervention for preterm labor in the United States. While calcium channel blockers are generally considered safer and more effective than many other tocolytics, they typically only delay birth up to 2 days, allowing time for maturation of fetal lungs through administration of a corticosteroid (3,21,29). In addition, because VGCCs are major conduits of Ca 2ϩ entry in vascular smooth muscle, therapeutic doses of dihydropyridines against uterine contractions can result in unacceptable decreases in maternal blood pressure (3,16,33).…”

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confidence: 99%

CyPPA, a positive modulator of small-conductance Ca²⁺-activated K⁺ channels, inhibits phasic uterine contractions and delays preterm birth in mice

Skarra

Cornwell

Solodushko

et al. 2011

American Journal of Physiology-Cell Physiology

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Skarra DV, Cornwell T, Solodushko V, Brown A, Taylor MS. CyPPA, a positive modulator of small-conductance Ca 2ϩ -activated K ϩ channels, inhibits phasic uterine contractions and delays preterm birth in mice. Am J Physiol Cell Physiol 301: C1027-C1035, 2011. First published July 27, 2011; doi:10.1152/ajpcell.00082.2011.-Organized uterine contractions, including those necessary for parturition, are dependent on calcium entry through voltage-gated calcium channels in myometrial smooth muscle cells. Recent evidence suggests that small-conductance Ca 2ϩ -activated potassium channels (K Ca 2), specifically isoforms K Ca2.2 and 2.3, may control these contractions through negative feedback regulation of Ca 2ϩ entry. We tested whether selective pharmacologic activation of K Ca2.2/2.3 channels might depress uterine contractions, providing a new strategy for preterm labor intervention. Western blot analysis and immunofluorescence microscopy revealed expression of both KCa2.2 and KCa2.3 in the myometrium of nonpregnant (NP) and pregnant (gestation day 10 and 16; D10 and D16, respectively) mice. Spontaneous phasic contractions of isolated NP, D10, and D16 uterine strips were all suppressed by the KCa2.2/2.3-selective activator CyPPA in a concentration-dependent manner. This effect was antagonized by the selective KCa2 inhibitor apamin. Whereas CyPPA sensitivity was reduced in D10 and D16 versus NP strips (pIC50 5.33 Ϯ 0.09, 4.64 Ϯ 0.03, 4.72 Ϯ 0.10, respectively), all contractions were abolished between 30 and 60 M. Blunted contractions were associated with CyPPA depression of spontaneous Ca 2ϩ events in myometrial smooth muscle bundles. Augmentation of uterine contractions with oxytocin or prostaglandin F2␣ did not reduce CyPPA sensitivity or efficacy. Finally, in an RU486-induced preterm labor model, CyPPA significantly delayed time to delivery by 3.4 h and caused a 2.5-fold increase in pup retention. These data indicate that pharmacologic stimulation of myometrial KCa2.2/2.3 channels effectively suppresses Ca 2ϩ -mediated uterine contractions and delays preterm birth in mice, supporting the potential utility of this approach in tocolytic therapies.

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Prematurity prevention: the role of acute tocolysis

Cited by 14 publications

References 55 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

A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor

CyPPA, a positive modulator of small-conductance Ca²⁺-activated K⁺ channels, inhibits phasic uterine contractions and delays preterm birth in mice

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Prematurity prevention: the role of acute tocolysis

Cited by 14 publications

References 55 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

A novel optical method to assess cervical changes during pregnancy and use to evaluate the effects of progestins on term and preterm labor

CyPPA, a positive modulator of small-conductance Ca2+-activated K+ channels, inhibits phasic uterine contractions and delays preterm birth in mice

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CyPPA, a positive modulator of small-conductance Ca²⁺-activated K⁺ channels, inhibits phasic uterine contractions and delays preterm birth in mice