Abstract
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.
Highlights
Pre-term birth (PTB) is one of the main clinical problems in obstetrical practice
These results suggest an increased relaxant effect of β2-agonists combined with Ca2+ channel blockers (CCBs) in the pregnant myometrium
CCBs are increasingly used for tocolysis, officially they are not licensed for this purpose
Summary
Pre-term birth (PTB) is one of the main clinical problems in obstetrical practice. Despite of the availability of several drugs that inhibit pre-term contractions (tocolytics), the pharmacotherapy of PTB is inappropriate. Ca2+ channel blockers (CCBs), and especially nifedipine and nicardipine, are among the frequently used tocolytics. They are constantly gaining in importance, and increasingly more significant than traditional tocolytics such as beta-adrenergic receptor (β-AR). They do not meet the criteria of ideal tocolytics, CCBs have certain properties that make them preferable to other tocolytics. Haas et al concluded that CCBs have high probability of delaying PTB and improving neonatal outcomes [2]
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