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

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.

The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus

“…Magnesium sulfate (MgSO 4 , mineral salt, soluble in water) is used as a laxative, tocolytic agent and it is known as a functional blocker of calcium channels [1,2]. Despite the long-standing experience of its application, the use of MgSO 4 in gynecology has been a source of controversy for years.…”

Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

“…Its incidence varies across the country from 5 to 11% [1]. About 75% of premature births are due to spontaneous premature labor [2] which is also the most frequent cause of hospitalization [3].…”

Success rate in preterm uterine contraction inhibition with tocolytic agents in a tertiary care center

“…Nevertheless, tocolysis does not appear to significantly lengthen the gestational age beyond 7 days 14. It is known that nifedipine is easy to administer and have fewer side effects relative to betamimetics 15. The authors’ results also support this notion as intolerable side effects occurred more in cases of betamimetics treatment.…”