Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations
Abstract
:1. Introduction
2. The Mechanism of Action of CCBs on the Pregnant Myometrium
2.1. Factor 1: Ca2+-Activated K+ (BKCa) Channels
2.2. Factor 2: Beta-Adrenergic Receptors
2.3. Factor 3: Progesterone
Physiological factor | Effect on L-type Ca2+ channel | Possible clinical relevance |
---|---|---|
BKCa channel activation | inhibition | presumably increases the tocolytic effect of CCBs |
β-AR activation | opening | increases the tocolytic effect of CCBs |
Long-term progesterone effect | expression of less sensitive form | presumably decreases the tocolytic effect of CCBs |
3. The Efficacy of CCBs against PTB
Class of drugs | Primarily licensed for | The most frequent side effects |
---|---|---|
Beta-adrenergic agonists | bronchial asthma | Maternal: tachycardia, hyperglycemia, pulmonary oedema Foetal: tachycardia, RDS |
Cyclooxygenase inhibitors | inflammation, pain, fever | Foetal: premature closure of ductus arteriosus, reduced amniotic fluid index |
Gestagens | hormonal substitution, contraception | no relevant side effect |
Magnesium sulphate | hypomagnesaemia, eclampsia in pregnancy | Maternal: constipation, visual blurring, headache |
CCBs (DHPs) | hypertension | Maternal: headache, tachycardia, hypotension |
Oxytocin antagonists | tocolysis | Maternal: tachycardia, chest pain |
4. Side-Effects of CCBs during Tocolysis
5. Tocolytic Effect of CCBs in Combination with Other Drugs
Combination | Change in myometrial relaxation | Risk of combination |
---|---|---|
Nifedipine + ritodrine | increased (in both human and animal studies in vivo) | pulmonary oedema, myocardial infarction |
Nifedipine + atosiban | increased (in a human study in vitro) | no information (data from in vitro experiments only) |
Nifedipine + celecoxib | decreased (in a human study in vitro) | no information (data from in vitro experiments only) |
Nifedipine + progesterone | decreased (in an animal study in vivo) unchanged (in a human study in vivo) | no special risk as compared with nifedipine monotherapy |
6. Conclusions
Conflict of Interest
References
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Gáspár, R.; Hajagos-Tóth, J. Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations. Pharmaceuticals 2013, 6, 689-699. https://doi.org/10.3390/ph6060689
Gáspár R, Hajagos-Tóth J. Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations. Pharmaceuticals. 2013; 6(6):689-699. https://doi.org/10.3390/ph6060689
Chicago/Turabian StyleGáspár, Róbert, and Judit Hajagos-Tóth. 2013. "Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations" Pharmaceuticals 6, no. 6: 689-699. https://doi.org/10.3390/ph6060689