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Therapeutic Drugs that Slow the Heart Rate of Early Rat Embryos. Is there a Risk for the Human?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2014 (English)In: Current pharmaceutical design, ISSN 1381-6128, Vol. 20, no 34, 5364-5376 p.Article in journal (Refereed) Published
Abstract [en]

During the organogenic period of development the cardiovascular system of the embryo fulfills several functions including delivery of oxygen and nutrients and a hemodynamic role necessary for cardiac morphogenesis, angiogenesis and hematopoiesis. It is expected that at each stage of embryonic development there is an ideal embryonic heart rate and contractility that maintains the optimal blood flow and pressure to fulfill these various functions. In vitro rat embryo culture studies have revealed that many therapeutic drugs (antiarrhythmics, antidepressants, antipsychotics and anticonvulsants), that may be taken during human pregnancy, cause a concentration-dependent slowing of the embryonic heart and irregular heart rate at higher concentrations. The concentrations causing bradycardia in vitro are often close to human therapeutic plasma concentrations and raise concern that these drugs can potentially cause embryonic death or malformations, and that current reproductive toxicity testing does not adequately examine possible effects of drugs on the embryo's cardiac function.

Place, publisher, year, edition, pages
2014. Vol. 20, no 34, 5364-5376 p.
Keyword [en]
Bradycardia, arrhythmia, antidepressants, hERG, antipsychotics, pregnancy, first trimester, heart, embryo, fetal, rat, human, cardiac, ion channels
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-235212DOI: 10.2174/1381612820666140205151146ISI: 000342004400002PubMedID: 24502593OAI: oai:DiVA.org:uu-235212DiVA: diva2:759379
Available from: 2014-10-29 Created: 2014-10-29 Last updated: 2014-10-29Bibliographically approved

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