Shen J J, Wanwimolruk S, Mills R G, Roberts M S
Department of Pharmacy, University of Otago Medical School, Dunedin, New Zealand.
Life Sci. 1991;48(18):1737-43. doi: 10.1016/0024-3205(91)90210-3.
The effects of beta-blockers on maternal and fetal heart rates have been assessed by comparing isoprenaline concentration-heart rate relationships of hearts isolated from pregnant rats. The normal and maximal heart rates obtained for the maternal and fetal hearts were similar to published data. A slightly but significantly higher concentration of isoprenaline was required to produce 50% of the maximal response of fetal hearts than maternal hearts, suggesting that fetal hearts were less sensitive to isoprenaline than the maternal hearts. The beta-blockers used (propranolol, labetalol, metoprolol and atenolol) all showed a lower affinity to the beta-receptors of fetal hearts than those of maternal hearts, as indicated by significant differences in the pA2 values. Given the similar effects of the beta-blockers in the maternal and fetal hearts it is concluded that pharmacokinetic considerations and beta-blocker selectivity should be used as the basis of choice when treating maternal hypertension during pregnancy.
通过比较从怀孕大鼠分离出的心脏的异丙肾上腺素浓度与心率关系,评估了β受体阻滞剂对母体和胎儿心率的影响。母体和胎儿心脏的正常心率和最大心率与已发表的数据相似。与母体心脏相比,胎儿心脏产生最大反应的50%需要略高但显著更高浓度的异丙肾上腺素,这表明胎儿心脏对异丙肾上腺素的敏感性低于母体心脏。所用的β受体阻滞剂(普萘洛尔、拉贝洛尔、美托洛尔和阿替洛尔)对胎儿心脏β受体的亲和力均低于母体心脏,这在pA2值上有显著差异。鉴于β受体阻滞剂在母体和胎儿心脏中的作用相似,得出结论,在治疗孕期母体高血压时,应将药代动力学因素和β受体阻滞剂的选择性作为选择的基础。