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Metoclopramide-Induced Acute Dystonic Reactions May Be Associated With the CYP2D6 Poor Metabolizer Status and Pregnancy-Related Hormonal Changes

机译:甲氧氯普胺诱导的急性张力障碍反应可能与CYP2D6的代谢者状态不良和妊娠相关的激素变化有关

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摘要

We report two cases of metoclopramide-induced acute dystonia in pregnant women and consider the role of genetic variation in the pathogenesis of the adverse effect. By whole-gene sequencing, we found that both women were CYP2D6 poor metabolizers. We theorize that CYP2D6 governs the risk of metoclopramide-related acute dystonia through its role in the synthesis of serotonin, which inhibits the dopamine tone. The effect of CYP2D6 poor metabolism is exaggerated by rises in the estrogen levels during pregnancy, as the hormone augments dopamine sensitivity. Together, the two factors may create a hyper-dopaminergic state that is easily upset by metoclopramide, resulting in acute dystonia.
机译:我们报告了两例甲氧氯普胺诱发的孕妇急性肌张力障碍,并考虑了遗传变异在不良反应发病机理中的作用。通过全基因测序,我们发现两名女性均为CYP2D6弱代谢者。我们推论CYP2D6通过其在5-羟色胺合成中的作用来控制与甲氧氯普胺相关的急性肌张力障碍的风险,5-羟色胺会抑制多巴胺的张力。 CYP2D6代谢不良的影响会因怀孕期间雌激素水平的升高而被夸大,因为该激素会增强多巴胺的敏感性。这两个因素在一起可能会导致高多巴胺能状态,而甲氧氯普胺很容易使人烦躁不安,从而导致急性肌张力障碍。

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