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西酞普兰与艾司西酞普兰:心脏毒性机制、毒理学易感性以及在老年和血液透析人群中的使用风险

Citalopram & escitalopram: Mechanisms of cardiotoxicity, toxicology predisposition and risks of use in geriatric & hemodialysis populations.

作者信息

Farhat Hadi, Tlaiss Yehya, Nassif Lea, Gutlapalli Sai Dheeraj, Abdulaal Razan

机构信息

Internal Medicine, University of Balamand, Beirut, Lebanon.

Internal Medicine, Richmond University Medical Center Mount Sinai, Staten Island, New York, USA.

出版信息

Glob Cardiol Sci Pract. 2024 Aug 1;2024(4):e202434. doi: 10.21542/gcsp.2024.34.

Abstract

The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are extensively prescribed for various psychopathies. Despite their reputation for safety compared to older antidepressants, concerns have arisen regarding their cardiotoxic potential, notably in prolonging the QTc interval. In this comprehensive review, we investigate the intricate mechanisms of cardiotoxicity induction by citalopram/escitalopram, with a special focus on their interactions with ion channels like Kv11.1, Nav1.5, and Cav1.2 which may contribute to QTc-prolongation, increasing the risk of life-threatening arrhythmias such as Torsades de Pointes (TdP). Moreover, we explore the predisposing factors to their associated cardiotoxicity along with an investigation of the QRS/QTc ratio as a potential biomarker for identifying patients at risk of ventricular arrhythmias, taking into consideration the impact of genetic variations and drug interactions, especially those involving the liver CYP2C19 metabolism. Our review extends to the geriatric population's use of citalopram and escitalopram, emphasizing the significance of assessing a patient's medical history and cumulative drug use to evaluate their susceptibility to cardiac adverse events. Finally, we scrutinize the compound relationship between QTc-prolongation, proton pump inhibitors (PPIs) and serum-to-dialysate potassium gradients in influencing the proarrhythmic potential of citalopram/escitalopram in hemodialysis patients.

摘要

选择性5-羟色胺再摄取抑制剂(SSRI)西酞普兰和艾司西酞普兰被广泛用于治疗各种精神疾病。尽管与旧的抗抑郁药相比,它们有安全的名声,但人们已经开始关注它们的心脏毒性潜力,特别是在延长QTc间期方面。在这篇全面的综述中,我们研究了西酞普兰/艾司西酞普兰诱发心脏毒性的复杂机制,特别关注它们与离子通道如Kv11.1、Nav1.5和Cav1.2的相互作用,这些相互作用可能导致QTc延长,增加危及生命的心律失常如尖端扭转型室速(TdP)的风险。此外,我们探讨了其相关心脏毒性的易感因素,并研究了QRS/QTc比值作为识别室性心律失常风险患者的潜在生物标志物,同时考虑到基因变异和药物相互作用的影响,特别是那些涉及肝脏CYP2C19代谢的相互作用。我们的综述还扩展到老年人群使用西酞普兰和艾司西酞普兰的情况,强调评估患者病史和累积用药情况以评估其对心脏不良事件易感性的重要性。最后,我们仔细研究了QTc延长、质子泵抑制剂(PPI)和血清与透析液钾梯度之间的复合关系对血液透析患者中西酞普兰/艾司西酞普兰促心律失常潜力的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e81a/11439416/091d9f225745/gcsp-2024-4-e202434-g001.jpg

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