Interindividual Variability of Anticonvulsant-Induced QT Prolongation Risk

N. M. Zhuravlev, N. Shnayder, E. Vaiman, A. Abdyrakhmanova, -. MarinaM.Pe, trova, E. Bochanova, Irina V. Romanova, Oksana A. Gavrilyuk, N. Lareva, R. Nasyrova
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引用次数: 5

Abstract

In connection with the widespread use of anticonvulsants (antiepileptic drugs – AEDs) in psychiatric and neurological practice and the need for their long-term use to treat a wide range of mental disorders and neurological diseases, the question of their safety profile, including the assessment of the risk of developing life-threatening conditions and adverse reactions (ADRs), becomes relevant. In this regard, from the position of personalized medicine, it is critical to develop an interdisciplinary approach with the participation of doctors of various specialties and a new strategy of a personalized approach to predicting AED-induced prolongation of the QT interval as one of the most prognostically unfavorable cardiological ADRs (including sudden death syndrome – SDS). We searched for full-text publications for the period from 2011 to 2021 databases using the following keywords and its combination. We have found and systematized monogenic and multifactorial forms of long QT syndrome (LQTS) and candidate genes that slow down AEDs metabolism in the liver. Identification of risk alleles of single nucleotide variants (SNVs) of the candidate genes predisposing to the development of AED-induced LQTS and SDS will make it possible to adjust the choice and dosage of these drugs and prevent the development of ADRs, which will improve the quality of life of patients and prevent SDS in the patients with psychiatric and neurological disorders.
抗惊厥药物诱导QT间期延长风险的个体差异性
鉴于抗惊厥药(抗癫痫药- aed)在精神病学和神经学实践中的广泛使用,以及需要长期使用抗惊厥药来治疗各种精神障碍和神经系统疾病,因此,抗惊厥药的安全性问题,包括评估发生危及生命的状况和不良反应(adr)的风险,变得具有相关性。在这方面,从个体化医学的角度来看,关键是要发展一种跨学科的方法,让不同专业的医生参与其中,并制定一种新的个性化方法来预测aed引起的QT间期延长,这是最不利于预后的心血管不良反应之一(包括猝死综合征- SDS)。我们使用以下关键词及其组合检索了2011年至2021年数据库的全文出版物。我们已经发现并系统化了单基因和多因子形式的长QT综合征(LQTS)以及减缓aed在肝脏代谢的候选基因。鉴定aed诱发LQTS和SDS的候选基因的单核苷酸变异(snv)风险等位基因,将有助于调整药物的选择和剂量,预防不良反应的发生,从而提高患者的生活质量,预防精神和神经系统疾病患者的SDS。
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