Slim Mahmoud, Medina-Caliz Inmaculada, Gonzalez-Jimenez Andres, Cabello M Rosario, Mayoral-Cleries Fermin, Lucena M Isabel, Andrade Raul J
Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
Unidad de Gestión Clínica de Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Málaga, Spain.
Drug Saf. 2016 Oct;39(10):925-43. doi: 10.1007/s40264-016-0436-7.
The newer atypical antipsychotic agents (AAPs) represent an attractive therapeutic option for a wide range of psychotic disorders, including schizophrenia and bipolar mania, because of the reduced risk of disabling extrapyramidal symptoms. However, their growing use has raised questions about their tolerability over the endocrine, metabolic, and cardiovascular axes. Indeed, atypical antipsychotic drugs are associated, to differing extents, with mild elevation of aminotransferases related to weight gain, AAP-induced metabolic syndrome, and nonalcoholic fatty liver disease. Although the hepatic safety of new AAPs seems improved over that of chlorpromazine, they can occasionally cause idiosyncratic liver injury with varying phenotypes and, rarely, lead to acute liver failure. However, AAPs are a group of heterogeneous, chemically unrelated compounds with distinct pharmacological and pharmacokinetic properties and substantially different safety profiles, which precludes the notion of a class effect for hepatotoxicity risk and highlights the need for an individualized therapeutic approach. We discuss the current evidence on the hepatotoxicity potential of AAPs, the emerging underlying mechanisms, and the limitations inherent to this group of drugs for both establishing a proper causality assessment and developing strategies for risk management.
新型非典型抗精神病药物（AAPs）因致残性锥体外系症状风险降低，成为包括精神分裂症和双相躁狂症在内的多种精神障碍颇具吸引力的治疗选择。然而，其使用的不断增加引发了关于其在内分泌、代谢和心血管系统方面耐受性的问题。事实上，非典型抗精神病药物在不同程度上与体重增加相关的转氨酶轻度升高、AAP 诱导的代谢综合征及非酒精性脂肪肝病有关。尽管新型 AAPs 的肝脏安全性似乎优于氯丙嗪，但它们偶尔会引起具有不同表型的特异质性肝损伤，且极少导致急性肝衰竭。然而，AAPs 是一组化学结构不相关的异质性化合物，具有独特的药理和药代动力学特性以及显著不同的安全性概况，这排除了肝毒性风险存在类效应的概念，并突出了个性化治疗方法的必要性。我们讨论了关于 AAPs 肝毒性潜力的现有证据、新出现的潜在机制以及这类药物在建立适当因果关系评估和制定风险管理策略方面固有的局限性。
