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胆淤积性瘙痒管理的安全性考虑。

Safety considerations for the management of cholestatic itch.

机构信息

Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Division of Digestive Health and Liver Disease, University of Miami Miller School of Medicine, Miami, Florida, USA.

出版信息

Expert Opin Drug Saf. 2021 Aug;20(8):915-924. doi: 10.1080/14740338.2021.1915984. Epub 2021 Apr 16.

Abstract

: Pruritus is adisabling symptom common to cholestatic liver disorders. Its pathophysiology has not been completely elucidated and although multiple mediators have been identified, only lysophosphatidic acid (LPA) and its synthetizing enzyme autotaxin (ATX) appear to consistently correlate with symptom intensity. This review aims to summarize the most relevant safety and efficacy data regarding both standard and new medications utilized to treat pruritus in cholestatic liver disease.: International societies like the AASLD and EASL recommend astepwise approach for the management of cholestatic itch. However, therapeutic response is variable. Cholestyramine is considered first-line, followed by rifampicin, naltrexone and sertraline. When used appropriately, these medications have afavorable adverse events profile with most side effects related to drug class and not to the underlying etiology of liver disease.: Although conventional therapies seem to be effective in aproportion of patients, asizable number of cases remain refractory and require the utilization of experimental treatments. Multiple potential targets, especially in the ATX-LPA axis have yet to be pharmacologically explored, with ongoing translational and clinical research. Novel drugs are currently being developed for the management of cholestatic itching with promising results and afavorable safety profile.

摘要

瘙痒是胆汁淤积性肝病常见的一种致残症状。其病理生理学尚未完全阐明,尽管已经确定了多种介质,但只有溶血磷脂酸 (LPA) 和其合成酶自分泌酶 (ATX) 似乎始终与症状强度相关。本文旨在总结与胆汁淤积性肝病瘙痒治疗相关的标准和新型药物的最相关安全性和疗效数据。国际协会,如 AASLD 和 EASL,建议对胆汁淤积性瘙痒采用逐步治疗方法。然而,治疗反应是可变的。考来烯胺被认为是一线治疗药物,其次是利福平、纳曲酮和舍曲林。如果使用得当,这些药物具有良好的不良事件谱,大多数副作用与药物类别有关,而不是与肝病的潜在病因有关。尽管传统疗法似乎对一部分患者有效,但仍有相当数量的病例仍然难以治疗,需要使用实验性治疗。许多潜在的靶点,尤其是在 ATX-LPA 轴,尚未进行药理学探索,目前正在进行转化和临床研究。新型药物目前正在开发用于管理胆汁淤积性瘙痒,具有有前景的结果和良好的安全性。

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