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丙硫氧嘧啶、甲巯咪唑及卡比马唑相关的肝毒性。

Propylthiouracil, and methimazole, and carbimazole-related hepatotoxicity.

作者信息

Akmal Anam, Kung Jacqueline

机构信息

Tufts Division of Endocrinology , 800 Washington St Box 268, Boston, MA 02111 , USA +1 617 636 1216 ; +1 617 636 4719 ;

出版信息

Expert Opin Drug Saf. 2014 Oct;13(10):1397-406. doi: 10.1517/14740338.2014.953796. Epub 2014 Aug 26.

Abstract

INTRODUCTION

Propylthiouracil (PTU) has been used for the treatment of hyperthyroidism since the 1940s, but over the years reports of significant hepatotoxicity have come forth, particularly in children. This led to a black box warning being issued by the US FDA in 2009, followed by a similar warning by the European Medicines Agency and the United Kingdom Medicines and Healthcare Regulatory Agency later that year.

AREAS COVERED

This article provides a concise review of the data on hepatotoxicity associated with the currently available antithyroid drugs: PTU, methimazole (MMI) and carbimazole. The differences in mechanism are examined in detail, as well as clinical presentation, management and monitoring. Use in special populations and trends in use of antithyroid medication are also discussed.

EXPERT OPINION

PTU is known to cause severe hepatic failure, particularly in children. Its use in children should be avoided. In adults, it is beneficial to use in the first trimester of pregnancy and thyroid storm. In the rest of the adult population, it should be used with caution. Carbimazole and MMI are associated with less severe hepatic injury and should be preferred when choosing thionamides as a treatment option.

摘要

引言

自20世纪40年代以来,丙硫氧嘧啶(PTU)一直用于治疗甲状腺功能亢进症,但多年来,尤其是在儿童中,出现了大量关于其严重肝毒性的报告。这导致美国食品药品监督管理局(FDA)在2009年发布了黑框警告,随后欧洲药品管理局和英国药品与医疗产品监管局在同年也发布了类似警告。

涵盖领域

本文简要回顾了与目前可用的抗甲状腺药物(PTU、甲巯咪唑(MMI)和卡比马唑)相关的肝毒性数据。详细研究了作用机制的差异,以及临床表现、处理和监测。还讨论了在特殊人群中的使用情况和抗甲状腺药物的使用趋势。

专家意见

已知PTU会导致严重肝衰竭,尤其是在儿童中。应避免在儿童中使用。在成人中,它在妊娠头三个月和甲状腺危象中使用有益。在其他成年人群中应谨慎使用。卡比马唑和MMI与较不严重的肝损伤相关,在选择硫代酰胺类作为治疗选择时应优先使用。

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