药物眼毒性反应及作用机制分析  

Ocular toxicity of drugs and analysis of mechanisms

作　　者：邵雪 王庆利 温泉 黄芳华 SHAO Xue;WANG Qing-li;WEN Quan;HUANG Fang-hua(Center for Drug Evaluation,National Medical Products Administration,Beijing 100022,China)

机构地区：[1]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国药理学与毒理学杂志》2021年第11期877-888,共12页Chinese Journal of Pharmacology and Toxicology

摘　　要：药物眼毒性反应及机制较为复杂,在药物研发早期阶段通过靶点特异性筛选、分子结构和药代特征优化等手段,对降低候选药物可能引起的眼毒性风险具有重要的意义。本文通过查阅大量国内外已上市药品的说明书,对不同适应证领域的经全身和眼球局部用药所引起的眼毒性反应进行梳理。常见的药物眼毒性反应包括青光眼、白内障、结膜炎(角膜炎)和视网膜病变等,可引起眼毒性的代表性药物涉及精神和神经系统疾病及肿瘤等多个适应证,其导致眼毒性的机制可能与多巴胺受体、毒蕈碱型胆碱受体、离子通道、表皮生长因子受体、血管内皮生长因子及其受体、丝裂原活化蛋白激酶及免疫反应等有关。本文对药物眼毒性反应、具有眼毒性的代表性药物及其眼毒性机制进行综合分析和讨论,以期为药物研发提供参考,在药物开发过程中重视对眼毒性反应的评价。The characteristics and mechanism of drug induced ocular toxicity are complex.It is of great significance to reduce the risk of ocular toxicity by means of target specific screening,molecular structure and pharmacokinetic characteristics optimization in the early stage of drug development.In this paper,based on labels of a large number of domestic and foreign marketed drugs,the ophthalmic adverse reactions caused by systemic and ophthalmic drugs in different areas of indication were sorted out,and the common types of ocular side effects,such as glaucoma,cataract,conjunctivitis,keratitis and retinopathy,were summarized.The representative drugs that cause ocular toxicities involve many indications,such as mental,neurological and tumor ones.The mechanisms may be related to dopa⁃mine receptors,muscarinic choline receptors,ion channel,epidermal growth factor receptors,vascular endothelial growth factors and its receptors,mitogen-activated protein kinase and immune response.

关 键 词：药物 眼毒性 靶点 

分 类 号：R99[医药卫生—毒理学]