目的:回顾酪氨酸激酶抑制剂(TKI)引起的高氨血症性脑病的罕见但致命的不良事件的证据以及这种情况的可能机制,并描述一例发生与TKI相关的药物诱发的高氨血症性脑病的患者。
方法:对1992年1月1日至2023年5月7日发表的研究进行了不同数据库的文献检索。使用的搜索词是高氨血症脑病,TKI,阿帕替尼,帕唑帕尼,舒尼替尼,伊马替尼,索拉非尼,Regorafenib,曲美替尼,尿素循环调节,索拉非尼,氨基甲酰磷酸合成酶1,鸟氨酸转碳淀粉酶,精氨酸琥珀酸合成酶,精氨酸琥珀酸裂解酶,精氨酸酶1,丝裂原活化蛋白激酶(MAPK)途径和mTOR途径,单独搜索或组合使用。
方法:共37篇。文章主要集中在高氨血症脑病病例报告,高氨血症脑病的管理,尿素循环调节,自噬,mTOR和MAPK途径,还有TKI.
结论:在各种多靶向TKI的文献中报道了18例高氨血症性脑病。该事件的机制尚不清楚,但一些作者假设血管原因,因为一些TKI是抗血管生成的,然而,我们的文献综述显示尿素循环与TKI施加的分子抑制作用之间可能存在关系。需要更多的临床前证据来揭示参与这一过程的生化机制,并且有必要进行临床研究来阐明患病率。危险因素,这种不良事件的管理和预防。重要的是监测神经系统症状并在检测到表现时测量氨水平。
OBJECTIVE: To review the evidence of uncommon but fatal adverse event of hyperammonemic encephalopathy by tyrosine kinase inhibitors (TKI) and the possible mechanisms underlying this condition and to describe the
case of a patient that developed drug-induced hyperammonemic encephalopathy related to TKI.
METHODS: Literature search of different databases was performed for studies published from 1 January 1992 to 7 May 2023. The search terms utilized were hyperammonemic encephalopathy, TKI, apatinib, pazopanib, sunitinib, imatinib, sorafenib, regorafenib, trametinib, urea cycle regulation, sorafenib, carbamoyl-phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase 1, Mitogen activated protein kinases (MAPK) pathway and mTOR pathway, were used individually search or combined.
METHODS: Thirty-seven articles were included. The articles primarily focused in hyperammonemic encephalopathy
case reports, management of hyperammonemic encephalopathy, urea cycle regulation, autophagy, mTOR and MAPK pathways, and TKI.
CONCLUSIONS: Eighteen cases of hyperammonemic encephalopathy were reported in the literature from various multitargeted TKI. The mechanism of this event is not well-understood but some authors have hypothesized vascular causes since some of TKI are antiangiogenic, however our literature review shows a possible relationship between the urea cycle and the molecular inhibition exerted by TKI. More preclinical evidence is required to unveil the biochemical mechanisms responsible involved in this process and clinical studies are necessary to shed light on the prevalence, risk factors, management and prevention of this adverse event. It is important to monitor neurological symptoms and to measure ammonia levels when manifestations are detected.