AMINOPHYLLINE FOR METHOTREXATE-INDUCED NEUROTOXICITY

被引:122
作者
BERNINI, JC
FORT, DW
GRIENER, JC
KANE, BJ
CHAPPELL, WB
KAMEN, BA
机构
[1] UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DALLAS,TX 75235
[2] UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235
[3] CHILDRENS MED CTR,DALLAS,TX 75235
来源
LANCET | 1995年 / 345卷 / 8949期
关键词
D O I
10.1016/S0140-6736(95)90464-6
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Methotrexate, a mainstay treatment for children with acute lymphoblastic leukaemia, can cause neurotoxicity, with paralysis, seizures, somnolence, anorexia, and headaches. The pathophysiology of this reaction is unknown. It has been suggested that the anti-inflammatory effect of methotrexate in patients with arthritis is due to adenosine release brought on by inhibition of purine synthesis. Since adenosine is a central nervous system depressant, we wondered whether adenosine release in the central nervous system could account for some of the neurotoxicity due to methotrexate, and whether that toxicity could be lessened by displacement of adenosine from its receptor by aminophylline. 6 patients (age 3-16 years) who had methotrexate-induced neurotoxicity unresponsive to standard treatment received 2.5 mg/kg aminophylline. In addition, the concentration of adenosine in the cerebrospinal fluid (CSF) from 11 children completing a 24-h systemic methotrexate protocol was compared with that in 8 newly diagnosed patients and 12 who had not received any treatment for at least a week. 4 of 6 patients with toxic signs and symptoms attributed to methotrexate and unrelieved by steroids, epidural blood patch, promethazine, 5-hydroytryptamine antagonists, paracetamol, and narcotics, had complete resolution of neurotoxicity after or during a l-h infusion of aminophylline; 2 others had a pronounced improvement but persistent nausea. CSF adenosine concentrations of patients receiving methotrexate, even when there was very slight or no toxicity, were greatly increased compared with control subjects (mean values of 217 and 51 nmol/L, median 175 and 52 nmol/L). Subacute methotrexate neurotoxicity may be mediated by adenosine and relieved by aminophylline.
引用
收藏
页码:544 / 547
页数:4
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