Gibbon B N, Manthey D E
Department of Emergency Medicine, San Antonio Uniformed Services Health Education Consortium, San Antonio, TX, USA.
Ann Emerg Med. 1999 Jul;34(1):98-100. doi: 10.1016/s0196-0644(99)70279-9.
Methotrexate is a chemotherapy antimetabolite, folic acid antagonist, that inhibits the enzyme dihydrofolate reductase resulting in decreased levels of tetrahydrofolate in the cells. This in turn blocks synthesis of thymidylate, a nucleotide necessary for DNA synthesis. It is readily absorbed from the gastrointestinal tract. Toxicity from overdose can affect multiple organ systems including bone marrow, liver, intestinal tract, kidneys, lungs, skin, and blood vessels, resulting in death in severe cases. Methotrexate is widely used to treat neoplastic disease, dermatologic disorders (psoriasis), and rheumatologic disorders (severe rheumatoid arthritis). As its indications for use increase, more accidental overdoses can be expected. We present the treatment and clinical course of one such case, that of a 2-year-old who accidentally took her grandmother's arthritis pills. Her initial serum level was 10 times greater than that needed to cause toxicity. She was treated with gastric lavage, activated charcoal, leucovorin rescue, and ICU admission. Her clinical course was unremarkable, and the only evidence of toxicity was a mild elevation in a liver-associated enzyme that resolved without any clinical sequela. Leucovorin at a dose equal to or greater than the possible ingestion should be given as soon as possible in methotrexate overdoses.
甲氨蝶呤是一种化疗抗代谢物、叶酸拮抗剂，它抑制二氢叶酸还原酶，导致细胞内四氢叶酸水平降低。这进而阻断胸苷酸的合成，胸苷酸是DNA合成所必需的一种核苷酸。它很容易从胃肠道吸收。过量使用的毒性可影响多个器官系统，包括骨髓、肝脏、肠道、肾脏、肺、皮肤和血管，严重时可导致死亡。甲氨蝶呤广泛用于治疗肿瘤疾病、皮肤病（银屑病）和风湿性疾病（严重类风湿性关节炎）。随着其使用指征的增加，预计会出现更多意外过量用药的情况。我们介绍了这样一个病例的治疗情况和临床过程，该病例是一名2岁儿童意外服用了她祖母的关节炎药物。她最初的血清水平比引起毒性所需的水平高10倍。她接受了洗胃、活性炭、亚叶酸钙解救治疗，并入住重症监护病房。她的临床过程无异常，唯一的毒性证据是一种肝脏相关酶轻度升高，该酶在没有任何临床后遗症的情况下自行恢复。在甲氨蝶呤过量用药时，应尽快给予剂量等于或大于可能摄入量的亚叶酸钙。
