Furst D E
Virginia Mason Research Center, Seattle, WA 98111, USA.
Br J Rheumatol. 1997 Nov;36(11):1196-204. doi: 10.1093/rheumatology/36.11.1196.
Methotrexate's mechanism of action affects both the inflammatory and immunosuppressive aspects of response. Its kinetics are defined and include variable absorption, intracellular metabolism, and both renal and biliary excretion. Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. It is also effective in psoriatic arthritis and is being used in a multiplicity of other rheumatic diseases. The most common toxicities ascribed to methotrexate are gastrointestinal (e.g. stomatitis) and central nervous system (e.g. headache, fatigue, malaise). Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. Haematological, renal and pulmonary toxicity occur, but are rare, while teratogenicity is well documented. A new and disturbing adverse event, pseudolymphomas are being reported at present.
甲氨蝶呤的作用机制影响反应的炎症和免疫抑制两个方面。其动力学已明确，包括吸收可变、细胞内代谢以及经肾和经胆汁排泄。甲氨蝶呤在类风湿关节炎的治疗中显然有效，并且可能能够降低新骨侵蚀的形成速率。它在银屑病关节炎中也有效，并且正在被用于多种其他风湿性疾病。归因于甲氨蝶呤的最常见毒性是胃肠道毒性（如口腔炎）和中枢神经系统毒性（如头痛、疲劳、不适）。甲氨蝶呤诱发的肝硬化在类风湿关节炎中比以前认为的少见，尽管其在银屑病中的发生率可能高于类风湿关节炎。血液学、肾脏和肺部毒性会发生，但很罕见，而致畸性已有充分记录。目前正在报告一种新的、令人不安的不良事件——假性淋巴瘤。
