Miller E
Colorado State University, College of Veterinary Medicine and Biomedical Sciences, Department of Clinical Sciences, Fort Collins, USA.
Semin Vet Med Surg Small Anim. 1997 Aug;12(3):157-60. doi: 10.1016/s1096-2867(97)80027-8.
Cytotoxic drugs are often combined with glucocorticoids in the therapy of immune-mediated diseases. Cyclophosphamide, azathioprine, chlorambucil, and methotrexate are cytotoxic drugs used most commonly for the purpose of immunosuppression. Cyclophosphamide and chlorambucil are alkylating agents, which cause cross-linking of DNA resulting in altered protein production, decreased cell division, and cell death. Azathioprine and methotrexate are anti-metabolites, which cause inhibition of DNA synthesis and a cascade of other effects. These drugs, in general, are more effective if administered during the initial phases of disease when immunocompetent lymphocytes are in a phase of rapid proliferation. This is often impractical in the clinical situation and may explain therapeutic failures. This article focuses on the use of these drugs in the treatment of immune-mediated diseases in dogs and cats and covers mechanisms of action, dosages, and side effects of individual cytotoxic agents.
细胞毒性药物在免疫介导性疾病的治疗中常与糖皮质激素联合使用。环磷酰胺、硫唑嘌呤、苯丁酸氮芥和甲氨蝶呤是最常用于免疫抑制目的的细胞毒性药物。环磷酰胺和苯丁酸氮芥是烷化剂，它们会导致DNA交联，从而改变蛋白质生成、减少细胞分裂并导致细胞死亡。硫唑嘌呤和甲氨蝶呤是抗代谢物，它们会抑制DNA合成并引发一系列其他效应。一般来说，如果在疾病的初始阶段给药，此时具有免疫活性的淋巴细胞处于快速增殖阶段，这些药物会更有效。但这在临床情况下往往不切实际，这可能解释了治疗失败的原因。本文重点介绍这些药物在犬猫免疫介导性疾病治疗中的应用，并涵盖了个别细胞毒性药物的作用机制、剂量和副作用。
