【肾内精品】免疫抑制药物.pptx

抗风湿性疾病的药物大致可分为三大类： 非甾体抗炎药(NSAIDs) 糖皮质类固醇 改变病情抗风湿药(disease modifying anti-rheumatic drug，DMARD) 非甾体类抗炎剂NSAIDs IndicationsPain and stiffness in inflammatory arthritisShort term and intermittent use in osteoarthritisSoft tissue conditions, including fibromyalgia 所有NSAIDs在治疗OA大于6-12周，疗效相同近来研究着重于改善胃肠道的耐受性COX-2特异性抑制剂（celecoxib, rofecoxib）胃肠道安全性高，由于不抑制COX-1，耐受性、安全性提高，严重上消化道副作用如穿孔、溃疡和出血明显降低 COX-2特异性抑制剂适应症Age over 65Using concomitant medications likely to increase GI adverse effects(e.g. steroids, warfarin)Those requiring prolonged use of maximum dose NSAIDs(e.g. persistent inflammatory arthritis)Serious co-morbidity, e.g. diabetes mellitus, renal or hepatic impairment COX-2特异性抑制剂禁忌With caution in those with a history of peptic ulcerationAvoided in those with previous haemorrhage or perforation 各种NSAIDs相比Many NSAIDs are availableNone is unequivoclly superior in terms of efficacyFrequency of adverse reactions – gastrointestinal, hepatic, renal and cardiovascular – associated with each NSAID variesPrescribing habits among rheumatologists also vary widely Disease-modifying Drugs (DMARDs) 本组药的共同点是抑制淋巴细胞的生成及增殖以达到免疫抑制作用其不同点是各个药物通过不同途径，抑制不同的但为细胞合成DNA所需的核苷酸而达到抑制淋巴细胞 常见不良反应骨髓抑制、周围血细胞减少肝功能损害肾功能损害肺纤维化脱发胃肠道症状感染等 免疫抑制的分类(根据合成方法)微生物酵解产物: CsA类、FK506、rapamycin及其衍生物SDZRAD、mizoribinine(MZ)等完全有机合成物:激素类、硫唑嘌呤、来氟米特等半合成化合物: MMF、SDZIMM125、DSG(脱氧精瓜素)等生物制剂: ATG、anti - TNF alpha antibody等 根据作用机制，可分为5类细胞因子合成抑制剂：CsA类、FK506细胞因子作用抑制剂: RPM、来氟米特DNA或RNA合成抑制剂: MZ、RS61443、 可能还有来氟米特细胞成熟抑制剂: DSG非特异性抑制细胞生长诱导剂: SKF105685 常用免疫抑制剂作用机制甲氨蝶呤干扰嘌呤和嘧啶核苷酸硫唑嘌呤干扰腺嘌呤及鸟嘌呤核苷酸来氟米特干扰嘧啶核苷酸麦考霉酚酯酸干扰鸟嘌呤核苷酸环噒酰胺交义联结干扰DNA合成环孢素抑制IL-2的合成及释放以抑制T淋巴细胞生长 Methotrexate(MTX) IndicationsUsed for treatment of active inflammatory arthritis-usually rheumatoid arthritis and psoriatic arthropathyMode of action unkown, slow acting over 4 weeks-4 months AdministrationOnce weekly oral doseMay be given intramuscularly or subcutaneously if response to oral route insufficientUsual dose 7.5-20 mg weekly; comes in 2.5 mg or 10 mg tab