Mishin V Iu, Vasil'eva I A, Makieva V G, Kuz'mina N V, Prikazchikova A V, Khoroshutina V V
Probl Tuberk Bolezn Legk. 2003(7):24-9.
The frequency and pattern of adverse reactions to essential antituberculous agents were studied in 480 patients with first diagnosed and recurrent pulmonary tuberculosis. Adverse reactions were found to occur in 16.9% of cases and to be mainly associated with concomitant diseases of different organs and systems wherein they occurred 15.6 times more frequently, rather than with the number (3-4-5) of used drugs. Adverse reactions were generally caused by an individual drug and predominantly streptomycin. At the same time no significant difference was established in the frequency of toxic (45.5%) and allergic (37%) reactions, but with a rather low frequency of mixed reactions (17.3%). The firstly performed cytochemical and immunological studies of lymphocytes and eosinophils provided new evidence for the pathogenesis of different patterns of adverse reactions. Lymphocytes from patients with toxic reactions showed significant intracellular structural and metabolic disturbances that led to a higher apoptosis of these cells. In patients with lymphocytic allergic reactions, on the contrary, displayed activated processes of anaerobic oxidation and their cytotoxic activity. In both types of adverse reactions, eosinophils exhibited severe intracellular metabolic disturbances that result in destruction and increased apoptosis, which determined the allergic component in virtually all types of side effects. Rational pathogenetic therapy using hormonal, vitamin, and metabolic agents and plasmapheresis could show a 2-fold reduction in the number of patients with adverse reactions without changing the routine chemotherapy regimen and only in 5.6% of cases, the reactions were intractable, which made a specific drug be discontinued and therapy used on an individual basis.
对480例初诊和复发性肺结核患者使用抗结核基本药物的不良反应频率和模式进行了研究。发现16.9%的病例出现不良反应,主要与不同器官和系统的伴发疾病有关,不良反应在伴发疾病患者中出现的频率是其他患者的15.6倍,而不是与所用药物的数量(3 - 4 - 5种)有关。不良反应一般由个别药物引起,主要是链霉素。同时,毒性反应(45.5%)和过敏反应(37%)的频率没有显著差异,但混合反应的频率相当低(17.3%)。首次对淋巴细胞和嗜酸性粒细胞进行的细胞化学和免疫学研究为不同模式不良反应的发病机制提供了新证据。出现毒性反应患者的淋巴细胞显示出明显的细胞内结构和代谢紊乱,导致这些细胞凋亡增加。相反,出现淋巴细胞过敏反应的患者表现出无氧氧化的激活过程及其细胞毒性活性。在两种类型的不良反应中,嗜酸性粒细胞均表现出严重的细胞内代谢紊乱,导致细胞破坏和凋亡增加,这决定了几乎所有类型副作用中的过敏成分。使用激素、维生素、代谢药物和血浆置换进行合理的病因治疗可使不良反应患者数量减少一半,且不改变常规化疗方案,仅5.6%的病例反应难以处理,需要停用特定药物并进行个体化治疗。