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氨基糖苷类药物的副作用:肾毒性(作者译)

[Side effects of aminoglycosides: nephrotoxicity (author's transl)].

作者信息

Sack K, Freiesleben H, Züllich B, Beck H, Schulz E

出版信息

Infection. 1976;4(4):231-8. doi: 10.1007/BF01638932.

Abstract

Animal experiments showed that all aminoglycosides cause similar toxic tubular and glomerular damage when investigated by qualitative morphology. Quantitative differences in the tubular nephrotoxicity of gentamicin, tobramycin, sisomicin, kanamycin, kanendomycin, amikacin, and butirosin can be demonstrated experimentally by evaluation of the excretion rates of tubular cells and urinary enzymes in rats. By this means dose-effect relationships were established resulting in varying reproduceable toxic threshold doses for each antibiotic, and thus in a scale of increasing nephrotoxicity. The aminoglycosides differed in their affinity to kidney tissue as measured by determination of the accumulating renal concentrations of the drugs at different times during multiple-dose administration. This had a modifying influence on excretion rates of cells and enzymes affecting the scale of toxicity in long-term studies. Comparative investigations on nephrotoxicity in rats and guinea pigs gave similar results. In addition, a study in man suggested that the test results of nephrotoxicity are not species-specific. For human therapy it is concluded that even more caution should be practised with the new aminoglycerides than with gentamicin in order to avoid renal damage.

摘要

动物实验表明,当通过定性形态学进行研究时,所有氨基糖苷类药物都会导致类似的肾小管和肾小球毒性损伤。通过评估大鼠肾小管细胞排泄率和尿酶,可通过实验证明庆大霉素、妥布霉素、西索米星、卡那霉素、卡那内多霉素、阿米卡星和丁胺卡那霉素在肾小管肾毒性方面的定量差异。通过这种方法建立了剂量效应关系,得出了每种抗生素不同的可重复毒性阈值剂量,从而形成了一个肾毒性递增的等级。通过测定多次给药期间不同时间药物在肾脏中的累积浓度来衡量,氨基糖苷类药物对肾组织的亲和力各不相同。这对细胞和酶的排泄率有调节作用,从而影响长期研究中的毒性程度。对大鼠和豚鼠肾毒性的比较研究得出了类似结果。此外,一项人体研究表明,肾毒性测试结果并非物种特异性的。对于人类治疗而言,得出的结论是,为避免肾脏损伤,使用新型氨基糖苷类药物时应比使用庆大霉素更加谨慎。

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