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化学抗生素的作用机制(作者译)

[Mechanisms of action of chemoantibiotics (author's transl)].

作者信息

Gargani G

出版信息

Quad Sclavo Diagn. 1979 Jun;15 Suppl 1:336-48.

PMID:555522
Abstract

An useful drug for infectious diseases should have a selective antimicrobial activity and no action on animal cell. The general target, besides some very restricted process like in M. tuberculosis, are: 1) purine synthesis, 2) DNA replication, 3) protein synthesis, 4) cell-wall synthesis, 5) cytoplasmic membrane. On purine synthesis are active the sulphamidic on DNA replication nalidixic acid on Gram-negative bacteria, and griseophulvin on dermatophites. Many drugs have their target in the sequential stages of protein synthesis, among these the aminoglycosides are mainly bactericidal. The antibiotics which block the building of cell-wall are the best, according the target does not exist in animal cell; among them, penicillins and cephalosporins are bactericidal. On contrary cytoplasmic membrane, which is similar to the animal cell membrane has to be evaluated as a bad target. Polimyxins on bacteria, polyene antibiotics on fungi, have this target and are bactericidal, but their use is restricted for toxicity. Antibiotics must be selected in therapy according to their mechanism of action and to the immunological state of the patient. Some bactericidal antibiotics have to be reserved for immuno suppressed people.

摘要

一种用于治疗传染病的有效药物应具有选择性抗菌活性,且对动物细胞无作用。除了像结核分枝杆菌中一些非常受限的过程外,一般的作用靶点有:1)嘌呤合成;2)DNA复制;3)蛋白质合成;4)细胞壁合成;5)细胞质膜。对嘌呤合成有活性的是磺胺类药物,对DNA复制有活性的是针对革兰氏阴性菌的萘啶酸以及针对皮肤癣菌的灰黄霉素。许多药物作用于蛋白质合成的连续阶段,其中氨基糖苷类主要是杀菌性的。根据动物细胞中不存在该靶点这一点,阻断细胞壁构建的抗生素是最佳选择;其中,青霉素和头孢菌素具有杀菌作用。相反,与动物细胞膜相似的细胞质膜被认为是一个不理想的靶点。作用于细菌的多粘菌素和作用于真菌的多烯类抗生素以细胞质膜为靶点且具有杀菌作用,但由于毒性其使用受到限制。在治疗中必须根据抗生素的作用机制和患者的免疫状态来选择抗生素。一些杀菌性抗生素必须留给免疫抑制人群使用。

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