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中国防痨杂志 ›› 2021, Vol. 43 ›› Issue (4): 305-309.doi: 10.3969/j.issn.1000-6621.2021.04.001
吴雪琼(
)
收稿日期:2021-03-05
出版日期:2021-04-10
发布日期:2021-04-09
通信作者:
吴雪琼
E-mail:xueqiongwu@139.com
基金资助:
Received:2021-03-05
Online:2021-04-10
Published:2021-04-09
吴雪琼. 关于耐药结核病化疗方案合理组合的思考和探讨[J]. 中国防痨杂志, 2021, 43(4): 305-309. doi: 10.3969/j.issn.1000-6621.2021.04.001
表1
临床常用抗结核药品的作用靶标和作用机制
| 药物作用分类及药品 | 作用靶标 | 作用机制 | 用于利福平 耐药结核病 的药品分类 |
|---|---|---|---|
| 抑制MTB细胞壁生物合成的药品 | |||
| 异烟肼(INH,H) | inhA、fabG1、ahpC、 acpM、kasA | 抑制许多大分子合成有关的途径,尤其是抑制MTB细胞壁脂肪酸(分枝菌酸)合成[ | |
| 乙硫异烟胺(Eto)和丙硫异烟胺(Pto) | inhA | 抑制MTB inhA对细胞壁分枝菌酸生物合成的调控作用[ | C |
| 帕司烟肼(Pa) | 对氨基水杨酸和异烟肼的化学合成物,在体内分解为对氨基水杨酸和异烟肼,对氨基水杨酸在肝脏与异烟肼竞争乙酰化酶,有效地延缓和阻滞了异烟肼在体内的乙酰化过程,使其浓度增高[ | 抑制MTB细胞壁脂肪酸(分枝菌酸)合成 | C |
| 德拉马尼(Dlm) | 甲氧基分枝菌酸、酮基分枝菌酸[ | 抑制MTB细胞壁分枝菌酸生物合成 | C |
| 普瑞玛尼(Pretomanid) | 甲氧基分枝菌酸、酮基分枝菌酸及脱氮黄素依赖型硝基还原酶(Ddn)[ | 抑制MTB细胞壁分枝菌酸合成和蛋白质合成 | A |
| D-环丝氨酸(Cs)和特立齐酮(苯环丝氨酸,Trd) | D-丙氨酸消旋酶(Alr)、D-丙氨酸-D-丙氨酸连接酶(DdlA)和ilvE编码的支链氨基转移酶(MtIlvE)[ | 抑制MTB细胞壁肽聚糖合成及MTB生长 | B |
| 乙胺丁醇(EMB,E) | 阿拉伯糖基转移酶 | 抑制MTB阿拉伯糖基聚合入阿拉伯半乳聚糖,从而影响细胞壁分枝菌酸-阿拉伯半乳聚糖-肽聚糖复合物的形成;并影响中间代谢和呼吸,抑制分枝菌酸的合成[ | C |
| 碳青霉烯类β内酰胺类抗生素 [亚胺培南-西司他丁(Ipm-Cln)和美罗培南(Mpm)] | 亚胺培南和美罗培南作用靶点为青霉素结合蛋白(PBPS)的L,D-转肽酶[ | 抑制肽聚糖层的生物合成和维持从而影响MTB细胞壁的合成。西司他丁是肾脱氢肽酶(DHP-1)抑制剂,无抗菌作用,但在体内可抑制肾细胞分泌的脱氢肽酶,使亚胺培南不被水解 | C |
| 抑制DNA和(或)RNA合成的药品 | |||
| 氟喹诺酮类[左氧氟沙星(Lfx)、莫西沙星(Mfx)和加替沙星(Gfx)] | DNA回旋酶 | 抑制MTB DNA回旋酶的活性,使DNA链超螺旋结构解离和松弛,阻断DNA的复制和转录,导致细菌死亡[ | A |
| 利福霉素类[利福平(R)、利福喷丁(Rft)、利福布汀(Rfb)] | RNA 聚合酶β亚单位(rpoB) | 干扰MTB转录的开始和RNA延伸,从而抑制MTB蛋白的合成[ | |
| 抑制蛋白质合成的药品 | |||
| 利奈唑胺(Lzd) | 50S核糖体亚基 | 与50S核糖体亚基结合,阻断MTB RNA翻译过程、抑制菌体蛋白质的合成[ | A |
| 链霉素(Sm) | 30S核糖体亚基 | 抑制MTB mRNA翻译的开始,干扰翻译过程中的校对,从而抑制蛋白质合成[ | C |
| 阿米卡星(Am) | 30S核糖体亚基 | 阻断MTB翻译、抑制蛋白质的合成[ | C |
| 卷曲霉素(Cm) | 70S核糖体(30和50S亚基) | 阻断MTB翻译、抑制蛋白质的合成[ | C |
| 吡嗪酰胺(PZA,Z) | 核糖体蛋白S1(RpsA) | 抑制MTB蛋白质合成[ | C |
| 抑制能量代谢的药品 | |||
| 贝达喹啉(Bdq) | 三磷酸腺苷合成酶 | 抑制结核分枝杆菌三磷酸腺苷合成酶活性,阻断其能量供应,导致细菌死亡[ | A |
| 氯法齐明(Cfz) | 主要作用于分枝杆菌外膜的呼吸链和离子转运蛋白[ | 抗菌作用机制尚不完全清楚,可能是呼吸系统氧化氯法齐明而不是NADH,导致所有细胞过程可用的三磷酸腺苷量减少 | B |
| 其他 | |||
| 对氨基水杨酸(PAS) | 二氢叶酸合酶 | 对MTB叶酸合成起竞争抑制作用[ | C |
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