氨基糖苷类抗生素8资料.ppt

* * * * * * * * * * * * * * * * * * * * * * * 氨基糖苷类的化学结构由2个或3个氨基糖分子通过氧桥与非糖部分结构连接成苷。结构中富含氨基，呈碱性，带多个正电荷，属于多聚阳离子，极性大。这些化学性质与该类药物的抗菌作用和体内过程密切相关。 Here is the common structure of aminoglycosides. We notice they have many amino-groups. So they are polycations(多聚阳离子). That mean they have many positive charges（带正电荷）. This chemical character contributes to their antibacterial mechanism. * * * * * * * * * * * * * * * * * * Let’s see an animation. The positively charged aminoglycoside binds to negatively charged sites on the outer bacterial membrane, thereby disrupting membrane integrity. What’s more, the abnormal nonfunctional protein may insert into the plasma membrane, enhancing the disruption of membrane integrity. Then, the essential components of the bacteria, such as the potassium, nucleic acid, amino acid, enzymes, etc leak out, leading to bacterial cell death. At the same time, more aminoglycosides enter the bacterial cell which inhibit protein synthesis. So, the two mechanisms of aminoglycosides are synergistic. * * * * * * * * * * * * aminoglycosides﹒pharmacokinetics氨基糖苷类﹒体内过程 吸收absorption： 口服 用于肠道术前消毒或肠道感染 注射 用于全身感染/非肠道感染 aminoglycosides﹒pharmacokinetics氨基糖苷类﹒体内过程 分布distribution： 主要分布在细胞外液 不易进入细胞内 不易进入脑脊液 易透过胎盘屏障 肾脏和内耳淋巴液中浓度高 aminoglycosides﹒pharmacokinetics氨基糖苷类﹒体内过程 消除elimination： 以原形从肾脏排出，尿中药物浓度高 碱性尿中作用增强 肾功能不良时慎用 aminoglycosides﹒clinical uses氨基糖苷类﹒临床应用 需氧Ｇ-杆菌引起的全身感染 铜绿假单胞菌感染 Ｇ+球菌感染 结核杆菌感染 aminoglycosides﹒adverse reactions氨基糖苷类﹒不良反应 四大毒性 aminoglycosides﹒adverse reactions氨基糖苷类﹒不良反应 耳毒性 ototoxicity 肾毒性 nephrotoxicity 神经肌肉接头阻滞 neuromuscular blockade 过敏反应 allergy aminoglycosides﹒adverse reactions氨基糖苷类﹒不良反应 ototoxicity： 第八对脑神经的损害 前庭功能损害 发生率：neomycin kanamycin streptomycin gentamicin,amikacin, tobramycin netilmicin aminoglycosides﹒adverse reactions氨基糖苷类﹒不良反应 ototoxicity： 第八对脑神经的损害 耳蜗功能受损：耳鸣、听力减退、永久性耳聋。 其发生率：neomycin kanamycin amikacin gentamicin tobramycin netilmicin streptomycin aminoglycosides﹒adverse reactions氨基糖苷类﹒不良反应 ototoxicity： 可能机