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1、人工合成抗菌药,Synthesized Antibacterial Agents,Antibacterial Agents III,分 类,喹诺酮类：诺氟沙星（norfloxacin）磺胺类：磺胺嘧啶(sulfadiazine)甲氧苄啶类：甲氧苄啶(trimethoprim)硝基呋喃类：呋喃妥因(nitrofurantoin)硝咪唑类：甲硝唑(metronidazole),第一节 喹诺酮类药物Quinolones,Fluoroquinolones,喹诺酮类发展简史,1962年Lesher 发现萘啶酸1974年吡哌酸1979年诺氟沙星 一系列氟喹诺酮类,Ciprofloxacin,Levoflo
2、xacin,概 述,喹诺酮类是含有4-喹诺酮母核基本结构的合成抗菌药,4-喹诺酮化构中引入基团与抗菌效果的关系,抗菌机制,抑制DNA回旋酶而影响细菌DNA的合成。,Structure of bacterial DNA gyrase complexed with DNA and two ciprofloxacin molecules(green),氟喹诺酮类药理学特性,抗菌谱体内过程临床应用不良反应耐药性,不 良 反 应,1.氟喹诺酮类影响骨骼发育，孕妇及婴幼儿慎用2.因其引起中枢神经系统不良反应，故有神经系统病史者慎用 3.可引起变态反应，有过敏史者禁用或慎用4.其抑制茶碱、口服抗凝药的肝中代
3、谢，应避免与之合用;与制酸药合用，可减少其吸收5.多数药物主要经肾排泄，肾功能减退时，应注意调整剂量,第二节 磺胺类药和甲氧苄啶Sulfonamides,磺胺类药物是三十年代发现的能有效防治全身性细菌感染的第一类化疗药物。,对氨基苯磺酰胺,荣获1939年诺贝尔生理学或医学奖发现了百浪多息的抗菌作用,杜马克Gerhard Domagk德国慕斯特大学1895年-1964年,分 类,抗菌机制,抗菌谱,G+球菌：对溶血性链球菌、肺炎球菌敏感G-球菌：脑膜炎奈瑟菌、淋病奈瑟菌有效杆菌：大肠埃希菌、布鲁斯菌、变形杆菌等衣原体 放线菌伤寒 疟原虫,磺胺嘧啶（SD）,体内过程（1）在脑脊液中浓度高，与血浆蛋白
4、 结合率低（2）肝代谢（3）肾脏排泄（4）肠道难吸收的随粪便排泄,2.应用,易通过血脑屏障,抑制脑膜炎奈瑟菌,（1）流脑,（2）泌尿道、呼吸道感染（3）丹毒、蜂窝组织炎,3.不良反应,（1）损害泌尿系统（2）抑制造血系统（3）过敏反应,甲氧苄啶类（TMP）,作用机制,二氢叶酸还原酶,二氢叶酸还原成四氢叶酸,核酸合成,甲氧苄啶,抗菌机制,2.临床应用,硝基呋喃类药物 Nitrofurans,呋喃妥因(nitrofurantoin，呋喃坦啶)呋喃唑酮(furazolidone，痢特灵),硝基咪唑类药物 Nitroimidazoles,甲硝唑(metronidazole,甲硝哒唑,灭滴灵),抗菌药物
5、作用机制示意图,Clinical Use of antibacterial agents,Community-acquired Shigella N.gonorrhea H.influenzae M.catarrhalis S.pneumoniaeHospital-acquired S.aureus VRSA Enterococci Enterobacteriaceae,MRSA,VRE,ESBL,Major resistance problems,1940 1950 1960 1970 1980 1990 2000,MRSA HA vs.CA,Community acquired(CA)MR
6、SAYounger population.More likely to produce skin and soft tissue infections.Not multi-drug resistant.Healthcare associated(HA)MRSAMulti-drug resistant.Associated with foreign bodies.,Multidrug resistanceis a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wid
7、e varietyof structure and function targeted at eradicating the organism.,Treatment,VancomycinClindamycinBactrimTetracyclineCombination therapy,Principles of antibacterial use,Basic principlesDiagnosis Rational useNewbornPregnancy Elderly,Synergetic mechanism of combination antibacterial therapy,Affe
8、ct different component of the same mechanismChanging the permeability of the cytoplasmic membrane or the cell wallInhibiting the inactiving enzyme of antibacterial drugsInhibiting the different resistant microbial population,Principles of antibacterial use,Antimicrobial agents combinationDrug catego
9、ries1.-Lactam antibiotics2.Aminoglycosides3.Tetracyclines,macrolide,chloramphenicol4.Sulfonamides1+2:Synergism1+3:antagonism2+3:synergism or plus3+4:plus,Rationale for combination antibacterial therapy,To Provide broad-spectrum therapy in seriously ill patientsSerious infection that can not be contr
10、olled by one drugTo decrease the emergence of resistant strainsTo decrease dose-related toxicityMeningitis and osteomyelitis caused by bacterial infection,Principles of antibacterial use,MisuseVirus infectionUnknown feverTopical useImproper prophylaxis and combination,Antimicrobials are routinely ad
11、ded to animal feed and water to promote animal growth.-Rationale is to promote more rapid growth reducing farming expenses.-Mechanisms are debated although most commonly invoked is the reduction of infections,especially in unsanitary conditions.Many of the antibiotics used in this setting are of the same class as those used to treat human infections.-macrolides,tetracyclines,glycopeptides,
