氨基糖苷四环素氯霉素.ppt
Aminoglycosides,Chapter 40,Aminoglycosides,氨基环醇环-多个氨基糖分子（糖苷键）苷类；,Aminoglycosides,链霉菌属菌类培养液streptomycin链霉素、新霉素、kanamycin卡那霉素、tobramycin妥布霉素、核糖霉素等；小单胞菌属培养液gentamycin庆大霉素、西索米星、小诺米星等；半合成：amikacin阿米卡星、奈替米星等。,common characteristics,antibacterial spectrumaerobic G-bacilli 需O2G-杆菌强杀菌G+菌（金葡菌），tubercle bacillus结核杆菌：streptomycin链霉素kanamycin卡那霉素对肠球菌和厌氧菌不敏感,mechanism of action,protein synthesis 影响蛋白质合成的起始，延伸，终止阶段；造成细菌胞膜缺损为杀菌药 对蛋白质合成的影响包括有：与细菌体内核糖体70S亚基始动复合物的形成；选择性地与细菌体内核糖体30S亚基上的靶位蛋白(P10)结合，使A位歪曲，造成mRNA上的“三联密码”在翻译时出现错误，导致异常或无功能蛋白质合成；,mechanism of action,阻滞肽链释放因子进入A位，使合成好的肽链不能释放；抑制核糖体70S亚基的解离，使菌体内核糖体循环利用受阻。氨基糖苷类还通过吸附作用与菌体胞浆膜结合，使通透性增加，胞质内大量重要物质外漏。,耐药机制,Production of modifying enzyme:产生修饰氨基苷类的钝化酶，可出现交叉耐药性。Alteration of permeability of cell membrane膜通透性的改变，菌体内药物浓度下降。Alteration of drug binding site靶位的修饰，致使对链霉素的亲和力降低。,pharmacokinetics,poor absorption orally.po.难吸收po.用于肠道感染、肠道消毒Distributionthe extracellular fluidthe kidneythe CSF可通过胎盘屏障,pharmacokinetics,Eliminationglomerular filtration 主要原形肾排used for urinary tract infections 可用于泌尿系感染renal disfunction 肾功不全应慎用或禁用,adverse reaction,Ototoxicity 耳毒性vestibular damage 前庭功能损害：vertigo and nausea(头晕，恶心）卡链阿庆妥auditory nerve damage耳蜗听N损害tinnitus and hearing loss耳鸣、听力减退卡 阿 西 庆 妥 链,adverse reaction,notices：经常询问早期中毒症状检测听力根据患者肾功能情况调整剂量避免与有耳毒性的药合用：Furosemide呋塞米vancomycin万古霉素,adverse reaction,Nephrotoxicity 肾毒性notice：combination of drugs with nephrotoxicity避免合用有肾损害药,adverse reaction,Neuromuscular blockade 神经肌肉接头阻滞：Reason:(-)the release of Ach产生原因：氨基苷与突触前膜钙结合部位结合Ca2+内流ACh释放肌松Therapeutic drugs:neostigmine,adverse reaction,allergic reaction:streptomycin,Individual aminoglycosides,streptomycin 链霉素Characterictics1、对多数G-杆菌有效，鼠疫首选 2、感染性心内膜炎：与penicillin合用（注意二者不可混合注射！）3、一线抗结核药：常需与其他抗结核药合用以延缓耐药性的产生；4、耳毒性较多见.,Individual aminoglycosides,Gentamicin 庆大霉素Characterictics1、抗菌谱广，抗菌活性强2、用途：严重G-杆菌感染：首选败血症、骨髓炎、肺炎、脑膜炎等绿脓杆菌感染：与羧苄青霉素合用po.治肠道感染、肠道术前准备3、可逆性肾损害，亦有前庭功能损害,Individual aminoglycosides,Amikacin 阿米卡星Characterictics1、同类药中抗菌谱最广，耐酶2、对其他氨基苷类耐药的感染有效；3、耳毒性庆大，肾毒性庆大,Individual aminoglycosides,Tobramycin 妥布霉素Characterictics1、对绿脓杆菌作用突出：gentamicin 2-4倍；对肺炎杆菌、肠杆菌、变形杆菌强对厌氧菌、肠球菌无效2、主治绿脓杆菌感染及严重的G-菌感染,Tetracyclines&Chloramphenicol,Chapter 41,Tetracyclines四环素类,natural drugs：tetracyclines 四环素Oxytetracycline土霉素semisynthetic drugs:doxycycline多西环素 minocycline米诺环素,natural tetracycline,Pharmacokinetics1.The absorption is impaired by food,metal ion(Ca2+,Mg2+,Fe2+,Al3+),and antacids.食物、高价阳离子和抗酸药可减少药物吸收 2.the concentration in the foetus胎儿 and breast milk,natural tetracycline,Pharmacokinetics3.-bind to bones and teeth 沉积于骨、牙组织4.Excretion:the bile and urine主要原形肾排及胆汁排泄,natural tetracycline,antibacterial spectrumbroad-spectrumG+-lactams antibiotics G-Aminoglycosides，Chloramphenicol（氯霉素）,natural tetracycline,mechanism of actiontetracycline binds to the 30S subunit inhibits protein synthesis 作用菌核糖体30S亚基抑制蛋白质合成,natural tetracycline,clinical uses1.Typhus,Q fever(rickettsiae):斑疹伤寒、Q热（立克次体感染）2.mycoplasma pneumonia 支原体肺炎3.psittacosis,trachoma(chlamydiae)鹦鹉热、沙眼(衣原体感染）4.relapsing fever 回归热5.cholera(vibrio cholerae)霍乱,natural tetracycline,adverse reaction1.GI reaction2.superinfection（二重感染）长期应用广谱抗生素，敏感菌受到抑制，不敏感菌趁机繁殖，破坏菌群共生平衡引起新的感染。常见：a、真菌感染：如鹅口疮等b、伪膜性肠炎,natural tetracycline,adverse reaction3.(-)bone and teeth growthteeth:yellow or brown pigmentation黄染 四环素牙pregnant woman and children under 8 years 孕妇及8岁儿童禁用4.hepatic and kidney disfunction5.allergic reaction,semisynthetic tetracyclines,Doxycycline 多西环素（强力霉素）Characteristics1、抗菌谱广，强效、速效、长效2、po.吸收完全，不受食物影响3、胃肠道反应常见：大量水送服;二重感染少见4、肾衰者可用5、用途同四环素,semisynthetic tetracyclines,Minocycline 米诺环素Characteristics1、广谱、高效、长效2、po吸收完全，影响因素少，分布广3、各部位感染均有效：尿路、胃肠道、呼吸道、眼科、五官科等感染耐药菌仍有效,2 Chloramphenicol,pharmacokinetics1.broad distribution:CSF 2.Elimination:liver(mainly)kidney,2 Chloramphenicol,antibacterial spectrum1.G+、G-：G-G+2.结核杆菌、真菌、病毒-无效,2 Chloramphenicol,Mechanism of actionChloramphenicol binds to the 50s subunit inhibit protein synthesis与50S亚基结合（-）肽酰基转移酶（-）蛋白合成,2 Chloramphenicol,Clinical uses1、伤寒、副伤寒2、立克次体感染3、细菌性脑膜炎：4、眼科：沙眼、结膜炎、角膜炎等,2 Chloramphenicol,adverse reactions1.Bone marrow damage 抑制骨髓造血系统reversible damage:dose-dependent 可逆性损害：与剂量和疗程有关nonreversible damage:不可逆性再障：较少见，死亡率高,2 Chloramphenicol,adverse reactions2.Grey syndrome:灰婴综合征：the failure of the liver to conjugate,and of the kidney to excrete the drug早产儿、新生儿肝功发育不全或肾排泄 功能不完善所致;3.others：superinfection、GI reaction、allergic reaction,2 Chloramphenicol,Notices:1、为肝药酶抑制剂与warfarin合用：自发性出血与甲磺丁脲合用：低血糖2、早产儿、新生儿慎用3、用药时间不宜长,
