β-内酰胺类抗生素.ppt

1,-内酰胺类抗生素,Chapter36,-lactamantibiotics,2/35,Allofthedrugsinthisgroupcontainabetalactamringintheirstructures.本类药化构中均含有内酰胺环,beta-lactamring,3/35,1.penicillins2.cephalosporins3.others本类药包括：青霉素类头孢菌素类其它类,Classesofbeta-lactamantibiotics:,4/35,penicillins,natural.天然青霉素,semisynthetic.半合成青霉素,1penicillins,6-APA,thesidechain,5/35,naturalpenicillins,penicillinG,6/35,Pharmacokinetics：,1.poororalabsorption口服不易吸收2.Distribution:widetheconcentrationinCSF,3.Elimination:thekidney,Whenthemeningesareacutelyinflamed脑膜有炎症时CSF浓度,主动分泌与丙磺舒竞争分泌通道,7/35,antibacterialspectrum,gram-positivebacteria,gram-negativecocci,spirochete,G+菌G-球菌螺旋体,8/35,theinfectionscausedbygram-positivebacteria,gram-negativecocci,andspirochete用于G+、G-菌、螺旋体引起的感染,Clinicaluses：,9/35,G+球菌(链球菌、肺炎球菌、金葡菌等）：扁桃体炎、咽炎、猩红热、中耳炎、败血症、大叶性肺炎、心内膜炎等G+杆菌：白喉、破伤风、气性坏疽等（与抗毒素合用）G-球菌：流脑（脑膜炎双球菌）、淋病（淋球菌）螺旋体：梅毒、钩端螺旋体病等,firstchoice,10/35,penicillinbindstopenicillin-bindingproteins（PBPs）blockstheeptidoglycansynthesisinhibitstheformationofthecellwallcausesthecelldeath青G与PBPs相结合抑制粘肽合成破坏菌体细胞壁菌体死亡,mechanismofaction,11/35,1.multiplicationstagebactericide(繁殖期杀菌药）2.G+bacteriaG-bacteria3.safetytothebody对人体毒性小,characteristics,12/35,Resistance：,beta-lactamase,bacteriaproducebeta-lactamaseopenthebeta-lactamringthedrugsaction,细菌产生beta-内酰胺酶打开beta-内酰胺药物效应,13/35,Adversereaction：,1.allergicreaction：symptom:skinhypersusceptibility(-)R,circulation,andCNSreasons:thecleavageproductofpenicillins致敏原为青霉素降解产物（青霉烯酸蛋白、青霉噻唑蛋白），6-APA高分子聚合物,14/35,1.Askallergichistory2.Makeskintest3.Observethereactionofskintest4.Prepareanemergencytreatment:Adrenaline、hydrocortisoneH1-receptorblockingdrugs,一问二试三观察四抢救,prophylaxisandtreatment：,15/35,2.others:herxheimerreaction赫氏反应:治疗梅毒或钩端螺旋体病、雅司、鼠咬热或炭疽时，症状加剧的现象。localreaction,16/35,Virtues:杀菌力强、毒性低、价廉Defects：不耐酸、不耐酶、抗菌谱窄、易过敏,Characteristicsofpenicillin,17/35,Semisyntheticpenicillins,18/35,penicillinVcharacteristics1.acid-resistant2.spectrumsimilartopenicillinG3.antibacterialactionpenicillinG耐酸，抗菌谱与青G相似抗菌活性弱于青G,acid-resistantpenicillins,19/35,oxacillin苯唑西林cloxacillin氯唑西林Dicloxacillin双氯西林flucloxacillin氟氯西林,beta-lactamase-resistantpenicillins,20/35,1.acid-resistant：耐酸2.beta-lactamase-resistant:耐酶firstchoicefortheinfectionsofthepenicillinase-productiveaurococcus主用于产酶金葡菌感染,Characteristics：,21/35,ampicillin氨苄西林amoxycillin阿莫西林,broad-spectrumpenicillins,22/35,1.acid-resistant耐酸2.beta-lactamasesensitive不耐酶3.broadspectrum：activeagainstG-bacilli，butinactiveagainstpseudomonas广谱：对G-杆菌有效，但绿脓杆菌无效用于敏感菌所致的呼吸道感染、伤寒、副伤寒、尿路感染、胃肠道感染等,characteristics,23/35,抗铜绿假单胞菌广谱青霉素类,Ticarcillin替卡西林Piperacillin哌拉西林（氧哌嗪青霉素）Carbenicillin羧苄西林,antipseudomonalpenicillins,24/35,1.spectrumsimilartoampicillin，butactiveagainstpseudomonas抗菌谱似氨苄西林，但对绿脓杆菌作用强2.acidandbeta-lactamasesensitive,3.treatment:mainlytheinfectionscausedbypseudomonasbacteria,不耐酸、不耐酶,主用于绿脓杆菌感染,characteristics,25/35,Notice,1、对敏感菌的抗菌活性penicillinsG2、与penicillinG有交叉过敏,26/35,2cephalosporins,commoncharacteristics1.basicstructure:7-ACA基本结构：7-氨基头孢烷酸（7-ACA）2.bactericidal：Mechanismofactionissimilartopenicillins3.therateofallergicreaction,27/35,Firstgeneration,1.Narrowspectrumsimilartobroadspectrumpenicillins2.Sensitivetobeta-lactamases,Secondgeneration,Increasedactivitytowardgram-negativeorganisms2.Increasedstability,Thirdgeneration,Evenbroaderinspectrumandmoreresistanttobeta-lactamases,Fourthgeneration,G-andG+activity,28/35,G+,G-,绿脓杆菌,酶稳定性,肾脏毒性,主要用途,一代,强,弱,无,弱,有,G+感染,二代,中,中,部分有效,稳定,弱,敏感菌感染,三代,弱,强,有效,高度稳定,无,G-致严重感染,四代,G+球菌强,强,强,极稳定,无,敏感菌致严重全身感受染,BBB,不,少数透,易透,Notice:二、三代谱广，易致二重感染,代数,可透,29/35,头孢噻吩、头孢唑啉、头孢氨苄等【特点】G+菌作用强G-杆菌作用弱CSF药浓低肾毒性较大,第一代头孢菌素,30/35,头孢孟多cefamand-ole头孢呋辛cefuroxime头孢克洛cefaclor【特点】1、抗G-杆菌作用2、部分对厌氧菌高效，对绿脓杆菌无效3、肾毒性有所,第二代头孢菌素,31/35,头孢噻肟cefotaxime头孢曲松ceftriaxone头孢哌酮cefoperazone【特点】1、对G+菌作用一、二代2、G-杆菌作用，绿脓杆菌、厌氧菌效强3、几无肾毒性4、t1/2长，穿透力强,第三代头孢菌素,32/35,others,1.Carbopenems(碳青霉烯类）imipenem(亚胺培南)characteristics:1.broadspectrum2.resistanttobeta-lactamases3.Antibacterialactivity,33/35,2.Cepharmycins(头霉素类）cefoxitin(头孢西丁)3.Oxacephalosporins(氧头孢烯类）latamoxef(拉氧头孢）4.Monobactams(单环beta-内酰胺类）aztreonam（氨曲南）,34/35,5.beta-lactamaseinhibitors,beta-内酰胺酶抑制剂,2、本身有抗菌活性吗？,3、应与哪些药物合用？