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macrolides lincomycins vancomycins section3 yun bilu phd卢韵碧dept ofpharmacology schoolofmedicine zhejianguniversityyunbi erythromycin 红霉素 clarithromycin 克拉霉素 azithromycin 阿奇霉素 telithromycin 泰利霉素 partamacrolides 14memberrings 15memberrings 14memberrings 1 antimicrobialspectrum g organismsg cocci streptococcuspyogenesandpneumoniaemycoplasmapneumoniae 肺支原体 andlegionnella 军团菌 etc 2 antimicrobialactivity bactericidalandbacteriostatic dependingontheconcentration moreactiveatalkaline generalpropertiesofmacrolides 3 mechanismofaction 4 mechanismofresistance modificationoftheribosomalbindingsiteproductionofesterasethathydrolyzemacrolides reducedpermeabilityofcellmembraneoractiveeffluxsystemisinvolved cross resistanceiscompletebetweenerythromycinandtheothermacrolides 4 adme1 absorption stearateandesteroferythromycinarefairlyacid resistantandsomewhatbatterabsorbed foodinterfereswithabsorption generalpropertiesofmacrolides 4 adme2 distribution doesnotcrossbbb 3 elimination itisconcentratedintheliver wheresomeisunactived whilesomeisexcretedinactiveforminthebile generalpropertiesofmacrolides 5 clinicaluses 1 mycoplasma 支原体 infections 2 legionnaire sdisease 军团菌病 3 chlamydiainfections 衣原体感染 4 streptococcus 链球菌 infections 5 diphtheria 白喉 chincough 百日咳 6 toxoplasmosis 弓形虫病 generalpropertiesofmacrolides 6 adverseresponse 1 gieffects nausea vomiting abdominalcramps 痉挛 2 livertoxicity cholestatichepatitis 胆汁淤积性肝炎 3 cardiotoxiceffects4 auditoryimpairment ototoxicity hypersensitivityreactionssuperinfections generalpropertiesofmacrolides 7 druginteractionserythromycinmetabolitescaninhibitcytochromep450enzyme generalpropertiesofmacrolides erythromycin 红霉素 clarithromycin 克拉霉素 azithromycin 阿奇霉素 telithromycin 泰利霉素 macrolides lincomycin 林可霉素 clindamycin 克林霉素 partblincomycin clindamycin antimicrobialpropertiesresembleerythromycininantibacterialspectrum activity mechanismandresistance lincomycin clindamycin mechanismofaction chloramphenicol macrolides clindamycin tetracyclines pharmacokineticsabout90 protein boundexcretionviatheliver bile andurinepenetratewellintomosttissue includingbone butnotcsf lincomycin clindamycin clinicalusessevereanaerobicinfectionaerobicg cocciinfectioncombinationwithpyrimethamine 乙胺嘧啶 foraids relatedtoxoplasmosis 弓形体病 combinationwithprimaquine 伯氨喹 foraids relatedpneumocystiscariniipneumonia 肺囊虫性肺炎 lincomycin clindamycin adverseresponse 1 gieffects antibiotic associatedcolitis pseudomembranouscolitis伪膜性结肠炎 2 allergicreaction3 impairedliverfunction lincomycin clindamycin vancomycin 万古霉素 norvancomycin 去甲万古霉素 teicoplanin 替考拉宁 太古霉素 vancomycins antibacterialactivitybactericidalforg bacteria especiallyg ococci includingmrsa mrse vancomycins antibacterialmechanisminhibitingcellwallsynthesisbybindingtothed ala d alaterminusofnascentpeptidoglycanpenta peptide resistanceoccurredbecauseofthealterationofd ala d alatothed ala d ser vancomycins fig antibacterialmechanismofvancomycins admeoraladministration poorlyabsorbed intravenousadministration isexcretedbyglomerularfiltration accumulateswhenrenalfunctionisimpaired widelydistributedinthebody includingcsfwhenthemeningesisinflamed vancomycins clinicaluses1 severeinfectioncausedbymrsaetc 2 alternativeforb lactam3 enterococcalorstaphyococcalendocarditis combinationwithgentamicin 4 pseudomembranouscolitis vancomycins pseudomembranousenterocolitis hurleyandngueynarchinternmed 2002 162 2177 2184 pseudomembranouscolitis endoscopicenfaceviewofcolonwalldemonstratingseveralpseudomembranes arrows focalulcerationcanbeseenatthetipsofthemucosa theexudateoffibrinandinflammatorytissue pseudomembranousenterocolitis normal adversereactions1 hypersensitivereaction e g redmansyndrome 2 ototoxicity3 nephrotoxicity4 gleffects etc vancomycins aminoglycosides polymyxins section4 historyandsource theresearchmadebywaksmanandcoworkswithin1939 1943clinicalapplications forthetreatmentofaerobicg bacterialinfectionsandtuberculosistwoclasses crudeproductandsemisyntheticderivative overview partaaminoglycosides aminoglycosides 1 antimicrobialactivity i rapidlybactericidaltorestingbacteriumii broad spectrumiii moreactiveatalkaline generalproperties 1 antimicrobialactivity iv concentration dependentactivityv thedurationofpostantibioticeffect pae isconcentration dependent 10hours vi firstexposureeffect fee generalproperties 2 antimicrobialspectrum aerobicg bacilliandcocciaerobicg organismsstreptomycinandkanamycinarealsoactiveagainstmycobacteriumtuberculosis generalproperties 3 mechanismofaction inhibitproteinsynthesisactasionic sorbent actdirectlyonpermeabilityofthecellmembraneofbacterium generalproperties blockstheinitiationofproteinsynthesis mechanismofaction inhibitproteinsynthesis mechanismofaction inhibitproteinsynthesis blockstheinitiationofproteinsynthesis mechanismofaction inhibitproteinsynthesis mechanismofaction inhibitproteinsynthesis incorporationofincorrectaminoacid mechanismofaction inhibitproteinsynthesis mechanismofaction inhibitproteinsynthesis blocksfurthertranslocationandelicitsprematureterminations disruptthenormalcycleofribosomal maketheribosomalexhausted mechanismofaction inhibitproteinsynthesis i interferingwiththeinitiationcomplexofpeptideformation ii inducingmisreadingofmrna whichcausestheincorporationofincorrectaminoacidintopeptide resultingnonfunctionalortoxicprotein mechanismofaction inhibitproteinsynthesis iii causingbreakupofpolysomesintononfunctionalmonosomes iv disruptthenormalcycleofribosomal maketheribosomalexhausted mechanismofaction inhibitproteinsynthesis mechanismofresistance producesenzymes alteredribosomalsubunit changesofporins activeeffluxsystem i themicroorganismproducesatransferaseenzymeorenzymesthatinactivatetheaminoglycosidebyadenylyation acetylation orphosphorylation ii impairedentryofaminoglycosideintothecell iii thereceptorproteinonthe30sribosomalsubunitmaybedeletedoralteredasaresultofmutation mechanismofresistance admei absorption notabsorbedafterpo butrapidlyabsorbedafterim peaktime0 5 2h ii distribution bindingtoplasmaproteinisminimal donotentercell nordotheycrossbbb buttheycrosstheplacenta reachhighconcentrationsinsecretionsandbodyfluids tissuelevelislowexpectinthecortexofkidney generalproperties admeiii elimination excretedmainlybyglomerularfiltration ifrenalfunctionisimpaired accumulationoccurswithaincreaseinthosetoxiceffectswhicharedoserelated t1 2 2 3h generalproperties clinicalusesbemostlyusedagainstaerobicg bacteria bacilli enteric andinsepsis bealmostalwaysusedincombinationwithb lactamantibioticorfluoroqunolones 氟喹诺酮类 againstaerobicg bacteriaandinsepsis bealmostalwaysusedincombinationwithpenicillinsorvancomycinagainstmycobacteriumtuberculosis generalproperties adversereactionsi ototoxicityinvolvesprogressivedamagetoanddestructionofthesensorycellsinthecochleaandvestibularorganintheear irreversible ototoxicity cochlea kanamycin 1 6 amikacin sisomicin gentamicin tobramycin 0 4 ototoxicity vestibularorgan kanamycin 4 7 streptomycin sisomicin gentamicin tobramycin 0 4 generalproperties adversereactionsii nephrotoxicityconsistsofdamagetothekidneytubulesandbereversedifstopusing amikacin streptomycinortobramycin gentamicin kanamycin neomycin generalproperties blue highfrequencyred lowfrequency nephrotoxicity ototoxicity adversereactionsiii neuromuscularblockade paralysis generallyoccurredafterintra pleuralorintra peritonealinstillationoflargedosesofanaminoglycosidestobramycin gentamicin kanamycinoramikacin streptomycin neomycincalciumsaltorinhibitorofcholinesterase neostigmine isthepreferredtreatmentforthistoxicity generalproperties adversereactionsiv allergicreactionskinrashesfever eosinophiliay 嗜酸粒细胞增多症 anaphylacticshock etc generalproperties streptomycin 链霉素 gentamicin 庆大霉素 tobramycin 妥布霉素 amikacin 阿米卡星 netilmicin 奈替米星 neomycin 新霉素 aminoglycosidesagents kanamycin 卡那霉素 arbekacin 阿贝卡星 dibekacin 地贝卡星 micronomicin 小诺米星 sisomicin 西索米星 etilmicin 依替米星 isepamicin 异帕米星 astromicin 阿司米星 福提霉素 spectinomycin 大观霉素 etc aminoglycosidesagents 1 admei absorption imii distribution mainlyatextracellularfluid crossesthebbbandachievestherapeuticconcentrationswithinflamedmenings iii excretion 90 kidneyage t1 2 streptomycin 2 clinicalusesi plague 鼠疫 andtularemia 兔热病 combinationwithanoraltetracycline ii tuberculosis asfirst lineagentiii bacterialendocarditis enterococcal肠球菌 viridansstreptococcal草绿色链球菌 etc streptomycinandpenicillinproduceasynergisticbactericidal streptomycin 3 adversereactionsi allergicreactionskinrashes fever anaphylacticshockii ototoxicity cochlea vestibularorgan iii neuromuscularblockade paralysis iv nephrotoxicity streptomycin 1 admegentamicincanaccumulateincortexofthekidney 2 clinicaluse ii importantagent firstchoice forseriousg bacillaryinfections sepsis pneumonia etc becauseofitslowcostandreliableactivity gentamicin 2 clinicaluses ii infectioninducedbyenterococcal viridansstreptococcal staphylococcaletc gentamicinisusedconcurrentlywithotherantibiotics e g b lactams iii preventtheinfectioninducedbyoperation gentamicin 2 clinicaluses iv localapplication fortreatmentofinfectedburn wounds orskinlesionsandthepreventionofintravenouscatheterinfections etc gentamicin 3 adversereactionsi ototoxicity vestibularorgan cochlea ii nephrotoxicityiii nauseaandvomitingetc gentamicin 1 antimicrobialactivity pharmacokinetics verysimilartothoseofgetamicin 2 adversereactions ototoxicityandnephrotoxicity maybelessthandosegentamicin tobramycin 1 antibacterialactivity thespectrumofantimicrobialactivityofamikacinisthebroadestinthegroup amikacin 2 clinicaluses treatmentofg bacillaryinfectionswhichresistancetogentamicinandtobramycin mbinationwithb lactams produceasynergisticbactericidal amikacin 3 adversereactionsi ototoxicity cochlea vestibularorgan ii nephrotoxicity maybelessthangentamicinortobramycin iii neuromuscularblockade paralysis rarelyiv skinrashes fever nauseaandvomitingetc amikacin i similartogentamicin tobramycininitspharmacokineticproperties ii broadspectrum againstaerobicg bacilli iii tolerancetomanyaminoglycosides inactivatingenzymes iv lesstoxic netilmicin partbpolymyxins 1 polymyxina b c d e2 notice becauseoftheextremetoxicity theyarenowrarelyused 3 antibacterialactivity theyarerestrictedtog bacilli narrowspectrum 4 mechanismofaction theyinteractwithphospholipidsandpenetrateintoanddisruptthestructureofcellmembranes partbpolymyxins 4 clinicaluses infectionofpseudomonasaeruginosa 铜绿假单胞菌属 andotherg bacilli localapplication resisitancerarelyhappened partbpolymyxins 5 adversereaction 25 i nephrotoxicity 22 2 ii neurotoxicity neuromuscularblockade paralysis iii allergicreactioniv others hepatotoxicity tetracyclines chloramphenicol section5 partatetracyclines twoclasses crudeproducttetracycline 四环素 cholortetracycline 金霉素 oxytetracycline 土霉素 semisyntheticderivativedoxycycline 多西环素 minocycline 米诺环素 partatetracyclines antimicrobialactivity bacteriostaticbactericidal highconcentration minocycline doxycycline tetracycline generalpropertiesoftetracyclines broad spectrum antibioticrickattsiae 立克次体 anumberofaerobicandanaerobicg g bacteriachlamydia 衣原体 coxiellaburnetii 螺旋体 mycoplasmapneumoniae 支原体 plasmodium 疟原虫 notactiveagainstfungi virus generalpropertiesoftetracyclines mechanismofaction bindto30ssubunitofribosome preventingaccessofaminoacyltrnatoacceptor a siteonthemrna ribosomecomplex generalpropertiesoftetracyclines generalpropertiesoftetracyclines mechanismofaction chloramphenicol macrolides clindamycin tetracyclines resistancemechanism 1 decreasedintracellularaccumulationduetoeitherimpairedinfluxorincreasedeffluxbyaactivetransportproteinpump 2 ribosomeprotectionthatinterferewiththetetracyclinebindingtotheribosome 3 enzymeinactivationoftetracycline generalpropertiesoftetracyclines adme 1 absorptionareimpairedbyfood exceptdoxycyclineandminocycline 2 distributedwidelytotissueandbodyfluidexceptforcsf acrosstheplacentaandarealsoexcretedinthemilk tetracyclinesareboundto anddamage growingbonesandteeth chelationwithcalcium 3 excretedmainlyinbileandurine generalpropertiesoftetracyclines clinicaluses 1 rickettsial 立克次体 infections 2 mycoplasma 支原体 infections 3 chlamydia 衣原体 infection 4 leptospira 螺旋体 infection 5 bacterialinfection generalpropertiesoftetracyclines adversereactions 1 gastrointestinaleffects 2 superinfections 3