2022抗結(jié)核藥物Antituberculosis-山東大學(xué)藥理學(xué)英文課件精選ppt

Chapter42Antituberculosisandantileprosydrugs結(jié)核結(jié)核：稱白色瘟疫，也稱癆?。╬hthisis，源自希臘語的“消耗”），人類最早的結(jié)核病可能由牛分支桿菌(Mycobacteriumbovis)導(dǎo)致，因喝牛奶而感染（由于牛奶滅菌技術(shù)的出現(xiàn)，目前這類病例已經(jīng)很罕見。一種毒性較弱的牛分支桿菌被用于結(jié)核病免疫，稱為卡介苗）自鏈霉素問世，PAS、雷米封、利福平、乙胺丁醇等相繼合成，已成為可治之癥，美國在上世紀(jì)80年代初甚至認(rèn)為世紀(jì)末可以消滅結(jié)核，

History

Before1930’s1944streptomycin1949

Aminosalicylicacid（PAS）1952Isoniazid1954pyrazinamide1955cycloserine(環(huán)絲氨酸)1962

Ethambutol1963Rifampin1990’sFluoroquinolones抗結(jié)核藥，從左至右分別為：異煙肼，利福平，吡嗪酰胺，乙胺丁醇First-linedrugsHighactivityagainstbothextracellularandintracellulartuberclebacilliNocross-resistancewithotherantituberculosisdrugsMechanismofactionPyrazinamide1954pyrazinamideFirst-linedrugsAdverseeffectGastrointestinaldisturbanceBefore1930’sAntituberculosisdrugsMycobacteria,someG+andG-cocci,chlamydiaandsomevirusBindtoβ-subunitofbacterialDNA-dependentRNApolymeraseandinhibitRNAsynthesis1949Aminosalicylicacid（PAS）AntimicrobialactivityHighactivityagainstbothextracellularandintracellulartuberclebacilliAntituberculosisdrugsFirst-linedrugs

Isoniazid,rifampin,pyrazinamide,ethambutolandstreptomycinSecond-linedrugsAminosalicylicacid（PAS）,kanamycin,capastatin(卷曲霉素),ethioniamide(乙硫異煙胺)Isoniazid

1952,themostactivedrugforthetreatmentoftuberculosisMechanismofacitonInhibitthesynthesisofmycolicacidwhichisessentialcomponentsofmycobacterialcellwallsAntimicrobialactivityHighactivityagainstbothextracellularandintracellulartuberclebacilliBindtoβ-subunitofbacterialDNA-dependentRNApolymeraseandinhibitRNAsynthesisNewantitubersclerosisdrugsGastrointestinaldisturbanceInconjunctionwithINHandrifampicininshort-courseregimenstopreventrelapseSparfloxacinPyrazinamideHighactivityagainstbothextracellularandintracellulartuberclebacilliPharmacokineticsMechanismofactionBindtoβ-subunitofbacterialDNA-dependentRNApolymeraseandinhibitRNAsynthesisFirst-linedrugsStreptomycinandpyrazinamideAntimicrobialactivityInconjunctionwithINHandrifampicininshort-courseregimenstopreventrelapseClinicalusesIsoniazidPharmacokineticsDiffusereadilyintoallbodyfluidsandtissuesMetabolizedbyacetylationClinicalusesFirstchoiceforalltypesoftuberculosisIsoniazidAdversereactionsPeripheralneuropathy(numbness,anunusualsensationsuchasburningorpricklingontheskin)

CNStoxicity:memoryloss,psychosis,seizuresHepatoxicity:themostfrequent,increaseinaminotransferase,hepatitisAllergicreactionsRifampicin

AntimicrobialactivityMycobacteria,someG+andG-cocci,chlamydiaandsomevirusMechanismofactionBindtoβ-subunitofbacterialDNA-dependentRNApolymeraseandinhibitRNAsynthesisRifampicinClinicalusesTuberculosisandleprosyInfectionscausedbystapylococciandotherrifampicin-susceptiblebacteriaAdversereactionsGastrointestinaldisturbanceLivertoxicity:cholestaticjaundice(膽汁郁積性黃疸),hepatitisEthambutolMechanism:interferingwithsynthesisofRNAbycombinationwithMg2+UsedincombinationwithINHorrifampicinAdverseeffectLossofvisualacuity,opticalneuritis,red-greencolorblindnessStreptomycinandpyrazinamideStreptomycinPenetrateintocellpoorly,activemainlyagainstextracellulartuberclebacilliPyrazinamideNocross-resistancewithotherantituberculosisdrugsInconjunctionwithINHandrifampicininshort-courseregimenstopreventrelapseNewantitubersclerosisdrugsRifandinRifapentineSparfloxacinRationalefortheuseof