人工合成抗菌藥2_1syntheticantimicrobialdrugs人工合成抗菌藥2_1ClassificationQuinolonesSulfonamidesNitrofuransandnitroimidazole(Metronidazole)人工合成抗菌藥2_1taskUnderstandingthemechanismsofdrugaction,pharmacokineticsanddruginteractionsMasteringantibacterialactivities,therapueticapplicationsandthemajoradversereactions.人工合成抗菌藥2_1Fluoroquinolones人工合成抗菌藥2_1ClassificationofquinolonesThefirstgeneration：nalidixicacid（1962）Thesecondgeneration：pipemidicacid（1973）Thethirdgeneration：fluoroquinolones（1980s）Theforthgeneration：fluoroquinolones（theendof1990s）人工合成抗菌藥2_1FluoroquinolonesNorfloxacinCiprofloxacinOfloxacinLevofloxacinLomefloxacinFleroxacinSparfloxacinMoxifloxacin人工合成抗菌藥2_1Antibacterialspectrum1.Broad-spectrum;GoodactivityagainstG-.Includinglegionella,pseudomonasaeruginasaandMRSA.2.Someiseffecttotuberculebacillus,mycoplasma,chlamydiaandanaerobianetc.Sparfloxacin’sactivityisthestrongest.3.TheforthgenerationsuchasmoxifloxacinimprovedactivityagainstG+.人工合成抗菌藥2_1MechanismofactionInhibitingtypeIItopoisomerases(DNA

gyrase)andtopoisomeraseIV人工合成抗菌藥2_1人工合成抗菌藥2_1PharmacokineticsWellabsorptionafteroraladministrationanddistributionwidelyinbodyfluidsandtissues.TherelativelylongT1/2Renalclearancepredominatesformostfluoroquinolones.人工合成抗菌藥2_1ResistanceCrossresistanceamongthedrugsofthisclass；Commondrug-risistancebacteria:Staphylococcusaureus,enterococcus,Escherichiacoli

and

Pseudomonasaeruginosa

etc.人工合成抗菌藥2_1MechanismofresistanceMutationsinthebacterialchromosomalgenesencodinggyrA,ortopoisomeraseIV.Achangeinthepermeabilityoftheorganism;e.g.Escherichiacoli

Activetransportofthedrugoutofthebacteria

;e.g.

StaphylococcusaureusClinicalapplicationUrinarytractinfections:urethritis,cervicitis,prostatitis.thefirstchoiceisciprofloxacin,gatifloxacinorofloxacinRespiratoryinfectionsIntestinalinfectionandtyphusBone,joint,skin,parenchyma,surgery,E.N.Tinfections.人工合成抗菌藥2_1Adverse

reaction

GastrointestinaleffectsCNSreaction：excitedSkinandphotosensitivityCartilagedamageLiverorrenalfunctionallesion，Achillestendinitis，hearttoxicity，eyetoxicity.人工合成抗菌藥2_1ContraindicationChildren,pregnantwomen

,sucklingwomen,insanepatientorpatientofepilepsyhistoryAllergicpatientCommonfluoroquinolonesinclinicNorfloxacinitsabsorptionisaffectedbyfood.（35-45%）LowplasmadrugconcentrationHighurineandintestinaltractdrugconcentrationNoclinicalvalueformycoplasma,chlamydia,legionella人工合成抗菌藥2_1CiprofloxacinThestrongestantibacterialactioninvitroBioavailabilityis38-60%StrongeffectforG-bacillianddrug-resistanceG+/G–TherapeuticapplicationismainlyforinfectionsofotherdrugresistanceG-bacilli.Noeffectformostanaerobian.ThesameantibacterialcharactertociprofloxacinInaddition,ofloxacinhaseffectformycobacteriumtuberculosis,chlamydiatrachomatisandsomeanaerobian.Thesecond-lineagentfortreatmentoftuberculosisLevofloxacinItsantibacterialactivityisdoubleofofloxacin’s.

Ofloxacin人工合成抗菌藥2_1

goodabsorptionbyoraladministrationItsbioacailabilityisabout99%.DistributedwidelyinbodyfluidsandtissuesStrongantibacterialactivityinvivoAdversereactionismore.Fleroxacin人工合成抗菌藥2_1SulfnamidesBroadspectrum，stable，convenience，easytoproduce，cheap人工合成抗菌藥2_1Chemicalconstitution

O

R2NH

S

NH

R1O

sulfanilamide人工合成抗菌藥2_1classificationSystemicinfection：Short-acting：SIZMiddle-acting：SD、SMZProlonged-acting：SMM、SDMIntestinaltract：SASPExternalusetoLocalinfection：SA-Na、SD-Ag、SML人工合成抗菌藥2_1AntibacterialspectrumBroad-spectrumbacteriostaticItiseffectivetomostofG+andG-,chlamydia,plasmodiumandactinomycesSML、SD-AgexternalusediseffecttoPseudomonasaeruginosa

ActionofmechanismDihydropteroicacidL-glumateDihydropteroicacidsynthaseFH2FH2reductaseFH4bacteriumPurine,PyrimidineSyntheticproteinTMPPABA人工合成抗菌藥2_1MechanismofactionSulfonamidescompletitivelyinhibitdihydropteroatesynthaseandpreventnormalbacterialutilizationofPABA.人工合成抗菌藥2_1MechanismofresistanceLoweredaffinityofdihydropteroatesynthasetosulfonamides;Decreasedbacterialpermeabilityoractiveeffluxofsulfonamides;Analterativemetabolicpathwayforsynthesisofanessentialmetaboliteorover-productionofPABA.CROSS-RESISTANCE人工合成抗菌藥2_1PharmacokineticsSystemicinfectiondrugsbyoraladministrationisabsorbedwellanddistributedwidely.人工合成抗菌藥2_1AdverseeffectUrinarytractdisturbancesAllergicreactionHematopoieticsystemdisordersNervoussystemreactionMiscellaneousreaction：nausea,vomiting,diarrhea,headache

,etc人工合成抗菌藥2_1Trimethoprim（TMP）TMPinhibitsbacterialdihydrofolicacidreductase.TMPgiventogetherwithsulfonamides,producessequentialblockingoffolicacidsynthesis,resultinginmarkedenhancement(synergism)ofthebacteriostaticactivity.ActionofmechanismDihydropteroicacidL-glumateDihydropteroicacidsynthaseFH2FH2reductaseFH4bacteriumPurine,PyrimidineSyntheticproteinTMPPABA人工合成抗菌藥2_1sulfadiazine（SD）SDachievestherapeuticconcentrationsincerebrospinalfluidandisafirst-linetherapyfortreatmentofepidemiccerebrospinalmeningitis.人工合成抗菌藥2_1Sulfisoxazole(SIZ)andsulfamethoxazole(SMZ)SIZandSMZareoftenusedtotreaturinarytractinfections.SMZgiventogetherwithTMP,SMZcoisusedwidelyforrespiratorytractinfections.人工合成抗菌藥2_1SASPitselfisnoantibacterialactivity.Resolvingintosulfapyridine

and5-aminosalicylateinintestinaltractacu