《藥理學》英文課件 Chemotherapeutic medicine 5

AntituberculousdrugFirst-lineagents:Isoniazid(INH)RifampinPyrazinamideEthambutol

StreptomycinSecond-lineagents:OfloxacinCiprofloxacinPara-aminosalicylicacidAmikacin

Isoniazid【Antibacterialaction】

IsoniazidhasnarrowantibacterialspectrumItisactiveagainstmycobacteriumtuberculosisItisbacteriostaticinthestationaryphaseitisbactericidalinrapidlydividingorganisms3.Itisabletopenetrateintophagocyticcells

Itinhibitstheenzymeresponsibleforassemblyofmycolicacidsintotheouterlayerofthemycobacteria,【Mechanismofaction

】【Clinicaluses】

Itisusedfortreatmentoflatenttuberculosis.Usuallyitcombinedwithotherdugswasgiventotreattuberculosis.【adverseeffect】

Peripheralneuritis:hand-foottrembling,anesthesia2.Hepatitisandidiosyncratichepatotoxicity:fatalhepatitis3.Otheradverseeffects:mentalabnormalities,seizures,opticneuritis,HypersensitivityreactionsRifampicinRifampinisbactericidalforbothintracellularandextracellular

mycobacteria

Itiseffectiveagainstmanygram(+)andgram(-)organismsRifampinisthemostactiveanti-leprosydrugatpresent.ItblockstranscriptionbyinteractingwithbacterialDNA-dependentRNApolymerase,thusinhibitingRNAsynthesis【ClinicalusesandAdverseeffects】Mycobacterialinfections:

rifampinisadministeredtogetherwithisoniazid,ethambutol,oranotherantituberculousdrug2.Seriousstaphylococcalinfections:

Rifampincombinationtherapyisusefortreatmentofseriousstaphylococcalinfections3.Rifampincausesnausea,vomiting,rash,andfeverAntiviraldrugandantifungalagentSectionIAntiviraldrug一、TreatmentofviralrespiratoryinfectionsAmantadine

RimantadineRibavirin【Antiviralactions】1.Antiviralspectrum:TheyareeffectiveagainstRNAvirusinfluenzaAvirus2.Mechanism:Blocktheviralmembranematrixprotein,M2Interferewiththereleaseofnewvirions

Amantadineandrimantadine【Clinicalusesandadverseeffect

】ItisusedfortreatmentofinfluenzaAinfectionAmantadine:CNSreactioninsomnia,dizziness,ataxia,hallucinations,seizures3.Contraindications:psychiatricproblems,cerebralatherosclerosis,epilepsy;pregnantandnursingmothersRibavirin【Antiviralactions】1.Antiviralspectrum:

RibaviriniseffectiveagainstabroadspectrumofRNAandDNAvirusesRSV,hepatitisAvirus,influenzaAandB2.Mechanism:InhibitingviralmRNAsynthesisRibavirinisusedintreatinginfantsandyoungchildreninfectedwithsevereRSV.ItisalsousedtotreatacutehepatitisAvirusandinfluenzaAandBinfections.RibavirinmayreducethemortalityandviremiaofLassafever.【Clinicaluses

】【Adverseeffect】Transientanemia,elevatedbilirubin.Ribaviriniscontraindicatedinpregnancy二、TreatmentofherpesvirusinfectionsAcyclovirGanciclovir

Acyclovir【Antiviralactionsandclinicaluses】1.AntiviralspectrumAcycloviriseffectiveagainstDNAvirusherpesviruses:herpessimplexvirus-1(HSV-1),HSV-2,varicella-zostervirusandEpstein-Barrvirus,butCMVisresistant2.Acycloviristhetreatmentofchoiceinherpessimplexencephalitis,genitalherpesinfections.【Mechanismofaction】

Acyclovirmonophosphatederivative

InhibitviralDNApolymeraseinhibitsviralDNAsynthesisincorporateintotheviralDNAthymidine

kinase

Acyclovirtriphosphate

host’scelluarenzymes

【Adverseeffect】1.Topicalapplication:

localirritation2.Oraladministration:headache,diarrhea,nausea,andvomiting3.Intravenousinfusion:

phlebitis,transientrenaldysfunction三、TreatmentforAIDSZidovudineDidanosineZalcitabineStavudineLamivudine

ZidovudineZidovudineisaantiretroviralagentsItactbycompetitiveinhibitionofHIV-1reversetranscriptaseandcanalsobeincorporatedintothegrowingviralDNAchaintocausetermination.ItisusedfortreatmentofpatientsinfectedwithHIVAdverseeffectismyelosuppression,gastrointestinalintolerance,headaches,andinsomnia【Features】四、Interferon【Features】Actions:antiviral,immunomodulatory,andantiproliferativeactivitiesUses:treatmentofbothHBVandHCVvirusinfectionsAdverseeffects:fever,lethargy,bonemarrowdepression,cardiovascularproblemsandacutehypersensitivityreactionsSectionIIAntifungalAgentSystemicantifungaldrugsforsystemicinfectionsTopicalantifungaldrugsformucocutaneousinfections一、SystemicantifungaldrugsforsystemicinfectionsAmphotericinBFlucytosine

Ketoconazole

AmphotericinBAntifungalspectrum:

ItiseitherfungistaticorfungicidalItiseffectiveagainstawiderangeoffungi

candida

albicans,Histoplasma

capsulatum,

cryptococcus

neoformans2.Modeofaction:bindtoergosterolincellmembranestoformporesorchannels【Antifungalactions】【Clinicaluses】

Itisoftenusedastheinitialinductionregimenforseriousfungalinfectionsandisthenreplacedbyoneofthenewerazoledrugsforchronictherapyorpreventionofrelapse.【Adverseeffect】Feverandchills,Renalimpairment,Hypotension,Anemia,Neurologicaleffects,ThrombophlebitisFlucytosine

Antifungalspectrum:

FlucytosineisfungistaticandeffectiveagainstCandidamonilia,andCryptococcus.2.Modeofaction:5-FCisconvertedto5-FdUMP,inhibits

thymidylate

synthetase,thusdisruptnucleicacidandproteinsynthesis【Antifungalactions】【Clinicaluses】FlucytosineisusedonlyincombinationwithamphotericinforthetreatmentofsystemicmycosesandmeningitiscausedbyCryptococcusneoformansandCandida.【Adverseeffect】Hematologictoxicity,Hepaticdysfunction,GastrointestinaldisturbancesKetoconazole

【Antifungalactions】Antifungalspectrum:

KetoconazoleiseitherfungistaticorfungicidalItisactiveagainstthe

samefungiasamphotericin

B2.Modeofaction:

Ketoconazoleblocksergosterolsynthesis,increasespermeabilityofcellmembrane【Clinicaluses】

Ketoconazoleismostusefulinthetreatmentofhistoplasmosis,blastomycosis,Candida,andvariousdermatophyticinfections【Adverseeffect】Gastrointestinaldistress,Endocrineeffects,HepaticdysfunctionContraindications:KetoconazoleandamphotericinBshouldnotbeusedtogether.二、DrugsforsuperficialmycosesGriseofulvin

Antifungalspectrum:

griseofulvinisprincipallyfungistaticItiseffectiveonlyagainstthedermatophytes--Trichophyton,Microsporum,andEpidermophyton2.Modeofaction:interactwiththemicrotubulestodisruptthemitoticspindleandinhibitmitosis.【Antifungalactions】【Clinicaluses】Itisusedinthetreatmentofseveretineainfectionsthatdonotrespondtootherantifungalagents.Therapymustbecontinueduntilnormaltissuereplacesinfectedtissue.【Adverseeffect】Allergicreactions,headache,nausea,hepatotoxicity

Summaryofantibacterialdrugsβ–LactamMacrolidesLincosamidesPolypeptidesAminoglycosidesTetracyclinesChloramphenicol

SynthesisantibacterialdrugsClassificationofantibacterialdrugsQuinolonesSulfonamidesAntibioticsβ–Lactamantibacterialdrugs

Penicillins

PenicillinGPenicillinase-resistantpenicillin(Oxacillin)Extendedspectrumpenicillins

(Ampicillin,Amoxicillin)Antipseudomonal

penicillins(Carbenicillin,Piperacillin)PenicillinGGram-positivecoccusGram-negativecoccusGram-positivebacilliHelicoidsPenicillinase-resistantpenicillin(Oxacillin)(1)Theykillpenicillinase-producingstaphylococci(2)Theycan’tkillMethicillin-resistantstrainsofStaphylococcusaureus(MRSA)VancomycinExtendedspectrumpenicillins(Ampicillin,Amoxicillin

)Theyaremoreeffectiveagainstgram-negativebacilliTheycannotkillpseudomonasaeruginosaAntipseudomonal

penicillinsCarbenicillinPiperacillinCephalosporinsFeature＋＋＋

First

Second

ThirdG＋＋＋＋＋＋＋G－＋＋＋＋＋＋Pseudomonasaeruginosa－－＋anaerobes－＋＋nephrotoxic＋＋＋－MacrolidesBacteriostaticAntibacterialspectrummostG+afewG-Mycoplasma

Chlamydia

Legionella

G+infectionLegionellamycoplasma

ChlamydiapneumoniaAminoglycosidesBactericidalAntibacterialspectrumTheyareeffectiveagainstaerobicgram-negativebacilliTheyareineffectiveagainstanaerobicorganismsTetracyclineandChloramphenicolantibacterialdrugsTetracyclinesChloramphenicolBacteriostatic??G＋+++++G－+++++anaerobes+++mycoplasma??spirochete??Rickettsia??SynthesisantibacterialdrugsBactericidalAntibacterialspectrumFirstgeneration:someG-Secondgeneration:MoreG-Third:G+,chlamydia,mycoplasma,LegionellaandBacillustuberculosisThefourth:anaerobicbacteriumQuinolonesSulfonamidesantibacterialdrugseffectiveagainstG＋

andG－effectiveagainstChlamydiaineffectiveagainstmycoplasma,

Rickettsiaandhelicoid

BacteriostaticAntibacterialspectrumMechanismofactionQuinolonesTetracyclinesAminoglycosides

Macrolides

ChloramphenicolLincomycinPolymyxinPolyenesAzoles

-lactamVancomycinDNAPlasmamembraneCellwallPABADHFATHFA50S50S50S30S30S30SmRNARifampinTMPSulfonamides