抗寄生蟲藥Antiparasitedrugs的學習教案

抗寄生蟲藥Antiparasitedrugs的學習教案第1頁/共55頁HumanparasiteProtozoa（原蟲）：孢子蟲－瘧原蟲鞭毛蟲－陰道毛滴蟲葉足蟲－阿米巴原蟲纖毛蟲－結腸小袋纖毛蟲Helminth（蠕蟲）：吸蟲－血吸蟲絳蟲－鏈狀帶絳蟲線蟲－蛔蟲、絲蟲Arthropod（節(jié)肢動物）：蛛形綱－蜱、螨昆蟲綱－蚊、蠅、虱第2頁/共55頁

Antimalarialdrugs第3頁/共55頁Themalarialparasite,Plasmodium,isaverysmall,single-cellorganism.Itlivesasaparasiteinotherorganisms,namelymanandmosquito.Theparasiteisthecauseofthetropicalorsubtropicaldiseasemalaria.Antimalarialdrugs

-Malarialparasite第4頁/共55頁第5頁/共55頁Fourspeciesofplasmodiumcanproducethediseaseinitsvariousforms:Plasmodiumfalciparum（惡性瘧原蟲）Plasmodiumvivax（間日瘧原蟲）Plasmodiumovale（卵形瘧原蟲）Plasmodiummalaria（三日瘧原蟲）第6頁/共55頁Antimalarialdrugs

-ParasiteLifeCycle紅細胞外期紅細胞內期按蚊－有性繁殖人體－無性繁殖第7頁/共55頁Nooneavailableagentcanreliablyeffectaradicalcure,ie,eliminatebothexo-erythrocyticanderythrocyticstages.Fewavailableagentsarecausalprophylacticdrugs,ie,capableofpreventingerythrocyticinfection.Antimalarialdrugs第8頁/共55頁控制復發(fā)Primaquine（伯氨喹）遲發(fā)病因預防Pyrimethamine（乙胺嘧啶）速發(fā)控制癥狀Chloroquine（氯喹）Quinine（奎寧）Mefloquine（甲氟喹）Artemisinin（青蒿素）阻止傳播Pyrimethamine（乙胺嘧啶）阻止傳播Primaquine（伯氨喹）Chloroquine（氯喹）Quinine（奎寧）（惡性瘧無效）紅細胞外期紅細胞內期按蚊－有性繁殖第9頁/共55頁Antimalarialdrugs

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Chloroquine（氯喹）Chloroquineisasynthetic4-aminoquinolinederivate控制癥狀Chloroquine氯喹Quinine奎寧Mefloquine甲氟喹Artemisinin青蒿素紅細胞內期第10頁/共55頁Pharmacologicaleffects1.AntimalarialeffectsRapidschizonticidalactivity（裂殖體殺滅劑）

againstallinfectionsofmalariaspecies

.Alsogametocytocidal（殺配子體）againstP.vivax,P.malariaeandP.ovale.Itisnotactiveagainstexo-erythrocyticform,andshouldthereforebeusedwithprimaquine（伯氨喹）toeffectradicalcureofP.vivax.Antimalarialdrugs

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Chloroquine第11頁/共55頁Pharmacologicaleffects2.ImmuneinhibitionTreatmentofrheumatoidarthritis,lupuserythematosus3.ExtraintestinalamebiasisAmoebatrophozoiteamebicliverabscess

Antimalarialdrugs

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Chloroquine第12頁/共55頁MechanismofactionsAccumulationinerythrocyte→pH↑→malarialpigmentsynthesis↓→heme↑Heme-quinolinecompound→hemeaccumulateinplasmodium↑InsertinthedoublestrandedDNAhelix→DNAreplicationandRNAtranscription↓Antimalarialdrugs

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Chloroquine第13頁/共55頁AdverseeffectsRareattheusualantimalarialdosagesPruritus(瘙癢癥)

commonamongdark-skinnedpeople.Transientheadaches,nausea,vomiting,gastrointestinalsymptomsand“blurredvision”.Others:aplasticbloodandneurologicaldisorders,suchaspolyneuritis(多發(fā)性神經炎),seizuresandneuromyopathy.Antimalarialdrugs

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Chloroquine第14頁/共55頁Quinine（奎寧）Mefloquine（甲氟喹）Pyronaridine(咯萘啶)Artemisinin(青蒿素)Artemetherandartesunate(蒿甲醚和青蒿琥酯)

Otherangentskillerythrocyticparasites第15頁/共55頁控制復發(fā)Primaquine(伯氨喹)遲發(fā)阻止傳播Primaquine(伯氨喹)Chloroquine(氯喹)Quinine(奎寧)（惡性瘧無效）紅細胞外期紅細胞內期按蚊－有性繁殖Antimalarialdrugs

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Primaquine（伯氨喹）第16頁/共55頁PharmacologicaleffectsHighlyactiveagainstthegametocytes(配子體)

ofallmalariaspecies→dissemination↓Activeagainsthypnozoites(遲發(fā)型子孢子)oftherelapsingmalarialparasites

TheonlydrugcurrentlyusedforthetreatmentofrelapsingmalariaAntimalarialdrugs

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Primaquine（伯氨喹）第17頁/共55頁MechanismofactionsInhibitionofcoenzymeQInhibitionofreductionofNADPAdverseeffectsTransientdizziness,nausea,vomiting,gastrointestinalsymptomsAcutehemolyticanemia,methemoglobinemia(高鐵血紅蛋白血癥)

Antimalarialdrugs

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Primaquine（伯氨喹）第18頁/共55頁紅細胞外期紅細胞內期按蚊－有性繁殖Antimalarialdrugs

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Pyrimethamine（乙胺嘧啶）病因預防Pyrimethamine(乙胺嘧啶)速發(fā)Pyrimethamine(乙胺嘧啶)第19頁/共55頁PharmacologicaleffectsInhibitionofproliferationofsporozoite(子孢子)toschizont(裂殖體)ProphylaxisofinfectionsMechanismofactionsDihydrofolatereductaseinhibitorAdverseeffectsFolatemetabolismdisturbtanceAntimalarialdrugs

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Pyrimethamine（乙胺嘧啶）第20頁/共55頁symptom？第21頁/共55頁復發(fā)？傳播？控制癥狀Chloroquine（氯喹）Quinine（奎寧）Mefloquine（甲氟喹）Artemisinin（青蒿素）第22頁/共55頁病因預防？控制復發(fā)Primaquine（伯氨喹）遲發(fā)阻止傳播Primaquine（伯氨喹）Chloroquine（氯喹）Quinine（奎寧）（惡性瘧無效）第23頁/共55頁病因預防Pyrimethamine(乙胺嘧啶)速發(fā)阻止傳播Pyrimethamine（乙胺嘧啶）第24頁/共55頁用于控制癥狀的抗瘧藥

Chloroquine（氯喹）、Quinine（奎寧）、

Mefloquine（甲氟喹）、Pyronaridine(咯萘啶)、Artemisinin(青蒿素)、

Artemetherandartesunate(蒿甲醚和青蒿琥酯)用于控制復發(fā)和傳播的抗瘧藥

Primaquine（伯氨喹）用于病因性預防的抗瘧藥

Pyrimethamine（乙胺嘧啶）第25頁/共55頁

Antiamebiasisdrugs第26頁/共55頁AmebiasisisinfectionwithEntamoebahistolytica.（溶組織內阿米巴原蟲）ClassificationofamebiasisAsymptomaticintestinalinfection;Mildtomoderatecolitis;Severeintestinalinfection(dysentery);Extraintestinalinfections:ameboma,liverabscess.Antiamebiasisdrugs

-Amebiasis第27頁/共55頁AmebiasisisinfectionwithEntamoebahistolytica,Atiny,one-celledorganism.Antiamebiasisdrugs

-Amebiasis第28頁/共55頁IntestinalAmebiasisExtraintestinalAmebiasisFeaturesofAmebiasis第29頁/共55頁MultiplicationandlifecycleofEhistolyticaAntiamebiasisdrugs

-Amebiasis第30頁/共55頁ClinicalManifestationsAcuteorchronicdiarrhea,whichmayprogresstodysentery.Extraintestinaldiseasemaybepresentasacomplicationorasaprimaryproblem(e.g.,liver,lungorbrainabscess,orskinorperianalinfection).Antiamebiasisdrugs

-Amebiasis第31頁/共55頁Antiamebiasisdrugs

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Metronidazole甲硝唑PharmacologicaleffectsAntibioticeffectiveagainstanaerobicbacteria.Anti-giardialamblia（賈第氏鞭毛蟲）effectAnti-amebaeffects（腸內、腸外）

ThetreatmentofalltissueinfectionswithEhistolytica4.Anti-infusorian（滴蟲）effects第32頁/共55頁MechanismofactionsThemethylgroupofmetronidazoleischemicallyreducedinanaerobicbacteriaandsensitiveprotozoans.（原生動物）Reactivereductionproductsappeartoberesponsibleforantimicrobialactivity.Rapidlyabsorbedandhasabioavailabilityofapproximately90%Antiamebiasisdrugs

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Metronidazole第33頁/共55頁AdverseeffectsSerioussideeffectsofmetronidazolearerare;andincludeseizuresanddamageofnervesresultinginnumbnessandtinglingofextremities(peripheralneuropathy).

Minorsideeffectsincludenausea,headaches,lossofappetite,ametallictaste,andrarelyarash.Antiamebiasisdrugs

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Metronidazole第34頁/共55頁Emetine依米丁&dehydroemetine去氫依米丁Amebicideeffects:sporadin(滋養(yǎng)體)Mechanismofactions:proteinsynthesisinhibitor.Clinicuses:

Amebicliverabscess,AcuteamebicdysenteryUsedincaseofresistancetometronidazole.

第35頁/共55頁Emetine依米丁&dehydroemetine去氫依米丁AdverseeffectsNausea,vomitinganddiarrhoea.Palpitations,tachycardia,retrosternalpain,hypotension,dyspnoea,ECGchanges(STdepression,QTprolongation,T-waveinversion).Tremor,myastheniaandparalysisincludingrespiratoryparalysis.Antiamebiasisdrugs

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Otheramebicides第36頁/共55頁Diloxanidefuroateisslowlyabsorbedfromthegastrointestinaltractandcanthereforeprovideanadequateconcentrationofthemedicationintheintestinallumenforalongperiodoftime.

Antiamebiasisdrugs

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Diloxanide二氯尼特第37頁/共55頁MechanismofactionsLuminalamebicide.DestroysthetrophozoitesofE.histolyticathateventuallyformintocysts.(包囊)Thecystsarethenexcretedbypersonsinfectedwithasymptomaticamebiasis.(無癥狀的阿米巴病)Antiamebiasisdrugs

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Diloxanide第38頁/共55頁AdverseeffectsNotcommonlyseenwiththismedicationunlessthepatientistakingespeciallyhighdoses.Minorsideeffectsincludenausea,headaches,andrarelyarash.Antiamebiasisdrugs

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Diloxanide第39頁/共55頁Antiamebiasisdrugs

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OtheramebicidesParomomycin巴龍霉素Aminoglycosidesantibiotics.NotsignificantlyabsorbedfromthegastrointestinaltractMechanismofactions:

Actsbyinhibitionproteinsynthesis.DirectandindirectactionofamebicideClinicalusage:

Amebicdysentery(阿米巴痢疾)Noeffectagainstextraintestinalamebicinfections.第40頁/共55頁ExtraintestinalamebiasisAmoebatrophozoiteamebicliverabscess

Antimalarialdrugs

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Chloroquine第41頁/共55頁

Anti-bilharziasis&filariasisDrug第42頁/共55頁Bilharziasis急性發(fā)熱過敏反應腹痛、腹瀉肝脾腫大第43頁/共55頁AnthelminticActionsSchistosomiasis(血吸蟲病)Clonorchiasis,Opisthorchiasis(支睪吸蟲病),andParagonimiasis(肺吸蟲病)Taeniasis(絳蟲病)、Diphyllobothriasis(裂頭絳蟲病）

HNana（縮小膜殼絳蟲）Neurocysticercosis（腦囊蟲?。〩ydatidDisease（包蟲囊病）OtherParasites：fasciolopsiasis,metagonimiasis,andotherformsofheterophyiasis.fascioliasis,Praziquantel吡喹酮第44頁/共55頁MechanismofactionsIncreasethepermeabilityofcellmembranestocalcium,resultinginparalysis,dislodgement,anddeath.Inschistosomeinfections,praziquanteliseffectiveagainstadultwormsandimmaturestagesProphylacticeffectagainstcercarial（尾蚴）infection.Praziquantel吡喹酮第45頁/共55頁AdverseeffectsMostfrequentareheadache,dizziness,drowsiness,andlassitude;Othersincludenausea,vomiting,abdominalpain,pruritus,urticaria,arthralgia,myalgia,andlow-gradefever.MildandtransientelevationsofliverenzymesPraziquantel吡喹酮第46頁/共55頁Filariasis淋巴管炎、淋巴結炎橡皮腫、乳糜尿第47頁/共55頁Diethylcarbamazine乙胺嗪AnthelminticActionsDiethylcarbamazineimmobilizesmicrofilariae（微絲蚴）andalterstheirsurfacestructure,displacingthemfromtissuesandmakingthemmoresusceptibletodestructionbyhostdefensemechanisms.ClinicalUsesWuchereriaBancrofti,BrugiaMalayi,BrugiaTimori,andLoaLoaAdverseeffectsGenerallymildandtransientIncludeheadache,malaise,anorexia,weakness,nausea,vomiting,anddizziness.第48頁/共55頁