抗寄生虫药Antiparasitedrugs的学习教案

抗寄生虫药Antiparasitedrugs的学习教案第1页/共55页HumanparasiteProtozoa（原虫）：孢子虫－疟原虫鞭毛虫－阴道毛滴虫叶足虫－阿米巴原虫纤毛虫－结肠小袋纤毛虫Helminth（蠕虫）：吸虫－血吸虫绦虫－链状带绦虫线虫－蛔虫、丝虫Arthropod（节肢动物）：蛛形纲－蜱、螨昆虫纲－蚊、蝇、虱第2页/共55页

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

-Malarialparasite第4页/共55页第5页/共55页Fourspeciesofplasmodiumcanproducethediseaseinitsvariousforms:Plasmodiumfalciparum（恶性疟原虫）Plasmodiumvivax（间日疟原虫）Plasmodiumovale（卵形疟原虫）Plasmodiummalaria（三日疟原虫）第6页/共55页Antimalarialdrugs

-ParasiteLifeCycle红细胞外期红细胞内期按蚊－有性繁殖人体－无性繁殖第7页/共55页Nooneavailableagentcanreliablyeffectaradicalcure,ie,eliminatebothexo-erythrocyticanderythrocyticstages.Fewavailableagentsarecausalprophylacticdrugs,ie,capableofpreventingerythrocyticinfection.Antimalarialdrugs第8页/共55页控制复发Primaquine（伯氨喹）迟发病因预防Pyrimethamine（乙胺嘧啶）速发控制症状Chloroquine（氯喹）Quinine（奎宁）Mefloquine（甲氟喹）Artemisinin（青蒿素）阻止传播Pyrimethamine（乙胺嘧啶）阻止传播Primaquine（伯氨喹）Chloroquine（氯喹）Quinine（奎宁）（恶性疟无效）红细胞外期红细胞内期按蚊－有性繁殖第9页/共55页Antimalarialdrugs

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Chloroquine（氯喹）Chloroquineisasynthetic4-aminoquinolinederivate控制症状Chloroquine氯喹Quinine奎宁Mefloquine甲氟喹Artemisinin青蒿素红细胞内期第10页/共55页Pharmacologicaleffects1.AntimalarialeffectsRapidschizonticidalactivity（裂殖体杀灭剂）

againstallinfectionsofmalariaspecies

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

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

Antimalarialdrugs

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

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Chloroquine第13页/共55页AdverseeffectsRareattheusualantimalarialdosagesPruritus(瘙痒症)

commonamongdark-skinnedpeople.Transientheadaches,nausea,vomiting,gastrointestinalsymptomsand“blurredvision”.Others:aplasticbloodandneurologicaldisorders,suchaspolyneuritis(多发性神经炎),seizuresandneuromyopathy.Antimalarialdrugs

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

Otherangentskillerythrocyticparasites第15页/共55页控制复发Primaquine(伯氨喹)迟发阻止传播Primaquine(伯氨喹)Chloroquine(氯喹)Quinine(奎宁)（恶性疟无效）红细胞外期红细胞内期按蚊－有性繁殖Antimalarialdrugs

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Primaquine（伯氨喹）第16页/共55页PharmacologicaleffectsHighlyactiveagainstthegametocytes(配子体)

ofallmalariaspecies→dissemination↓Activeagainsthypnozoites(迟发型子孢子)oftherelapsingmalarialparasites

TheonlydrugcurrentlyusedforthetreatmentofrelapsingmalariaAntimalarialdrugs

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Primaquine（伯氨喹）第17页/共55页MechanismofactionsInhibitionofcoenzymeQInhibitionofreductionofNADPAdverseeffectsTransientdizziness,nausea,vomiting,gastrointestinalsymptomsAcutehemolyticanemia,methemoglobinemia(高铁血红蛋白血症)

Antimalarialdrugs

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Primaquine（伯氨喹）第18页/共55页红细胞外期红细胞内期按蚊－有性繁殖Antimalarialdrugs

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Pyrimethamine（乙胺嘧啶）病因预防Pyrimethamine(乙胺嘧啶)速发Pyrimethamine(乙胺嘧啶)第19页/共55页PharmacologicaleffectsInhibitionofproliferationofsporozoite(子孢子)toschizont(裂殖体)ProphylaxisofinfectionsMechanismofactionsDihydrofolatereductaseinhibitorAdverseeffectsFolatemetabolismdisturbtanceAntimalarialdrugs

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Pyrimethamine（乙胺嘧啶）第20页/共55页symptom？第21页/共55页复发？传播？控制症状Chloroquine（氯喹）Quinine（奎宁）Mefloquine（甲氟喹）Artemisinin（青蒿素）第22页/共55页病因预防？控制复发Primaquine（伯氨喹）迟发阻止传播Primaquine（伯氨喹）Chloroquine（氯喹）Quinine（奎宁）（恶性疟无效）第23页/共55页病因预防Pyrimethamine(乙胺嘧啶)速发阻止传播Pyrimethamine（乙胺嘧啶）第24页/共55页用于控制症状的抗疟药

Chloroquine（氯喹）、Quinine（奎宁）、

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

Artemetherandartesunate(蒿甲醚和青蒿琥酯)用于控制复发和传播的抗疟药

Primaquine（伯氨喹）用于病因性预防的抗疟药

Pyrimethamine（乙胺嘧啶）第25页/共55页

Antiamebiasisdrugs第26页/共55页AmebiasisisinfectionwithEntamoebahistolytica.（溶组织内阿米巴原虫）ClassificationofamebiasisAsymptomaticintestinalinfection;Mildtomoderatecolitis;Severeintestinalinfection(dysentery);Extraintestinalinfections:ameboma,liverabscess.Antiamebiasisdrugs

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

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

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

-Amebiasis第31页/共55页Antiamebiasisdrugs

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Metronidazole甲硝唑PharmacologicaleffectsAntibioticeffectiveagainstanaerobicbacteria.Anti-giardialamblia（贾第氏鞭毛虫）effectAnti-amebaeffects（肠内、肠外）

ThetreatmentofalltissueinfectionswithEhistolytica4.Anti-infusorian（滴虫）effects第32页/共55页MechanismofactionsThemethylgroupofmetronidazoleischemicallyreducedinanaerobicbacteriaandsensitiveprotozoans.（原生动物）Reactivereductionproductsappeartoberesponsibleforantimicrobialactivity.Rapidlyabsorbedandhasabioavailabilityofapproximately90%Antiamebiasisdrugs

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

Minorsideeffectsincludenausea,headaches,lossofappetite,ametallictaste,andrarelyarash.Antiamebiasisdrugs

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Metronidazole第34页/共55页Emetine依米丁&dehydroemetine去氢依米丁Amebicideeffects:sporadin(滋养体)Mechanismofactions:proteinsynthesisinhibitor.Clinicuses:

Amebicliverabscess,AcuteamebicdysenteryUsedincaseofresistancetometronidazole.

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

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Otheramebicides第36页/共55页Diloxanidefuroateisslowlyabsorbedfromthegastrointestinaltractandcanthereforeprovideanadequateconcentrationofthemedicationintheintestinallumenforalongperiodoftime.

Antiamebiasisdrugs

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Diloxanide二氯尼特第37页/共55页MechanismofactionsLuminalamebicide.DestroysthetrophozoitesofE.histolyticathateventuallyformintocysts.(包囊)Thecystsarethenexcretedbypersonsinfectedwithasymptomaticamebiasis.(无症状的阿米巴病)Antiamebiasisdrugs

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

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Diloxanide第39页/共55页Antiamebiasisdrugs

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OtheramebicidesParomomycin巴龙霉素Aminoglycosidesantibiotics.NotsignificantlyabsorbedfromthegastrointestinaltractMechanismofactions:

Actsbyinhibitionproteinsynthesis.DirectandindirectactionofamebicideClinicalusage:

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

Antimalarialdrugs

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Chloroquine第41页/共55页

Anti-bilharziasis&filariasisDrug第42页/共55页Bilharziasis急性发热过敏反应腹痛、腹泻肝脾肿大第43页/共55页AnthelminticActionsSchistosomiasis(血吸虫病)Clonorchiasis,Opisthorchiasis(支睾吸虫病),andParagonimiasis(肺吸虫病)Taeniasis(绦虫病)、Diphyllobothriasis(裂头绦虫病）

HNana（缩小膜壳绦虫）Neurocysticercosis（脑囊虫病）HydatidDisease（包虫囊病）OtherParasites：fasciolopsiasis,metagonimiasis,andotherformsofheterophyiasis.fascioliasis,Praziquantel吡喹酮第44页/共55页MechanismofactionsIncreasethepermeabilityofcellmembranestocalcium,resultinginparalysis,dislodgement,anddeath.Inschistosomeinfections,praziquanteliseffectiveagainstadultwormsandimmaturestagesProphylacticeffectagainstcercarial（尾蚴）infection.Praziquantel吡喹酮第45页/共55页AdverseeffectsMostfrequentareheadache,dizziness,drowsiness,andlassitude;Othersincludenausea,vomiting,abdominalpain,pruritus,urticaria,arthralgia,myalgia,andlow-gradefever.MildandtransientelevationsofliverenzymesPraziquantel吡喹酮第46页/共55页Filariasis淋巴管炎、淋巴结炎橡皮肿、乳糜尿第47页/共55页Diethylcarbamazine乙胺嗪AnthelminticActionsDiethylcarbamazineimmobilizesmicrofilariae（微丝蚴）andalterstheirsurfacestructure,displacingthemfromtissuesandmakingthemmoresusceptibletodestructionbyhostdefensemechanisms.ClinicalUsesWuchereriaBancrofti,BrugiaMalayi,BrugiaTimori,andLoaLoaAdverseeffectsGenerallymildandtransientIncludeheadache,malaise,anorexia,weakness,nausea,vomiting,anddizziness.第48页/共55页