抗寄生虫药(Anti-parasite_drugs)——方三华.ppt

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1、Fang SanhuaAnti-parasite drugs Human parasiteHuman parasiteProtozoa（原虫）：（原虫）：孢孢子虫子虫疟疟原虫原虫 鞭毛虫鞭毛虫阴阴道毛滴虫道毛滴虫 叶足虫叶足虫阿米巴原虫阿米巴原虫 纤纤毛虫毛虫结肠结肠小袋小袋纤纤毛虫毛虫 Helminth（蠕虫）：吸虫（蠕虫）：吸虫血吸虫血吸虫 绦绦虫虫链状带绦链状带绦虫虫 线线虫虫蛔虫、蛔虫、丝丝虫虫Arthropod（节节肢肢动动物）：蛛形物）：蛛形纲纲蜱蜱、螨螨 昆虫昆虫纲纲蚊、蚊、蝇蝇、虱、虱 Antimalarial drugsThe malarial parasite,Plasmo

2、dium,is a very small,The malarial parasite,Plasmodium,is a very small,single-cell organism.single-cell organism.It lives as a parasite in other organisms,namely It lives as a parasite in other organisms,namely man man and mosquitoand mosquito.The parasite is the cause of the tropical or subtropical

3、The parasite is the cause of the tropical or subtropical disease disease malaria.malaria.AntimalarialAntimalarial drugs drugs -Malarial parasite-Malarial parasiteFour species of plasmodium can produce the disease Four species of plasmodium can produce the disease in its various forms:in its various

4、forms:Plasmodium Plasmodium falciparumfalciparum （恶性疟原虫）恶性疟原虫）恶性疟原虫）恶性疟原虫）Plasmodium Plasmodium vivaxvivax （间日疟原虫）间日疟原虫）间日疟原虫）间日疟原虫）Plasmodium Plasmodium ovaleovale （卵形疟原虫）卵形疟原虫）卵形疟原虫）卵形疟原虫）Plasmodium malaria Plasmodium malaria（三日疟原虫）三日疟原虫）三日疟原虫）三日疟原虫）AntimalarialAntimalarial drugs drugs -Parasite L

5、ife Cycle Parasite Life Cycle红细胞外期红细胞内期按蚊有性繁殖人体无性繁殖No one available agent can reliably effect a radical No one available agent can reliably effect a radical cure,cure,ie ie,eliminate both,eliminate both exo-exo-erythrocyticerythrocytic and and erythrocyticerythrocytic stages.stages.Few available age

6、nts are causal prophylactic drugs,Few available agents are causal prophylactic drugs,ie ie,capable of preventing,capable of preventing erythrocyticerythrocytic infection.infection.AntimalarialAntimalarial drugs drugs控制控制复复发Primaquine（伯（伯氨氨喹）迟发病因病因预防防Pyrimethamine（乙（乙胺胺嘧啶）速）速发控制症控制症状状Chloroquine（氯喹）Q

7、uinine（奎宁）（奎宁）Mefloquine（甲（甲氟氟喹）Artemisinin（青青蒿素）蒿素）阻止阻止传播播Pyrimethamine（乙（乙胺胺嘧啶）阻止阻止传播播Primaquine（伯（伯氨氨喹）Chloroquine（氯喹）Quinine （奎宁）（奎宁）（恶性性疟无效）无效）红细胞外期红细胞内期按蚊有性繁殖AntimalarialAntimalarial drugs drugs ChloroquineChloroquine （氯喹氯喹）ChloroquineChloroquine is a synthetic 4-aminoquinoline derivate is a s

8、ynthetic 4-aminoquinoline derivate 控制症状控制症状Chloroquine 氯喹氯喹Quinine 奎宁奎宁Mefloquine 甲氟喹甲氟喹Artemisinin 青蒿素青蒿素红细胞内期Pharmacological effects1.Antimalarial effectsRapid Rapid schizonticidalschizonticidal activity activity（裂殖体杀灭剂）裂殖体杀灭剂）裂殖体杀灭剂）裂殖体杀灭剂）against all infections of malaria speciesagainst all infe

9、ctions of malaria species.Also Also gametocytocidalgametocytocidal（杀配子体）杀配子体）杀配子体）杀配子体）against P.against P.vivaxvivax,P.,P.malariaemalariae and P.and P.ovaleovale.It is not active against It is not active against exo-erythrocyticexo-erythrocytic form,and form,and should therefore be used with should

10、 therefore be used with primaquineprimaquine（伯氨喹）伯氨喹）to effect radical cure of P.to effect radical cure of P.vivaxvivax.AntimalarialAntimalarial drugs drugs -ChloroquineChloroquinePharmacological effects2.Immune inhibitionTreatment of rheumatoid arthritis,lupus erythematosus 3.Extraintestinal amebia

11、sisAmoeba trophozoite amebic liver abscess AntimalarialAntimalarial drugs drugs -ChloroquineChloroquineMechanism of actionsAccumulation in Accumulation in erythrocytepHerythrocytepH malarial malarial pigment synthesis pigment synthesis hemeheme Heme-quinolineHeme-quinoline compound compound hemeheme

12、 accumulate in accumulate in p plasmodiumlasmodium Insert in Insert in the double stranded DNA helix the double stranded DNA helix DNA DNA replication and RNA transcription replication and RNA transcription AntimalarialAntimalarial drugs drugs -ChloroquineChloroquineAdverse effectsRare at the usual

13、Rare at the usual antimalarialantimalarial dosages dosagesPruritusPruritus(瘙痒症瘙痒症瘙痒症瘙痒症)common among dark-skinned common among dark-skinned people.people.Transient headaches,nausea,vomiting,Transient headaches,nausea,vomiting,gastrointestinal symptoms and“blurred vision”.gastrointestinal symptoms an

14、d“blurred vision”.Others:Others:aplasticaplastic blood and neurological disorders,blood and neurological disorders,such as polyneuritis(such as polyneuritis(多发性神经炎多发性神经炎多发性神经炎多发性神经炎),seizures and,seizures and neuromyopathyneuromyopathy.AntimalarialAntimalarial drugs drugs -ChloroquineChloroquine1.Qu

15、inine（奎宁）奎宁）2.Mefloquine（甲氟喹）甲氟喹）3.Pyronaridine (咯萘啶咯萘啶)4.Artemisinin(青蒿素青蒿素)5.Artemether and artesunate (蒿甲醚和青蒿琥酯蒿甲醚和青蒿琥酯)Other Other angentsangents kill kill erythrocyticerythrocytic parasites parasites控制控制复复发Primaquine(伯伯氨氨喹)迟发阻止阻止传播播Primaquine(伯伯氨氨喹)Chloroquine(氯喹)Quinine (奎宁奎宁)（恶性性疟无效）无效）红细胞外期红

16、细胞内期按蚊有性繁殖AntimalarialAntimalarial drugs drugs PrimaquinePrimaquine （伯氨（伯氨（伯氨（伯氨喹喹）Pharmacological effectsHighly active against the gametocytes(Highly active against the gametocytes(配子体配子体配子体配子体)of all of all malaria species malaria species dissemination dissemination Active against Active against h

17、ypnozoiteshypnozoites(迟发型子孢子迟发型子孢子迟发型子孢子迟发型子孢子)of the of the relapsing malarial parasitesrelapsing malarial parasites The only drug currently used for the treatment of The only drug currently used for the treatment of relapsing malariarelapsing malariaAntimalarialAntimalarial drugs drugs PrimaquineP

18、rimaquine （伯氨（伯氨（伯氨（伯氨喹喹）Mechanism of actionsInhibition of coenzyme Q Inhibition of coenzyme Q Inhibition of reduction of NADPInhibition of reduction of NADPAdverse effectsTransient dizziness,nausea,vomiting,Transient dizziness,nausea,vomiting,gastrointestinal symptomsgastrointestinal symptomsAcute

19、hemolytic anemia,Acute hemolytic anemia,methemoglobinemiamethemoglobinemia(高铁高铁高铁高铁血红蛋白血症血红蛋白血症血红蛋白血症血红蛋白血症)AntimalarialAntimalarial drugs drugs PrimaquinePrimaquine （伯氨喹）（伯氨喹）（伯氨喹）（伯氨喹）红细胞外期红细胞内期按蚊有性繁殖AntimalarialAntimalarial drugs drugs PyrimethaminePyrimethamine （乙（乙（乙（乙胺胺胺胺嘧啶嘧啶）病因病因预防防Pyrimetham

20、ine(乙乙胺胺嘧啶)速速发Pyrimethamine(乙乙胺胺嘧啶)Pharmacological effectsPharmacological effectsInhibition of proliferation of Inhibition of proliferation of sporozoitesporozoite(子孢子子孢子子孢子子孢子)to)to schizontschizont(裂殖体裂殖体裂殖体裂殖体)Prophylaxis of infectionsProphylaxis of infectionsMechanism of actionsMechanism of acti

21、onsDihydrofolateDihydrofolate reductasereductase inhibitor inhibitorAdverse effectsAdverse effectsFolateFolate metabolism metabolism disturbtancedisturbtance AntimalarialAntimalarial drugs drugs PyrimethaminePyrimethamine （乙胺（乙胺（乙胺（乙胺嘧啶嘧啶）symptomsymptom？复发？复发？复发？复发？传播？传播？传播？传播？控制症控制症状状Chloroquine（氯喹

22、）Quinine（奎宁）（奎宁）Mefloquine（甲（甲氟氟喹）Artemisinin（青青蒿素）蒿素）病因病因病因病因预预防？防？防？防？控制控制复复发Primaquine（伯（伯氨氨喹）迟发阻止阻止传播播Primaquine（伯（伯氨氨喹）Chloroquine（氯喹）Quinine （奎宁）（奎宁）（恶性性疟无效）无效）病因病因预防防Pyrimethamine(乙乙胺胺嘧啶)速速发阻止阻止传播播Pyrimethamine（乙（乙胺胺嘧啶）用于控制症状的抗疟药 ChloroquineChloroquine （氯喹氯喹氯喹氯喹）、Quinine Quinine（奎宁）、（奎宁）、（奎宁）

23、、（奎宁）、MefloquineMefloquine （甲（甲（甲（甲氟喹氟喹氟喹氟喹）、）、）、）、PyronaridinePyronaridine (咯咯咯咯萘啶萘啶萘啶萘啶)、ArtemisininArtemisinin(青青青青蒿素蒿素蒿素蒿素)、ArtemetherArtemether and and artesunateartesunate(蒿甲蒿甲蒿甲蒿甲醚醚醚醚和和和和青青青青蒿琥蒿琥蒿琥蒿琥酯酯酯酯)用于控制复发和传播的抗疟药 PrimaquinePrimaquine （伯（伯（伯（伯氨喹氨喹氨喹氨喹）用于病因性预防的抗疟药 PyrimethaminePyrimethamin

24、e （乙（乙（乙（乙胺嘧啶胺嘧啶胺嘧啶胺嘧啶）Antiamebiasis drugsAmebiasisAmebiasis is infection with is infection with EntamoebaEntamoeba histolyticahistolytica.（溶组织内阿米巴原虫（溶组织内阿米巴原虫（溶组织内阿米巴原虫（溶组织内阿米巴原虫 ）Classification of Classification of amebiasisamebiasisAsymptomatic intestinal infection;Asymptomatic intestinal infecti

25、on;Mild to moderate colitis;Mild to moderate colitis;Severe intestinal infection(dysentery);Severe intestinal infection(dysentery);ExtraintestinalExtraintestinal infections:infections:amebomaameboma,liver abscess.,liver abscess.Antiamebiasis drugs-AmebiasisAmebiasisAmebiasis is infection with is inf

26、ection with EntamoebaEntamoeba histolyticahistolytica,A tiny,one-celled organism.A tiny,one-celled organism.Antiamebiasis drugs-AmebiasisIntestinal Intestinal AmebiasisAmebiasisExtraintestinalExtraintestinal AmebiasisAmebiasisFeatures of AmebiasisMultiplication and life cycle of Multiplication and l

27、ife cycle of E E histolyticahistolyticaAntiamebiasis drugs-AmebiasisClinical Manifestations Acute or chronic diarrhea,which may progress to Acute or chronic diarrhea,which may progress to dysentery.dysentery.ExtraintestinalExtraintestinal disease may be present as a disease may be present as a compl

28、ication or as a primary problemcomplication or as a primary problem(e.g.,liver,lung or brain abscess,or skin or (e.g.,liver,lung or brain abscess,or skin or perianalperianal infection).infection).Antiamebiasis drugs-AmebiasisAntiamebiasis drugs-MetronidazoleMetronidazole 甲硝唑甲硝唑甲硝唑甲硝唑Pharmacological

29、effects1.Antibiotic effective against anaerobic bacteria.Antibiotic effective against anaerobic bacteria.2.Anti-Anti-giardiagiardia lamblialamblia （贾第氏鞭毛虫）贾第氏鞭毛虫）贾第氏鞭毛虫）贾第氏鞭毛虫）effecteffect3.Anti-ameba effects Anti-ameba effects（肠内、肠外）（肠内、肠外）（肠内、肠外）（肠内、肠外）The treatment of all tissue infections with E

30、 The treatment of all tissue infections with E histolyticahistolytica4.Anti-4.Anti-infusorianinfusorian （滴虫）滴虫）滴虫）滴虫）effectseffectsMechanism of actionsThe methyl group of The methyl group of metronidazolemetronidazole is chemically is chemically reduced in anaerobic bacteria and sensitive reduced in

31、 anaerobic bacteria and sensitive protozoansprotozoans.（原生动物）原生动物）原生动物）原生动物）Reactive reduction products appear to be Reactive reduction products appear to be responsible for antimicrobial activity.responsible for antimicrobial activity.Rapidly absorbed and has a bioavailability of Rapidly absorbed a

32、nd has a bioavailability of approximately 90%approximately 90%Antiamebiasis drugs-MetronidazoleMetronidazoleAdverse effectsSerious side effects of Serious side effects of metronidazolemetronidazole are rare;and are rare;and include seizures and damage of nerves resulting in include seizures and dama

33、ge of nerves resulting in numbness and tingling of extremities(peripheral numbness and tingling of extremities(peripheral neuropathy).neuropathy).Minor side effects include nausea,headaches,loss of Minor side effects include nausea,headaches,loss of appetite,a metallic taste,and rarely a rash.appeti

34、te,a metallic taste,and rarely a rash.Antiamebiasis drugs-MetronidazoleMetronidazoleEmetine依米丁依米丁&dehydroemetine去氢依米丁去氢依米丁AmebicideAmebicide effects:effects:sporadinsporadin(滋养体滋养体滋养体滋养体)Mechanism of actions:Mechanism of actions:protein synthesis inhibitor.protein synthesis inhibitor.Clinic uses:Cli

35、nic uses:Amebic liver abscess,Acute amebic Amebic liver abscess,Acute amebic dysenterydysenteryUsed in case of resistance to Used in case of resistance to metronidazolemetronidazole.Emetine依米丁依米丁&dehydroemetine去氢依米去氢依米丁丁Adverse effectsNausea,vomiting and Nausea,vomiting and diarrhoeadiarrhoea.Palpit

36、ations,tachycardia,Palpitations,tachycardia,retrosternalretrosternal pain,pain,hypotension,hypotension,dyspnoeadyspnoea,ECG changes(ST depression,ECG changes(ST depression,QT prolongation,T-wave inversion).QT prolongation,T-wave inversion).Tremor,myasthenia and paralysis including Tremor,myasthenia

37、and paralysis including respiratory paralysis.respiratory paralysis.Antiamebiasis drugs-Other amebicidesDiloxanideDiloxanide furoatefuroate is slowly absorbed from the is slowly absorbed from the gastrointestinal tract and can therefore provide an gastrointestinal tract and can therefore provide an

38、adequate concentration of the medication in the intestinal adequate concentration of the medication in the intestinal lumen for a long period of time.lumen for a long period of time.Antiamebiasis drugs-DiloxanideDiloxanide 二氯尼特二氯尼特二氯尼特二氯尼特Mechanism of actionsLuminal Luminal amebicideamebicide.Destro

39、ys the Destroys the trophozoitestrophozoites of E.of E.histolyticahistolytica that that eventually form into cysts.(eventually form into cysts.(包囊包囊包囊包囊)The cysts are then excreted by persons infected with The cysts are then excreted by persons infected with asymptomatic asymptomatic amebiasisamebia

40、sis.(.(无症状的阿米巴病无症状的阿米巴病无症状的阿米巴病无症状的阿米巴病)Antiamebiasis drugs-DiloxanideDiloxanideAdverse effectsNot commonly seen with this medication unless the Not commonly seen with this medication unless the patient is taking especially high doses.patient is taking especially high doses.Minor side effects includ

41、e nausea,headaches,and Minor side effects include nausea,headaches,and rarely a rash.rarely a rash.Antiamebiasis drugs-DiloxanideDiloxanideAntiamebiasis drugs-Other amebicidesParomomycin 巴龙霉素巴龙霉素AminoglycosidesAminoglycosides antibiotics.antibiotics.Not significantly absorbed from the gastrointestin

42、al Not significantly absorbed from the gastrointestinal tract tract Mechanism of actions:Mechanism of actions:Acts by inhibition protein synthesis.Acts by inhibition protein synthesis.Direct and indirect action of Direct and indirect action of amebicideamebicideClinical usage:Clinical usage:Amebic A

43、mebic dysentery(dysentery(阿米巴痢疾阿米巴痢疾阿米巴痢疾阿米巴痢疾)No effect against No effect against extraintestinalextraintestinal amebic infections.amebic infections.Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess AntimalarialAntimalarial drugs drugs -ChloroquineChloroquine Anti-bilharziasis&filari

44、asis DrugBilharziasis急性发热过敏反应腹痛、腹泻肝脾肿大Anthelmintic ActionsSchistosomiasisSchistosomiasis(血吸虫病血吸虫病血吸虫病血吸虫病)ClonorchiasisClonorchiasis,OpisthorchiasisOpisthorchiasis(支睾吸虫病支睾吸虫病支睾吸虫病支睾吸虫病),and),and ParagonimiasisParagonimiasis(肺吸虫病肺吸虫病肺吸虫病肺吸虫病)TaeniasisTaeniasis(绦虫病绦虫病绦虫病绦虫病)、DiphyllobothriasisDiphyllo

45、bothriasis(裂头绦虫病）裂头绦虫病）裂头绦虫病）裂头绦虫病）H Nana H Nana（缩小膜壳绦虫）（缩小膜壳绦虫）（缩小膜壳绦虫）（缩小膜壳绦虫）NeurocysticercosisNeurocysticercosis （脑囊虫病）（脑囊虫病）（脑囊虫病）（脑囊虫病）HydatidHydatid Disease Disease（包虫囊病）（包虫囊病）（包虫囊病）（包虫囊病）Other ParasitesOther Parasites：fasciolopsiasisfasciolopsiasis,metagonimiasismetagonimiasis,and,and other

46、forms of other forms of heterophyiasisheterophyiasis.fascioliasisfascioliasis,Praziquantel 吡吡喹酮喹酮Mechanism of actionsIncrease the permeability of cell membranes to Increase the permeability of cell membranes to calcium,resulting in paralysis,dislodgement,and calcium,resulting in paralysis,dislodgeme

47、nt,and death.death.In In schistosomeschistosome infections,infections,praziquantelpraziquantel is effective is effective against adult worms and immature stages against adult worms and immature stages Prophylactic effect against Prophylactic effect against cercarialcercarial （尾蚴）（尾蚴）（尾蚴）（尾蚴）infectio

48、n.infection.Praziquantel 吡吡喹酮喹酮Adverse effectsMost frequent are headache,dizziness,drowsiness,Most frequent are headache,dizziness,drowsiness,and lassitude;and lassitude;Others include nausea,vomiting,abdominal pain,Others include nausea,vomiting,abdominal pain,prurituspruritus,urticariaurticaria,ar

49、thralgiaarthralgia,myalgiamyalgia,and low-,and low-grade fever.grade fever.Mild and transient elevations of liver enzymesMild and transient elevations of liver enzymesPraziquantel 吡吡喹酮喹酮 Filariasis淋巴管炎、淋巴淋巴管炎、淋巴结炎结炎橡皮肿、乳糜尿橡皮肿、乳糜尿Diethylcarbamazine 乙胺嗪乙胺嗪AnthelminticAnthelmintic Actions ActionsDiethy

50、lcarbamazineDiethylcarbamazine immobilizes immobilizes microfilariaemicrofilariae （微丝蚴）微丝蚴）微丝蚴）微丝蚴）and and alters their surface structure,displacing them from tissues and alters their surface structure,displacing them from tissues and making them more susceptible to destruction by host defense makin