抗寄生虫药Antiparasitedrugs——方三华.ppt

Fang SanhuaAnti-parasite drugs 1.Human parasiteProtozoa（原虫）：（原虫）：孢子虫子虫疟原虫原虫 鞭毛虫阴道毛滴虫鞭毛虫阴道毛滴虫 叶足虫叶足虫阿米巴原虫阿米巴原虫 纤毛虫毛虫结肠小袋小袋纤毛虫毛虫 Helminth（蠕虫）：吸虫（蠕虫）：吸虫血吸虫血吸虫 绦虫虫链状状带绦虫虫 线虫虫蛔虫、蛔虫、丝虫虫Arthropod（节肢肢动物）：蛛形物）：蛛形纲蜱、蜱、螨 昆虫昆虫纲蚊、蚊、蝇、虱、虱2.Antimalarial drugs3.The malarial parasite,Plasmodium,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 The parasite is the cause of the tropical or subtropical disease disease malaria.malaria.Antimalarial drugs Antimalarial drugs-Malarial parasite-Malarial parasite4.5.Four species of plasmodium can produce the disease Four species of plasmodium can produce the disease in its various forms:in its various forms:Plasmodium falciparum Plasmodium falciparum（恶恶性性性性疟疟原虫）原虫）原虫）原虫）Plasmodium vivax Plasmodium vivax（间间日日日日疟疟原虫）原虫）原虫）原虫）Plasmodium ovale Plasmodium ovale（卵形卵形卵形卵形疟疟原虫）原虫）原虫）原虫）Plasmodium malaria Plasmodium malaria（三日三日三日三日疟疟原虫）原虫）原虫）原虫）6.Antimalarial drugs Antimalarial drugs-Parasite Life 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7.No one available agent can reliably effect a radical No one available agent can reliably effect a radical cure,ie,eliminate both exo-cure,ie,eliminate both exo-erythrocyticerythrocytic and and erythrocytic stages.erythrocytic stages.Few available agents are causal prophylactic drugs,Few available agents are causal prophylactic drugs,ie,capable of preventing erythrocytic infection.ie,capable of preventing erythrocytic infection.Antimalarial drugsAntimalarial drugs8.控制复控制复发Primaquine（伯氨（伯氨喹）迟发病因病因预防防Pyrimethamine（乙胺（乙胺嘧啶）速）速发控制症状控制症状Chloroquine（氯喹）Quinine（奎宁）（奎宁）Mefloquine（甲氟（甲氟喹）Artemisinin（青蒿素）（青蒿素）阻止阻止传播播Pyrimethamine（乙胺（乙胺嘧啶）阻止阻止传播播Primaquine（伯氨（伯氨喹）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9.Antimalarial drugs Antimalarial drugs Chloroquine Chloroquine（氯喹氯喹）Chloroquine is a synthetic 4-aminoquinoline derivate Chloroquine is a synthetic 4-aminoquinoline derivate 控制症状控制症状Chloroquine 氯喹Quinine 奎宁奎宁Mefloquine 甲氟甲氟喹Artemisinin 青蒿素青蒿素红细胞内期10.Pharmacological effects1.Antimalarial effectsRapid schizonticidal activity Rapid schizonticidal activity（裂殖体裂殖体裂殖体裂殖体杀灭剂杀灭剂）against all infections of malaria speciesagainst all infections of malaria species.Also gametocytocidalAlso gametocytocidal（杀杀配子体）配子体）配子体）配子体）against P.against P.vivax,P.malariae and P.ovale.vivax,P.malariae and P.ovale.It is not active against exo-erythrocytic form,and It is not active against exo-erythrocytic form,and should therefore be used with primaquineshould therefore be used with primaquine（伯氨伯氨喹喹）to effect radical cure of P.vivax.to effect radical cure of P.vivax.Antimalarial drugs Antimalarial drugs-ChloroquineChloroquine11.Pharmacological effects2.Immune inhibitionTreatment of rheumatoid arthritis,lupus erythematosus 3.Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugs Antimalarial drugs-ChloroquineChloroquine12.Mechanism of actionsAccumulation in erythrocytepH malarial Accumulation in erythrocytepH malarial pigment synthesis hemepigment synthesis hemeHeme-quinoline compound heme accumulate in Heme-quinoline compound heme 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 Antimalarial drugs Antimalarial drugs-ChloroquineChloroquine13.Adverse effectsRare at the usual antimalarial dosagesRare at the usual antimalarial dosagesPruritus(Pruritus(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 and“blurred vision”.Others:aplastic blood and neurological disorders,Others:aplastic blood and neurological disorders,such as polyneuritis(such as polyneuritis(多多多多发发性神性神性神性神经经炎炎炎炎),seizures and,seizures and neuromyopathy.neuromyopathy.Antimalarial drugs Antimalarial drugs-ChloroquineChloroquine14.1.Quinine（奎宁）奎宁）2.Mefloquine（甲氟甲氟喹）3.Pyronaridine (咯咯萘啶)4.Artemisinin(青蒿素青蒿素)5.Artemether and artesunate (蒿甲蒿甲醚和青蒿琥和青蒿琥酯)Other angents kill erythrocytic parasitesOther angents kill erythrocytic parasites15.控制复控制复发Primaquine(伯氨伯氨喹)迟发阻止阻止传播播Primaquine(伯氨伯氨喹)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Antimalarial drugs Antimalarial drugs Primaquine Primaquine（伯氨（伯氨（伯氨（伯氨喹喹）16.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 hypnozoites(Active against hypnozoites(迟发迟发型子型子型子型子孢孢子子子子)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 malariaAntimalarial drugs Antimalarial drugs Primaquine Primaquine（伯氨（伯氨（伯氨（伯氨喹喹）17.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 hemolytic anemia,methemoglobinemia(Acute hemolytic anemia,methemoglobinemia(高高高高铁铁血血血血红红蛋白血症蛋白血症蛋白血症蛋白血症)Antimalarial drugs Antimalarial drugs Primaquine Primaquine（伯氨（伯氨（伯氨（伯氨喹喹）18.红细胞外期红细胞内期按蚊有性繁殖Antimalarial drugs Antimalarial drugs Pyrimethamine Pyrimethamine（乙胺（乙胺（乙胺（乙胺嘧啶嘧啶）病因病因预防防Pyrimethamine(乙胺乙胺嘧啶)速速发Pyrimethamine(乙胺乙胺嘧啶)19.Pharmacological effectsPharmacological effectsInhibition of proliferation of sporozoite(Inhibition of proliferation of sporozoite(子子子子孢孢子子子子)to)to schizont(schizont(裂殖体裂殖体裂殖体裂殖体)Prophylaxis of infectionsProphylaxis of infectionsMechanism of actionsMechanism of actionsDihydrofolate reductase inhibitorDihydrofolate reductase inhibitorAdverse effectsAdverse effectsFolate metabolism disturbtance Folate metabolism disturbtance Antimalarial drugs Antimalarial drugs Pyrimethamine Pyrimethamine（乙胺（乙胺（乙胺（乙胺嘧啶嘧啶）20.symptomsymptom？21.复复复复发发？传传播？播？播？播？控制症状控制症状Chloroquine（氯喹）Quinine（奎宁）（奎宁）Mefloquine（甲氟（甲氟喹）Artemisinin（青蒿素）（青蒿素）22.病因病因病因病因预预防？防？防？防？控制复控制复发Primaquine（伯氨（伯氨喹）迟发阻止阻止传播播Primaquine（伯氨（伯氨喹）Chloroquine（氯喹）Quinine （奎宁）（奎宁）（恶性性疟无效）无效）23.病因病因预防防Pyrimethamine(乙胺乙胺嘧啶)速速发阻止阻止传播播Pyrimethamine（乙胺（乙胺嘧啶）24.用于控制症状的抗疟药Chloroquine Chloroquine（氯喹氯喹）、Quinine Quinine（奎宁）、（奎宁）、（奎宁）、（奎宁）、Mefloquine Mefloquine（甲氟（甲氟（甲氟（甲氟喹喹）、）、）、）、Pyronaridine (Pyronaridine (咯咯咯咯萘啶萘啶)、Artemisinin(Artemisinin(青蒿素青蒿素青蒿素青蒿素)、Artemether and artesunate(Artemether and artesunate(蒿甲蒿甲蒿甲蒿甲醚醚和青蒿琥和青蒿琥和青蒿琥和青蒿琥酯酯)用于控制复发和传播的抗疟药 Primaquine Primaquine（伯氨（伯氨（伯氨（伯氨喹喹）用于病因性预防的抗疟药 Pyrimethamine Pyrimethamine（乙胺（乙胺（乙胺（乙胺嘧啶嘧啶）25.Antiamebiasis drugs26.Amebiasis is infection with Entamoeba histolytica.Amebiasis is infection with Entamoeba histolytica.（溶（溶（溶（溶组织组织内阿米巴原虫内阿米巴原虫内阿米巴原虫内阿米巴原虫 ）Classification of amebiasisClassification of amebiasisAsymptomatic intestinal infection;Asymptomatic intestinal infection;Mild to moderate colitis;Mild to moderate colitis;Severe intestinal infection(dysentery);Severe intestinal infection(dysentery);Extraintestinal infections:ameboma,liver abscess.Extraintestinal infections:ameboma,liver abscess.Antiamebiasis drugs-Amebiasis27.Amebiasis is infection with Entamoeba histolytica,Amebiasis is infection with Entamoeba histolytica,A tiny,one-celled organism.A tiny,one-celled organism.Antiamebiasis drugs-Amebiasis28.Intestinal AmebiasisIntestinal AmebiasisExtraintestinal AmebiasisExtraintestinal AmebiasisFeatures of Amebiasis29.Multiplication and life cycle of Multiplication and life cycle of E histolyticaE histolyticaAntiamebiasis drugs-Amebiasis30.Clinical Manifestations Acute or chronic diarrhea,which may progress to Acute or chronic diarrhea,which may progress to dysentery.dysentery.Extraintestinal disease may be present as a Extraintestinal disease may be present as a complication or as a primary problemcomplication or as a primary problem(e.g.,liver,lung or brain abscess,or skin or perianal (e.g.,liver,lung or brain abscess,or skin or perianal infection).infection).Antiamebiasis drugs-Amebiasis31.Antiamebiasis drugs-Metronidazole Metronidazole 甲硝甲硝甲硝甲硝唑唑Pharmacological effects1.Antibiotic effective against anaerobic bacteria.Antibiotic effective against anaerobic bacteria.2.Anti-giardia lamblia Anti-giardia lamblia（贾贾第氏鞭毛虫）第氏鞭毛虫）第氏鞭毛虫）第氏鞭毛虫）effecteffect3.Anti-ameba effects Anti-ameba effects（肠肠内、内、内、内、肠肠外）外）外）外）The treatment of all tissue infections with E histolyticaThe treatment of all tissue infections with E histolytica4.Anti-infusorian 4.Anti-infusorian（滴虫）滴虫）滴虫）滴虫）effectseffects32.Mechanism of actionsThe methyl group of metronidazole is chemically The methyl group of metronidazole is chemically reduced in anaerobic bacteria and sensitive reduced in anaerobic bacteria and sensitive protozoans.protozoans.（原生原生原生原生动动物）物）物）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 and has a bioavailability of approximately 90%approximately 90%Antiamebiasis drugs-MetronidazoleMetronidazole33.Adverse effectsSerious side effects of metronidazole are rare;and Serious side effects of metronidazole are rare;and include seizures and damage of nerves resulting in include seizures and damage 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.appetite,a metallic taste,and rarely a rash.Antiamebiasis drugs-MetronidazoleMetronidazole34.Emetine依米丁依米丁&dehydroemetine去去氢依米丁依米丁Amebicide effects:Amebicide effects:sporadin(sporadin(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:Clinic uses:Amebic liver abscess,Acute amebic Amebic liver abscess,Acute amebic dysenterydysenteryUsed in case of resistance to metronidazole.Used in case of resistance to metronidazole.35.Emetine依米丁依米丁&dehydroemetine去去氢依米依米丁丁Adverse effectsNausea,vomiting and diarrhoea.Nausea,vomiting and diarrhoea.Palpitations,tachycardia,retrosternal pain,Palpitations,tachycardia,retrosternal pain,hypotension,dyspnoea,ECG changes(ST depression,hypotension,dyspnoea,ECG changes(ST depression,QT prolongation,T-wave inversion).QT prolongation,T-wave inversion).Tremor,myasthenia and paralysis including Tremor,myasthenia and paralysis including respiratory paralysis.respiratory paralysis.Antiamebiasis drugs-Other amebicides36.Diloxanide furoate is slowly absorbed from the Diloxanide furoate is slowly absorbed from the gastrointestinal tract and can therefore provide an gastrointestinal tract and can therefore provide an 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-Diloxanide Diloxanide 二二二二氯氯尼特尼特尼特尼特37.Mechanism of actionsLuminal amebicide.Luminal amebicide.Destroys the trophozoites of E.histolytica that Destroys the trophozoites of E.histolytica 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 amebiasis.(asymptomatic amebiasis.(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-DiloxanideDiloxanide38.Adverse 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 include nausea,headaches,and Minor side effects include nausea,headaches,and rarely a rash.rarely a rash.Antiamebiasis drugs-DiloxanideDiloxanide39.Antiamebiasis drugs-Other amebicidesParomomycin 巴巴龙霉素霉素Aminoglycosides antibiotics.Aminoglycosides antibiotics.Not significantly absorbed from the gastrointestinal 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 amebicideDirect and indirect action of amebicideClinical usage:Clinical usage:Amebic Amebic 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 extraintestinal amebic infections.No effect against extraintestinal amebic infections.40.Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugs Antimalarial drugs-ChloroquineChloroquine41.Anti-bilharziasis&filariasis Drug42.Bilharziasis急性发热过敏反应腹痛、腹泻肝脾肿大43.Anthelmintic ActionsSchistosomiasis(Schistosomiasis(血吸虫病血吸虫病血吸虫病血吸虫病)Clonorchiasis,Opisthorchiasis(Clonorchiasis,Opisthorchiasis(支睾吸虫病支睾吸虫病支睾吸虫病支睾吸虫病),and),and Paragonimiasis(Paragonimiasis(肺吸虫病肺吸虫病肺吸虫病肺吸虫病)Taeniasis(Taeniasis(绦绦虫病虫病虫病虫病)、Diphyllobothriasis(Diphyllobothriasis(裂裂裂裂头绦头绦虫病）虫病）虫病）虫病）H Nana H Nana（缩缩小膜壳小膜壳小膜壳小膜壳绦绦虫）虫）虫）虫）Neurocysticercosis Neurocysticercosis（脑脑囊虫病）囊虫病）囊虫病）囊虫病）Hydatid Disease Hydatid Disease（包虫囊病）（包虫囊病）（包虫囊病）（包虫囊病）Other ParasitesOther Parasites：fasciolopsiasis,metagonimiasis,and fasciolopsiasis,metagonimiasis,and other forms of heterophyiasis.fascioliasis,other forms of heterophyiasis.fascioliasis,Praziquantel 吡吡喹酮44.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,dislodgement,and death.death.In schistosome infections,praziquantel is effective In schistosome infections,praziquantel is effective against adult worms and immature stages against adult worms and immature stages Prophylactic effect against cercarial Prophylactic effect against cercarial（尾蚴）（尾蚴）（尾蚴）（尾蚴）infection.infection.Praziquantel 吡吡喹酮45.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,pruritus,urticaria,arthralgia,myalgia,and low-pruritus,urticaria,arthralgia,myalgia,and low-grade fever.grade fever.Mild and transient elevations of liver enzymesMild and transient elevations of liver enzymesPraziquantel 吡吡喹酮46.Filariasis淋巴管炎、淋巴淋巴管炎、淋巴结炎炎橡皮橡皮肿、乳糜尿、乳糜尿47.Diethylcarbamazine 乙胺乙胺嗪Anthelmintic ActionsAnthelmintic ActionsDiethylcarbamazine immobilizes microfilariae Diethylcarbamazine immobilizes microfilariae（微微微微丝丝蚴）蚴）蚴）蚴）and and alters their surface structure,displacing them from tissues and alters their surface structure,displacing them from tissues and making them more sus