抗寄生蟲藥專題知識課件

1、Human parasiteProtozoa （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(jié)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Human parasiteProtozoa （原蟲）：孢子 Antimalarial drugs Antimalarial drugThe malarial parasite, Plasmodium, is a very small, single-cell organism. It lives as a parasite in ot

2、her organisms, namely man and mosquito. The parasite is the cause of the tropical or subtropical disease malaria.Antimalarial drugs -Malarial parasiteThe malarial parasite, Plasmod抗寄生蟲藥專題知識課件Four species of plasmodium can produce the disease in its various forms: Plasmodium falciparum （惡性瘧原蟲）Plasmod

3、ium vivax （間日瘧原蟲）Plasmodium ovale （卵形瘧原蟲）Plasmodium malaria （三日瘧原蟲）Four species of plasmodium canAntimalarial drugs - Parasite Life Cycle紅細(xì)胞外期紅細(xì)胞內(nèi)期按蚊有性繁殖人體無性繁殖Antimalarial drugs - Parasite No one available agent can reliably effect a radical cure, ie, eliminate both exo-erythrocytic and erythrocytic

4、 stages. Few available agents are causal prophylactic drugs, ie, capable of preventing erythrocytic infection.Antimalarial drugsNo one available agent can rel控制復(fù)發(fā)Primaquine（伯氨喹） 遲發(fā)病因預(yù)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Primaqu

5、ine （伯氨喹） Chloroquine （氯喹）Quinine （奎寧）（惡性瘧無效）紅細(xì)胞外期紅細(xì)胞內(nèi)期按蚊有性繁殖控制復(fù)發(fā)病因預(yù)防控制癥狀阻止傳播阻止傳播紅細(xì)胞外期紅細(xì)胞內(nèi)期Antimalarial drugs Chloroquine （氯喹）Chloroquine is a synthetic 4-aminoquinoline derivate 控制癥狀Chloroquine 氯喹Quinine 奎寧Mefloquine 甲氟喹Artemisinin 青蒿素紅細(xì)胞內(nèi)期Antimalarial drugs ChloroquiPharmacological effects1. Antim

6、alarial effectsRapid schizonticidal activity （裂殖體殺滅劑） against all infections of malaria species . Also gametocytocidal（殺配子體）against P. vivax, P. malariae and P. ovale . It is not active against exo-erythrocytic form, and should therefore be used with primaquine（伯氨喹）to effect radical cure of P. vivax

7、. Antimalarial drugs - ChloroquinePharmacological effectsAntimalPharmacological effects2. Immune inhibitionTreatment of rheumatoid arthritis, lupus erythematosus 3. Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugs - ChloroquinePharmacological effectsAntimalMechanis

8、m of actionsAccumulation in erythrocytepH malarial pigment synthesis hemeHeme-quinoline compound heme accumulate in plasmodium Insert in the double stranded DNA helix DNA replication and RNA transcription Antimalarial drugs - ChloroquineMechanism of actionsAntimalariAdverse effectsRare at the usual

9、antimalarial dosagesPruritus (瘙癢癥) common among dark-skinned people.Transient headaches, nausea, vomiting, gastrointestinal symptoms and “blurred vision”.Others: aplastic blood and neurological disorders, such as polyneuritis (多發(fā)性神經(jīng)炎), seizures and neuromyopathy.Antimalarial drugs - ChloroquineAdver

10、se effectsAntimalarial drQuinine （奎寧）Mefloquine （甲氟喹）Pyronaridine (咯萘啶)Artemisinin (青蒿素)Artemether and artesunate (蒿甲醚和青蒿琥酯) Other angents kill erythrocytic parasitesQuinine （奎寧）Other angents kill控制復(fù)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(xì)胞外期紅細(xì)胞內(nèi)期按蚊有性繁殖Antimalari

11、al drugs Primaquine （伯氨喹）控制復(fù)發(fā)阻止傳播紅細(xì)胞外期紅細(xì)胞內(nèi)期按蚊有性繁殖AntimPharmacological effectsHighly active against the gametocytes (配子體) of all malaria species dissemination Active against hypnozoites (遲發(fā)型子孢子) of the relapsing malarial parasites The only drug currently used for the treatment of relapsing malariaAnt

12、imalarial drugs Primaquine （伯氨喹）Pharmacological effectsAntimalMechanism of actionsInhibition of coenzyme Q Inhibition of reduction of NADPAdverse effectsTransient dizziness , nausea, vomiting, gastrointestinal symptomsAcute hemolytic anemia, methemoglobinemia (高鐵血紅蛋白血癥)Antimalarial drugs Primaquine

13、（伯氨喹）Mechanism of actionsAntimalari紅細(xì)胞外期紅細(xì)胞內(nèi)期按蚊有性繁殖Antimalarial drugs Pyrimethamine （乙胺嘧啶）病因預(yù)防Pyrimethamine(乙胺嘧啶) 速發(fā)Pyrimethamine(乙胺嘧啶)紅細(xì)胞外期紅細(xì)胞內(nèi)期按蚊有性繁殖Antimalarial Pharmacological effectsInhibition of proliferation of sporozoite (子孢子) to schizont (裂殖體)Prophylaxis of infectionsMechanism of actionsDih

14、ydrofolate reductase inhibitorAdverse effectsFolate metabolism disturbtance Antimalarial drugs Pyrimethamine （乙胺嘧啶）Pharmacological effectsAntimalsymptom？symptom？復(fù)發(fā)？傳播？控制癥狀Chloroquine（氯喹）Quinine（奎寧）Mefloquine（甲氟喹）Artemisinin（青蒿素）復(fù)發(fā)？傳播？控制癥狀病因預(yù)防？控制復(fù)發(fā)Primaquine（伯氨喹） 遲發(fā)阻止傳播Primaquine （伯氨喹） Chloroquine （氯

15、喹）Quinine （奎寧）（惡性瘧無效）病因預(yù)防？控制復(fù)發(fā)阻止傳播病因預(yù)防Pyrimethamine(乙胺嘧啶) 速發(fā)阻止傳播Pyrimethamine（乙胺嘧啶）病因預(yù)防阻止傳播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) 、 Artemether and artesunate (蒿甲醚和青蒿琥酯) 用于控制復(fù)發(fā)和傳播的抗瘧藥 Primaquine （伯氨喹）用于病因性預(yù)防的抗瘧藥 Pyrimethamine （乙胺嘧啶）用于控制癥狀的抗瘧藥 A

16、ntiamebiasis drugs Antiamebiasis drugAmebiasis is infection with Entamoeba histolytica.（溶組織內(nèi)阿米巴原蟲 ）Classification of amebiasisAsymptomatic intestinal infection;Mild to moderate colitis;Severe intestinal infection (dysentery);Extraintestinal infections: ameboma, liver abscess.Antiamebiasis drugs -Ame

17、biasisAmebiasis is infection with EnAmebiasis is infection with Entamoeba histolytica, A tiny, one-celled organism. Antiamebiasis drugs -AmebiasisAmebiasis is infection with EnIntestinal AmebiasisExtraintestinal AmebiasisFeatures of AmebiasisIntestinal AmebiasisExtraintesMultiplication and life cycl

18、e of E histolyticaAntiamebiasis drugs -AmebiasisMultiplication and life cycle Clinical Manifestations Acute or chronic diarrhea, which may progress to dysentery. Extraintestinal disease may be present as a complication or as a primary problem (e.g., liver, lung or brain abscess, or skin or perianal

19、infection). Antiamebiasis drugs -AmebiasisClinical Manifestations AntiamAntiamebiasis drugs - Metronidazole 甲硝唑Pharmacological effectsAntibiotic effective against anaerobic bacteria. Anti-giardia lamblia （賈第氏鞭毛蟲）effectAnti-ameba effects （腸內(nèi)、腸外） The treatment of all tissue infections with E histolyti

20、ca4. Anti-infusorian （滴蟲）effectsAntiamebiasis drugs - MetronidMechanism of actionsThe methyl group of metronidazole is chemically reduced in anaerobic bacteria and sensitive protozoans. （原生動物）Reactive reduction products appear to be responsible for antimicrobial activity.Rapidly absorbed and has a b

21、ioavailability of approximately 90% Antiamebiasis drugs - MetronidazoleMechanism of actionsAntiamebiaAdverse effectsSerious side effects of metronidazole are rare; and include seizures and damage of nerves resulting in numbness and tingling of extremities (peripheral neuropathy). Minor side effects

22、include nausea, headaches, loss of appetite, a metallic taste, and rarely a rash.Antiamebiasis drugs - MetronidazoleAdverse effectsAntiamebiasis dEmetine依米丁& dehydroemetine去氫依米丁Amebicide effects : sporadin (滋養(yǎng)體)Mechanism of actions: protein synthesis inhibitor.Clinic uses: Amebic liver abscess , Acu

23、te amebic dysenteryUsed in case of resistance to metronidazole. Emetine依米丁& dehydroemetine去氫依米Emetine依米丁& dehydroemetine去氫依米丁Adverse effectsNausea, vomiting and diarrhoea. Palpitations, tachycardia, retrosternal pain, hypotension, dyspnoea, ECG changes (ST depression, QT prolongation, T-wave inversi

24、on). Tremor, myasthenia and paralysis including respiratory paralysis.Antiamebiasis drugs - Other amebicidesEmetine依米丁& dehydroemetine去氫依米Diloxanide furoate is slowly absorbed from the gastrointestinal tract and can therefore provide an adequate concentration of the medication in the intestinal lume

25、n for a long period of time. Antiamebiasis drugs - Diloxanide 二氯尼特Diloxanide furoate is slowly aMechanism of actionsLuminal amebicide. Destroys the trophozoites of E. histolytica that eventually form into cysts. (包囊)The cysts are then excreted by persons infected with asymptomatic amebiasis. (無癥狀的阿米

26、巴病)Antiamebiasis drugs - DiloxanideMechanism of actionsAntiamebiaAdverse effectsNot commonly seen with this medication unless the patient is taking especially high doses. Minor side effects include nausea, headaches, and rarely a rash.Antiamebiasis drugs - DiloxanideAdverse effectsAntiamebiasis dAnt

27、iamebiasis drugs - Other amebicidesParomomycin 巴龍霉素Aminoglycosides antibiotics. Not significantly absorbed from the gastrointestinal tract Mechanism of actions: Acts by inhibition protein synthesis.Direct and indirect action of amebicideClinical usage: Amebic dysentery (阿米巴痢疾)No effect against extra

28、intestinal amebic infections.Antiamebiasis drugs - Other amExtraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugs - ChloroquineAntimalarial drugs - Chloroqui Anti-bilharziasis & filariasis Drug Anti-bilharziasis & filaBilharziasis急性發(fā)熱過敏反應(yīng)腹痛、腹瀉肝脾腫大BilharziasisAnthelmintic

29、 ActionsSchistosomiasis (血吸蟲病)Clonorchiasis, Opisthorchiasis (支睪吸蟲病), and Paragonimiasis (肺吸蟲病)Taeniasis (絳蟲病)、Diphyllobothriasis (裂頭絳蟲病） H Nana （縮小膜殼絳蟲） Neurocysticercosis （腦囊蟲?。〩ydatid Disease （包蟲囊病）Other Parasites： fasciolopsiasis, metagonimiasis, and other forms of heterophyiasis. fascioliasis,P

30、raziquantel 吡喹酮Anthelmintic ActionsPraziquantMechanism of actionsIncrease the permeability of cell membranes to calcium, resulting in paralysis, dislodgement, and death.In schistosome infections, praziquantel is effective against adult worms and immature stages Prophylactic effect against cercarial

31、（尾蚴）infection.Praziquantel 吡喹酮Mechanism of actionsPraziquantAdverse effectsMost frequent are headache, dizziness, drowsiness, and lassitude;Others include nausea, vomiting, abdominal pain, pruritus, urticaria, arthralgia, myalgia, and low-grade fever.Mild and transient elevations of liver enzymesPra

32、ziquantel 吡喹酮Adverse effectsPraziquantel 吡喹 Filariasis淋巴管炎、淋巴結(jié)炎橡皮腫、乳糜尿 FilariasisDiethylcarbamazine 乙胺嗪Anthelmintic ActionsDiethylcarbamazine immobilizes microfilariae （微絲蚴）and alters their surface structure, displacing them from tissues and making them more susceptible to destruction by host defense mechanisms. Clinical Uses Wuchereria Bancrofti, Brugia Malayi, Brugia Timori, and Loa LoaAdverse effectsGenerally mild and transientInclude headache, malaise, anorexia, weakness, nausea, vomiting, and dizziness.Diethylcarba