抗寄生虫药专题知识课件

1、Human parasiteProtozoa （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Human parasiteProtozoa （原虫）：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抗寄生虫药专题知识课件Four species of plasmodium can produce the disease in its various forms: Plasmodium falciparum （恶性疟原虫）Plasmod

3、ium vivax （间日疟原虫）Plasmodium ovale （卵形疟原虫）Plasmodium malaria （三日疟原虫）Four species of plasmodium canAntimalarial drugs - 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Primaqu

5、ine （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控制复发病因预防控制症状阻止传播阻止传播红细胞外期红细胞内期Antimalarial drugs Chloroquine （氯喹）Chloroquine is a synthetic 4-aminoquinoline derivate 控制症状Chloroquine 氯喹Quinine 奎宁Mefloquine 甲氟喹Artemisinin 青蒿素红细胞内期Antimalarial drugs ChloroquiPharmacological effects1. Antim

6、alarial effectsRapid schizonticidal activity （裂殖体杀灭剂） against all infections of malaria species . Also gametocytocidal（杀配子体）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 (瘙痒症) common among dark-skinned people.Transient headaches, nausea, vomiting, gastrointestinal symptoms and “blurred vision”.Others: aplastic blood and neurological disorders, such as polyneuritis (多发性神经炎), seizures and neuromyopathy.Antimalarial drugs - ChloroquineAdver

10、se effectsAntimalarial drQuinine （奎宁）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 （奎宁）Other angents kill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Antimalari

11、al drugs Primaquine （伯氨喹）控制复发阻止传播红细胞外期红细胞内期按蚊有性繁殖AntimPharmacological effectsHighly active against the gametocytes (配子体) of all malaria species dissemination Active against hypnozoites (迟发型子孢子) 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 (高铁血红蛋白血症)Antimalarial drugs Primaquine

13、（伯氨喹）Mechanism of actionsAntimalari红细胞外期红细胞内期按蚊有性繁殖Antimalarial drugs Pyrimethamine （乙胺嘧啶）病因预防Pyrimethamine(乙胺嘧啶) 速发Pyrimethamine(乙胺嘧啶)红细胞外期红细胞内期按蚊有性繁殖Antimalarial Pharmacological effectsInhibition of proliferation of sporozoite (子孢子) to schizont (裂殖体)Prophylaxis of infectionsMechanism of actionsDih

14、ydrofolate reductase inhibitorAdverse effectsFolate metabolism disturbtance Antimalarial drugs Pyrimethamine （乙胺嘧啶）Pharmacological effectsAntimalsymptom？symptom？复发？传播？控制症状Chloroquine（氯喹）Quinine（奎宁）Mefloquine（甲氟喹）Artemisinin（青蒿素）复发？传播？控制症状病因预防？控制复发Primaquine（伯氨喹） 迟发阻止传播Primaquine （伯氨喹） Chloroquine （氯

15、喹）Quinine （奎宁）（恶性疟无效）病因预防？控制复发阻止传播病因预防Pyrimethamine(乙胺嘧啶) 速发阻止传播Pyrimethamine（乙胺嘧啶）病因预防阻止传播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) 、 Artemether and artesunate (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）用于控制症状的抗疟药 A

16、ntiamebiasis drugs Antiamebiasis drugAmebiasis is infection with Entamoeba histolytica.（溶组织内阿米巴原虫 ）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 （贾第氏鞭毛虫）effectAnti-ameba effects （肠内、肠外） The treatment of all tissue infections with E histolyti

20、ca4. Anti-infusorian （滴虫）effectsAntiamebiasis drugs - MetronidMechanism of actionsThe methyl group of metronidazole is chemically reduced in anaerobic bacteria and sensitive protozoans. （原生动物）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去氢依米丁Amebicide effects : sporadin (滋养体)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去氢依米Emetine依米丁& dehydroemetine去氢依米丁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去氢依米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. (无症状的阿米

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 巴龙霉素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急性发热过敏反应腹痛、腹泻肝脾肿大BilharziasisAnthelmintic

29、 ActionsSchistosomiasis (血吸虫病)Clonorchiasis, Opisthorchiasis (支睾吸虫病), and Paragonimiasis (肺吸虫病)Taeniasis (绦虫病)、Diphyllobothriasis (裂头绦虫病） H Nana （缩小膜壳绦虫） Neurocysticercosis （脑囊虫病）Hydatid Disease （包虫囊病）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、淋巴结炎橡皮肿、乳糜尿 FilariasisDiethylcarbamazine 乙胺嗪Anthelmintic ActionsDiethylcarbamazine immobilizes microfilariae （微丝蚴）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