1、Fang SanhuaAnti-parasite drugs 1Human 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2 Antimalarial drugs3The malarial parasite, Plasmodium, is a very small, single-cell organism. It lives as a parasite in other organisms,

2、 namely man and mosquito. The parasite is the cause of the tropical or subtropical disease malaria.Antimalarial drugs -Malarial parasite45Four species of plasmodium can produce the disease in its various forms: Plasmodium falciparum （惡性瘧原蟲）Plasmodium vivax （間日瘧原蟲）Plasmodium ovale （卵形瘧原蟲）Plasmodium m

3、alaria （三日瘧原蟲）6Antimalarial 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7No one available agent can reliably effect a radical cure, ie, eliminate both exo-erythrocytic and erythrocytic stages. Few available agents are causal prophylactic drugs, ie, capable of preventing erythrocytic infection.A

4、ntimalarial drugs8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9Antimalarial drugs Chloroquine （氯喹）Chloroquine is a synthetic 4-aminoquinoline

5、 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10Pharmacological effects1. Antimalarial 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 e

6、xo-erythrocytic form, and should therefore be used with primaquine（伯氨喹）to effect radical cure of P. vivax. Antimalarial drugs - Chloroquine11Pharmacological effects2. Immune inhibitionTreatment of rheumatoid arthritis, lupus erythematosus 3. Extraintestinal amebiasisAmoeba trophozoite amebic liver a

7、bscess Antimalarial drugs - Chloroquine12Mechanism 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 - Chloroquine13Adverse effe

8、ctsRare at the usual 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 dru

9、gs - Chloroquine14Quinine （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 parasites15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Antimalarial drugs Primaquine （伯氨喹）16Pharmaco

10、logical 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 malariaAntimalarial drugs Primaquine （伯氨喹）17Mechanism of actionsInhibiti

11、on 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 （伯氨喹）18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)Py

12、rimethamine(乙胺嘧啶)19Pharmacological effectsInhibition of proliferation of sporozoite (子孢子) to schizont (裂殖體)Prophylaxis of infectionsMechanism of actionsDihydrofolate reductase inhibitorAdverse effectsFolate metabolism disturbtance Antimalarial drugs Pyrimethamine （乙胺嘧啶）20symptom？21復(fù)發(fā)？傳播？控制癥狀Chloroqu

13、ine（氯喹）Quinine（奎寧）Mefloquine（甲氟喹）Artemisinin（青蒿素）22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 （氯喹）Quinine （奎寧）（惡性瘧無效）23病因預(yù)防Pyrimethamine(乙胺嘧啶) 速發(fā)阻止傳播Pyrimethamine（乙胺嘧啶）24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

14、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）25 Antiamebiasis drugs26Amebiasis 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);Extr

15、aintestinal infections: ameboma, liver abscess.Antiamebiasis drugs -Amebiasis27Amebiasis is infection with Entamoeba histolytica, A tiny, one-celled organism. Antiamebiasis drugs -Amebiasis28Intestinal AmebiasisExtraintestinal AmebiasisFeatures of Amebiasis29Multiplication and life cycle of E histol

16、yticaAntiamebiasis drugs -Amebiasis30Clinical 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 infection). Antiamebiasis drugs -Amebiasi

17、s31Antiamebiasis 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 histolytica4. Anti-infusorian （滴蟲）effects32Mechanism of actionsThe methyl grou

18、p 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 bioavailability of approximately 90% Antiamebiasis drugs - Metronidazole33Adverse effectsSerious s

19、ide effects of metronidazole are rare; and include seizures and damage of nerves resulting in numbness and tingling of extremities (peripheral neuropathy). Minor side effects include nausea, headaches, loss of appetite, a metallic taste, and rarely a rash.Antiamebiasis drugs - Metronidazole34Emetine

20、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 , Acute amebic dysenteryUsed in case of resistance to metronidazole. 35Emetine依米丁& dehydroemetine去氫依米丁Adverse effectsNausea, vomiting and diarrhoea. Palpitati

21、ons, tachycardia, retrosternal pain, hypotension, dyspnoea, ECG changes (ST depression, QT prolongation, T-wave inversion). Tremor, myasthenia and paralysis including respiratory paralysis.Antiamebiasis drugs - Other amebicides36Diloxanide furoate is slowly absorbed from the gastrointestinal tract a

22、nd can therefore provide an adequate concentration of the medication in the intestinal lumen for a long period of time. Antiamebiasis drugs - Diloxanide 二氯尼特37Mechanism of actionsLuminal amebicide. Destroys the trophozoites of E. histolytica that eventually form into cysts. (包囊)The cysts are then ex

23、creted by persons infected with asymptomatic amebiasis. (無癥狀的阿米巴病)Antiamebiasis drugs - Diloxanide38Adverse 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 - Diloxani

24、de39Antiamebiasis 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 agains

25、t extraintestinal amebic infections.40Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugs - Chloroquine41 Anti-bilharziasis & filariasis Drug42Bilharziasis急性發(fā)熱過敏反應(yīng)腹痛、腹瀉肝脾腫大43Anthelmintic ActionsSchistosomiasis (血吸蟲病)Clonorchiasis, Opisthorchiasis (支睪吸蟲病), and Paragoni

26、miasis (肺吸蟲病)Taeniasis (絳蟲病)、Diphyllobothriasis (裂頭絳蟲病） H Nana （縮小膜殼絳蟲） Neurocysticercosis （腦囊蟲病）Hydatid Disease （包蟲囊病）Other Parasites： fasciolopsiasis, metagonimiasis, and other forms of heterophyiasis. fascioliasis,Praziquantel 吡喹酮44Mechanism of actionsIncrease the permeability of cell membranes t

27、o calcium, resulting in paralysis, dislodgement, and death.In schistosome infections, praziquantel is effective against adult worms and immature stages Prophylactic effect against cercarial （尾蚴）infection.Praziquantel 吡喹酮45Adverse effectsMost frequent are headache, dizziness, drowsiness, and lassitud

28、e;Others include nausea, vomiting, abdominal pain, pruritus, urticaria, arthralgia, myalgia, and low-grade fever.Mild and transient elevations of liver enzymesPraziquantel 吡喹酮46 Filariasis淋巴管炎、淋巴結(jié)炎橡皮腫、乳糜尿47Diethylcarbamazine 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, wea