Huifang Tang ( ) & Anti-amebiasis and anti- trichomoniasis drugs ( ) & Anthelmintic drugs ( ) A. Anti-amebiasis and anti-trichomoniasis drugs ( ) Amebiasis is infection with Entamoeba histolytica( ), A tiny, one-celled organism. A1. Anti-amebiasis drugs (amebicides) Life cycle of amebic parasite Multiplication and life cycle of E histolytica A1. Anti-amebiasis drugs (amebicides) Classification of amebiasis: Luminal amebiasis( ): Amebic dysentery( ), Asyptomatic carrier( ) Systemic amebiasis( ) Amebic hepatitis( ), hepatic abscess( ) Mixed amebiasis. Anti-amebiasis drugs Intestinal Amebiasis Extraintestinal Amebiasis Features of Amebiasis A1. Anti-amebiasis drugs (amebicides) ( ) ( ) The drugs used in amebiasis: Metronidazole( ), Tinidazole( ); Emetine( ), Dehydroemetine; Halogenate quinolines( ): Chiniofon( ), Clioquinol( ), Diiodohydroxyquinoline( ); Diloxannide( ); Paromomycin( ); Chlorpromaquin( ), etc. Anti-amebiasis drugs Metronidazole( , ) (1)Pharmacological effects & clinical uses: Anti-amebiasis effects: It has potent amebicidal activity to large trophozoite( ) grown, but no affect to small trophozoite( ). Effective to acute amebic dysentery and all systemic amebiasis, but ineffec-tive to asyptomatic passers. Therefore, it need be used comban-tion of purely intestinal amebicides, such as diloxanide to radically treatment. Anti-amebiasis drugs Metronidazole Anti-trichomoniasis effects: Metronidazole can kill Trichomonas vaginalis( ) directly. After oral administration, it is absorbed fast, distribute to the whole body, and secreted into vaginal secretion(in female), sperm(in male) and urine. Therefore, it is effective toTrichomonas infection of male and female. Its curative rate( ) reach 90%. Anti-amebiasis drugs Metronidazole Anti-anaerobic bacteria infection: The sensitive anaerobic bacteria to metronidazole including: All anaerobic cocci( ); G - anaerobic bacillus(G - ) and G + spore anaerobic bacillus(G + ); Therefore, this drug is used to treat: 1)vary anaerobic bacteria infection of pelvic cavity and abnormal cavity; 2)peridentitis( ); 3)infection of helicobacter pylori (HP) also, HP is the main cause of gastric and duodenal ulcer. Anti-amebiasis drugs Metronidazole Anti-giardiasis: Giardiasis( ) caused by Giardia lamblia( ), which is a intestinal protozoiasis( ), and there are process of cyst and trophozoite also, Giardia lamblia is mainly parasitic lived in duodenum and biliary tract( ). Metronidazole is the most effective drug to treat Giardiasis, Its curative rate reach 90%. (2)Adverse reaction: GI and CNS reaction, there is WBC reduction in some patients. Anti-amebiasis drugs Metronidazole Tinidazole ( ) (1)The t (12~24h) is longer than metronidazole(t 8h), (2) After once oral administration, its effective blood concentration keep 72h, (3) its toxicity is less than metronidazole. Anti-amebiasis drugs Emetine( , ) & Dehydroemetine( ) They can kill amebic trophozoite ( )in tissue directly. Adverse reaction are more and severe irritative action is strong, can cause vomiting(emesis) by oral administration, therefore, they are only injected by deep muscle. heart toxicity, so that they are only used in severe amebic infection and when metronidazole is no effect. Anti-amebiasis drugs Diloxanide( ) It can kill amebic cyst( ). The parts of unabsorption can kill amebic cyst and small trophozoite in intestinal cavity, effective to asymptomatic passers and the patients of evacuating amebic cyst. The therapeutic effect is not so good to acute amebic dysentery( ), after controlling symptoms by metronidazole, treat it with diloxanide to kill the small trophozoite in intestinal tract, can radically cure amebic infection. Diloxanide is ineffective to systematic amebiasis. Anti-amebiasis drugs Paromomycin( ) After oral administration it cannot be absorbed. Direct action: It can kill the amebic trophozoite in intestinal tract. Indirect action: It can inhibit the symbiotic bacteria ( )of amebic protozoan( ), then inhibit survivor and proliferation of ameba. It is used to treat acute amebiasis. Anti-amebiasis drugs Chloroquine( ) It can kill amebic trophozoite also. Owing to absorption fast by p.o. and the concentration in intestinal cavity low, it is ineffective to intestinal amebiasis, but the concentration of chloroquine is very high in liver (the Concentration in liver is 700 times higher than the Cp). Clinical use: exo-intestinal amebic infection(e.g. amebic hepatitis & hepatic abscess). Its toxicity larger than metronidazole, only used in the patients ineffective or un- tolerant to metronidazole. Anti-amebiasis drugs + + + + + + + Anti-amebiasis drugs A2. Anti-trichomoniasis drugs (Trichomonacides) Trichomoniasis( , ) caused byTrichomonas vaginalis( ) infection. Male and female all can be infected, male is not onset, but can become the source of infection. Therefore, only should husband and wife be treated at the same time that thorough cure. Metronidazole( ) It is the most effective drug to infection of Trichomonas vaginalis. It is effective to patients, regardless of male and female patient. 0.2g, tid, po.7 days. Its curative rate( ) reach 90%, or once large dose(2 g) po. 0.5g suppository( ) of metronida-zole, local application. Anti-trichomoniasis drugs Acetarsol( ) Acetarsol is a preparation of five- valence arsine. In clinic, devegan( ) the complex preparation of acetarsol, one tablet of devegan contains acetarsol 0.25g, and boric acid 0.03g, local appli-cation, can kill Trichomonas vaginalis directly, used to the patients of metronidazole resistance. Anti-trichomoniasis drugs B. Anthelmintic drugs ( ) hookworm ( ) Pinworm( ) Whipworm( ) Fasciolopsis ( ) ascaris( )Tapeworm( ) Intestinal helminth( ) including eelworm( ): ascaris( ), hookworm ( ), pinworm( ), whipworm( ), fasciolopsis( ) and tapeworm( ), et al. In the past, the kinds of anthelmintic drugs are very more, and the sensitivity to intestinal helminth is different also. Now, the main anthelmintic drugs are broad spectrum and high potency, therefore, to treat helminthiasis become very easy in clinic. At the same time, the drugs that we learn are very less. Mebendazole( ) (1)Anthelmintic action: It is a broad spectrum and high potency anthelmintic drug, it can kill many kinds of nematoindea( ), e.g. ascaris( ), hookworm( ), pinworm( ), whipworm( ), and tapeworm( ), including imago, larva and ovum. The effective rate is over 90%, it is suit-ed to mixed infection of helminth especially. It can kill ovum of helminth, and control the transmission of helminth too. (2)Adverse reaction: less, GI reaction; anaphylaxis; terato- genesis and embryotoxicity. Anthelmintic drugs Albendazole( , ) It is a broad spectrum & high potency anthelmintic drug, it compare with mebendazole, the anthelmintic spectrum is more broad, and the ADRs are less. (1)Anthelmintic action: Intestinal parasitosis( ): Nematoindea( ): e.g. ascaris( ), hookworm( ), pinworm( ), whip-worm( ); Tapeworm( ): pork tapemorm( ), beef tapemorm( ). The therapeutic effects are the same as mebendazole. Anthelmintic drugs Albendazole Exo-intestinal parasitosis: It is a very efficacious drug for exo- intestinal parasitic disease, such as hyda- tidosis( ), cysticercosis( ), tri- chinosis( ), clonorchiasis( ), paragonimiasis( ). Mebendazole is ineffective to those diseases, because albendazole is absorbed fast, its blood concentration is 100 times higher than that of mebendazole, the concentration in liver and lung is relatively high, therefore, albendazole can enter hydatidocystis( ). Anthelmintic drugs Albendazole (2)Clinical Uses: Intestinal nematodiasis( ): including Ancylostomiasis( ), Ascariasis( ), Trichuriasis( ), once draft: 400mg; Intestinal taeniasis( ): effective to infection of pork t. and beef t., 800mg/day, 3 days; Cysticercosis( ): common patients( - ): 200~ 300mg, tid, 10 days course, 2~3 courses. cerebral patients( ): hospita- lization. Anthelmintic drugs Albendazole Hydatidosis( , ): a course: 30 days, the second course after 2 weeks. Clonorchiasis( ): a course: 7 days. Trichinosis( ): a course: 5 days, 1 or 2 courses. Paragonimiasis( ). Anthelmintic drugs Albendazole (3)Adverse reaction: To treat intestinal parasitosis: the ADRs are less. To treat exo-intestinal parasitosis: e.g. cysticercosis( ) and hydatidosis ( ): The ADRs are more, because the therapeutic dose is larger and the course of treatment is longer. The toxicity of albendazole is less. after getting therapeutic effect, cysticerci( ) died and disintegrated, releasing allo-protein to cause anaphylaxis, such as skin rash, headache, fever, and muscular aching pain( ), etc. Anthelmintic drugs Albendazole 1.Piperazine 2.Levamisole 3.Pyrantel 4.Niclosamide 5.Praziquantel Other Anthelmintic Drugs Anthelmintic drugs Piperazine( , ) Effective to ascaris( ) & pinworm ( ), but the curative effect is less than albendazole, the merit of albendazole is side action less. Pyrantel( , ) Broad spectrum antiematodiasis drug ( ), effective to ascaris( ), hookworm( ), pinworm( ) and trichostrongylus( ) infection, but ineffective to whipworm ( ). Anthelmintic drugs Pyrvinum ambonate ( , ) It is a cyanine dyes( ), the therapeutic effect to pinworm( ) is high, and its toxicity is less. 5 mg/kg/day, total dose 0.25 g, an interval of 2~3 week treated again, 2~3 times. Anthelmintic drugs Niclosamide( ) It was formerly an molluscacide( ) to be sprinkled in paddy field and riverside to kill oncomelania( ), which is intermediate host( ) of schistosoma( ). It can also kill cercaria( ) and miracidium( ) of schistosoma also. Later found it effective to varied taenia ( ) infection, especially effective to beef taenia infection. Application: draft 1 g, and draft 1 g again 1 h later, after 1 ~ 2 hr then orally take MgSO 4 to purgation( ). Anthelmintic drugs Praziquantel( ) It is a broad spectrum anti-parasitic drug too. It can be used to treat schistosomiasis, and used to treat certain intestinal parasitosis also. It is ineffective to nematodiasis( ) and amebiasis. It can be used to treat Taeniasis( ): Including varied imago( ) and larva ( ) infective disease, such as cysticercisis( ) and hydatidosis( ). Anthelmintic drugs Praziquantel (1)intestinal taenia infection( ): 10 or 25mg/kg, . (2)cysticercosis( ): common patients( - ): 4 days course; cerebral patients( ): 9 days course, after 3~4 months to 2nd course. (3)hydatidosis( ): the drug can kill protoscolex( ), have its infective ability , but cant get cure, the effect is less than albendazole. Anthelmintic drugs Praziquantel Therapiutic drugs : Mebendazole, Albendazole, Pyrantel, Piperazine : Mebendazole, Albendazole, Pyrantel, Pyrvinum ambonates : Mebendazole, Albendazole, Pyrantel : Mebendazole : Praziquantel, Niclosamide, : Praziquantel, Albendazole : Albendazole, Praziquantel, Mebendazole Anthelmintic drugs ( ) ATP ( ) ATP ( ) Ach ( ) ( ) ATP Anthelmintic drugs The class is over !