Transcript 汤慧芳_抗阿米巴_滴虫
Anti-amebiasis and anti-trichomoniasis drugs (抗阿米巴病和抗滴虫病药) & Anthelmintic drugs (抗肠蠕虫药) A1. Anti-amebiasis drugs (amebicides) Amebiasis is infection with Entamoeba histolytica(溶组织内 阿米巴), A tiny, one-celled organism. Life cycle of amebic parasite A1. Anti-amebiasis drugs (amebicides) Multiplication and life cycle of E histolytica Anti-amebiasis drugs Classification of amebiasis: Luminal amebiasis(肠内阿米巴): Amebic dysentery(阿米巴痢疾), Asyptomatic carrier(无症状带虫者) Systemic amebiasis(肠外阿米巴) Amebic hepatitis(阿米巴肝炎), hepatic abscess(阿米巴肝脓肿) Mixed amebiasis. Features of Amebiasis Extraintestinal Amebiasis Intestinal Amebiasis A1. Anti-amebiasis drugs (amebicides) (肠内阿米巴) 非痢疾性肠胃炎 (肠外阿米巴) Anti-amebiasis drugs The drugs used in amebiasis: Metronidazole(甲硝唑), Tinidazole(替硝唑); Emetine(依米丁), Dehydroemetine; Halogenate quinolines(卤化喹啉类): Chiniofon(喹碘仿), Clioquinol(氯碘羟喹), Diiodohydroxyquinoline(双碘喹啉); Diloxannide(二氯尼特); Paromomycin(巴龙霉素); Chlorpromaquin(氯喹), etc. Anti-amebiasis drugs Metronidazole Metronidazole(甲硝唑, 灭滴灵) (1)Pharmacological effects & clinical uses: ①Anti-amebiasis effects: It has potent amebicidal activity to large trophozoite(大滋养体) grown, but no affect to small trophozoite(小滋养体). 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 ②Anti-trichomoniasis effects: Metronidazole can kill Trichomonas vaginalis(阴道毛滴虫) 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(治愈率) reach 90%. Anti-amebiasis drugs Metronidazole ③Anti-anaerobic bacteria infection: The sensitive anaerobic bacteria to metronidazole including: ▲All anaerobic cocci(所有的厌氧球菌); -厌氧杆菌) and G+ ▲G- anaerobic bacillus(G spore anaerobic bacillus(G+芽孢厌氧杆菌); Therefore, this drug is used to treat: 1)vary anaerobic bacteria infection of pelvic cavity and abnormal cavity; 2)peridentitis(牙周炎); 3)infection of helicobacter pylori (HP) also, HP is the main cause of gastric and duodenal ulcer. Anti-amebiasis drugs Metronidazole ④Anti-giardiasis: Giardiasis(贾第鞭毛虫病) caused by Giardia lamblia(蓝氏贾第鞭毛虫), which is a intestinal protozoiasis(肠道原虫病), and there are process of cyst and trophozoite also, Giardia lamblia is mainly parasitic lived in duodenum and biliary tract(胆道). 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 Tinidazole (替硝唑) (1)The t½(12~24h) is longer than metronidazole(t½ 8h), (2) After once oral adminis-tration, its effective blood concentration keep 72h, (3) its toxicity is less than metronidazole. Anti-amebiasis drugs Emetine(依米丁, 吐根碱) & Dehydroemetine(去氢依米丁) They can kill amebic trophozoite (阿米 巴滋养体)in tissue directly. Their adverse reaction are more and severe, their irritative action is strong, can cause vomiting(emesis) by oral administration, therefore, they are only injected by deep muscle. And they may cause heart toxicity, so that they are only used in severe amebic infection and when metronidazole is no effect. Anti-amebiasis drugs Diloxanide(二氯尼特) •It can kill amebic cyst(阿米巴囊肿). •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(急性阿米巴性痢疾), 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(巴龙霉素) 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 (共生细 菌)of amebic protozoan(阿米巴原虫), then inhibit survivor and proliferation of ameba. It is used to treat acute amebiasis. Anti-amebiasis drugs Chloroquine(氯喹) 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 untolerant to metronidazole. Anti-amebiasis drugs 抗阿米巴病药物治疗 临床类型 首选药物 其他药物 无症状包囊携带者 二氯尼特 巴龙霉素 阿米巴痢疾 甲硝唑+二氯尼 特 甲硝唑+巴龙霉素 依米丁 肠外阿米巴病 甲硝唑+二氯尼 特 依米丁+氯喹+二氯尼特 甲硝唑+氯喹 A2. Anti-trichomoniasis drugs (Trichomonacides) • Trichomoniasis(滴虫病, 滴虫性阴道炎) caused byTrichomonas vaginalis(阴道毛滴 虫) 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. Anti-trichomoniasis drugs Metronidazole(甲硝唑) • It is the most effective drug to infection of Trichomonas vaginalis. • It is effective to patients, regardless of male and female patient. • ①0.2g, tid, po.×7 days. Its curative rate(治愈率) reach 90%, or once large dose(2 g) po. • ②0.5g suppository(栓剂) of metronida-zole, local application. Anti-trichomoniasis drugs Acetarsol(乙酰胂胺) • Acetarsol is a preparation of fivevalence arsine. • In clinic, devegan(滴维净) —— 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. B. Anthelmintic drugs (抗肠蠕虫药) hookworm (钩虫) Pinworm(蛲虫) Tapeworm(绦虫) ascaris(蛔虫) Whipworm(鞭虫) Fasciolopsis (姜片虫) • Intestinal helminth(肠蠕虫) including eelworm(线虫): ascaris(蛔虫), hookworm (钩虫), pinworm(蛲虫), whipworm(鞭虫), fasciolopsis(姜片虫) and tapeworm(绦虫), 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. Anthelmintic drugs Mebendazole(甲苯达唑) (1)Anthelmintic action: It is a broad spectrum and high potency anthelmintic drug, it can kill many kinds of nematoindea(线虫), e.g. ascaris(蛔虫), hookworm(钩虫), pinworm(蛲虫), whipworm(鞭虫), and tapeworm(绦虫), 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 Albendazole(阿苯达唑, “肠虫清”) 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: ①Intestinal parasitosis(肠寄生虫病): Nematoindea(线虫): e.g. ascaris(蛔虫), hookworm(钩虫), pinworm(蛲虫), whip-worm(鞭虫); Tapeworm(绦虫): pork tapemorm(猪肉绦虫), beef tapemorm(牛肉绦虫). The therapeutic effects are the same as mebendazole. Anthelmintic drugs Albendazole ②Exo-intestinal parasitosis: It is a very efficacious drug for exointestinal parasitic disease, such as hydatidosis(包虫病), cysticercosis(囊虫病), trichinosis(旋毛虫病), clonorchiasis(华支睾吸虫), paragonimiasis(肺吸虫病). 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(棘球幼囊). (2)Clinical Uses: Anthelmintic drugs Albendazole ①Intestinal nematodiasis(肠线虫病): including Ancylostomiasis(钩虫病), Ascariasis(蛔虫 病), Trichuriasis(鞭虫病), once draft: 400mg; ②Intestinal taeniasis(肠绦虫病): effective to infection of pork t. and beef t., 800mg/day, 3 days; ③Cysticercosis(囊虫病): common patients(皮下-肌肉型): 200~ 300mg, tid, 10 days course, 2~3 courses. cerebral patients(脑型病例): hospita-lization. Anthelmintic drugs Albendazole ④Hydatidosis(包虫病, 细粒棘球蚴病): a course: 30 days, the second course after 2 weeks. ⑤Clonorchiasis(华支睾吸虫病): a course: 7 days. ⑥Trichinosis(旋毛虫病): a course: 5 days, 1 or 2 courses. ⑦Paragonimiasis(肺吸虫病). Anthelmintic drugs Albendazole (3)Adverse reaction: ①To treat intestinal parasitosis: the ADRs are less. ②To treat exo-intestinal parasitosis: e.g. cysticercosis(囊虫病) and hydatidosis (包虫 病): 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(囊尾蚴) died and disintegrated, releasing allo-protein to cause anaphylaxis, such as skin rash, headache, fever, and muscular aching pain(肌肉酸痛), etc. Anthelmintic drugs Other Anthelmintic Drugs 1. Piperazine 哌嗪 2. Levamisole 左旋咪唑 3. Pyrantel 噻嘧啶 4. Niclosamide 氯硝柳胺 5. Praziquantel 吡喹酮 Anthelmintic drugs Piperazine (哌嗪,驱蛔灵) 1. Mechanism—Piperazine paralyzes ascaris by acting as an agonist at GABA receptors. The paralyzed roundworms are expelled live by normal peristalsis. 2. Clinical use— Effective to ascaris(蛔虫) & pinworm (蛲虫), but the curative effect is less than albendazole, the merit of albendazole is side action less. 3. Toxicity—Mild gastrointestinal irritation is the most common side effect. Piperazine should not be used in pregnant patients or those with hepatic or renal dysfunction or seizure disorders Anthelmintic drugs Pyrantel Pamoate (噻嘧啶, 驱虫 灵) 1. Mechanism—Pyrantel pamoate stimulates nicotinic receptors present at neuromuscular junctions of nematodes. Contraction of muscles occurs, followed by a depolarization-induced paralysis. 2. Clinical use— – – – Broad spectrum antiematodiasis drug (抗线虫病药), effective to ascaris(蛔虫), hookworm(钩虫), pinworm(蛲虫) and trichostrongylus(毛圆线虫) infection, but ineffective to whipworm (鞭虫). It can kill adult worms in the colon but not the eggs. The drug has no actions on flukes (吸虫)or tapeworms(绦虫). 3. Toxicity—Adverse effects are minor but include gastrointestinal distress, headache, and weakness. Use with caution in patients with hepatic dysfunction. Anthelmintic drugs Pyrvinum ambonate (恩波吡维胺, 扑蛲灵) It is a cyanine dyes(花青类染料), the therapeutic effect to pinworm(蛲虫) 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 DRUGS THAT ACT AGAINST CESTODES (TAPEWORMS) Niclosamide(氯硝柳胺) It was formerly an molluscacide(灭螺剂) to be sprinkled in paddy field and riverside to kill oncomelania(钉螺), which is intermediate host(中间宿主) of schistosoma(血吸虫). It can also kill cercaria(尾蚴) and miracidium(毛蚴) of schistosoma also. Later found it effective to varied taenia (绦虫) infection, especially effective to beef taenia infection. DRUGS THAT ACT AGAINST CESTODES (TAPEWORMS) Niclosamide(氯硝柳胺) 1. Mechanism—Niclosamide may act by uncoupling oxidative phosphorylation or by activating ATPases. 2. Clinical use • Niclosamide is an alternative drug to praziquantel for infections caused by beef, pork, and fish tapeworm. • It is not effective in cysticercosis (for which albendazole or praziquan-tel is used) or hydatid disease caused by Echinococcus granulosus (for which albendazole is used). • Scoleces and cestode segments are killed, but ova are not. • Niclosamide is effective in the treatment of infections from small and large intestinal flukes. • Application: • draft 1 g, and draft 1 g again 1 h later, after 1 ~ 2 hr then orally take MgSO4 to purgation(导泻). DRUGS THAT ACT AGAINST CESTODES (TAPEWORMS) Niclosamide(氯硝柳胺) 3. Toxicity • Toxic effects are usually mild but include gastrointestinal distress, headache, rash, and fever. • Some of these effects may result from systemic absorption of antigens from disintegrating parasites. • Ethanol consumption should be avoided for 24–48 h. Anthelmintic drugs Praziquantel Praziquantel(吡喹酮) •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(线虫病) and amebiasis. •It can be used to treat Taeniasis(绦虫病): Including varied imago(成虫) and larva (幼虫) infective disease, such as cysticercisis(囊虫病) and hydatidosis(包虫病). Anthelmintic drugs Praziquantel (1)intestinal taenia infection(肠绦虫感染): 10 or 25mg/kg, 一次顿服. (2)cysticercosis(囊虫症): ①common patients(皮下-肌肉型): 4 days course; ②cerebral patients(脑型病例): 9 days course, after 3~4 months to 2nd course. (3)hydatidosis(包虫病): the drug can kill protoscolex(原头蚴), have its infective ability , but can’t get cure, the effect is less than albendazole. Anthelmintic drugs 病 种 蛔虫感染: 蛲虫感染: 钩虫感染: 鞭虫感染: 绦虫感染: 囊虫病: 包虫病: Therapiutic drugs Mebendazole, Albendazole, Pyrantel, Piperazine Mebendazole, Albendazole, Pyrantel, Pyrvinum ambonates Mebendazole, Albendazole, Pyrantel Mebendazole Praziquantel, Niclosamide, Praziquantel, Albendazole Albendazole, Praziquantel, Mebendazole Anthelmintic drugs 药物 主要抗虫谱 作用机制 甲苯咪唑 线虫 (钩 鞭 蛲 蛔) 抑制虫体的微管功能 抑制葡萄糖摄取→ATP↓ 线虫 绦虫 吸虫 抑制葡萄糖摄取→ ATP↓ 少 脑囊虫治疗注意颅高压 线虫 (蛔 蛲) 对抗Ach → 松弛性麻痹 少 噻 嘧 啶 线虫 (蛔 钩 蛲) 去极化→ 痉挛性麻痹 少 不能与哌嗪合用 氯硝柳胺 各类绦虫 (牛肉 猪肉等) 抑制氧化磷酸化→ ATP↓ 少 三步曲防止虫卵逆行 阿苯达唑 (肠虫清) 哌 嗪 不良反应注意事项 少 蛔虫骚动 游走 The class is over !