section 15

Section 15.

感染性疾病与抗感染药(Infection disease and Anti-infective

drugs)第四部分

Anti-parasitic drugs( 抗寄生虫药 )

Part 11.

Part 11. Anti-parasitic Part 11. Anti-parasitic drugsdrugsA. Anti-malarial drugs( 抗疟药 )B. Anti-amebiasis and anti-

tricho-moniasis drugs( 抗阿米巴病和抗滴虫病药 )C. Anti-schistosomiasis and anti-

filariasis drugs( 抗血吸虫病和抗丝虫病药 )D. Anthelmintic drugs( 抗肠蠕虫药 )

A. Anti-malarial drugs ( 抗疟药 )1. Biology of malarial parasite: (1)Classification of malaria: Human malaria is caused by 4 species of

malarial parasite(plasmodium, 疟原虫 ), include: P. falciparum( 恶性疟原虫 ), P. vivax( 间日疟原虫 ), P. malariae( 三日疟原虫 ), P. ovale( 卵形疟原虫 ). Common malaria in our country are subtertian

malaria( 恶性疟 ) and tertian malaria( 间日疟 ). The conditions of tertian malaria are milder,

therefore, it is called benign malaria( 良性疟 ) too.

Anti-malarial drugsAnti-malarial drugs

•The malarial parasite, Plasmodium(The malarial parasite, Plasmodium( 疟原虫 ), is a very small, single-cell blood ), is a very small, single-cell blood organism. organism. •It lives as a parasite in other It lives as a parasite in other organisms, namely man and mosquito. organisms, namely man and mosquito.

•The parasite is the cause of the The parasite is the cause of the tropical disease malaria.tropical disease malaria.

AntimalarialAntimalarial drugsdrugs --MalarialMalarial parasiteparasiteAnti-malarial drugsAnti-malarial drugs

Antimalarial drugsAntimalarial drugs - - Parasite Life Cycle Parasite Life CycleAnti-malarial Anti-malarial

drugsdrugs

(2)Life cycle of malarial parasite: Although malaria can be transmitted by transfusion of infected blood, human beings are infected more commonly by sporozoites( 子孢子 ) injected by the bite of infected female mosquitoes.

①Asexual propagated stage in human body;

②Sexual propagated stage in female mosquitoes.

Anti-malarial Anti-malarial drugsdrugs

①Asexual propagated stage in human body:

▲Exo-erythrocytic stage: There are two types of sporozoites of tertian malaria( 间日疟 ), that is:

Tackysporozoite( 速发型子孢子 ), and Bradysporozoite( 迟发型子孢子 ). The tackysporozoites leave the circula-tion and localized in liver cells, then they rapidly transform, multiply and develop into schizonts( 裂殖体 ) and merozoites( 裂殖子 ).

There are no symptoms in this stage.


The bradysporozoites enter liver cells, then go into hypnozoite( 休眠期 ), they become to dormancytes( 休眠子 ), which is the source of tertian malaria relapse.

Pyrimethamine( 乙胺嘧啶 ) can kill tacky-sporozoites in the exo-erythrocytic stage.

Primaquine( 伯氨喹 ) can kill bradyspor-ozoites to radically treat tertian malaria ( 间日疟 ), and prevent tertian malaria rel-apse.


▲Erythrocytic stage: The schizonts( 裂殖体 ) then rupture, each releasing thousands of merozoites ( 裂殖子 ), then enter the circulation and invade erythrocytes, initiate the eryth-rocytic stage, and transform trophozoite ( 滋养体 ) and schizonts, then release many merozoites.

There are a lot of symptoms in this stage. Chloroquine( 氯喹 ), Quinine( 奎宁 ), and Artemisinin( 青蒿素 ) are effective to this stage, they can control the symptoms, and prevent attack of malaria.


②Sexual propagated stage in female mosquitoes:

Some erythrocytic malarial parasites differentiate into sexual forms known as gametocytes( 配子体 ).

The ♂ and ♀ gametocytes in the gut of the mosquito combine to thezygote( 合子 ), which develops in the gut wall to in-fective sporozoites( 子孢子 ), which invad-es salivary gland, become the source of infection.

Pyrimethamine can inhibit the deve-lopment of ♂ and ♀ gametocytes in mos-quito to control transmission of malaria.

Primaquine can kill various gameto-cytes of subtertian and tertian malaria.


1.1. Tissue schizonticidesTissue schizonticides 裂殖体杀灭剂裂殖体杀灭剂 eliminate eliminate developing or dormant liver forms; developing or dormant liver forms;

2.2. Blood schizonticidesBlood schizonticides act on erythrocytic act on erythrocytic parasites; parasites;

3.3. GametocidesGametocides 杀配子药杀配子药 kill sexual stages and kill sexual stages and prevent transmission to mosquitoes. prevent transmission to mosquitoes.

4.4. No one available agent can reliably effect a No one available agent can reliably effect a radical cure, ie, eliminate both hepatic and radical cure, ie, eliminate both hepatic and erythrocytic stages. erythrocytic stages.

5.5. Few available agents are causal prophylactic Few available agents are causal prophylactic drugs, ie, capable of preventing erythrocytic drugs, ie, capable of preventing erythrocytic infection.infection.

AntimalarialAntimalarial drugsdrugs -- DrugDrug ClassificationClassification


AntimalarialAntimalarial drugsdrugs -- ChloroquineChloroquine( 氯喹 )

•Chloroquine is a synthetic 4-aminoquinoline derivate


Pharmacological effectsPharmacological effects1. Antimalarial effects: 1. Antimalarial effects: erythrocytic stage•Rapid schizonticidal(Rapid schizonticidal( 裂殖体杀灭剂裂殖体杀灭剂 )activity )activity against all infections of malaria species . against all infections of malaria species . •gametocytocidal(gametocytocidal( 杀配子体杀配子体 )against P. vivax, )against P. vivax, P. malariae and P. ovale as well as immature P. malariae and P. ovale as well as immature gametocytes (stages 1-3) of P. falciparum. gametocytes (stages 1-3) of P. falciparum. •The effects are fast and lasting. The effects are fast and lasting. •The symptoms will vanish after oral administration The symptoms will vanish after oral administration of chloroquine in 24~48 h, blood malarial parasites of chloroquine in 24~48 h, blood malarial parasites disappear in 48 ~72 h, the recurrence rate in one disappear in 48 ~72 h, the recurrence rate in one month is low. month is low.

AntimalarialAntimalarial drugsdrugs -- ChloroquineChloroquineAnti-malarial Anti-malarial

drugsdrugsChloroquiChloroquinene

Pharmacological effectsPharmacological effects

2. Immune inhibition2. Immune inhibition•Treatment of rheumatoid Treatment of rheumatoid arthritis, lupus erythematosus arthritis, lupus erythematosus

3. Extraintestinal amebiasis3. Extraintestinal amebiasis•Amoeba trophozoite amebic Amoeba trophozoite amebic liver abscessliver abscess



Mechanism of actionsMechanism of actions

•Accumulation in erythrocyte→PH↑ → Accumulation in erythrocyte→PH↑ → malarial pigment sythesis↓malarial pigment sythesis↓•Haemoglobin-quinolineHaemoglobin-quinoline 喹啉喹啉 compound → haemoglobin accumulate compound → haemoglobin accumulate in plasmodium ↑in plasmodium ↑•Insert in the double stranded DNA Insert in the double stranded DNA helix → DNA replication and RNA helix → DNA replication and RNA transcription ↓transcription ↓



(2)(2)ADME of ADME of chloroquine:chloroquine:well absorbed after oral well absorbed after oral administration;administration; TTmaxmax = 3 = 3 ~~ 5 hr, t5 hr, t½½> 1 week;> 1 week; Widely distributed, the Widely distributed, the concentration in liver, lung, and concentration in liver, lung, and kidney is higher 200 ~ 700 times kidney is higher 200 ~ 700 times than blood;than blood; The concentration in erythrocyte The concentration in erythrocyte is higher 20 ~ 30 times than plasma; is higher 20 ~ 30 times than plasma; the concentration in infected the concentration in infected erythrocyte by malarial parasite is erythrocyte by malarial parasite is higher 25 times than normal higher 25 times than normal erythrocyte.erythrocyte.

Anti-malarial Anti-malarial drugsdrugsChloroquiChloroqui

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①Malaria: ▲ to control the symptoms of benign malaria( 良性疟 );

▲ to cure subtertian malaria( 恶性疟 ); ▲ symptomatic prevention in epidemic area( 疫区的症状性预防 ).

②Amebiasis( 阿米巴病 ): It can kill amebic trophozoite( 滋养体 ), to treat systemic amebiasis( 肠外阿米巴病 ), such as amebic hepatitis( 阿米巴肝炎 ) and amebic hepatic abscess( 阿米巴肝脓肿 ).

③Immune disease( 免疫性疾病 ).


(3)Clinical uses:ChloroquiChloroqui

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(4)Adverse reaction:Rare at the usual antimalarial dosagesRare at the usual antimalarial dosagesPruritus (Pruritus ( 搔痒症搔痒症 ) common among dark-) common among dark-skinned people.skinned people.

Transient headaches, nausea, vomiting, Transient headaches, nausea, vomiting, gastrointestinal symptoms and "blurred gastrointestinal symptoms and "blurred vision“.vision“.

Others: aplastic blood and neurological Others: aplastic blood and neurological disorders, such as polyneuritisdisorders, such as polyneuritis 多发性神经炎多发性神经炎 , , ototoxicity, seizures and neuromyopathy.ototoxicity, seizures and neuromyopathy.

Anti-malarial Anti-malarial drugsdrugsChloroquiChloroqui

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1.1.QuinineQuinine• MefloquineMefloquine 甲氟喹甲氟喹1.1.Pyronaridine Pyronaridine 咯萘啶咯萘啶• ArtemisininArtemisinin 青蒿素青蒿素• Artemether and artesunate Artemether and artesunate 蒿甲醚和青蒿琥酯蒿甲醚和青蒿琥酯

OtherOther angentsangents killkill erythrocyticerythrocytic parasitesparasites


Quinine( 奎宁 )Quinine is the chief alkaloid of cincho-na( 金鸡纳 ), the bark of the South Ameri-can

cinchona tree.(1)Anti-malarial action and clinical uses: Quinine acts primarily as a blood schi-zontocide( 杀裂殖体药 ) to control the clini-cal symptoms; It is a gametocide for gametocytes( 配子体 ) of P. vivax( 间日疟原虫 ) & P. malariae( 三日疟原虫 ) also, but not effective for game-tocytes of P. falciparum( 恶性疟原虫 ).

Anti-malarial Anti-malarial drugsdrugsquiniquini

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Quinine is more toxic and less effective than chloroquine.

but, it is especially valuable to treat: ①chloroquine-resistant and multidrug-resistant subtertian malaria( 耐氯喹和多药耐受的恶性疟 ),

②severe cerebral malaria( 严重的脑型疟 ). (2)Adverse reaction: more. ①Cinchonism( 金鸡纳反应 ): ringing in the ears( 耳鸣 ), headache, nausea, disturbed vision, etc.


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②Myocardial depression( 心肌抑制作用 ): to reduce myocardial contractility, and slow down conduction and prolong refra-ctory period, but weaker than quinidine ( 奎尼丁 , dextrogyre of quinine).

③Stimulating womb( 兴奋子宫 ): can induce abortion, not to be take by pregnant woman.

④Idiosyncrasy( 特异质反应 ): acute hemolytic reaction.


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Mefloquine( 甲氟喹 ) (1)Anti-malarial action:　 It is an efficient schizontocide in ery-throcytic stage, effective to chloroquine-resistant subtertian malaria.

(2)Clinical uses: ①to treat chloroquine-resistant subter-tian malaria.

②to prevent and control the symptoms of benign malaria, once/two week.

(3)Adverse reaction: GI reaction, nervous and pschic reaction.

Anti-malarial Anti-malarial drugsdrugsmefloquimefloqui

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Artemisinin(Qinghaosu, 青蒿素 ) (1)Anti-malarial action:　 It is a highly efficient malariacide of schizonts in erythrocytic stage.

The effects are faster than that of chloroquine, and effective to chloroquine-resistant subtertian malaria, especially effective to cerebral malaria.

(2)Clinical uses: to treat chloroquine-resistant subter-tian malaria, and to treat benign malaria also. but its recurrence rate is high.

(3)Adverse reaction: less, GI reaction, occasionally serum GPT .


Primaquine ( 伯氨喹 )(1)Anti-malarial action: can kill dormancytes( 休眠子 ) of tertian malaria and various gametocytes( 配子体 ) of subtertian malaria. Owing to elimination fast, the effects are not lasting.

Pharmacological effects Highly 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 parasitesThe only drug currently used for the treatment of relapsing malaria

Anti-malarial Anti-malarial drugsdrugsprimaquiprimaqui

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Pharmacological effectsPharmacological effects•Inhibition of proliferation of sporozoiteInhibition of proliferation of sporozoite子孢子子孢子 to schizont to schizont 裂殖体裂殖体•Prophylaxis of infectionsProphylaxis of infections

Mechanism of actionsMechanism of actions•Dihydrofolate reductase inhibitorDihydrofolate reductase inhibitor

Adverse effectsAdverse effects•Folate metabolism disturbtance Folate metabolism disturbtance

AntimalarialAntimalarial drugsdrugs -- PyrimethaminePyrimethamineAnti-malarial Anti-malarial

drugsdrugs

AntimalarialAntimalarial drugsdrugs -- PrimaquinePrimaquineAnti-malarial Anti-malarial

drugsdrugs

(2)Mechanism of actionsInhibition of coenzyme Q Inhibition of reduction of NADP

(3)Clinical uses: ①use it with chloroquine to radically treat benign malaria( 良性疟 ); ②to prevent transmission of subterti-an malaria( 恶性疟 ).

primaquiprimaquinene

(3)Adverse reaction: Its toxicity is large nervous system :Transient dizziness ,

nausea, vomiting, gastrointestinal symptoms

blood system:Acute hemolytic anemia(( 急性溶血性贫血 ), methemoglobinemia 高铁血红蛋白血症

primaquiprimaquinene


Pyrimethamine( 乙胺嘧啶 )(1)Anti-malarial action: ①It can kill schizonts( 裂殖体 ) of subter-tian malarial parasites and benign mala-rial parasites in exo-erythrocytic stage;

② It can also kill immature schizonts of erythrocytic stage;

③It can not kill gametocytes( 配子体 ), but can inhibit development of sporop-hytes( 孢子体 ) in mosquito.

Anti-malarial Anti-malarial drugsdrugsprimethamiprimethami

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(2)Clinical uses:　 It is mainly used to prevent malaria, the first chosen drug for malarial prev-ention.

(3)Adverse reaction: Its toxicity is less. But long-term and larger dose admi-nistration, it can cause megaloblastic anemia( 巨红细胞贫血 ).

This adverse reaction can be treated by formyl tetrahydrofolic acid( 甲酰四氢叶酸 ).

In addition, once large dose can cause acute intoxication.

Anti-malarial Anti-malarial drugsdrugsprimethamiprimethami

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3. Summarization:(1)Selection of antimalarial drugs:①Symptom control: Chloroquine;②Cerebral malaria: Artemisinin, im. Quinine dihydrochloride, iv gtt; ③Chloroquine-resistant subtertian malaria: Artemisinin, Quinine, Mefloquine; ④Resting stage: Pyrimethamine + Primaquine;⑤Prevent transmission: Pyrimethamine. (2)Combined administration: Chloroquine + Primaquine; Pyrimethamine + Primaquine( 防止复发 ).


B. Anti-amebiasis and anti-trichomoniasis drugs

( 抗阿米巴病和抗滴虫病药 )

Life cycle of amebic parasite

B1. Anti-amebiasis drugs(amebicides)

Life cycle of amebic parasite: 当机体抵抗力包囊　小滋养体　　大滋养体　　肠壁　肝、脑、肺　在小肠下段伪足 , 溶组织酶引起肠外阿米巴病

阿米巴痢疾　　　　　　包囊排出体外

当当机体抵机体抵抗力强时抗力强时

Amebiasis is infection with Entamoeba histolytica,Amebiasis is infection with Entamoeba histolytica, A tiny, one-celled organism. A tiny, one-celled organism.

B1. Anti-amebiasis drugs (amebicides)

http://www.enchantedlearning.com/cgi-bin/paint/fa/subjects/protists/amoeba.shtml

Intestinal AmebiasisIntestinal Amebiasis

Extraintestinal AmebiasisExtraintestinal Amebiasis

Features of AmebiasisFeatures of Amebiasis

http://content.nejm.org/content/vol348/issue16/images/large/09f2.jpeg

http://content.nejm.org/content/vol348/issue16/images/large/09f3.jpeg

Multiplication and life cycle of Multiplication and life cycle of E histolyticaE histolytica


Classification of amebiasis: Luminal amebiasis(): Amebic dysentery( 阿米巴痢疾 ), Asyptomatic carrier( 无症状带虫者 ) Systemic amebiasis: Amebic hepatitis( 阿米巴肝炎 ), hepatic abscess( 阿米巴肝脓肿 ) Mixed amebiasis.

Anti-amebiasis Anti-amebiasis drugsdrugs

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.


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.


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%.


③Anti-anaerobic bacteria infection: The sensitive anaerobic bacteria to metronidazole including: ▲ All anaerobic cocci( 所有的厌氧球菌 ); ▲G- anaerobic bacillus(G-厌氧杆菌 ) and 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.


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.


Tinidazole ( 替硝唑 )Its pharmacological effects are the same as that of metronidazole. Its characteristics is that: The t½(12~24h) is longer than metro-nidazole(t½ 8h), after once oral adminis-tration, its effective blood concentration keep 72h, and its toxicity is less than me-tronidazole.


Emetine( 依米丁 , 吐根碱 ) & Dehydroemetine( 去氢依米丁 )They can kill amebic trophozoite in tissue directly. Their adverse reaction are more and severe, their irritative action is strong, can cause vomiting(emesis) by oral ad-ministration, 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.


Halogenate quinolines( 卤化喹啉类 ): Chiniofon ( 喹碘仿 ) Clioquinol( 氯碘羟喹 ), Diiodohydroxyquinoline( 双碘喹啉 ) They can kill amebic protozoa directly. Its

absorption is less by oral administra-tion, so that they are used to treat intestinal

amebiasis, such as the patients of evacu-ating cyst( 包囊 ).

In 1960s, find those drugs cause sub-acute myelo-opticoneurooathy( 亚急性脊髓 - 视神经病 ) in Japan, clioquinol can cause blindness, therefore, it is not used now.


Diloxanide( 二氯尼特 )It can kill amebic cyst. The parts of unabsorption can kill amebic cyst and small trophozoite in intestinal cavity, effective to asyptomatic passers and the patients of evacuating amebic cyst.

The therapeutic effect is not so good to acute amebic dysentery, after control-ling symptoms by metronidazole, treat it with diloxanide to kill the small tropho-zoite in intestinal tract, can radically cure amebic infection.

Diloxanide is ineffective to systematic amebiasis.


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 of amebic protozoan, then inhibit survi-vor and proliferation of ameba.

It is used to treat acute amebiasis.


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 lever (the Concentration in lever is 700 times higher than the Cp). Therefore, chloroquine can treat 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.


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二氯尼特喹碘方 / 巴龙霉素急性阿米巴痢疾甲硝唑甲硝唑甲硝唑甲硝唑 ++ 二氯尼特二氯尼特

甲硝唑甲硝唑 ++ 喹碘方甲硝唑甲硝唑 ++ 巴龙霉素甲硝唑甲硝唑 ++ 依米丁依米丁

慢性阿米巴痢疾甲硝唑甲硝唑二氯尼特二氯尼特 + 喹碘方阿米巴肝脓肿甲硝唑甲硝唑依米丁依米丁 ++ 氯喹氯喹 ++ 二氯尼二氯尼

特特甲硝唑甲硝唑 ++ 氯喹氯喹甲硝唑甲硝唑 ++ 喹碘方 / 巴龙霉素


B2. 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.

Metronidazole( 甲硝唑 )　　　 It is the most effective drug to infec-tion 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 Anti-trichomoniasis drugsdrugs

Acetarsol( 乙酰胂胺 )Acetarsol is a preparation of five-valence 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 metro-nidazole-resistance.

Anti-trichomoniasis Anti-trichomoniasis drugsdrugs

Let’s take a rest !

C. Anti-schistosomiasis and

anti-filariasis drugs( 抗血吸虫病和抗丝虫病药 )

C1. Anti-schistosomiasis drugs( 抗血吸虫病药 )

Schistosomiasis( 血吸虫病 ) is caused by Schistosoma( 血吸虫 , 裂体吸虫 ) infection.

There are five kinds of Schistosoma caused Schistosomiasis of human:

S. japonia( 日本血吸虫 ), S. heamatobium ( 埃及血吸虫 ), S. mansoni( 曼索血吸虫 ), S. intercalatum( 间插血吸虫 ) and S. mekongi ( 湄公血吸虫 ).

In our country, the schistosomiasis is caused mainly by S. japonia.

肝硬化主征肝硬化主征巨脾巨脾腹水腹水门脉高压门脉高压

In the past, the drug treated schisto-somiasis was PAT( 酒石酸锑钾 , potassium antimony tartrate), its course of treat-ment was longer, the toxicity larger, need iv administration, and the ADRs were severe. Since 1970’, praziquantel( 吡喹酮 ) had be discovered, because its ADRs is less, praziquantel became the main drug to treat schistosomiasis.

Anti-schistosomiasis Anti-schistosomiasis drugsdrugs

Praziquantel( 吡喹酮 )(1)Anti-parasite effects: It is a highly effective and broad spec-trum anti-parasite drug.

It can kill schistosoma( 血吸虫 ) directly; and it can kill other trematde( 吸虫 ) too, e.g. clonorchis sinensis( 华支睾吸虫 , 即“肝吸虫” ), lung fluke( 肺吸虫 ), fasciolopsis( 布氏姜片虫 , 即“肠吸虫” ); certain intestinal parasites(e.g. tapeworm( 绦虫 ).

Mechanism of anti-schistosoma effects: It can increase the membrane perme-ability to certain monovalent and dival-ent cation, particularly Ca2+, to cause schistosoma muscular contraction and spastic paralysis.


(2)Clinical uses:①Schistosomiasis( 血吸虫病 ): It is effective to both acute & chronic schistosomiasis.

To acute schistosomiasis: It is to bring down the fever, and alleviate the systematic symptoms fast, the late results reach 90%;

To chronic schistosomiasis: The curative effect is well too, only 1 ～ 2 days of course of treatment, the late results reach 90% too.

To the later period patients with cardiac and hepatic complication:

can accept the course of treatment smoothly.


②Clonorchiasis( 华枝睾吸虫病 ): It is the first-chosen drug.③Other trematode( 其他吸虫 ): Used to treat paragonimiasis( 肺吸虫病 ) and fasciolopsiasis( 姜片虫病 ). It is the first-chosen drug.④Taeniasis( 绦虫病 ): Including imago( 成虫 ) & larva( 幼虫 ) of various tapeworm( 绦虫 ) infective disease, such as cysticercisis( 囊虫症——猪囊虫尾蚴病 ) and hydatidosis( 包虫病——由细粒棘球绦虫的幼虫引起 ). It is the first-chosen drug too.


(3)Adverse reaction less and lighter (than potassium anti-mony tartrate, 酒石酸锑钾 ). After oral administration, it can cause abdominal pain, nausea, dizziness, and headache in short-term.


C2. Anti-filariasis

drugs( 抗丝虫病药 )

Anti-filariasis Anti-filariasis drugsdrugs

下肢象皮肿

阴囊象皮肿


Diethylcarbamazine Diethylcarbamazine 乙乙胺嗪胺嗪Pharmacology actionPharmacology actionDiethylcarbamazine immobilizes Diethylcarbamazine immobilizes microfilariae(microfilariae( 微丝蚴微丝蚴 )and alters their )and alters their surface structure, displacing them from surface structure, displacing them from tissues and making them more tissues and making them more susceptible to destruction by host susceptible to destruction by host defense mechanisms. defense mechanisms. The mode of action against adult The mode of action against adult worms is unknown.worms is unknown.


DiethylcarbamazineDiethylcarbamazineAdverse effectsAdverse effectsGenerally mild and transientGenerally mild and transientInclude headache, malaise, anorexia, Include headache, malaise, anorexia, weakness, nausea, vomiting, and weakness, nausea, vomiting, and dizziness.dizziness.


D. Anthelmintic drugs ( 抗肠蠕虫药 )

hookworm ( 钩虫 )

Pinworm( 蛲虫 )

Whipworm( 鞭虫 )

Fasciolopsis

( 姜片虫 )

ascaris( 蛔虫 )

Tapeworm( 绦虫 )

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, there-fore, to treat helminthiasis become very easy in clinic.

At the same time, the drugs that we learn are very less.

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 Anthelmintic drugsdrugs

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: ① Intestinal 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.


②Exo-intestinal parasitosis: It is a very efficacious drug for exo-intestinal parasitic disease, such as hyda-tidosis( 包虫病 ), cysticercosis( 囊虫病 ), tri-chinosis( 旋毛虫病 ), clonorchiasis( 华支睾吸虫 ), paragonimiasis( 肺吸虫病 ).

Mebendazole is ineffective to those diseases, because abendazole is absorb-ed fast, its blood concentration is 100 times higher than that of mebendazole, the concentration in liver and lung is re-latively high, therefore, abendazole can enter hydatidocystis( 棘球幼囊 ).


(2)Clinical Uses: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.


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 ).


(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.


1.1. Piperazine Piperazine 哌嗪哌嗪2.2. Levamisole Levamisole 左旋咪唑左旋咪唑3.3. Pyrantel Pyrantel 噻嘧啶噻嘧啶4.4. Niclosamide Niclosamide 氯硝柳胺氯硝柳胺5.5. Praziquantel Praziquantel 吡喹酮吡喹酮

Other Anthelmintic DrugsOther Anthelmintic Drugs


Piperazine( 哌嗪 , 驱蛔灵 ) Effective to ascaris( 蛔虫 ) & pinworm ( 蛲虫 ), but the curative effect is less than albendazole, the merit of albendazole is side action less. Pyrantel( 噻嘧啶 , 驱虫灵 ) 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 ).


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.


Niclosamide( 氯硝柳胺 )It was formerly an molluscacide( 灭螺剂 ) to be sprinkled in paddy field and riversi-de to kill oncomelania(钉螺 ), which is int-ermediate host(中间宿主 ) of schistosoma.

It can also kill cercaria( 尾蚴 ) and mira-cidium( 毛蚴 ) of schistosoma also.

Later found it effective to varied taenia ( 绦虫 ) infection, especially effective to be-ef taenia infection.

Application: draft 1 g, and draft 1 g again 1 h later, after 1 ~ 2 hr then orally take MgSO4 to purgation(导泻 ).


Praziquantel( 吡喹酮 )It is a broad spectrum anti-parasitic drug too. It can be used to treat schisto-somiasis, and used to treat certain intes-tinal 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 cysticer-cisis( 囊虫病 ) and hydatidosis( 包虫病 ).


(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.


病种　 Therapiutic drugs 蛔虫感染 : Mebendazole, Albendazole, Pyrantel, Piperazine 蛲虫感染 : Mebendazole, Albendazole, Pyrantel, Pyrvinum ambonates 钩虫感染 : Mebendazole, Albendazole, Pyrantel 鞭虫感染 : Mebendazole 绦虫感染 : Praziquantel, Niclosamide, 囊虫病 : Praziquantel, Albendazole 包虫病 : Albendazole, Praziquantel, Mebendazole


药物主要抗虫谱作用机制不良反应注意事项甲苯咪唑线虫

( 钩鞭蛲蛔 )抑制虫体的微管功能

抑制葡萄糖摄取→ ATP↓少

蛔虫骚动游走阿苯达唑

( 肠虫清 )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哌嗪线虫

( 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


The class is over The class is over !!

section 15

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