Download Anthelmintic drugs

Anti-amebiasis and anti-trichomoniasis
drugs (抗阿米巴病和抗滴虫病药)
& Anthelmintic drugs (抗肠蠕虫药)
Huifang Tang
[email protected]
A. Anti-amebiasis and
anti-trichomoniasis drugs
(抗阿米巴病和抗滴虫病药)
Life cycle of amebic parasite
A1. 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
当机体抵
抗力强时
包囊
阿米巴痢疾
排出体外
A1. Anti-amebiasis drugs (amebicides)
Amebiasis is infection with Entamoeba histolytica(溶组织内
阿米巴), A tiny, one-celled organism.
Features of Amebiasis
Extraintestinal Amebiasis
Intestinal Amebiasis
A1. Anti-amebiasis drugs (amebicides)
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.
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);
▲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.
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)
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 metronidazole.
Anti-amebiasis drugs
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.
Anti-amebiasis drugs
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.
Anti-amebiasis drugs
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 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 of
amebic protozoan, then inhibit survi-vor 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
lever (the Concentration in lever is 700 times
higher than the Cp).
Therefore, chloroquine can treat exointestinal 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
喹碘方/巴龙霉素
急性阿米巴痢疾
甲硝唑
甲硝唑+二氯尼特
甲硝唑+喹碘方
甲硝唑+巴龙霉素
甲硝唑+依米丁
慢性阿米巴痢疾
甲硝唑
二氯尼特+喹碘方
阿米巴肝脓肿
甲硝唑
依米丁+氯喹+二氯尼特
甲硝唑+氯喹
甲硝唑+喹碘方/巴龙霉素
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
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 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 metro-nidazole-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, there-fore,
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; teratogenesis and embryotoxicity.
Anthelmintic drugs
Albendazole(阿苯达唑, “肠虫
Albendazole
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 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).
Anthelmintic drugs
Albendazole
(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): hospitalization.
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)
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).
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
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).
Anthelmintic drugs
Praziquantel
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).
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 !