Anti-parasitic drugs ( 抗寄生虫药 ). huifang Tang [email protected] Anti-parasitic drugs. 1. Anti-malarial drugs ( 抗疟药 ) 2. Anti-schistosomiasis and anti-filariasis drugs ( 抗血吸虫病和抗丝虫病药 ) 3. Anti-amebiasis and anti-trichomoniasis drugs ( 抗阿米巴病和抗滴虫病药 ) 4. Anthelmintic drugs ( 抗肠蠕虫药 ).
1. Anti-malarial drugs(抗疟药)
2. Anti-schistosomiasis and anti-filariasis drugs(抗血吸虫病和抗丝虫病药)
3. Anti-amebiasis and anti-trichomoniasis drugs(抗阿米巴病和抗滴虫病药)
4. Anthelmintic drugs(抗肠蠕虫药)
1. Biology of malarial parasite:
(1)Classification of malaria:
Human malaria is caused by 4 species of malarial parasite(plasmodium,疟原虫), include:
Common malaria in our country aresubtertian malaria(恶性疟) andtertianmalaria(间日疟).
The conditions of tertian malariaare milder, therefore, itis calledbenign malaria(良性疟)too.
Parasite Life Cycle
(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.
There are two types of sporozoites of tertian malaria(间日疟), that is:
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.
Thebradysporozoitesenter liver cells, then go into hypnozoite(休眠期), they become to dormancytes(休眠子), which is the source of tertian malaria relapse.
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 infective sporozoites(子孢子), which invades salivary gland, become the source of infection.
Pyrimethamine can inhibit the development of ♂ and ♀ gametocytes in mosquito to control transmission of malaria.
Primaquine can kill various gametocytes of subtertian and tertian malaria.
Mechanism of actions
well absorbed after oral administration;
Tmax = 3~5 hr, t½> 1 week;
Widely distributed, the concentration in liver, lung, and kidney is higher 200 ~ 700 times than blood;
The concentration in erythrocyte is higher 20 ~ 30 times than plasma; the concentration in infected erythrocyte by malarial parasite is higher 25 times than normal erythrocyte.
▲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).
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).
Rare at the usual antimalarial dosage
Pruritus (搔痒症) common among dark-skinned people.
Transient headaches, nausea, vomiting, gastrointestinal symptoms and "blurred vision“.
Others: aplastic blood and neurological disorders, such as polyneuritis多发性神经炎, ototoxicity, seizures and neuromyopathy.
Artemether and artesunate
Quinineis 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:
Quinineacts 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).
Quinineis 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).
ringing in the ears(耳鸣), headache, nausea, disturbed vision, etc.
to reduce myocardial contractility, and slow down conduction and prolong refra-ctory period,but weaker thanquinidine (奎尼丁, dextrogyre of quinine).
can induce abortion, not to be take by pregnant woman.
acute hemolytic reaction.
It isan efficient schizontocide in ery-throcytic stage, effective to chloroquine-resistant subtertian malaria.
①to treat chloroquine-resistant subter-tian malaria.
②to prevent and control the symptoms of benign malaria, once/two week.
nervous and pschic reaction.
It isa 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.
to treat chloroquine-resistant subter-tian malaria,and to treatbenign malaria also. but its recurrence rate is high.
(3)Adverse reaction: less,
GI reaction, occasionally serum GPT.
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.
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 parasites
The only drug currently used for the treatment of relapsing malaria
(2)Mechanism of actions
Inhibition of coenzyme Q
Inhibition of reduction of NADP
①use it withchloroquineto radically treat benign malaria(良性疟);
②to prevent transmission ofsubterti-an malaria(恶性疟).
Itstoxicity 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
①It can killschizonts(裂殖体) of subter-tian malarial parasites and benign mala-rial parasites in exoerythrocytic stage;
②It can also killimmature schizonts of erythrocytic stage;
③It can not kill gametocytes(配子体), but can inhibit development of sporop-hytes(孢子体) in mosquito.
Mechanism of actions
Dihydrofolate reductase inhibitor
Itis mainly used to prevent malaria, the first chosen drug for malarial prevention.
(3)Adverse reaction: Folate metabolism disturbtance
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.
(1)Selection of antimalarial drugs:
①Symptom control: Chloroquine;
Quinine dihydrochloride, iv gtt(静脉滴注);
③Chloroquine-resistant subtertian malaria:
Artemisinin, Quinine, Mefloquine;
Pyrimethamine + Primaquine;
⑤Prevent transmission: Pyrimethamine.
Chloroquine + Primaquine;
Pyrimethamine + Primaquine(防止复发).
Part2 Anti-schistosomiasis drugs(抗血吸虫药)
It is a highly effective and broad spectrum anti-parasite drug.
Mechanism of anti-schistosoma effects:
It can increase the membrane permeability to certain monovalent and divalent cation, particularly Ca2+, to cause schistosoma muscular contraction and spastic paralysis.
It is effective to both acute & chronicschistosomiasis.
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.
It is the first-chosen drug.
Used to treat paragonimiasis(肺吸虫病) and fasciolopsiasis(姜片虫病).
It is the first-chosen drug.
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.
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.
C. anti-filariasis drugs (抗丝虫病药)
Generally mild and transient