1. Antiparasitic Chemotherapy
Chapter 46
Antiparasitic Chemotherapy
Yun-Bi Lu, PhD 卢韵碧 Dept. of Pharmacology, School of Medicine, Zhejiang University

2. Human parasite Protozoa （原虫）：孢子虫－疟原虫 鞭毛虫－阴道毛滴虫 叶足虫－阿米巴原虫 纤毛虫－结肠小袋纤毛虫
Helminth （蠕虫）：吸虫－血吸虫
绦虫－链状带绦虫
线虫－蛔虫、丝虫
Arthropod （节肢动物）：蛛形纲－蜱、螨
昆虫纲－蚊、蝇、虱

3. Contents 1. Anti-malarial drugs (抗疟药)
2. Anti-amebiasis and anti-trichomoniasis drugs (抗阿米巴病和抗滴虫病药)
3. Anti-schistosomiasis and anti-filariasis drugs (抗血吸虫病和抗丝虫病药)
4. Anthelmintic drugs (抗肠蠕虫药)

5. Anti-malarial Drugs Malarial parasite (plasmodium, 疟原虫)
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) & tertian malaria (间日疟). The conditions of tertian
malaria are milder, therefore, the latter is called benign
malaria(良性疟).

6. 红细胞外期
按蚊－有性繁殖
人体－无性繁殖
红细胞内期

7. Anti-malarial Drugs Drugs controlling symptoms
-Chloroquine (氯喹), quinine(奎宁), artemisinin (青蒿素)
Drugs controlling relapse and transmission
-primaquine(伯氨喹)
Drugs for etiological prevention
-primethamine(乙胺嘧啶)
No one available agent can reliably effect a radical cure, ie, eliminate both exo-erythrocytic and erythrocytic stages.
Few available agents are causal prophylactic drugs, ie, capable of preventing erythrocytic infection.

9. 红细胞外期 按蚊－有性繁殖 红细胞内期 病因预防 Pyrimethamine （乙胺嘧啶）速发 控制复发 Primaquine
（伯氨喹） 迟发
红细胞内期
阻止传播
Pyrimethamine
（乙胺嘧啶）
控制症状
Chloroquine（氯喹）
Quinine（奎宁）
Mefloquine（甲氟喹）
Artemisinin（青蒿素）
阻止传播
Primaquine （伯氨喹）
Chloroquine （氯喹）
Quinine （奎宁）
（恶性疟无效）

10. Antimalarial drugs – Chloroquine （氯喹）
红细胞内期
控制症状
Chloroquine 氯喹
Quinine 奎宁
Mefloquine 甲氟喹
Artemisinin 青蒿素
Chloroquine is a synthetic 4-aminoquinoline derivate

11. Antimalarial drugs - Chloroquine
1. Antimalarial effects
Schizonticidal activity (裂殖体杀灭剂) and
gametocytocidal (杀配子体, but not for P.falciparum).
The effects are fast and lasting.
The clinical symptoms will vanish after administration of
chloroquine in h, blood malarial parasites
disappear in h.

12. Antimalarial drugs - Chloroquine
Mechanism of anti-malarial action:
Alkalinization of food vacuole
Damage mediated by accumulated heme
Decreased DNA synthesis
Clinical Uses:
Treatment of malaria:
Controlling the symptoms of malaria
Symptomatic prevention in epidemic area.
It is not active against exo-erythrocytic form, and should therefore be used with primaquine（伯氨喹）to effect radical cure of P. vivax (间日疟).

13. Antimalarial drugs - Chloroquine
Clinical Uses:
2. Treatment of amebiasis(阿米巴病):
treating 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).
Immunosuppression
Treatment of rheumatoid arthritis, lupus erythematosus

14. Antimalarial drugs - Chloroquine
Adverse Reactions:
Be less in anti-malarial dose, occasionally dizziness, tinnitus(耳鸣), dysphoria(烦躁), skin itching, and GI reaction.
In high dose, visual disturbance can occur
Quinidine-like effects
Others: aplastic blood and neurological disorders, such as polyneuritis (多发性神经炎), seizures and neuromyopathy.
Teratogenesis(致畸作用)

15. Antimalarial drugs – Primaquine （伯氨喹）
红细胞外期
按蚊－有性繁殖
控制复发
Primaquine
(伯氨喹) 迟发
红细胞内期
阻止传播
Primaquine (伯氨喹)
Chloroquine (氯喹)
Quinine (奎宁)
（恶性疟无效）

16. Pharmacological effects
Antimalarial drugs – Primaquine (伯氨喹)
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 parasites
The only drug currently used for the treatment of relapsing malaria (疟疾复发).

17. Mechanism of actions Adverse effects
Antimalarial drugs – Primaquine （伯氨喹）
Mechanism of actions
Inhibition of coenzyme Q
Inhibition of reduction of NADP
Adverse effects
Transient dizziness , nausea, vomiting, gastrointestinal symptoms
Acute hemolytic anemia (急性溶血性贫血), methemoglobinemia (高铁血红蛋白血症)

18. Antimalarial drugs – Pyrimethamine （乙胺嘧啶）
红细胞外期
按蚊－有性繁殖
病因预防
Pyrimethamine
(乙胺嘧啶) 速发
Pyrimethamine
(乙胺嘧啶)
红细胞内期

19. Antimalarial drugs – Pyrimethamine （乙胺嘧啶）
Pharmacological effects
Inhibition of proliferation of sporozoite (子孢子) to schizont (裂殖体)
Prophylaxis of infections
Mechanism of actions
Dihydrofolate reductase inhibitor
Adverse effects
Folate metabolism disturbtance

20. 用于控制症状的抗疟药
Chloroquine （氯喹）、Quinine （奎宁）、
Mefloquine （甲氟喹）、Pyronaridine (咯萘啶)、Artemisinin (青蒿素) 、
Artemether and artesunate (蒿甲醚和青蒿琥酯)
用于控制复发和传播的抗疟药
Primaquine （伯氨喹）
用于病因性预防的抗疟药
Pyrimethamine （乙胺嘧啶）

21. symptom？

22. 复发？ 传播？ 控制症状 Chloroquine（氯喹） Quinine（奎宁） Mefloquine（甲氟喹）
Artemisinin（青蒿素）
传播？

23. 病因预防？ 控制复发 Primaquine （伯氨喹） 迟发 阻止传播 Primaquine （伯氨喹） Chloroquine （氯喹）
Quinine （奎宁）
（恶性疟无效）

24. 病因预防
Pyrimethamine
(乙胺嘧啶) 速发
阻止传播
Pyrimethamine
（乙胺嘧啶）

25. Antimalarial drugs – Summary
Selection of antimalarial drugs
Symptom control: Chloroquine;
Cerebral malaria: Artemisinin, im.
Quinine dihydrochloride, iv
Chloroquine-resistant subtertian malaria:
Quinine, Artemisinin.
Resting stage: Pyrimethamine+ Primaquine
Prevent transmission: Pyrimethamine
Combined administration
Chloroquine+ Primaquine
Pyrimethamine+ Primaquine

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

27. Extraintestinal Amebiasis
Features of Amebiasis
Amebiasis is infection with Entamoeba histolytica.
（溶组织内阿米巴原虫 ）
Classification of amebiasis
Asymptomatic intestinal infection;
Mild to moderate colitis;
Severe intestinal infection (dysentery);
Extraintestinal infections: ameboma, liver abscess.
Extraintestinal Amebiasis
Intestinal Amebiasis

28. Classification of amebiasis
1. Luminal amebiasis(肠内感染): Amebic dysentery(阿米巴痢疾) Asyptomatic passers(无症状带虫者)
2. Systemic amebiasis(肠外感染):
Amebic hepatitis(阿米巴肝炎) &
Hepatic abscess (阿米巴肝脓肿) , etc.　
3. Mixed amebiasis

29. Anti-amebiasis drugs (amebicides)
Metronidazole(甲硝唑);
Emetine(依米丁) & Dehydroemetine(去氢依米丁);
Diloxannide(二氯尼特);
Paromomycin(巴龙霉素);
Chlorpromaquin(氯喹), etc.

30. Antiamebiasis drugs - Metronidazole 甲硝唑
Pharmacological effects
1. Anti-ameba effects (肠内、肠外)
The treatment of all tissue infections with E histolytica
2. Anti-trichomoniasis (抗滴虫)
3. Anti-anaerobic bacteria infection
All anaerobic cocci (所有的厌氧球菌);
G- anaerobic bacillus (厌氧杆菌);
G+ spore anaerobic bacillus (芽孢厌氧杆菌);
4. Anti-giardia lamblia (贾第氏鞭毛虫)effect
Anti-amebiasis effects:
Potent amebicidal activity against large trophozoite, but no affect to small trophozoite.
Treating acute amebic dysentery and all systemic amebiasis, but having no affect to asyptomatic passers.
To radically treatment of purely luminal amebicides, it is used in combination with diloxanide(二氯尼特).

31. Antiamebiasis drugs - Metronidazole
Mechanism of actions
The methyl group of metronidazole is chemically reduced in anaerobic bacteria and sensitive protozoans.
Reactive reduction products appear to be responsible for antimicrobial activity.
Rapidly absorbed and has a bioavailability of approximately 90%

32. Antiamebiasis drugs - Metronidazole
Adverse effects
Minor side effects：nausea, headaches, loss of appetite, a metallic taste, and rarely a rash.
Serious side effects：seizures and damage of nerves resulting in numbness and tingling of extremities (肢体麻木，peripheral neuropathy).
Teratogenesis

33. Emetine依米丁& dehydroemetine去氢依米丁
Amebicide effects: kill trophozoite (滋养体)
Mechanism of actions: protein synthesis inhibitor.
Clinic uses:
Amebic liver abscess , Acute amebic dysentery(痢疾)
Used in case of resistance to metronidazole.

34. Emetine依米丁& dehydroemetine去氢依米丁
Adverse effects
GI effect: Nausea, vomiting and diarrhoea.
Cardiac toxicity: Palpitations, tachycardia, retrosternal pain, hypotension, dyspnoea, ECG changes (ST depression, QT prolongation, T-wave inversion).
Neuromuscular blockade: Tremor, myasthenia and paralysis including respiratory paralysis.
Injection site effect

35. Antiamebiasis drugs - Other amebicides
Diloxanide 二氯尼特
persons infected with asymptomatic amebiasis (无症状的阿米巴病) .
Paromomycin 巴龙霉素
Acute amebic dysentery (痢疾)
Chloroquine 氯喹
Extraintestinal amebiasis
Diloxanide furoate is slowly absorbed from the gastrointestinal tract and can therefore provide an adequate concentration of the medication in the intestinal lumen for a long period of time. Destroys the trophozoites of E. histolytica that eventually form into cysts. (包囊)
Paromomycin 巴龙霉素
Aminoglycosides antibiotics.
Not significantly absorbed from the gastrointestinal tract
Mechanism of actions:
Acts by inhibition protein synthesis.
Direct and indirect action of amebicide
Clinical usage:
Amebic dysentery (阿米巴痢疾)
No effect against extraintestinal amebic infections.

36. Diloxanide 二氯尼特, Paromomycin 巴龙霉素
Antiamebiasis drugs
Persons infected with asymptomatic amebiasis
(无症状的阿米巴病):
Diloxanide 二氯尼特, Paromomycin 巴龙霉素
Amebic dysentery (痢疾):
Metronidazole 甲硝唑 + Diloxanide
Metronidazole 甲硝唑 + Paromomycin
Extraintestinal amebiasis:
Diloxanide furoate is slowly absorbed from the gastrointestinal tract and can therefore provide an adequate concentration of the medication in the intestinal lumen for a long period of time. Destroys the trophozoites of E. histolytica that eventually form into cysts. (包囊)
Paromomycin 巴龙霉素
Aminoglycosides antibiotics.
Not significantly absorbed from the gastrointestinal tract
Mechanism of actions:
Acts by inhibition protein synthesis.
Direct and indirect action of amebicide
Clinical usage:
Amebic dysentery (阿米巴痢疾)
No effect against extraintestinal amebic infections.

37. Anti-trichomoniasis drugs (Trichomonacides)
Metronidazole (甲硝唑)
The most effective drug to treat the infection of Trichomonas vaginalis.
Acetarsol (乙酰胂胺)
Preparation of five-valence arsine and can kill Trichomonas vaginalis directly.

38. Bilharziasis 急性 发热 过敏反应 腹痛、腹泻 肝脾肿大
Anti-bilharziasis (血吸虫) & filariasis (丝虫) Drug
Bilharziasis 急性 发热
过敏反应
腹痛、腹泻
肝脾肿大

39. Anthelmintic Actions (驱虫作用)
Praziquantel 吡喹酮
Anthelmintic Actions (驱虫作用)
Schistosomiasis (血吸虫病)
Clonorchiasis, Opisthorchiasis (支睾吸虫病),
Paragonimiasis (肺吸虫病)
Taeniasis (绦虫病)、Diphyllobothriasis (裂头绦虫病）
H Nana (缩小膜壳绦虫)
Neurocysticercosis (脑囊虫病)
Hydatid Disease (包虫病)
Others： fasciolopsiasis(布氏姜片虫病),
metagonimiasis(后殖吸虫病)
heterophyiasis(异形吸虫病)
Fascioliasis(片形吸虫病)

40. Praziquantel 吡喹酮 Mechanism of actions
Mechanism of anti-Schistosoma action:
Increase the membrane permeability for certain monovalent & divalent cation, particular Ca2+, and cause Schistosoma muscular contraction and spastic paralysis.
Damage the epidermis of schistosoma.

41. Mechanism of Praziquantel anti-Schistosoma action.

42. Praziquantel 吡喹酮 Adverse reactions:
Abdominal pain, nausea, dizziness, and headache in short-term
Hypersensitive effects

43. Anti-filariasis drug - Diethylcarbamazine 乙胺嗪

44. Filariasis
淋巴管炎、淋巴结炎
橡皮肿、乳糜尿

45.   Diethylcarbamazine (乙胺嗪, Hetrazan, 海群生)
Anti-filaria effects:
Destroying the epidermis of microfilaremia(微丝蚴) of Brugia malayi’s filaria(马来丝虫) & Bancroft’s filaria(班氏丝虫).
The large dose of hetrazan can act on imago(成虫) in lymphatic system too.
Adverse reactions:
GI reaction, such as anorexia, nausea, vomit, and headache, asthenia(乏力),etc.
Anaphylaxis caused by alloprotein of died microfilaremia(微丝蚴).
Lymphadenectasis(淋巴结肿大) caused by died imago(成虫).

46. Anthelmintic Drugs 驱(蠕)虫药
Albendazole
(阿苯达唑, “肠虫清”)
Anthelmintic activity:
Intestinal parasitosis(肠寄生虫病):
Broad spectrum & high potency:

47. Anthelmintic drugs-Albendazole (阿苯达唑)
Nematoindea(线虫): e.g. ascaris(蛔虫), hookworm(钩虫), pinworm(蛲虫), whipworm (鞭虫);
Tapeworm(绦虫): pork t.(猪肉绦虫), beef t.(牛肉绦虫).
Exo-intestinal parasitosis(肠外寄生虫病): hydatidosis(包虫病), cysticercosis(囊虫病), trichinosis(旋毛虫病), clonorchiasis(华支睾吸虫), paragonimiasis(肺吸虫病), ang hydatidocystis(棘球幼囊).

48. Anthelmintic drugs - Albendazole (阿苯达唑)
Clinical Uses:
Intestinal nematodiasis (肠线虫病)
Intestinal taeniasis (肠绦虫病)
Cysticercosis (囊虫病)
Hydatidosis (包虫病, 细粒棘球蚴病)
Clonorchiasis (华支睾吸虫病)
Trichinosis (旋毛虫病)
Paragonimiasis (肺吸虫病)

49. Anthelmintic drugs - Albendazole (阿苯达唑)
Adverse reactions:
Less when treating intestinal parasitosis
More sever when treating exo-intestinal parasitosis (because of larger dose & longer treatment course)
Anaphylaxis: headache, fever, skin rash & muscular aching pain, etc.
teratogenesis(致畸) and embryotoxicity(胚胎毒性).

50. Anthelmintic Drugs – Mebendazole（甲苯达唑）
synthetic benzimidazole that has a wide spectrum of anthelmintic activity
Anthelmintic Drugs - Other Anthelmintic Drugs
Piperazine （哌嗪）:蛔虫、绦虫
Levamisole （左旋咪唑）：蛔虫、钩虫、绦虫
Pyrantel （噻嘧啶）：蛔虫、钩虫、绦虫
Niclosamide （氯硝柳胺）：绦虫
Praziquantel （吡喹酮）：吸虫、绦虫

51. Anthelmintic Drugs – Summary
Therapiutic drugs
蛔虫感染
Mebendazole, Albendazole,Pyrantel, Piperazine
蛲虫感染
Mebendazole, Albendazole, Pyrantel
钩虫感染
鞭虫感染
Mebendazole
绦虫感染
Praziquantel, Niclosamide,
囊虫病
Praziquantel, Albendazole
包虫病
Albendazole, Praziquantel, Mebendazole

52. Thanks !