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1、Anti-parasite drugs Human parasiteHuman parasiteProtozoa （原虫）：（原虫）：孢子虫子虫疟原虫原虫 鞭毛虫阴道毛滴虫鞭毛虫阴道毛滴虫 叶足虫叶足虫阿米巴原虫阿米巴原虫 纤毛虫毛虫结肠小袋小袋纤毛虫毛虫 Helminth （蠕虫）：吸虫（蠕虫）：吸虫血吸虫血吸虫 绦虫虫链状状带绦虫虫 线虫虫蛔虫、蛔虫、丝虫虫Arthropod （节肢肢动物）：蛛形物）：蛛形纲蜱、蜱、螨 昆虫昆虫纲蚊、蚊、蝇、虱、虱 Antimalarial drugsThe malarial parasite, Plasmodium, is a very small, T
2、he malarial parasite, Plasmodium, is a very small, single-cell organism. single-cell organism. It lives as a parasite in other organisms, namely It lives as a parasite in other organisms, namely man man and mosquitoand mosquito. . The parasite is the cause of the tropical or subtropical The parasite
3、 is the cause of the tropical or subtropical disease disease malaria.malaria.Antimalarial drugsAntimalarial drugs -Malarial parasite-Malarial parasiteFour species of plasmodium can produce the disease Four species of plasmodium can produce the disease in its various forms: in its various forms: Plas
4、modium falciparum Plasmodium falciparum （恶性疟原虫）恶性疟原虫）恶性疟原虫）恶性疟原虫）Plasmodium vivax Plasmodium vivax （间日疟原虫）间日疟原虫）间日疟原虫）间日疟原虫）Plasmodium ovale Plasmodium ovale （卵形疟原虫）卵形疟原虫）卵形疟原虫）卵形疟原虫）Plasmodium malaria Plasmodium malaria （三日疟原虫）三日疟原虫）三日疟原虫）三日疟原虫）Antimalarial drugsAntimalarial drugs - - Parasite Life
5、 Cycle Parasite Life Cycle红细胞外期红细胞内期按蚊有性繁殖人体无性繁殖No one available agent can reliably effect a radical No one available agent can reliably effect a radical cure, ie, eliminate both exo-cure, ie, eliminate both exo-erythrocyticerythrocytic and and erythrocytic stages. erythrocytic stages. Few available
6、 agents are causal prophylactic drugs, Few available agents are causal prophylactic drugs, ie, capable of preventing erythrocytic infection.ie, capable of preventing erythrocytic infection.Antimalarial drugsAntimalarial drugs控制控制复复发Primaquine（伯（伯氨氨喹） 迟发病因病因预防防Pyrimethamine（乙（乙胺胺嘧啶）速）速发控制症控制症状状Chloro
7、quine（氯喹）Quinine（奎宁）（奎宁）Mefloquine（甲（甲氟氟喹）Artemisinin（青青蒿素）蒿素）阻止阻止传播播Pyrimethamine（乙（乙胺胺嘧啶）阻止阻止传播播Primaquine （伯（伯氨氨喹） Chloroquine （氯喹）Quinine （奎宁）（奎宁）（恶性性疟无效）无效）红细胞外期红细胞内期按蚊有性繁殖Antimalarial drugsAntimalarial drugs Chloroquine Chloroquine （氯喹）（氯喹）（氯喹）（氯喹） Chloroquine is a synthetic 4-aminoquinoline d
8、erivate Chloroquine is a synthetic 4-aminoquinoline derivate 控制症状控制症状Chloroquine 氯喹氯喹Quinine 奎宁奎宁Mefloquine 甲氟喹甲氟喹Artemisinin 青蒿素青蒿素红细胞内期Pharmacological effects1. Antimalarial effectsRapid schizonticidal activity Rapid schizonticidal activity （裂殖体裂殖体裂殖体裂殖体杀灭剂杀灭剂） against all infections of malaria sp
9、eciesagainst all infections of malaria species . . Also gametocytocidalAlso gametocytocidal（杀杀配子体）配子体）配子体）配子体）against P. against P. vivax, P. malariae and P. ovale . vivax, P. malariae and P. ovale . It is not active against exo-erythrocytic form, and It is not active against exo-erythrocytic form,
10、and should therefore be used with primaquineshould therefore be used with primaquine（伯氨伯氨喹喹）to effect radical cure of P. vivax. to effect radical cure of P. vivax. Antimalarial drugsAntimalarial drugs - - ChloroquineChloroquinePharmacological effects2. Immune inhibitionTreatment of rheumatoid arthri
11、tis, lupus erythematosus 3. Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugsAntimalarial drugs - - ChloroquineChloroquineMechanism of actionsAccumulation in erythrocytepH malarial Accumulation in erythrocytepH malarial pigment synthesis hemepigment synthesis hemeHe
12、me-quinoline compound heme accumulate in Heme-quinoline compound heme accumulate in p plasmodiumlasmodium Insert in Insert in the double stranded DNA helix the double stranded DNA helix DNA DNA replication and RNA transcription replication and RNA transcription Antimalarial drugsAntimalarial drugs -
13、 - ChloroquineChloroquineAdverse effectsRare at the usual antimalarial dosagesRare at the usual antimalarial dosagesPruritus (Pruritus (瘙痒症瘙痒症瘙痒症瘙痒症) ) common among dark-skinned common among dark-skinned people.people.Transient headaches, nausea, vomiting, Transient headaches, nausea, vomiting, gast
14、rointestinal symptoms and “blurred vision”.gastrointestinal symptoms and “blurred vision”.Others: aplastic blood and neurological disorders, Others: aplastic blood and neurological disorders, such as polyneuritis (such as polyneuritis (多发性神经炎多发性神经炎多发性神经炎多发性神经炎) ), seizures and , seizures and neuromy
15、opathy.neuromyopathy.Antimalarial drugsAntimalarial drugs - - ChloroquineChloroquine1.Quinine （奎宁）奎宁）2.Mefloquine （甲氟喹）甲氟喹）3.Pyronaridine (咯萘啶咯萘啶)4.Artemisinin (青蒿素青蒿素)5.Artemether and artesunate (蒿甲醚和青蒿琥酯蒿甲醚和青蒿琥酯) Other angents kill erythrocytic parasitesOther angents kill erythrocytic parasites控制控
16、制复复发Primaquine(伯伯氨氨喹) 迟发阻止阻止传播播Primaquine (伯伯氨氨喹) Chloroquine (氯喹)Quinine (奎宁奎宁)（恶性性疟无效）无效）红细胞外期红细胞内期按蚊有性繁殖Antimalarial drugsAntimalarial drugs Primaquine Primaquine （伯氨喹）（伯氨喹）（伯氨喹）（伯氨喹）Pharmacological effectsHighly active against the gametocytes (Highly active against the gametocytes (配子体配子体配子体配子体)
17、 ) of all of all malaria species malaria species dissemination dissemination Active against hypnozoites (Active against hypnozoites (迟发型子孢子迟发型子孢子迟发型子孢子迟发型子孢子) ) of the of the relapsing malarial parasitesrelapsing malarial parasites The only drug currently used for the treatment of The only drug curr
18、ently used for the treatment of relapsing malariarelapsing malariaAntimalarial drugsAntimalarial drugs Primaquine Primaquine （伯氨喹）（伯氨喹）（伯氨喹）（伯氨喹）Mechanism of actionsInhibition of coenzyme Q Inhibition of coenzyme Q Inhibition of reduction of NADPInhibition of reduction of NADPAdverse effectsTransien
19、t dizziness , nausea, vomiting, Transient dizziness , nausea, vomiting, gastrointestinal symptomsgastrointestinal symptomsAcute hemolytic anemia, methemoglobinemia (Acute hemolytic anemia, methemoglobinemia (高铁高铁高铁高铁血红蛋白血症血红蛋白血症血红蛋白血症血红蛋白血症) )Antimalarial drugsAntimalarial drugs Primaquine Primaquin
20、e （伯氨喹）（伯氨喹）（伯氨喹）（伯氨喹）红细胞外期红细胞内期按蚊有性繁殖Antimalarial drugsAntimalarial drugs Pyrimethamine Pyrimethamine （乙（乙（乙（乙胺胺胺胺嘧啶嘧啶）病因病因预防防Pyrimethamine(乙乙胺胺嘧啶) 速速发Pyrimethamine(乙乙胺胺嘧啶)Pharmacological effectsPharmacological effectsInhibition of proliferation of sporozoite (Inhibition of proliferation of sporozo
21、ite (子孢子子孢子子孢子子孢子) to ) to schizont (schizont (裂殖体裂殖体裂殖体裂殖体) )Prophylaxis of infectionsProphylaxis of infectionsMechanism of actionsMechanism of actionsDihydrofolate reductase inhibitorDihydrofolate reductase inhibitorAdverse effectsAdverse effectsFolate metabolism disturbtance Folate metabolism dis
22、turbtance Antimalarial drugsAntimalarial drugs Pyrimethamine Pyrimethamine （乙胺嘧啶）（乙胺嘧啶）（乙胺嘧啶）（乙胺嘧啶）symptomsymptom？复发？复发？复发？复发？传播？传播？传播？传播？控制症控制症状状Chloroquine（氯喹）Quinine（奎宁）（奎宁）Mefloquine（甲（甲氟氟喹）Artemisinin（青青蒿素）蒿素）病因病因病因病因预预防？防？防？防？控制控制复复发Primaquine（伯（伯氨氨喹） 迟发阻止阻止传播播Primaquine （伯（伯氨氨喹） Chloroquine （
23、氯喹）Quinine （奎宁）（奎宁）（恶性性疟无效）无效）病因病因预防防Pyrimethamine(乙乙胺胺嘧啶) 速速发阻止阻止传播播Pyrimethamine（乙（乙胺胺嘧啶）用于控制症状的抗疟药Chloroquine Chloroquine （氯喹氯喹）、Quinine Quinine （奎宁）、（奎宁）、（奎宁）、（奎宁）、 Mefloquine Mefloquine （甲氟（甲氟（甲氟（甲氟喹喹）、）、）、）、Pyronaridine Pyronaridine ( (咯咯咯咯萘啶萘啶) )、Artemisinin (Artemisinin (青蒿素青蒿素青蒿素青蒿素) ) 、 Ar
24、temether and artesunate (Artemether and artesunate (蒿甲蒿甲蒿甲蒿甲醚醚和青蒿琥和青蒿琥和青蒿琥和青蒿琥酯酯) ) 用于控制复发和传播的抗疟药 Primaquine Primaquine （伯氨（伯氨（伯氨（伯氨喹喹）用于病因性预防的抗疟药 Pyrimethamine Pyrimethamine （乙胺（乙胺（乙胺（乙胺嘧啶嘧啶） Antiamebiasis drugsAmebiasis is infection with Entamoeba histolytica.Amebiasis is infection with Entamoeba
25、histolytica.（溶组织内阿米巴原虫（溶组织内阿米巴原虫（溶组织内阿米巴原虫（溶组织内阿米巴原虫 ）Classification of amebiasisClassification of amebiasisAsymptomatic intestinal infection;Asymptomatic intestinal infection;Mild to moderate colitis;Mild to moderate colitis;Severe intestinal infection (dysentery);Severe intestinal infection (dysen
26、tery);Extraintestinal infections: ameboma, liver abscess.Extraintestinal infections: ameboma, liver abscess.Antiamebiasis drugs -AmebiasisAmebiasis is infection with Entamoeba histolytica,Amebiasis is infection with Entamoeba histolytica, A tiny, one-celled organism. A tiny, one-celled organism. Ant
27、iamebiasis drugs -AmebiasisIntestinal AmebiasisIntestinal AmebiasisExtraintestinal AmebiasisExtraintestinal AmebiasisFeatures of AmebiasisMultiplication and life cycle of Multiplication and life cycle of E histolyticaE histolyticaAntiamebiasis drugs -AmebiasisClinical Manifestations Acute or chronic
28、 diarrhea, which may progress to Acute or chronic diarrhea, which may progress to dysentery. dysentery. Extraintestinal disease may be present as a Extraintestinal disease may be present as a complication or as a primary problemcomplication or as a primary problem (e.g., liver, lung or brain abscess
29、, or skin or perianal (e.g., liver, lung or brain abscess, or skin or perianal infection). infection). Antiamebiasis drugs -AmebiasisAntiamebiasis drugs - Metronidazole Metronidazole 甲硝唑甲硝唑甲硝唑甲硝唑Pharmacological effects1.Antibiotic effective against anaerobic bacteria. Antibiotic effective against an
30、aerobic bacteria. 2.Anti-giardia lamblia Anti-giardia lamblia （贾贾第氏鞭毛虫）第氏鞭毛虫）第氏鞭毛虫）第氏鞭毛虫）effecteffect3.Anti-ameba effects Anti-ameba effects （肠内、肠外）（肠内、肠外）（肠内、肠外）（肠内、肠外） The treatment of all tissue infections with E histolyticaThe treatment of all tissue infections with E histolytica4. Anti-infusori
31、an 4. Anti-infusorian （滴虫）滴虫）滴虫）滴虫）effectseffectsMechanism of actionsThe methyl group of metronidazole is chemically The methyl group of metronidazole is chemically reduced in anaerobic bacteria and sensitive reduced in anaerobic bacteria and sensitive protozoans. protozoans. （原生原生原生原生动动物）物）物）物）Reac
32、tive reduction products appear to be Reactive reduction products appear to be responsible for antimicrobial activity.responsible for antimicrobial activity. Rapidly absorbed and has a bioavailability of Rapidly absorbed and has a bioavailability of approximately 90% approximately 90% Antiamebiasis d
33、rugs - MetronidazoleMetronidazoleAdverse effectsSerious side effects of metronidazole are rare; and Serious side effects of metronidazole are rare; and include seizures and damage of nerves resulting in include seizures and damage of nerves resulting in numbness and tingling of extremities (peripher
34、al numbness and tingling of extremities (peripheral neuropathy).neuropathy). Minor side effects include nausea, headaches, loss of Minor side effects include nausea, headaches, loss of appetite, a metallic taste, and rarely a rash.appetite, a metallic taste, and rarely a rash.Antiamebiasis drugs - M
35、etronidazoleMetronidazoleEmetine依米丁依米丁& dehydroemetine去氢依米丁去氢依米丁Amebicide effects :Amebicide effects : sporadin ( sporadin (滋养体滋养体滋养体滋养体) )Mechanism of actions:Mechanism of actions: protein synthesis inhibitor. protein synthesis inhibitor.Clinic uses:Clinic uses: Amebic liver abscess , Acute amebic
36、Amebic liver abscess , Acute amebic dysenterydysenteryUsed in case of resistance to metronidazole.Used in case of resistance to metronidazole. Emetine依米丁依米丁& dehydroemetine去去氢依米依米丁丁Adverse effectsNausea, vomiting and diarrhoea. Nausea, vomiting and diarrhoea. Palpitations, tachycardia, retrosternal
37、pain, Palpitations, tachycardia, retrosternal pain, hypotension, dyspnoea, ECG changes (ST depression, hypotension, dyspnoea, ECG changes (ST depression, QT prolongation, T-wave inversion). QT prolongation, T-wave inversion). Tremor, myasthenia and paralysis including Tremor, myasthenia and paralysi
38、s including respiratory paralysis.respiratory paralysis.Antiamebiasis drugs - Other amebicidesDiloxanide furoate is slowly absorbed from the Diloxanide furoate is slowly absorbed from the gastrointestinal tract and can therefore provide an gastrointestinal tract and can therefore provide an adequate
39、 concentration of the medication in the intestinal adequate concentration of the medication in the intestinal lumen for a long period of time.lumen for a long period of time. Antiamebiasis drugs - Diloxanide Diloxanide 二氯尼特二氯尼特二氯尼特二氯尼特Mechanism of actionsLuminal amebicide. Luminal amebicide. Destroy
40、s the trophozoites of E. histolytica that Destroys the trophozoites of E. histolytica that eventually form into cysts. (eventually form into cysts. (包囊包囊包囊包囊) )The cysts are then excreted by persons infected with The cysts are then excreted by persons infected with asymptomatic amebiasis. (asymptoma
41、tic amebiasis. (无症状的阿米巴病无症状的阿米巴病无症状的阿米巴病无症状的阿米巴病) )Antiamebiasis drugs - DiloxanideDiloxanideAdverse effectsNot commonly seen with this medication unless the Not commonly seen with this medication unless the patient is taking especially high doses. patient is taking especially high doses. Minor side
42、 effects include nausea, headaches, and Minor side effects include nausea, headaches, and rarely a rash.rarely a rash.Antiamebiasis drugs - DiloxanideDiloxanideAntiamebiasis drugs - Other amebicidesParomomycin 巴龙霉素巴龙霉素Aminoglycosides antibiotics. Aminoglycosides antibiotics. Not significantly absorb
43、ed from the gastrointestinal Not significantly absorbed from the gastrointestinal tract tract Mechanism of actions:Mechanism of actions: Acts by inhibition protein synthesis.Acts by inhibition protein synthesis.Direct and indirect action of amebicideDirect and indirect action of amebicideClinical us
44、age:Clinical usage: Amebic Amebic dysentery (dysentery (阿米巴痢疾阿米巴痢疾阿米巴痢疾阿米巴痢疾) )No effect against extraintestinal amebic infections.No effect against extraintestinal amebic infections.Extraintestinal amebiasisAmoeba trophozoite amebic liver abscess Antimalarial drugsAntimalarial drugs - - Chloroquine
45、Chloroquine Anti-bilharziasis & filariasis DrugBilharziasis急性发热过敏反应腹痛、腹泻肝脾肿大Anthelmintic ActionsSchistosomiasis (Schistosomiasis (血吸虫病血吸虫病血吸虫病血吸虫病) )Clonorchiasis, Opisthorchiasis (Clonorchiasis, Opisthorchiasis (支睾吸虫病支睾吸虫病支睾吸虫病支睾吸虫病), and ), and Paragonimiasis (Paragonimiasis (肺吸虫病肺吸虫病肺吸虫病肺吸虫病) )Ta
46、eniasis (Taeniasis (绦虫病绦虫病绦虫病绦虫病) )、Diphyllobothriasis (Diphyllobothriasis (裂头绦虫病）裂头绦虫病）裂头绦虫病）裂头绦虫病） H Nana H Nana （缩小膜壳绦虫）（缩小膜壳绦虫）（缩小膜壳绦虫）（缩小膜壳绦虫） Neurocysticercosis Neurocysticercosis （脑囊虫病）（脑囊虫病）（脑囊虫病）（脑囊虫病）Hydatid Disease Hydatid Disease （包虫囊病）（包虫囊病）（包虫囊病）（包虫囊病）Other ParasitesOther Parasites： fa
47、sciolopsiasis, metagonimiasis, and fasciolopsiasis, metagonimiasis, and other forms of heterophyiasis. fascioliasis,other forms of heterophyiasis. fascioliasis,Praziquantel 吡吡喹酮Mechanism of actionsIncrease the permeability of cell membranes to Increase the permeability of cell membranes to calcium,
48、resulting in paralysis, dislodgement, and calcium, resulting in paralysis, dislodgement, and death.death.In schistosome infections, praziquantel is effective In schistosome infections, praziquantel is effective against adult worms and immature stages against adult worms and immature stages Prophylac
49、tic effect against cercarial Prophylactic effect against cercarial （尾蚴）（尾蚴）（尾蚴）（尾蚴）infection.infection.Praziquantel 吡吡喹酮Adverse effectsMost frequent are headache, dizziness, drowsiness, Most frequent are headache, dizziness, drowsiness, and lassitude;and lassitude;Others include nausea, vomiting, ab
50、dominal pain, Others include nausea, vomiting, abdominal pain, pruritus, urticaria, arthralgia, myalgia, and low-pruritus, urticaria, arthralgia, myalgia, and low-grade fever.grade fever.Mild and transient elevations of liver enzymesMild and transient elevations of liver enzymesPraziquantel 吡吡喹酮 Fil
51、ariasis淋巴管炎、淋巴淋巴管炎、淋巴结炎结炎橡皮肿、乳糜尿橡皮肿、乳糜尿Diethylcarbamazine 乙胺嗪乙胺嗪Anthelmintic ActionsAnthelmintic ActionsDiethylcarbamazine immobilizes microfilariae Diethylcarbamazine immobilizes microfilariae （微微微微丝丝蚴）蚴）蚴）蚴）and and alters their surface structure, displacing them from tissues and alters their surfa
52、ce structure, displacing them from tissues and making them more susceptible to destruction by host defense making them more susceptible to destruction by host defense mechanisms. mechanisms. Clinical UsesClinical Uses Wuchereria Bancrofti, Brugia Malayi, Brugia Wuchereria Bancrofti, Brugia Malayi, B
53、rugia Timori, and Loa LoaTimori, and Loa LoaAdverse effectsAdverse effectsGenerally mild and transientGenerally mild and transientInclude headache, malaise, anorexia, weakness, nausea, Include headache, malaise, anorexia, weakness, nausea, vomiting, and dizziness.vomiting, and dizziness. Anthelminti
54、c Drugs 驱(蠕)虫药Anthelmintic DrugsAnthelmintic Drugs Albendazole Albendazole （阿（阿（阿（阿苯达苯达苯达苯达唑唑）Pharmacological effectsA broad-spectrum oral anthelmintic, is the drug of A broad-spectrum oral anthelmintic, is the drug of choice for treatment of hydatid disease choice for treatment of hydatid disease （
55、包虫病）（包虫病）（包虫病）（包虫病）and and cysticercosis. cysticercosis. （囊虫病）（囊虫病）（囊虫病）（囊虫病）Also used for the treatment of pinworm Also used for the treatment of pinworm （蛲虫）（蛲虫）（蛲虫）（蛲虫）and hookworm infections, ascariasisand hookworm infections, ascariasis（蛔虫病）（蛔虫病）（蛔虫病）（蛔虫病） , , trichuriasistrichuriasis（鞭虫病）（鞭虫病）
56、（鞭虫病）（鞭虫病）and strongyloidiasisand strongyloidiasis（类圆线（类圆线（类圆线（类圆线虫病）虫病）虫病）虫病）Anthelmintic DrugsAnthelmintic Drugs - -AlbendazoleAlbendazoleAdverse effectsMild and transient epigastric distress, diarrhea, Mild and transient epigastric distress, diarrhea, headache, nausea, dizziness, lassitude, and i
57、nsomnia headache, nausea, dizziness, lassitude, and insomnia can occur. can occur. Abdominal distress, headaches, fever, fatigue, Abdominal distress, headaches, fever, fatigue, alopecia, increases in liver enzymes, and alopecia, increases in liver enzymes, and pancytopenia in long-term use pancytope
58、nia in long-term use Anthelmintic DrugsAnthelmintic Drugs - -AlbendazoleAlbendazoleA synthetic benzimidazole that has a wide A synthetic benzimidazole that has a wide spectrum of anthelmintic activityspectrum of anthelmintic activityAnthelmintic DrugsAnthelmintic Drugs - - MebendazoleMebendazole1.Pi
59、perazine Piperazine （哌嗪）哌嗪）哌嗪）哌嗪）: :蛔虫、绦虫蛔虫、绦虫蛔虫、绦虫蛔虫、绦虫2.Levamisole Levamisole （左旋咪唑）：蛔虫、钩虫、绦虫左旋咪唑）：蛔虫、钩虫、绦虫左旋咪唑）：蛔虫、钩虫、绦虫左旋咪唑）：蛔虫、钩虫、绦虫3.Pyrantel Pyrantel （噻嘧啶）：蛔虫、钩虫、绦虫噻嘧啶）：蛔虫、钩虫、绦虫噻嘧啶）：蛔虫、钩虫、绦虫噻嘧啶）：蛔虫、钩虫、绦虫4.Niclosamide Niclosamide （氯硝柳胺）：绦虫氯硝柳胺）：绦虫氯硝柳胺）：绦虫氯硝柳胺）：绦虫5.Praziquantel Praziquantel （吡喹酮）：吸虫、绦虫吡喹酮）：吸虫、绦虫吡喹酮）：吸虫、绦虫吡喹酮）：吸虫、绦虫Anthelmintic DrugsAnthelmintic Drugs - - Other Anthelmintic DrugsOther Anthelmintic Drugs
