Antiprotozoal Study Sheet 1. What is the most common, non-lethal, and recurrent type of malaria? Vivax 2.

What is the most deadly, non recurrent malaria? Falciparum 3. How is malaria diagnosed? Serum and microscopy 4. What is the name of the part of the lifecycle of malaria that occurs in the liver? Exoerythrocytic 5. What is the part of the cycle that happens in red blood cells? Erythrocytic 6. What part of the lifecycle do most drugs target? Erythrocytic 7. In what part of the cycle does hemolysis occur? Erythrocytic 8. What is the bite me signal? P. falciparum can trigger changes in ones breath or body odors that attract other mosquitoes 9. What is special about persons that have mutations in the promoter region of the gene coding for inducible nitric oxide synthase? They have resistance to malaria 10. Why cant acute attack (clinical cure) drugs prevent relapse of P. vivax? There are still hepatic form parasites 11. What is the drug of choice for acute attacks of malaria caused by choloquine sensitive strains of vivax and falciparum? Chloroquine 12. If a parasite is chloroquine resistant, what drugs are used? Artesunate, quinine with doxycycline, clindamycin, or Fansidar 13. What drug prevents the relapse of P. vivax? Primaquine 14. Can prophylactic drugs prevent hepatic forms of the parasite? No, only erythrocytic

15. What is the prophylactic drug of choice? Chloroquine 16. If the parasite is resistant to cholorquine, what drug is used for prophylaxis? Mefloquine 17. What is the MOA of DEET? Inhibits bites by making attracting odors for mosquitoes 18. Can DEET be used on children? No 19. Which drugs inhibit heme metabolism? Chloroquine Metfloquine Quinine Artemisinin 20. Which drugs inhibit the electron transport chain? Primaquine and Atovaquone 21. Which drugs inhibit DNA metabolism? Daraprim Fansidar Maloprim Malarone 22. How is Chloroquine administered? Once per week orally or IM 23. What are adverse effects of Chloroquine? Visual disturbances Pruritis HA GI effects, concentrations in the liver 24. What is the metabolite of Chloroquine? Desethylchloroquine 25. What does cholorquine do to the urine? Increases acidity 26. Resistance to Metfloquine, is due to what? Mutations in the Pgh1

27. What are adverse effects of metfloquine? GI disturbances Nightmares Altered vision HA Toxicity: vertigo, confusion, psychosis 28. If you are living on Long Island and contract malaria, your doctor tells the health department and what happens next? Quinine is flown in from Washington D.C. 29. What are adverse effects of Quinine? Cinchonism: tinnitus, HA, visual disturbances, nausea, diarrhea Hemolysis Hypotension Hypoglycemia Fetal abnormalities CNS CV toxicities 30. What is Artemether or Artensunate used for? Severe attacks of falciparum in locations where multi-drug resistant is an endemic 31. How does this work? Compound is activated by heme to irreversibly decompose generating free radicals that alkylate and oxidize proteins and lipids 32. What is special about Artemisinin? Kills parasites 10X faster then any other drug 33. Has resistance been reported to Artemisinin? Nope (that is why it is used in ACT, so resistance is less likely to develop. Lets not ruin a good thing!) 34. What are some ways in which ACT works? Reduces number of parasites Rapid parasite clearance Resolution of symptoms Effective against multi-resistant falciparum Reduces transmission of alleles 35. What is Artemether + Lumefantrine (Coartem, Riamet) used for? 1st and 2nd line treatment, but not for severe cases Very expensive

36. What is Primaquine (Malirid) used for? Radical cure for hepatic forms of vivax (I remember this one because MaliRID, gets RID of liver parasites) 37. What is G-6-PD deficiency? Adverse reaction (hemolysis) develops in patients whose erythrocytes are deficient in glucose 6 phosphate dehydrogenase 38. Most deficiency is found in what population? Blacks Dark skinned whites Greeks Iranians, Sephardic Jews 39. What is pyrimethamine (Daraprim) used for? Acute attacks Chloroquine resistant falciparum Prophylaxis 40 What is the MOA of Pyrimethamine? Inhibits dihydrofolate reductase which normally converts folic acid to its active form (cells cannot form RNA and DNA without folic acid) 40. What are characteristics of Pyrimethamine + Sulfadoxine (Fansidar)? MOA: blocks folic acid synthesis Secreted by kidneys Only works on falciparum SE: folic acid deficiency 41. Pyrimethamine + Dapsone (Maloprim) Dapsone: folic acid synthesis inhibitor Can cause agranulocytosis Not recommended for prophylaxis Used for people traveling to Australasia or Oceana 42. Atovaquone + Proguanil (Malarone) ATOVAQUONE (Mepron) Used for prophylaxis Interferes with electron transport chain Used to treat PCP, malaria, and toxoplasmosis PROGUANIL (Paludrine) Forms active metabolite cycloguanil MOA: acts by inhibiting plasmodial dihydrofolate reductase preventing nucleis acid synthesis SE: diarrhea, HA, loss of appetite, mouth sores or ulcers, vomiting, temp. hair loss

43. What are tetracycline and doxycycline used for? Acute malarial attacks with resistant strains Short term prophylaxis due to toxicity SE: sensitivity to sunlight 44. How do Quarternary ammonium salts (G25) work? Block the release of parasites from infected wrythrocytes 45. How do glycosaminoglycans work? Could maybe have a effect on lining in mosquito guts and human livers 46. Why is it difficult to make a malaria vaccine? Multi drug life cycle of the parasite Side effects 47. What is mosquirix? The worlds most promising malaria vaccine 48. What are the drugs of choice for amebiasis? Iodoquinol and metronidazole and paromomycin Iodoquinol and paromomycin: active against amebas in intestines Metronidazole: intestine, liver and others 49. How do you treat Leishmaniasis? Sodium stibogluconate or Amphotericin 50. How do you treat Toxoplasmosis? Pyrimethamine and sulfadiazine 51. How do you treat Giardiasis? Metroniadzole 52. Metroniadzole is also used to treat what? Trich 53. American Trypanosomiasis is also called. Chagas Disease (kissing bug) 54. How do you treat it? Nifutimox (Lampit) 55. How does Lampit work? Generates reactive oxygen radicals resulting in lipid peroxidation and DNA damage 56. What is another name for African Trypanosomasis?

Sleeping disease 57. It is transmitted by what bug? Tsetse fly 58. Early stages are treated with what drugs? Suramin and eflornithine 59. Late stages are treated with what drugs? Melarsoprol amd eflornithine 60. Metronidazole (Flagyl) is mostly used for what parasitic infections? Amebiasis, giardia, tric 61. Unfortunately, Flagyl does not kill parasites in the colon. What do you need to use for that? Iodoquinol 62. Flagyl only kills what type of organisms? Anaerobic 63. Flagyl has disulfiram like qualities. What does this mean? It could cause severe effects if used with alcohol 64. Flagyl increases levels of what drugs? Warfarin, phenytoin, lithium, cyclosporine 65. What does Melarsoprol target? African trypanosomiasis 66. What is its MOA? Reacts with sulfhydryl groups inhibiting enzymes 67. What are adverse effects? Hypertension, albuminuria, peripheral neuropathy, heart damage 68. What is Eflornithine used for? Late stage African Tryp. 69. How does it work? Irreversible inhibition of ornithine decarboxylase 70. What are adverse effects? Anemia, diarrhea, leucopenia *Expensive 71. What does Nifurtimox target?

American Tryp. 71. How does it work? Generates reactive oxygen radicals resulting in lipid peroxidation and DNA damage 72. What does Pentamide target? African Tryp. 73. How does it work? Interferes with adenine uptake and polyamine iosynthesis 74. What are adverse effects? Hypotension Hypo or hyperglycemia, leucopenia, thrombocytopenia, acute renal failure, Hypocalcemia, dysrhythmias (Not well tolerated) 75. What does Sodium Stibogluconate treat? Leishmaniasis 76. How does it work? Interferes with energetics of amastigotes *Potential anti-tumor activity