DA Exam II Anti-malarial Agents.txt

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  1. Malaria afflicts _________ individuals world-wide with _______ deaths per year.
    • About 500 million
    • 2 million
  2. Malaria is caused by which parasite and what is it generally carried by?
    • Plasmodium falciparum
    • Anopheline mosquito
  3. What populations are particularly sensitive to malaria?
    • Children < 5 yoa,
    • pregnant women
    • non-immune individuals.
  4. What interrupted the transimission of malaria in the USA in the 1950s?
    • DDT
    • other pesticide use controlling mosquitoes
  5. What causes all cases of malaria within the USA today?
    Exposure from outside the country.
  6. Name the three cities/states with the highest number of reported cases of malaria in 2007.
    • NYC,
    • California
    • Texas
    • (where most people from outside the country visit)
  7. When are the symptoms of malaria most pronounced?
    During disruption of the erythrocytes.
  8. What are the symptoms of malaria?
    Headache, fever, muscular fatigue and pain, back pain, chills, sweating, dry cough, spleen enlargement, and n/v.
  9. Plasmodium infection transmission is by blood transfer, primarily by the mosquito bite of the _______________.
    female Anopheline
  10. What in the Anopheline salivary glands enters the body and homes to the liver?
  11. Within the liver, sporozoites transform into tissue ______ and ________.
    • schizonts
    • multiply
  12. How long does the liver stage last? What symptoms are usually present?
    • 5 to 15 days.
    • Generally asymptomatic depending on which of 4 Plasmodium species involved.
  13. During which phase do tissue schizonts rupture, each releasing thousands of merozoites that enter the RBCs?
    Erythrocytic Phase
  14. Merozoites asexually develop into ______ and then into mature ______.
    • trophozoites
    • schizonts
  15. During the erythrocytic phase, when RBCs rupture, what are released?
    Merozoites, which can infect other erythrocytes
  16. What type of attaches can result from rupture of the erythrocytes?
  17. Put the following in order based on which comes first: tissue schizonts, trophozoites, merozoites, mature schizonts, sporozoites
    • Sporozoites transform into tissue schizonts in the liver,
    • tissue schizonts rupture and release merozoites,
    • merozoites asexually develop into trophozoites then mature schizonts.
  18. Name the two species variations of Plasmodium that, once the tissue schizonts leave the liver, that organ is devoid of parasites and there are no relapses of malaria.
    • P. falciparum
    • P. malariae
  19. _______ and ______ are two species variations of Plasmodium where parasites persist in
    the liver and relapses of malaria can occur years later.
    • P. vivax
    • P. ovale
  20. For species P. falciparum, P. vivax, and P. ovale it takes about _____ hours to generate new schizonts to ruptures while for __________ it takes about 72 hours.
    • 48
    • P. malariae
  21. Name the two ways anti-malaria drugs are classified.
    • 1) State of the parasite targeted
    • 2) Use (prophylaxis or treatment)
  22. How many agents kill sporozoites?
  23. Prophylaxis is to prevent the _____________ stage of the disease.
  24. __________ can kill both liver and erythrocyte forms of the organism.
    No one drug (so at least two drugs are required for treatment)
  25. Class I anti-malarial drugs are effective against which form of the organism and what are they used for?
    • asexual erythrocytic
    • can treat or prevent symptomatic malaria
  26. Why are class I drugs given prophylatically for several weeks after potential exposure?
    To ensure asymptomatic phase is complete before stopping.
  27. Class II and III anti-malarial drugs are effective against the ___________ form of the organism plus the liver phase of ______________ which allows for a shorter post-exposure dosing schedule.
    • Asexual erythrocytic
    • P. falciparum
  28. Name the only class III anti-malarial drug, what it is effective for and what it is used for.
    • Primaquine
    • Primary liver infections and the latent hypnozoites & erythrocytic gametocytes
    • Clear the liver to prevent relapses
  29. List examples of class I drugs.
    • Artemisinin
    • Pyrimethamine
    • Chloroquine
    • Quinine
    • Tetracycline
  30. Artemisinin has a potency of _______ fold greater than other traditional class I agents and acts rapidly against which phase of the organism?
    • 10-100
    • Asexual erythrocytic (no effect on liver stage organism)
  31. _____ ____ within the parasite catalyzes cleavage of an ________ bridge in the artemisinin molecule.
    • Heme iron
    • endoperoxide
  32. Once the endoperoxide bridge is cleaved in the artemisinin molecule, the rearrangement produces a ___________ radical that ________ parasitic macromolecules. Name one target of this.
    • Carbon-centered
    • alkylates
    • ortholog of sarco/endoplasmic reticulum Ca++-ATPase
  33. In the body, artemisinin is converted to ________ which has anti-malarial activity.
  34. Aretmisinin is indicated for the initial treatment of what type of infections?
    P. falciparum
  35. What is ACT? Why is it used?
    • Artemisinin combination therapy
    • artemisinin is used to rapidly reduce (incompletely) the level of parasite burden while another agent is used to eliminate organisms at other phases. It will also help prevent resistance.
  36. List examples of class II drugs.
    • Atovaquone
    • Proguanil
  37. __________ is a highly lipophilic analog of ubiquinone.
  38. Atovaquone is active against liver stage of P. falciparum, but not ___________ hypnozoites.
    P. vivax
  39. Atovaquone acts at the _____________________ of the malaria mitochondria to inhibit ____________ which collapses the mitochondrial membrane potential and stop _____ production.
    • Cytochrome bc1
    • electron transport
    • ATP
  40. Atovaquone can be administered with a ________ to get a more complete collapse of membrane potential.
    Biguanide (such as proguanil)
  41. Resistance to Atovaquone can occur rapidly due to _________ in the _____________ gene.
    • Mutations
    • Cytochrome b
  42. Pyrimethamine is a class ___ drug based on its _______________ structure.
    • I
    • Diaminopyrimidine ring
  43. Although resistance is fairly widespread, pyrimethamine is used in combination with _______ helps to synergize its action.
  44. Pyrimethamine works by inhibiting what type of activity? This activity takes place in humans, so why can it still be used?
    • Dihydrofolate reductase
    • It inhibits the dihydrofolate reductase activity of plasmodia at concentrations far less than human enzymes.
  45. Dihydrofolate reductase activity is present in the same protein as _________ which will be suppressed as well.
    Thymidylate synthase
  46. What is the effect of adding a sulfonamide to pyrimethamine?
    It blocks two steps in nucleotide biosynthesis
  47. Describe the two steps in nucleotide biosynthesis blocked by giving a combination of pyrimethamine and sulfonamide.
    • Step one: sulfonamides inhibit dihydropteroic acid formation from p-aminobenzoate by dihydropteroate synthase.
    • Step two: pyrimethamine inhibits dihydrofolate reductase reducing tetrahydrofolate formation. (Results in a late effect on plasmodial development to schizonts in the liver and erythrocytes)
  48. Combination therapy of pyrimethamine and sulfonamide or sulfone is restricted to treatment of _________-resistant P. falciparum.
  49. Proguanil is use for P. falciparum infections and controls which two stages?
    Primary liver and asexual erythrocyte
  50. What is the active metabolite of proguanil?
  51. For proguanil, _________ selectively inhibits plasmoidial dihydrofolate reductase-thymidylate shynthetase causing ______ synthesis to be inhibited.
    • Triazine metabolite
    • DNA (along with folate cofactors)
  52. Proguanil is metabolized by ______ to cycloguanil. About 20% of which two ethnicities are deficient in this oxidative activity?
    CYP2C; Asians and Kenyans
  53. Why is proguanil usually given in combination with
    Due to rapid resistance development
  54. What are the mainstay anti-malarial agents for the past 400 years?
    Quinolines (chloroquine and hydroxycholroquine more widely used)
  55. Chloroquine is very effective against _______ forms of all species of Plasmodium except for some strains of __________. They are the agents of choice for both prophylaxis and treatment of these infections.
    • Erythrocytic
    • P. falciparum
  56. Describe the mechanism of action for chloroquine.
    Plasmodium use hemoglobin as primary source of amino acids. Acts by concentrating in parasite food vacuoles, preventing the polymerization of heme (Ferriprotoporphyrin IX) into hemozoin and thus eliciting parasite toxicity due to buildup of free heme.
  57. What is Crt?
    • Chloroquine resistance transporter. It may code for
    • a vacule transporter by which chloroquine enters.
  58. What are the two active metabolites of chloroquine?
    • Desethylchloroquine
    • Bisdesethlychloroquine
  59. Chloroquine is used for prophylaxis and treatment for ________, _____, and ________ in non-resistant areas.
    • P. malariae
    • ovale
    • vivax
  60. Chloroquine is used with primaquine because chloroquine has no activity against what?
    Liver plasmoidial forms
  61. Other than malaria, what else is chloroquine indicated for?
    Rheumatoid arthritis
  62. When is toxicity seen with chloroquine and what results?
    • Too rapid IV infusion; extensive CNS toxicity
    • including convulsions and coma. Can also have cardiovascular toxicity.
  63. Chloroquine is an inhibitor of CYP___.
  64. The mechanism of action of quinine is the same as _________.
  65. Quinine is _____ toxic and _____ effective than chloroquine.
    • More
    • less
  66. Why can quinine be used for symptomatic relief of myotonia congenita?
    It can antagonize tetanic stimulation of skeletal muscle.
  67. Quinine is extensively metabolized by CYP____.
  68. The active metabolite of quinine is ________ which can cause toxicity in ______________ patients.
    • 3-hydroxyquinine
    • renally impaired.
  69. Quinine is the treatment of choice for _________.
    Drug-resistant P. falciparum
  70. Quinine is available in the U.S. as _______ and, prior to 1995, was marketed to treat ________.
    • Quinidine
    • nocturnal leg cramps
  71. Primaquine is effective against ______ forms of the plasmoidial organisms.
  72. Primaquine is used for ___________ and _____ for P. vivax and P. ovale.
    Terminal prophylaxis; cure
  73. At high doses, primaquine can cause ________________ because it is an analog of methylene blue.
  74. In patients with _____________________, primaquine can cause acute hemolysis and hemolytic anemia.
    G6P dehydrogenase deficiency
  75. ____________ are slow-acting blood schizontocides used as monotherapy.
  76. Tetracylcines are used for travelers going to which two resistant endemic areas?
    Chloroquine and methoquine
  77. _________________ is equivalent to tetracycline action.
  78. Malarial resistance to ___________/___________, ___________ and ________ has been found in Southeast Asia.
    • Sulfadoxine/pyrimethamine
    • mefloquine
    • halofantrine
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DA Exam II Anti-malarial Agents.txt
Anti malarial agents from DA
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