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PHRM 865 > Exam 6 - Antimalarial > Flashcards

Exam 6 - Antimalarial Flashcards

1
Q

Malaria:

what are the different parasites?

A 
plasmodium falciparum***
plasmodium vivax*** - causes relapses
plasmodium ovale -- causes relapses
plasmodium malariae
plasmodium knowlesi
*** = most common
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2
Q

what vaccine is available for malaria?

A

noneee

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3
Q

Life Cycle of Plasmodium Falciparum:

1. infected ______ inject _______

A

mosquito

sporozoites

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4
Q

Life Cycle of Plasmodium Falciparum:

2. Sporozites migrate to the _____ where they become _______

A

liver;

merozoites

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5
Q

Life Cycle of Plasmodium Falciparum:

3. Merozoites are released and invade ______

A

red blood cells

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6
Q

Life Cycle of Plasmodium Falciparum:

4. Once the merozoite is in the red blood cel it becomes a _______

A

trophozoite

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7
Q

Life Cycle of Plasmodium Falciparum:

Some merozoites can become ________ (not just trophozoite)

A

gametocytes

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8
Q

Ways to prevent malaria?

A

Prevention: insect repellents/insecticides/bed nets

or Chemoprophylaxis

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9
Q

what are some common malaria chemoprophylaxis

A
  • atovaquone-proguanil
  • chloroquine
  • mefloquine
  • primaquine
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10
Q

how are antimalarial drugs classified?

A

based on what stage the drug kills the malaria bugs

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11
Q

what are the 3 different stages a drug could attack the malaria?

A

tissue schizonticides
blood schizonticides
gametocytocides

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12
Q

tissue schizonticides: kill the ______ parasites

A

liver stage

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13
Q

blood schizonticides kills ______ forms

A

erythrocytic

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14
Q

gametocytocides: kill the _______ and block ______

A

sexual stages;

block transmission

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15
Q

what are the 6 different antimalarial drug classes

A 
artemisinin
4-aminoquinolines
8-aminoquinolines
atovaquone
antifolates
antibiotics
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16
Q

Artemisinin:
High or low toxicity?
Works fast or low?

A

LOW toxicity

and works fast (but also lasts not a long time..)

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17
Q

MOA of Artemisinin:
must be activated via _______
once activated it may form ________
and targets parasite proteins and lipids

A

via heme-iron

form free radicals

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18
Q

Artemisinin mechanism of resistance:

Mutations in _____ gene and causes _________

A

kelch 13; delays in progression through the life cycle

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19
Q

how does kelch13 work against artemisinin?

A

it enhances the stress response/helps malaria resist the drug

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20
Q

Artemisinin:

is active against what form of malaria?

A

blood schizonticide

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21
Q

Artemisinin:

bolus or infusion is best and why?

A

bolus bc PEAK/MIC is how it works

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22
Q

Artemisinin gets converted to ________ which is the active part

A

dihydroartemisinin

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23
Q

what drugs are 4-aminoquinolines

A

quinine
chloroquine
mefloquine

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24
Q

the -N group on the 4-aminoquinolines is a (weak or strong) (acid or base)

and what is that substiuients role

A

weak base

assists in drug accumulation via pH trapping

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25
Q

Malaria and its mechanism:

it ingests _______ from host cells

A

hemoglobin

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26
Q

Malaria and its mechanism:

it degrades hemoglobin to amino acids and _______ (which is toxic) in the food vacuole

A

free heme

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27
Q

Malaria and its mechanism:

Parasites ___________ heme into hemozoin to make it nontoxic

A

polymerize

28
Q

how do 4-aminoquinlones works

A

accumulate in the food vacuole and inhibit heme polymerization

29
Q

resistance seen against 4-aminoquinolones

A
  • lack of accumulation of the aminoquinolone in food vacuole

- mutation in PfCRT1

30
Q

Quinine or Chloroquine:

shorter half life and toxicity is worse aka it cannot be chemoprophylaxis

A

quinine

31
Q

MOA atovaquone?

A

selective inhibitor of malaria mitochondrial cytochrome bc1 complex

32
Q

MOA proguanil?

A

when convereted to cycloguanil – selective inhibitor for DHFR-TS (dihydrofolate reductase thmidylate synthetase)

and regular proguanil is synergistic with atovaquone

33
Q

MOA of artemesinin?

A

free radical

34
Q

MOA of chloroquine?

A

accum. in food vacuole/heme toxin build up

35
Q

MOA quinine?

A

accum. in food vacuole/heme toxin build up

36
Q

MOA of primaquine?

A

Produce H2O2 to kill plasmodium parasites

37
Q

MOA doxycycline?

A

targets apicloplast (plant like organelle that carries out many biochemical processes

38
Q

how is primaquine activated

A

CYP 2D6

39
Q

Contraindications of primaquine?

A
  • granulocytopenia

- concurrent use of other hemolytic drugs/drugs that suppress myeloid cell development

40
Q

Primaquine: high risk of _______ if G6PD deficiency

A

hemolysis

41
Q

key functional group in artemisinin?

A

endoperoxide

42
Q

ADEs of Quinine?

A
  • cinchonism: tinnitis, HA, nausea, dizziness, flushing, visual disturbances
  • stimulate uterine contractions
  • hemolysis (G6PD)
  • severe hypotension if too rapid of infusion
43
Q

ADEs of Primaquine?

A

hemolysis high risk
avoid in breastfeeding women

CIs:-granulocytopenia
-concurrent use of other hemolytic drugs/drugs that suppress myeloid cell development

44
Q

what drug is DOC for liver stages of P.vivax and P.ovale

A

primaquine

45
Q

Sxs of giardiasis

A

diarrheal disease

46
Q

Sxs amebiasis

A

diarrhea/flatulence/abdominal cramps

47
Q

drugs to treat toxoplasma

A

1st line: pyrimethamine + sulfadiazene

alternative: atovaquone or pentamidine

48
Q

drugs to treat amebiasis

A

paromomycin

idoquinol

49
Q

drugs to treat trichomonas

A

metronidazole

50
Q

Spectrum of Metronidazole?

A

Giardiasis
trichamoniasis

(anaerobes)

51
Q

Spectrum of Nitazoxanide?

A

inhibits growh of sporozoites andoocysts of cryptosporidiu parvum and trophozoites of giardia lamblia

52
Q

Spectrum of Paromomycin?

A

an aminoglycoside for INTESTINAL FORM of amebiasis and cryptosporidium

53
Q

MOA of nitazoxanide?

A

interferes with PFOR (pyruvate ferredoxin oxidoreductase)

inhibits anaerobic metabolism

54
Q

MOA of metronidazole?

A

free radicals/anaerobes have electron transport proteins with low redox potential

55
Q

what bug causes river blindness

A

onchocerciasis

56
Q

what bug causes elephantiasis

A

filariasis

57
Q

what do benzimidazoles cover

ex: mebendazole, thiabendazole, albendazole

A

helminths

58
Q

MOA of Benzimidazoles?

A

bind to tubulin/inhibit formation of microtubules

59
Q

Praziquantel: spectrum covers 2 of the following - what are they?

cestodes
nematodes
treamtodes

A

cestodes and treamtodes

60
Q

MOA of ivermectin

A

paralyzes microfilarie/binds to glutamate activated chloride channels on nerve muscle cells

61
Q

Ivermectin is primarily used for ______

A

onchocercisasis

62
Q

MOA of pyrantel pamoate

A

worms are paralyzed/expelled

depolarizing neuromuscular blocking agent/Ach/cholinesterae effects

63
Q

MOA of nifurtimox and benznidazole?

A

activated by NADH dependent mitochondrial nitroreductase

generates nitro radical anions

64
Q

treatment of Giardia?

A

metronidazole

nitazoxanide

65
Q

what is the nickname for T.Cruzi and T. brucei

A

Sleeping sickness:
Cruz: American one
Brucei: African

66
Q

Nifurtimox/Benznidazole:

covers what bugs

A

T.Cruzi/Brucei aka trypanosomiasis aka sleeping sickness

PHRM 865 (59 decks)

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