Exam 5 - Antimalarial Flashcards
Malaria:
what are the different parasites?
plasmodium falciparum*** plasmodium vivax*** - causes relapses plasmodium ovale -- causes relapses plasmodium malariae plasmodium knowlesi *** = most common
what vaccine is available for malaria?
noneee
Life Cycle of Plasmodium Falciparum:
1. infected ______ inject _______
mosquito
sporozoites
Life Cycle of Plasmodium Falciparum:
2. Sporozites migrate to the _____ where they become _______
liver;
merozoites
Life Cycle of Plasmodium Falciparum:
3. Merozoites are released and invade ______
red blood cells
Life Cycle of Plasmodium Falciparum:
4. Once the merozoite is in the red blood cel it becomes a _______
trophozoite
Life Cycle of Plasmodium Falciparum:
Some merozoites can become ________ (not just trophozoite)
gametocytes
Ways to prevent malaria?
Prevention: insect repellents/insecticides/bed nets
or Chemoprophylaxis
what are some common malaria chemoprophylaxis
- atovaquone-proguanil
- chloroquine
- mefloquine
- primaquine
how are antimalarial drugs classified?
based on what stage the drug kills the malaria bugs
what are the 3 different stages a drug could attack the malaria?
tissue schizonticides
blood schizonticides
gametocytocides
tissue schizonticides: kill the ______ parasites
liver stage
blood schizonticides kills ______ forms
erythrocytic
gametocytocides: kill the _______ and block ______
sexual stages;
block transmission
what are the 6 different antimalarial drug classes
artemisinin 4-aminoquinolines 8-aminoquinolines atovaquone antifolates antibiotics
Artemisinin:
High or low toxicity?
Works fast or low?
LOW toxicity
and works fast (but also lasts not a long time..)
MOA of Artemisinin:
must be activated via _______
once activated it may form ________
and targets parasite proteins and lipids
via heme-iron
form free radicals
Artemisinin mechanism of resistance:
Mutations in _____ gene and causes _________
kelch 13; delays in progression through the life cycle
how does kelch13 work against artemisinin?
it enhances the stress response/helps malaria resist the drug
Artemisinin:
is active against what form of malaria?
blood schizonticide
Artemisinin:
bolus or infusion is best and why?
bolus bc PEAK/MIC is how it works
Artemisinin gets converted to ________ which is the active part
dihydroartemisinin
what drugs are 4-aminoquinolines
quinine
chloroquine
mefloquine
the -N group on the 4-aminoquinolines is a (weak or strong) (acid or base)
and what is that substiuients role
weak base
assists in drug accumulation via pH trapping
Malaria and its mechanism:
it ingests _______ from host cells
hemoglobin
Malaria and its mechanism:
it degrades hemoglobin to amino acids and _______ (which is toxic) in the food vacuole
free heme
Malaria and its mechanism:
Parasites ___________ heme into hemozoin to make it nontoxic
polymerize
how do 4-aminoquinlones works
accumulate in the food vacuole and inhibit heme polymerization
resistance seen against 4-aminoquinolones
- lack of accumulation of the aminoquinolone in food vacuole
- mutation in PfCRT1
Quinine or Chloroquine:
shorter half life and toxicity is worse aka it cannot be chemoprophylaxis
quinine
MOA atovaquone?
selective inhibitor of malaria mitochondrial cytochrome bc1 complex
MOA proguanil?
when convereted to cycloguanil – selective inhibitor for DHFR-TS (dihydrofolate reductase thmidylate synthetase)
and regular proguanil is synergistic with atovaquone
MOA of artemesinin?
free radical
MOA of chloroquine?
accum. in food vacuole/heme toxin build up
MOA quinine?
accum. in food vacuole/heme toxin build up
MOA of primaquine?
free radical
MOA doxycycline?
targets apicloplast (plant like organelle that carries out many biochemical processes
how is primaquine activated
CYP 2D6
Contraindications of primaquine?
- granulocytopenia
- concurrent use of other hemolytic drugs/drugs that suppress myeloid cell development
Primaquine: high risk of _______ if G6PD deficiency
hemolysis
key functional group in artemisinin?
endoperoxide
ADEs of Quinine?
- cinchonism: tinnitis, HA, nausea, dizziness, flushing, visual disturbances
- stimulate uterine contractions
- hemolysis (G6PD)
- severe hypotension if too rapid of infusion
ADEs of Primaquine?
hemolysis high risk
avoid in breastfeeding women
CIs:-granulocytopenia
-concurrent use of other hemolytic drugs/drugs that suppress myeloid cell development
what drug is DOC for liver stages of P.vivax and P.ovale
primaquine
Sxs of giardiasis
diarrheal disease
Sxs amebiasis
diarrhea/flatulence/abdominal cramps
drugs to treat toxoplasma
1st line: pyrimethamine + sulfadiazene
alternative: atovaquone or pentamidine
drugs to treat amebiasis
paromomycin
idoquinol
drugs to treat trichomonas
metronidazole
Spectrum of Metronidazole?
Giardiasis
trichamoniasis
(anaerobes)
Spectrum of Nitazoxanide?
inhibits growh of sporozoites andoocysts of cryptosporidiu parvum and trophozoites of giardia lamblia
Spectrum of Paromomycin?
an aminoglycoside for INTESTINAL FORM of amebiasis and cryptosporidium
MOA of nitazoxanide?
interferes with PFOR (pyruvate ferredoxin oxidoreductase)
inhibits anaerobic metabolism
MOA of metronidazole?
free radicals/anaerobes have electron transport proteins with low redox potential
what bug causes river blindness
onchocerciasis
what bug causes elephantiasis
filariasis
what do benzimidazoles cover
ex: mebendazole, thiabendazole, albendazole
helminths
MOA of Benzimidazoles?
bind to tubulin/inhibit formation of microtubules
Praziquantel: spectrum covers 2 of the following - what are they?
cestodes
nematodes
treamtodes
cestodes and treamtodes
MOA of ivermectin
paralyzes microfilarie/binds to glutamate activated chloride channels on nerve muscle cells
Ivermectin is primarily used for ______
onchocercisasis
MOA of pyrantel pamoate
worms are paralyzed/expelled
depolarizing neuromuscular blocking agent/Ach/cholinesterae effects
MOA of nifurtimox and benznidazole?
activated by NADH dependent mitochondrial nitroreductase
generates nitro radical anions
treatment of Giardia?
metronidazole
nitazoxanide
what is the nickname for T.Cruzi and T. brucei
Sleeping sickness:
Cruz: American one
Brucei: African
Nifurtimox/Benznidazole:
covers what bugs
T.Cruzi/Brucei aka trypanosomiasis aka sleeping sickness
