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pharmacology > antiprotozoal drugs > Flashcards

antiprotozoal drugs Flashcards

1
Q

trypanosoma cruzi causes

A

chagas disease

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2
Q

taenia solium

A

pork tapeworm, cysticercosis, neurocysticercosis

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3
Q

toxacara

A

dog and cat roundworms, causes blindness in children

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4
Q

toxoplasma gondii

A

cat feces, new infections in pregnancy lead to birth defects

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5
Q

trichomonas

A

sexually transmitted

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6
Q

HIV associated parasitic infections in US

A

pneumocystis jirovecii - pneumonia
toxoplasma gondii - encephalitis
cryptosporidium - cryptosporidiosis

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7
Q

HIV associated parasitic infections globally

A

malaria
leishmania
trypanosoma cruzi - chagas disease

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8
Q

5 human malaria parasites

A

plasmodium: falciparum, vivax, ovale, malariae, knowlesi

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9
Q

parasite responsible for most malaria deaths

A

plasmodium falciparum

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10
Q

relapsing malaria

A 
plasmodium vivax (subtropics and temperate regions)
plasmodium ovale (west africa)
*caused by latent hypnozoites in liver
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11
Q

exoerythrocytic schizonticide

A

primaquine (merozoites and hypnozoites

atovoquone, artemisins (not hypnozoites

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12
Q

erythrocytic schizonticide

A

chloroquine, mefloquine, artemisinins, quinine, doxycycline

also tetracycline and clindiamycin

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13
Q

chloroquine and hydroxychloroquine sulfate - malaria prevention

A

only chloroquine sensitive areas, start 1-2 wk prior and continue 4 wk after leaving

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14
Q

atovaquone and proguanil - malaria prevention

A

all areas

start 1-2 days prior, continue 7 days after

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15
Q

mefloquine - malaria prevention

A

mefloquine sensitive areas, start >2 wk early and continue 4 weeks

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16
Q

primaquine - malaria prevention

A

P. vivax areas, start 1-2 d prior and continue 7 days after

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17
Q

doxycyline - malaria prevention

A

all areas, start 1-2 d prior and continue 4 weeks

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18
Q

Rx uncomplicated malaria and unknown species- chloroquine sensitive areas

A

chloroquine and hydroxychloroquine sulfate

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19
Q

Rx uncomplicated malaria and unknown species - chloroquine resistant areas

A

atovaquone + proguanil
artemether (artemesinin derivative) + lumafantrine (availability?)
quinine sulfate + doxycycline or tetracycline or clindamycin
mefloquine

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20
Q

Rx uncomplicated malaria - P. vivax or P. ovale, cq sensitive

A

chlorquine or hydroxychloroquine sulfate PLUS primaquine

14 days

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21
Q

Rx uncomplicated malaria - P. vivax or P. ovale, cq resistant

A

quinine sulfate PLUS doxycyline or tetracycline PLUS primaqine
atovaquone + proguanil PLUS primaquine
mefloquine PLUS primaquine

22
Q

Rx uncomplicated malaria - P. malariae or P. knowlesi

A

chloroquine or hydroxychloroquine sulfate

23
Q

complicated/severe malaria symptoms

A

impaired consciousness, coma, severe normocytic anemia, renal failure, pulmonary edema…

24
Q

Rx complicated/severe malaria - first

A

IV: quinidine gluconate
PLUS doxycyline, tetracycline, or clindamycine
Cardio consult and experienced physician
monitor hypotension, hypoglycemia, cardiac function (widening QRS, lengthening QTc interval)

25
Q

Rx complicated/severe malaria - second

A

Artesunate (artemesinin derivative) - if quinidine gluconate not available or not tolerated
follwed by: malarone or doxycyline (clindamycin if pregnant) or mefloquine
IV only
has IND (cal CDC malaria hotline)

26
Q

artemisin

A

standard treatment globally
endoperoxide
blood schizonticide - 4 log reduction in numbers in 48 hours
used for chloroquine resistant P. falciparum
short half life, paired with other drugs (mefloquine, lumefantrine)
not given in first trimester

27
Q

artemisinin combo therapy

A

combined with longer half life drugs
artemether + lumefantrine
artesunate + mefloquine
dinydroartemisinin + piperaquine

28
Q

artemisinin derivatives

A

artesunate - water soluble, oral, IV, intramusc, rectal
dihydroartemisinin - soluble, oral
artemether - lipid soluble, oral, intramusc, rectal

29
Q

chloroquine

A

4-susbstituted quinoline
erythrocytic forms
interferes with heme polymerization to nontoxic hemozoin inside food vacuole
resistance - no drug accumulation in food vacuole
designed for oral, well absorbed

30
Q

contraindications for chlorquine

A

psoriasis or porphyria
retina or visual field abnormalities
myopathy

31
Q

quinine and quinidine

A

rapidly acting blood schizonticide
first line alternative for falciparum but toxic (IV for severe, oral for uncomplicated)
MOA similar to chloroquine
metabolized by CYP3A4 - warfarin, digoxin, antiretroviral drugs (HIV prevalent areas)

32
Q

adverse effects of quinine

A

cinchonism (tinnitus, dizziness, headaches, nausea, flushing, visual disturbances)
cardiotox
uterine contractions
hemolysis - G6PD deficiency, blackwater fever (hemoglobinurea)
hypotension - too rapid infusion

33
Q

mefloquine

A

increasing resistance
prophylaxix and Rx
erythrocytic forms
adverse efects - neuropsych tox

34
Q

primaquine

A

8-aminoquinoline
unknown mechanism, probably ROS
liver stages - only drug active against hyponozoites
gametocidal against all four malaria parasites
well absorbed orally
too toxic for long term

35
Q

primaquine contraindications

A

G6PD deficiency - hemolytic anemia, pregnancy (fetus G6PD deficient)
granulocytopenia or methemoglubinemia
myelosuppression (drugs, disorders)

36
Q

antifolates for malaria

A

pyrimethamine, proguanil, fansidar (pyrimethamine-sulfadoxine)
folate synth inhibitors
slow acting erythrocytic schizonticides

37
Q

MOA pyrimethamine

A

inhibits plasmodia DHF-reductase (1000 fold selectivity for plasmodium)

38
Q

other uses antifolates

A

toxoplasmosis - pyrimethamine plus sulfadizine is first line, clindamycin can replace sulfadizine
pneumocystis - fungal pathogen, trimethoprim plus sulfamethoxazole, atavaquone is alternative

39
Q

malarone

A

combination of proguanil and atavaquone

atavaquone - disrupts mitochondrial electron transport (fails when used alone)

40
Q

antibiotics for malaria

A

tetracycline, doxycycline, and clindamycin
blood schizonticides
targets the apicoplast (organelle)

41
Q

metronidazole

A

anaerobic parasites
extraintestinal entamoeba histolytica, giardiasis, trichomoniasis
kills trophozoites, not cysts

42
Q

tinidazole

A

similar to metronidazole with less toxicity, anaerobic parasites

43
Q

metroindazole antabuse effect

A

blocks acetaldehyde dehydrogenase, build up acetaldehyde causes hypotension, nausea, vomiting, discomfort

44
Q

iodoquinol

A

luminal amebicide, low bioavailability
asymptomatic carriers (combine with metronidazole)
kills trophozoites

45
Q

pentamidine

A 
parental administration
accumulates in parasites
highly toxic 
west african trypanosomiasis 
alternate treatment for visceral leishmania and pneumocystosis
46
Q

nifurtimox

A

T. cruzi (chagas disease)
reduces severity of acute phase, unlikely to eliminate parasite, does not prevent progression of disease
orally available
3-4 month course
toxicity common –> premature stoppage of treatment

47
Q

miltefosine

A 
phospholipid analog 
developed as anticancer drug
approved for use against visceral leishmaniasis
28 daily doses 
teratogenic
48
Q

nitazoxanide

A

giardia and cryptosporidium

49
Q

chagas disease treatment

A

nifurtimox or benznidazole

50
Q

sleeping sickness treatment west african

A

west african: early stage - pentamidine, late stages - eflornithine

51
Q

sleeping sickness treatmetn east african

A

east african: early stage - suramin, late stage, melarsoprol

pharmacology (2 decks)

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