antiprotozoal drugs Flashcards
trypanosoma cruzi causes
chagas disease
taenia solium
pork tapeworm, cysticercosis, neurocysticercosis
toxacara
dog and cat roundworms, causes blindness in children
toxoplasma gondii
cat feces, new infections in pregnancy lead to birth defects
trichomonas
sexually transmitted
HIV associated parasitic infections in US
pneumocystis jirovecii - pneumonia
toxoplasma gondii - encephalitis
cryptosporidium - cryptosporidiosis
HIV associated parasitic infections globally
malaria
leishmania
trypanosoma cruzi - chagas disease
5 human malaria parasites
plasmodium: falciparum, vivax, ovale, malariae, knowlesi
parasite responsible for most malaria deaths
plasmodium falciparum
relapsing malaria
plasmodium vivax (subtropics and temperate regions) plasmodium ovale (west africa) *caused by latent hypnozoites in liver
exoerythrocytic schizonticide
primaquine (merozoites and hypnozoites
atovoquone, artemisins (not hypnozoites
erythrocytic schizonticide
chloroquine, mefloquine, artemisinins, quinine, doxycycline
also tetracycline and clindiamycin
chloroquine and hydroxychloroquine sulfate - malaria prevention
only chloroquine sensitive areas, start 1-2 wk prior and continue 4 wk after leaving
atovaquone and proguanil - malaria prevention
all areas
start 1-2 days prior, continue 7 days after
mefloquine - malaria prevention
mefloquine sensitive areas, start >2 wk early and continue 4 weeks
primaquine - malaria prevention
P. vivax areas, start 1-2 d prior and continue 7 days after
doxycyline - malaria prevention
all areas, start 1-2 d prior and continue 4 weeks
Rx uncomplicated malaria and unknown species- chloroquine sensitive areas
chloroquine and hydroxychloroquine sulfate
Rx uncomplicated malaria and unknown species - chloroquine resistant areas
atovaquone + proguanil
artemether (artemesinin derivative) + lumafantrine (availability?)
quinine sulfate + doxycycline or tetracycline or clindamycin
mefloquine
Rx uncomplicated malaria - P. vivax or P. ovale, cq sensitive
chlorquine or hydroxychloroquine sulfate PLUS primaquine
14 days
Rx uncomplicated malaria - P. vivax or P. ovale, cq resistant
quinine sulfate PLUS doxycyline or tetracycline PLUS primaqine
atovaquone + proguanil PLUS primaquine
mefloquine PLUS primaquine
Rx uncomplicated malaria - P. malariae or P. knowlesi
chloroquine or hydroxychloroquine sulfate
complicated/severe malaria symptoms
impaired consciousness, coma, severe normocytic anemia, renal failure, pulmonary edema…
Rx complicated/severe malaria - first
IV: quinidine gluconate
PLUS doxycyline, tetracycline, or clindamycine
Cardio consult and experienced physician
monitor hypotension, hypoglycemia, cardiac function (widening QRS, lengthening QTc interval)
Rx complicated/severe malaria - second
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)
artemisin
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
artemisinin combo therapy
combined with longer half life drugs
artemether + lumefantrine
artesunate + mefloquine
dinydroartemisinin + piperaquine
artemisinin derivatives
artesunate - water soluble, oral, IV, intramusc, rectal
dihydroartemisinin - soluble, oral
artemether - lipid soluble, oral, intramusc, rectal
chloroquine
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
contraindications for chlorquine
psoriasis or porphyria
retina or visual field abnormalities
myopathy
quinine and quinidine
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)
adverse effects of quinine
cinchonism (tinnitus, dizziness, headaches, nausea, flushing, visual disturbances)
cardiotox
uterine contractions
hemolysis - G6PD deficiency, blackwater fever (hemoglobinurea)
hypotension - too rapid infusion
mefloquine
increasing resistance
prophylaxix and Rx
erythrocytic forms
adverse efects - neuropsych tox
primaquine
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
primaquine contraindications
G6PD deficiency - hemolytic anemia, pregnancy (fetus G6PD deficient)
granulocytopenia or methemoglubinemia
myelosuppression (drugs, disorders)
antifolates for malaria
pyrimethamine, proguanil, fansidar (pyrimethamine-sulfadoxine)
folate synth inhibitors
slow acting erythrocytic schizonticides
MOA pyrimethamine
inhibits plasmodia DHF-reductase (1000 fold selectivity for plasmodium)
other uses antifolates
toxoplasmosis - pyrimethamine plus sulfadizine is first line, clindamycin can replace sulfadizine
pneumocystis - fungal pathogen, trimethoprim plus sulfamethoxazole, atavaquone is alternative
malarone
combination of proguanil and atavaquone
atavaquone - disrupts mitochondrial electron transport (fails when used alone)
antibiotics for malaria
tetracycline, doxycycline, and clindamycin
blood schizonticides
targets the apicoplast (organelle)
metronidazole
anaerobic parasites
extraintestinal entamoeba histolytica, giardiasis, trichomoniasis
kills trophozoites, not cysts
tinidazole
similar to metronidazole with less toxicity, anaerobic parasites
metroindazole antabuse effect
blocks acetaldehyde dehydrogenase, build up acetaldehyde causes hypotension, nausea, vomiting, discomfort
iodoquinol
luminal amebicide, low bioavailability
asymptomatic carriers (combine with metronidazole)
kills trophozoites
pentamidine
parental administration accumulates in parasites highly toxic west african trypanosomiasis alternate treatment for visceral leishmania and pneumocystosis
nifurtimox
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
miltefosine
phospholipid analog developed as anticancer drug approved for use against visceral leishmaniasis 28 daily doses teratogenic
nitazoxanide
giardia and cryptosporidium
chagas disease treatment
nifurtimox or benznidazole
sleeping sickness treatment west african
west african: early stage - pentamidine, late stages - eflornithine
sleeping sickness treatmetn east african
east african: early stage - suramin, late stage, melarsoprol
