Antiparasitic drugs Flashcards
which enzyme is unique to parasites?
pyruvate:ferredoxin oxidoreductase (PFOR)
what are the three targets for antiparasitic chemotherapy?
- enzymes found only in parasite (PFOR)
- enzymes in both host and parasite but indispensable only in the parasite (purine salvage)
- common biochem functions in both host and parasite, but different pharmacological properties (DHFR, microtubule disrupters)
what organism causes amebiasis?
entamoeba histolytica
what organism causes giardiasis?
giardia lamblia
what are the features of giardia, entamoeba, and trichomonas?
anaerobic lumen dwelling protozoans
what enzyme is expressed by giardia, entamoeba, and trichomonas?
PFOR
what is the function of PFOR?
converts pyruvate to acetyl CoA
how does metronidazole (Flagyl) kill parasites?
acts as an electron sink within the cell
activated (reduced) by PFOR under anaerobic conditions
reactive intermediates form which bind to and disrupt protein and DNA structure and function
what are the main adverse effects of metronidazole (Flagyl)?
disulfiram effect
what is the drug of choice for treating SYMPTOMATIC DZ?
metronidazole (Flagyl)
what is the problem with metronidazole in amebiasis treatment?
does not kill cyst forms
what drugs are effective at eliminating trophozoite and cyst forms of e. histolytica from the LUMEN of the intestine? are they effective in the tissues?
iodoquinol and paromomycin
no
when should iodoquinol be used?
following metronidazole
which drug is less toxic - iodoquinol or paromomycin?
paromomycin
what are the opportunistic parasitic infections of AIDS patients and the immunocompromised?
cryptosporidium parvum
pneumocystis jirovecii
toxoplasma gondii
what drug is used against c. parvum?
nitazoxanide
what is the MOA of nitazoxanide?
PFOR inhibitor - disrupts energy metabolism
which agents inhibit folate synthesis in parasites, and which organisms do they target?
TMP-SMX - pneumocystis jirovecii
pyramethamine-sulfadiazine - toxoplasma gondii
what drug is used against pneumocystis jirovecii?
TMP-SMX
what drug is used against toxoplasma gondii?
pyrimethamine sulfadiazine
what are the inhibitors of folate synthesis?
sulfonamides
diaminopyrimidines
what is the MOA of the sulfonamides?
PABA analogs that inhibit production of pteroic acid from PABA by the enzyme dihydropteroate synthase
what is the MOA of diaminopyrimidine?
inhibit DHFR - prevents formation of THF
what is the main adverse reaction of the sulfonamides?
rash
what drug is used to treat toxoplasmosis?
pyrimethamine-sulfadiazine
what drug is administered to prevent folate deficiency from pyrimethadine-sulfadiazine treatment?
leucovorin
what drug can kill the dormant forms of p. vivax and p. ovale?
primaquine
is there resistance to chloroquine?
yes
what are the adverse effects of quinine?
cinchonism - tinnitus, temporary hearing loss, headache, nausea, vomiting
hypoglycemia - induces insulin release
what is the MOA of quinine?
eliminates asexual erythrocytic stage of all plasmodium species
what is the main adverse reaction for mefloquine?
severe neuropsychiatric reactions
what is the major toxicity associated with primaquine?
hemolysis in G6PD patients
malarone is a combination of which drugs? what is the clinical use?
atovaquone and proguanil
p. falciparum treatment, prophylaxis
what must be checked prior to primaquine administration?
G6PD status
what is the MOA of proguanil?
DHFR inhibitor
what is the indication for doxycycline in malaria treatment?
prophylaxis and treatment
what is the major side effect of doxycycline?
photosensitivity dermatitis
which drug works well against multidrug resistant strains of p. falciparum?
artemisinin
what are the general (proposed) MOAs of antihelminthics?
inhibit mitosis in parasite
muscle paralysis of parasite
what are the benzimidazole antihelminthics?
albendazole
mebendazole
thiabendazole
what is the toxicity associated with benzimidazoles?
thiabendazole
GI - anorexia, nausea, vomiting
CNS - delirium, hallucinations
albendazole and mebendazole
GI
which antihelminthic drugs are contraindicated during pregnancy?
benzimidazoles
albendazole and mebendazole are useful against which worms?
ascariasis
pinworm
hookworm
whipworm
what is the clinical use for thiabendazole?
second line for strongyloidiasis (intestinal and tissue)
topical for cutaneous larval migrans
what is the MOA of ivermectin?
hyperpolarization is muscle cells - paralysis
ivermectin is the drug of choice for which worm(s) / condition(s)?
strongyloidiasis
river blindness, eye worm, filarial worms
what is the drug of choice for strongyloidiasis?
ivermectin
what is the drug of choice for pinworm?
pyrantel pamoate
what is the MOA of pyrantel pamoate?
activates cholinergic nicotinic receptors in somatic muscles of nematodes - neuromuscular blockade
what is the drug of choice for tapeworms and flukes?
praziquantel
what is the MOA of praziquantel?
increases calcium permeability of worm’s tegument - causes depolarization
