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vandy's antiparasitic drugs
N/A
148
Pharmacology
Graduate
02/10/2010

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Term
what is the mechanism of action of Nitazoxanide?
Definition
interferes with PFDR enzyme-dependent *electron transfer reaction* which is critical for anaerobic metabolism
Term
What is metronidazole used to treat?
Definition
anaerobic bacteria, Giardia lambia, Entamoeba histolytica, Trichomonas vaginalis
Term
What is the mechanism of metronidazole?
Definition
1)acts as an electron sink, depriving cells of reducing equivalents
2)inhibits DNA synthesis (induces strand breaks and alters repair)
Term
What part of the life cycle of protozoa does metronidazole work on?
Definition
trophozoites
Term
what is the bioavailability of metronidazole if taken orally?
Definition
almost 100% - absorbed very well
Term
When should metronidazole not be perscribed?
Definition
during the first trimester of pregnancy
Term
What happens if metronidazole is given to an alcoholic?
Definition
disulfiram-like reaction - violent emesis
Term
what are the side effects of metronidazole?
Definition
headache, metallic taste, vomiting, diarrhea, peripheral neuropathy, CNS toxicity, **disulfiram-like reaction
Term
When treating Entamoeba with metronidazole, you should also use _____________
Definition
luminal agent
Term
Name two Luminal Amoebicides.
Definition
Iodoquinol
Diloxanide Furoate
Term
What is a major side effect seen with prolonged use of Iodoquinol?
Definition
**subacute myelo-optic neuropathy
Term
what are the side effects of diloxanide furoate?
Definition
GI intolerance
CNS toxicity
Term
what are the side effects of Nitazoxanide?
Definition
abdominal pain, headache, nausea, diarrhea
Term
what is nitazoxanide used to treat?
Definition
giardia and cryptosporidia
Term
what stage of Giardia is inhibited by nitazoxanide?
Definition
trophozoite stage
Term
what stage of Cryptosporidia is inhibited by nitazoxanide?
Definition
oocysts and sporozoites
Term
what drugs are used to treat visceral Leishmania?
Definition
pentostam
pentamidine
ampho B
Term
what is the mechanism of action of Pentostam (sodium-stibogluconate)?
Definition
used to treat Leshmania -interferes with parasitic glycolysis/energy production by blocking phosphorylation of Fructose6P dehydrogenase in amastigotes
Term
what stage of Leshmania is targeted by drugs?
Definition
amastigote
Term
how is pentostam administered to treat Leshmaniaisis?
Definition
parenteral ONLY (injection)
Term
What are the side effects of Pentostam?
Definition
nausea, myalgia,arthralgia, flattening of T waves on EKG, increases hepatic transaminases (cardiac/liver toxicity)
Term
what drugs are used for the prophylaxis of malaria?
Definition
Mefloquine-once a week
Atovaquone/proguanil
Doxycycline - once a day/ stay out of sun
chloroquine phosphate if susceptible
Term
what drug targets the hynozoites of plasmodium vivax?
Definition
primaquine
Term
what can be used to treat chloroquine-resistant strains of Plasmodium falciparum?
Definition
1)quinine + pyrimethamine/sulfadoxine
2)quinine + tetracycline or clindamycin
3)artesunate + amodiaquine or sulfadoxine/pyrimethamine
Term
why do patients have trouble completing a course of quinine for P. falciparum?
Definition
GI side effects
Term
what is used for the treatment and prophylaxis of P. malariae?
Definition
Chloroquine phosphate
Term
what is the treatment for P. vivax/ovale?
Definition
Cholorquine phosphate(trophozoites-shizogony stage) + Primaquine phosphate(hypnozoites)
Term
what is the primary mechanism of chloroquine?
Definition
binds to hemeoglobin complex and inhibits heme polymerase causing an accumulation of heme byproducts(ferriprotoporphyrin 9) which are toxic/ lytic to the parasite
Term
what stage of malaria is targeted by chloroquine?
Definition
asexual erythrocytic stages
Term
what genes are associated with resistance to chloroquine?
Definition
pfmdr1 and cg2
Term
How is chloroquine administered?
Definition
1)usually orally - very good absorption
2)IM injections for kids
Term
what part of the body does chloroquine distribute to?
Definition
accumulates in all tissues but GREATEST IN RBCs
Term
what are the side effects of chloroquine?
Definition
GI intolerance, headache, pruritis
CNS toxicity, hemolysis
visual disturbances, alopecia, skin eruptions, **cardiac toxicity
Term
what side effects are seen with PROLONGED use of chlorquine?
Definition
**cardiac toxicity- QT prolongation
visual problems
retinopathy
alopecia
skin eruptions
Term
Is a loading dose required for chloroquine or quinine?
Definition
chloroquine
Term
where does quinine accumulate?
Definition
in the tissues much more than in RBC
Term
what are the side effects of quinine?
Definition
GI intolerance
**Cinchonism - headache, tinnitus, visual disturbances
hemolysis
cardiotoxicity
Term
what must be done if giving IV quinine?
Definition
must monitor in intensive care environment
Term
what mediates resistance to mefloquine?
Definition
MDR gene
Term
what is the mechanism of pyrimethamine/sulfadoxine?
Definition
inhibits synthesis of folic acid by PABA competition and inhibition of dihydrofolate reductase
Term
what is pyrimethamine/sulfadoxine used for?
Definition
used as a helper drug to prevent resistance when treating malaria
Term
what should patients be screened for before giving primaquine and why?
Definition
G6PD deficiency - can cause hemolytic anemia
Term
what is the mechanism of action of Atovaquone?
Definition
inhibits ETC, nucleic acid and ATP synthesis
Term
what is the mechanism of action of Proquanil?
Definition
inhibits parasite dihyrdofolate reductase
Term
which antimalarial drug is active aginst ALL erythrocytic stages?
Definition
Artesunate
Term
what is the mechanism of action of Artesunate?
Definition
1)free radical production in parasite food vacuole
2)inhibits parasite calcium ATPase
Term
what must be given in combination with pyrimethamine/sulfadiazine when treating toxoplamosis and why?
Definition
Leucovorin - reduces the hematological toxicity of pyrimethamine
Term
what are the side effects of mefloquine?
Definition
dizziness, GI upset, nightmares, insomnia, panic attacks, seizures, **psychosis, cardiotoxicity
Term
where does pyrimethamine/sulfadoxine accumulate?
Definition
kidneys, liver, lungs, spleen
Term
How does pyrimethamine/suladoxine work?
Definition
inhibits folic acid synthesis by PABA competition and inhibting dihydrofolate reductase
Term
why is hemolytic anmeia seen in G6PD deficient individuals that take primaquine?
Definition
in their erythrocytes there is a failure to replenish NADPH - primaquine metabolites generate free radicals/peroxides which cause lysis of the RBC (older cells more susceptible)
Term
what are the treatments for Pneumocystis jiroveci? (4)
Definition
1)**trimethoprim/sulfamethoxazole
2)pentamidine isethionate
3)atovaquone
4)clindamycin + primaquine
Term
what is used for the prophylaxis of P. jiroveci?
Definition
1)trimethoprim/sulfamethoxazole
2)dapsone - use if allergic to sulfa drugs
3)atovaquone
4)aerosolized pentamidine
Term
How is pentamidine isethionate administered?
Definition
IV or aerosolized form ONLY (poor oral absorption)
Term
what are the side effects of pentamidine isethionate?
Definition
nephrotoxicity, hypotension, hypoglycemia,diabetes melltius, bone marrow suppression, pancreatitis
Term
what is the mechanism of dapson used to treat P. jiroveci?
Definition
inhibits utilization of PABA for folic acid synthesis
Term
what is dapsone used for?
Definition
PROPHYLAXIS of P. jiroveci
Term
what are the side effects of dapsone?
Definition
nausea, anorexia, fever
**methemoglinemia,**hemolysis in G6PD deficiency
photsensitivity, agranulocytosis, aplastic anemia
Term
what drugs are used to treat Toxoplasma gondii?
Definition
1)pyrimethamine/sulfadiazine
2)pyrimethamine + clindamycin
Term
what is used a prophylaxis for Toxoplasma gondii?
Definition
trimethoprim/sulfamethoxazole (Bactrim)
Term
what two drugs are used to treat Hookworm, Ascaris, or Whipworm?
Definition
1)Mebendazole
2)*Albendazole - DOC bc better activity/toleration
Term
what should be used as adjunst therapy for Ascaris?
Definition
piperazine - muscle relaxer that can help with obstruction (esp in kids)
Term
what is the mechanism of action of mebendazole?
Definition
inhibits polymerization to form microtubules which prevents glucose uptake by the worm - gycogen depleted, ATP synthesis prevented so worm starves
Term
how is mebendazole administered?
Definition
oral only
Term
what is the mechanism of albendazole?
Definition
prevents glucose uptake in helminths
Term
what is piperazine citrate active against?
Definition
Ascaris, pinworm
Term
what is the mechanism of piperazine citrate?
Definition
agonist of GABA-gated chloride channels in nematode muscle - results in worm being paralyzed (flaccid paralysis) and then passed in stool alive
Term
what is used as treatment for Strongyloidiasis?
Definition
1)albendazole
2)ivermectin
Term
what is the mechanism of ivermectin?
Definition
causes release/binding of GABA at postsynaptic site on NMJ which paralyzes the worm
also affects a glutamate-gated chloride channel in nerve and muscle
Term
what is ivermectin used to treat?
Definition
1)nematodes - strongyloidiasis
2)arthropods - mites, fleas, ticks
3) heartworms in dogs
Term
what is the drug of choice for the treatment of pinworm?
Definition
albendazole
Term
what two drugs can be used to treat pinworm?
Definition
pyrantel pamoate
albendazole - drug of choice
Term
what is the mechanism of pyratel pamoate?
Definition
depolarizing nueromuscular-blocking agent/ inhibits cholinesterase ----**causes worm paralysis and expulsion from GI tract
Term
what is the drug of choice when treating tapeworms?
Definition
praziquantel
Term
what is the problem with treating neurocysticercosis?
Definition
precipitate an inflammatory response, cerebral edema and icreased mass effect, and increased intracranial pressure
Term
what two drugs can be used to treat neurocysticercosis?
Definition
praziquantel
albendazole
Term
when should drugs be used to treat neurocysticercosis?
Definition
if there are multiple lesions, esp at the basilar cisterns or sylvian fissure
Term
what is the mechanism of praziquantel?
Definition
1)increasees membrane permeability resulting in small holes in the worm
2)causes prolonged parasite muscle contraction and spastic paralysis
Term
what are the side effects of praziquantel?
Definition
headache, dizziness, nausea
Term
what is praziquantel used to treat?
Definition
tapeworms and trematodes(flukes)
Term
what is used to treat cysticercosis of T. solium and hydatid cysts of Echinococcus?
Definition
albendazole
Term
what are the side effects of albendazole?
Definition
diarrhea, epigastric abdominal pain, leukopenia, hepatotoxicity
Term
Drug of choice for e. histolytica?
Definition
Metronidazole
Term
How do luminal agents work?
Definition
they act in the bowel lumen
Term
What bacterial infection is associated with a higher mortality rate with treatment?
Definition
e. coli 0157H7 (enterohemorrhagic)
Term
Treat giardi lamblia with?
Definition
metronidazole
Term
treat trichomonas vaginalis with?
Definition
metronidazole
Term
Mechanism of metronidazole ? (according to vande's transcript)
Definition
Deprives reducing equivalents in protozoa and may inhibit DNA synthesis. Effects trophozoites rather than cysts b/c affects the actively metabolizing bugs
Term
_____________ may cause violent emesis in alcoholics
Definition
metronidazole
Term
side effects of metronidazole?
Definition
headache, nausea, vomiting, diarrhea (from a disulfram-rxn)
Term
2 luminal agents dr. vande mentioned in case of resistance or intolerance to metronidazole?
Definition
1)iodoquinol
2)diloxanide furoate
Term
side effects of iodoquinol?
Definition
subacute myelo-optic neuropathy and some peripheral neuropathy
Term
side effects of diloxanide furoate?
Definition
GI intolerance (dont really see CNS toxicity)
Term
Nitazoxanide is mainly aimed at what 2 protozoa?
Definition
1)giardia (trophozoite)
2)crytposporidia (oocysts and sporozoites)
Term
what is the mechanism of action of nitazoxanide?
Definition
interferes with pyruvate ferredoxin oxidoreductase (PFDR)
Term
Pentostam, pentamidine and ampho B can all be used to treat what?
Definition
viceral leishmania and cutaneous is needed (it usually spontaneously resolves)
Term
what is the mechanism of action of Pentastam (sodium-stibogluconate)?
Definition
interferes with parasite glycolysis in the amastigote (leishmania) decreasing ATP production.
Term
how do you administer pentastam?
Definition
parenterally
Term
side effects of pentostam?
Definition
(for leishmania) nausea, myalgia, arthralgia, flattening of T waves, increase in hepatic enzymes (just BAD)
Term
chinchona alkaloids can be used to treat?
Definition
chloroquine resistant malaria
Term
Artemisin (artesunate) can be used to treat?
Definition
chloroquine resistant plasmodium
falciparum
Term
primaquine treats?
Definition
hypnozoites
Term
name 2 chinchona alkaloids
Definition
1)quinine
2)quinidine
Term
mefloquine is used for?
Definition
prophylaxis of malaria (falciparum)
Term
for chloroquine resistant malaria use? (falciparum)
Definition
artesunate or quinine + another drug (b/c srtessunate clears quicly and quinine can cause GI problems)
Term
for prophylaxis of chloroquine resistant malaria use? (falciparum)
Definition
mefloquin or doxycyccline or atovaquone
Term
Mechansim of action of chloroquine (aralen)
Definition
inhibits a heme polymerase causing a buildup of toxic metabolites in RBC, keeps bug from using heme (also kills rbc)
Term
PFMDR1 and cg2 are involved with?
Definition
choloroquine resistance
Term
side effects of chloroquine?
Definition
hemolysis in G6PDH deficiency, visual disturbances, CARDIAC TOXICITY (there are more than just this)
Term
dont use chloroquine with?
Definition
another arrhythmogenic agent (can cause long QT syndrome)
Term
chloroquine and quinine both kill what form of the plasmodium?
Definition
schizont
Term
mechanism of quinine?
Definition
causes an accumulation of heme pigment but doesnt not affect the heme polymerase directly
Term
side effects of quinidine?
Definition
1)GI intolerance
2)cinchonism (headache, tinnitus, visual disturbances)
2)hemolysis

(IV quinidine must be monitored in ICU)
Term
side effects of mefloquine? (worse in elderly)
Definition
dizziness, GI upset, nightmares and insomnia, night terrors, insomnia, can cause panic attacks, seizures and psychosis. Cardiotoxicity can occur,
Term
pyrimethamine/sulfadoxine is mainly used for?
Definition
as a helper drug to decrease resistance
Term
mechanism of action of pyrimehtamine/sulfadoxine?
Definition
folate antagonist
Term
what side effects from sulfonamides are frequent?
Definition
allergic rxns
Term
atovaquone/proquanil can be used for?
Definition
prophylaxis vs. chloroquine resistant falciparum
Term
what is the mechanism of action of atovaquone?
Definition
inhibits electron transport chain leading to decrease in ATP and nucleic acid synthesis
Term
the mechanism of action of proquanil is?
Definition
dihydrofolate reductase inhibtor
Term
what is the mechanism of action of artesunate?
Definition
It inhibits Ca ATPase which helps kill all forms of plasmodium including he gametocyte
Term
ground glass appearance
Definition
pneumocystis jiroveci
Term
main treatment for pneumocystis jiroveci?
Definition
trimethoprim/sulfamethoxazole
Term
Bactrim = __________________
Definition
trimethoprim/sulfamethoxazole
Term
pentamidine is used to treat?
Definition
leishmania and pneumocystis jiroveci
Term
dapsone may be used as a prophylactic for?
Definition
pneumocystis jiroveci
Term
side effects of dapsone?
Definition
1)methemoglobin
2)hemolysis in G6PD
Term
how do you treat toxoplasma gondii?
Definition
pyrimethamine/sulfadiazine or pyrimethamine + clindamycin
Term
what do you use for prophylaxis of tosoplasma gondii?
Definition
trimethoprim/sulfamethoxazole
Term
what drug do you use with pyrimethamine/sulfadiazine to reduce toxicity?
Definition
leucovorin
Term
tsetse fly is the vector for ?
Definition
t.cruzi
Term
reduviids is the vector for ?
Definition
t. brucei
Term
Mebendazole or abendazole* can be used for
Definition
Hookworm, ascaris or whipworm
Term
a drug used as an adjunct therapy for ascaris and pinworm?
Definition
piperazine; it kinda paralyzes the worms so the can be flushed out
Term
mechanism of action of mebendazole?
Definition
depolymerizes microtubules causing a decreases in glycogen
Term
mechanism of action of albendazole?
Definition
blocks glucose uptake of helminthes
Term
One of the few parasitic infections they screen for before transplants
Definition
strongyloids b/c immunocomp state allows hyperinfection causing atypical pneumonia
Term
treat strongyloides with?
Definition
albendazole or ivermectin
Term
This drug may be used to treat strongyloides and heart worms in dogs
Definition
Ivermectin
Term
Mechanism of action of ivermectin?
Definition
Binds GABA at post synaptic sites and also affects glutamate gated ca channel, paralyzes worms respiratory muscles
Term
adverse effects from ivermectin are only noted in conjunction with ___________
Definition
onchocerciasis
Term
Pinworm is treated with?
Definition
albendazole or pyrantel pamoate
Term
the machanism of action of pyrantel palmoate?
Definition
causes paralysis of the worm
Term
DRug of choice for tapeworms
Definition
Praziquantel
Term
How do you treat neurocystocercosis?
Definition
praziquantel or albendazole, but really just need to leave untreated unless some kind of blockage
Term
how do you treat hydrocephalus asscoiated with neurocysticercosis?
Definition
shunt prior to tx
Term
mechanism of action of praziquantel?
Definition
This drug causes prolonged parasite muscle CONTRACTION, so it’s not like the other drugs that caused paralysis! It causes a tonic phase in the parasite. Praziquantel is readily absorbed, which is what you want for treatment of the tissue phase.
Term
how do you treat tapeworm?
Definition
praziquantel
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