What are the 3 species of Entamoeba and which one requires treatment?
E. histolytica (requires treatment)
E. dispar
E. moshkovskii
Extraluminal amebiasis infections can be treated with what compounds?
nitroimidazole compounds
Intraluminal amebiasis trophozoites can be treated with what 2 non-absorbable antibiotics?
aminoglycosides or 8-hydroxyquinolone
What is the most commonly seen intestinal protozoa infection seen in the US? How is it transmitted?
Giardia intestinalis
Injestion of comtaminated food/water
Fecal-oral route in day care settings
What 3 agents are used to treat giardiasis?
Metronidazole (nitroimidazole)
Paromomycin (non-absorbed antibiotic)
Nitazoxanide (anti-protozoal)
Which protozoa is transmitted sexually and causes vaginitis in women and urethritis in men?
Trichomonas Vaginalis
What is the drug of choice (w/class) for treating trichomoniasis?
metronidazole (a nitroimidazole)
Which protozoa is typically transmitted through cat feces?
Toxoplasma gondii
Primary treatment of toxoplasmosis is with the antifolates _______ and sulfadiazine; and ________.
_______ substituted for sulfadiazine due to toxicity w/o loss
of effect.
Pyrimethamine
Folinic acid
Clindamycin
Which 2 species of Cryptosporidium cause disease in humans? How do treat them?
C parvum and C. hominis
Immunmodulators in the immunosuppressed
Nitazoxanide (anti-protozoal)
What African protozoa produces CNS effects and "sleeping sickness"?
Trypanosoma brucei
American trypanosomiasis is caused by T. _____ and the disease is called _______
cruzi
Chagas
T. cruzi can be transmitted by the ____ bug
T. brucei can be transmitted by the ____ bug
Leishmania can be transmitted by the ______ bug
Triatomid bug
Tsetse (fly)
Phlebotomine sandfly
This disease present in Central/South America results in cardiomyopathy, megaesophagus, megacolon, and death.
Chagas Disease
What 2 agents are used for treatment of Chagas disease?
Nifurtimox and Benznidazole
What is the MOA for paromomycin?
Aminoglycoside so binds 30S ribosomal subunit
Not absorbed -- intraluminal effects
What is the MOA for nitazoxanide?
Blocks the PFOR (pyruvate: ferredoxin oxidoreductase) enzyme-dependent electron transfer used by anaerobic protozoans
Hydrolized to tizoxanide then glucuronidated
What is the MOA of metronidazole
Prodrug taken up by the target anaerobe, reduced by ferrodoxin, electron transferred to nitroimidazole forming a reactive nitro group that attacks DNA
Catalytically recycled to 5-nitro form
The antiprotozoal _______ can be used for Crohn's patients with anal fistulas
metronidazole
What ADR of metronidazole may require discontinuation?
Peripheral neuropathy and central toxicity.
Also chronic use may be mutagenic and carcinogenic.
T/F The MOA of pentamidine is unknown and may vary by organism.
True
Pentamidine is quite toxic with its 3 ADRs being...
hypoglycemia
nephrotoxicity
hematopathologies
T/F Suramin is active against all forms of trypanosomiasis
False: active against W and E African, not Chagas disease
Suramin may be used prior to melarsoprol administration in order to reduce _________
encephalopathy
What arsenic containing agent is used to treat late stage T brucei rhodesiense infection
melarsoprol
What is the MOA of melarsoprol?
Prodrug metabolized to melarsen oxide, reacts against trypan-othione cellular antioxidant in T brucei
What agent is used to treat late stage T brucei gambiense infection?
eflornithine
What is the MOA for eflornithine?
Suicide inhibitor of ornithine decarboxylase, the first step for polyamine biosynthesis, essential for cell division and differentiation, also glutathione conjugate formation.
What is the MOA for nifurtimox and benznidazole
Activated by NADPH-dependent mitochondrial nitroreductase, forms intracellular nitro radical anions, covalently attack molecules and generate ROS.
What 4 drugs are used to treat leishmaniasis?
Amphotericin B
miltefosine
paromomycin
pentamidine
What is MOA of amphotericin B in protozoa?
binds sterol moieties similar to ergosterol, forms pores allowing ions to flux
What is the suspected MOA for miltefosine?
alkylphosphocholine analog, may interfere with PKC or sphingomyelin synthesis, increases ceramide levels and induces apoptosis
What is the classic drug for leishmaniasis but shows resistance
pentavalent antimony (sodium stibogluconate)
What is the MOA of sodium stibogluconate
Reduced to Sb3+ in macrophage phagolysosomes, disrupts trypanothione redox metabolism, redox injury results