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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?
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?
What is the drug of choice (w/class) for treating trichomoniasis?
metronidazole (a nitroimidazole)
Which protozoa is typically transmitted through cat feces?
Primary treatment of toxoplasmosis is with the antifolates _______ and sulfadiazine; and ________.
_______ substituted for sulfadiazine due to toxicity w/o loss
- Folinic acid
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"?
American trypanosomiasis is caused by T. _____ and the disease is called _______
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.
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
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.
Pentamidine is quite toxic with its 3 ADRs being...
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 _________
What arsenic containing agent is used to treat late stage T brucei rhodesiense infection
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?
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
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