17b Parasites (Protozoan) Duncan Flashcards
What are the 3 main types of Protozoan in the US?
Entamoeba (amoebiasis: fecal/oral). Giardia (giardiasis: fecal/oral). Trichomonas (trichomoniasis: sexual)
What is the general life cycle of Protozoan?
Dispersal of cysts through fecal material. Ingestion of cysts. Colonization of intestine. If it migrates to liver, causes severe disease
What are some other clinically significant Protozoans?
Trypanosoma cruzii and T. brucei. Leishmania donovanii. Toxoplasma gondii. Cryptosporidium parvum
What are the primary treatments used for the 3 US endemic main types?
Metronidazole. Nitazoxanide. Additional agents used as needed: Diloxanide furoate (for less severe, intestines only)
What are the structural characteristics of Metronidazole?
1) Imidazole-based: 5 membered ring, with double bonds, 2 nitrogens. 2) Nitro group on one side (C2 position). 3) R group at the base
What is the MOA of Metronidazole?
Prodrug: Activated by Pyruvate-Ferredoxin Oxidoreductase (PFOR). Readily enters cells. Nitro group accepts electrons, becomes free radical (highly active in this form). Intracellular “land mine” (destroys anything that gets too close: DNA, RNA, proteins, membranes)
What is the Specificity of Metronidazole?
Radicals are inactivated by reduction. Higher activity of “detoxifying” enzymes in humans. Metronidazole is concentrated in the liver! Resistance occurs when activating enzymes mutate to decreased activity
What is this structure?
Nitazoxanide. “Prodrug”: rapidly metabolized to the desacetyl form (tizoxanide) which is the circulating, and active, form of the agent
What is the MOA of Nitazoxanide?
Target is pyruvate-ferredoxin oxidoreductase (PFOR). PFOR catalyzes an electron transfer reaction essential to anaerobic energy production. Protozoan enzyme reduces nitazoxanide or tizoxanide without ferrodoxin
What is Iodoquinol?
For asymptomatic amebiasis in intestine (poor absorption). Amebicidal. Chelates Fe ions essential for life (of amoeba)
What is Diloxanide furoate?
Lumenal amoebicide. 2 part structure: 1) Furoate (no anti-microbial activity, insolubilizer; concentrates agent in intestine). 2) Diloxanide (dichloroacetamide derivative). Benzene ring bridges the two parts
How do Tetracycline and Erythromycin work as Amebicides?
Inhibit infection by killing off the amoeba’s food source (bacteria)
What is used for Giardiasis and Trichomoniasis?
Primary agent: Metronidazole. Secondary agent for Giardiasis: Furazolidone (a Nitrofuran, Liquid; good for kids). Paromomycin is also secondary agent for Giardiasis
What is this structure?
Secondary agent for Giardiasis
What is Trypanosomiasis caused by?
Trypanosomes: T. brucei (Africa; sleeping sickness; transmitted by tsetse fly), T. cruzi (South America; Chagas disease; transmitted by triatomid bug)