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Thera VIII > 17b Parasites (Protozoan) Duncan > Flashcards

17b Parasites (Protozoan) Duncan Flashcards

1
Q

What are the 3 main types of Protozoan in the US?

A

Entamoeba (amoebiasis: fecal/oral). Giardia (giardiasis: fecal/oral). Trichomonas (trichomoniasis: sexual)

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2
Q

What is the general life cycle of Protozoan?

A

Dispersal of cysts through fecal material. Ingestion of cysts. Colonization of intestine. If it migrates to liver, causes severe disease

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3
Q

What are some other clinically significant Protozoans?

A

Trypanosoma cruzii and T. brucei. Leishmania donovanii. Toxoplasma gondii. Cryptosporidium parvum

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4
Q

What are the primary treatments used for the 3 US endemic main types?

A

Metronidazole. Nitazoxanide. Additional agents used as needed: Diloxanide furoate (for less severe, intestines only)

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5
Q

What are the structural characteristics of Metronidazole?

A

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

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6
Q

What is the MOA of Metronidazole?

A

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)

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7
Q

What is the Specificity of Metronidazole?

A

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

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8
Q

What is this structure?

A

Nitazoxanide. “Prodrug”: rapidly metabolized to the desacetyl form (tizoxanide) which is the circulating, and active, form of the agent

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9
Q

What is the MOA of Nitazoxanide?

A

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

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10
Q

What is Iodoquinol?

A

For asymptomatic amebiasis in intestine (poor absorption). Amebicidal. Chelates Fe ions essential for life (of amoeba)

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11
Q

What is Diloxanide furoate?

A

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

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12
Q

How do Tetracycline and Erythromycin work as Amebicides?

A

Inhibit infection by killing off the amoeba’s food source (bacteria)

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13
Q

What is used for Giardiasis and Trichomoniasis?

A

Primary agent: Metronidazole. Secondary agent for Giardiasis: Furazolidone (a Nitrofuran, Liquid; good for kids). Paromomycin is also secondary agent for Giardiasis

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14
Q

What is this structure?

A

Secondary agent for Giardiasis

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15
Q

What is Trypanosomiasis caused by?

A

Trypanosomes: T. brucei (Africa; sleeping sickness; transmitted by tsetse fly), T. cruzi (South America; Chagas disease; transmitted by triatomid bug)

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16
Q

What is Leishmaniasis caused by?

A

Leishmania. Transmitted by sand fly bites. Antimony-based agents most useful. Causes cutaneous lesion and visceral disease (most serious, life-threatening)

17
Q

What medications are used for Trypanosomiasis?

A

Nifurtimox (Nitrofuran). Melarsoprol. Suramin. Eflornithine (DFMO). Benznidazole

18
Q

What is this structure?

A

Used for Trypanosomiasis. MOA: Withdraws electrons from donor compounds. Converted into a free radical compound. Reacts like a bomb with cellular components (similar to Metronidazole)

19
Q

What are the important structural features of Nifurtimox (Nitrofuran)?

A

1) Two ring groups. 2) Both contain strongly electron withdrawing groups. 3) Creates polarized, electron mobile structure

20
Q

What is this structure?

A

Used for Trypanosomiasis. MOA: Arsenic toxicity (up to 5% treated patients may die of the agent). Reacts rapidly with, and inhibits, sulfer-containing compounds. Concentrated by the trypanosome

21
Q

What are the important structural features of Melarsoprol?

A

1) Arsenical. 2) Sulfer minimizes arsenic toxicity, stabilizes it

22
Q

What is this structure?

A

Used for Trypanosomiasis

23
Q

What is this structure?

A

Used for Trypanosomiasis. MOA: Suicide substrate for ornithine decarboxylase. Blocks rate limiting step in polyamine biosynthesis. Effective without the toxicity of Melarsoprol. Derivative of the amino acid ornithine

24
Q

What is this structure?

A

Benznidazole. Used for Trypanosomiasis (specifically for Chagas’ disease in South America). MOA: Creates oxidative stress. Damages DNA, RNA, lipids, etc. ADRs d/t its MOA

25
Q

What are the important structural features of Benznidazole?

A

1) Fusion of an imidazole and benzene with linker structure. 2) Nitro group on the imidazole

26
Q

What is this structure?

A

Used for Leishmaniasis. MOA: Antimony toxicity, reacts rapidly with, and inhibits, sulfer-containing compounds

27
Q

What are the important structural features of Stibogluconate?

A

1) Pentavalent antimonial; generally toxic. 2) Pentavalent binding minimizes antimony toxicity. 3) May need to be converted to the trivalent form for activity

28
Q

What are the other agents used for Leishmaniasis?

A

Amphotericin. Miltefosine. Paromomycin (Aminoglycoside)

29
Q

What is this structure?

A

A breakthrough in oral treatment of Leishmaniasis. Orphan drug status in the US. Generally well-tolerated

30
Q

How is Toxoplasmosis spread?

A

Cats are the main mammalian infected species, but can grow and infect most mammals including humans. Can be in uncooked (undercooked) foods, unwashed fruits and vegetables, soil contacting “open” skin

31
Q

What does Toxoplasma gondii look like?

A

Apicomplexan, which refers to the unique structure called the “apical complex” from which their name derives

32
Q

What are the most serious situations with Toxoplasmosis?

A

Pregnant women: maternal –> fetal transmission, with severe consequences to fetus. Immunocompromised adults (has been a serious component of AIDS)

33
Q

What type of treatment is effective for Toxoplasmosis?

A

Folate biosynthesis inhibitors: Pyrimethamine, Sulfa drug (Sulfadiazine)

34
Q

What is Cryptosporidium parvum?

A

Crypt. is considered to be the MOST significant water-borne pathogen in developed countries

35
Q

What are the treatment options like for Cryptosporidium parvum?

A

Resistant to chlorination. An apicocomplexan. Nitazoxanide may be effective. Paromomycin can be used

Thera VIII (24 decks)

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