Lecture 14: Pharm. of GI Infections: Antibiotic and Anti-Parasitic Flashcards

1
Q

What is the preferred tx for severe C. difficile infection?

i.e., first-line tx

A

Vancomycin (glycopeptide)

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2
Q

What is the preferred tx for mild C. difficile infection or if oral administration won’t work for the patient?

A

Metronidazole

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3
Q

What is the preferred tx for recurrent C. difficile infection?

A

Fidaxomicin (macrolide)

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4
Q

What are the adverse effects associated w/ Metronidazole?

A
  • Metallic taste in mouth
  • Disulfiram-like effect = vomiting if alcohol is ingested
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5
Q

What is the MOA (3 of them) of the macrolide: fidaxomicin used in the treatment of recurrent C. difficile infections?

A
  • Prevent translocation of tRNA from A-site to P-site on bacterial ribosome = halts protein synthesis
  • Elicit conformational change in bacterial ribosome –> inhibit transpeptidation
  • Inhibit formation of the 50S ribosomal subunit
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6
Q

What are 2 major adverse effects associated with Vancomycin?

A
  • Red-man syndrome
  • Nephrotoxicity (dose-dependent)
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7
Q

What is the MOA of Vancomycin?

A

Binds D-alanyl-D-alanine terminus of cell wall precursor units, inhibits transglycolase and prevents extension and cross-linking of peptidoglycans = inhbits cell wall synthesis

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8
Q

What do you need to see to determine that a E. histolytica infection is pathogenic?

A

RBC’s in the cytoplasm of trophozoites (stool sample)

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9
Q

What 2 drugs can be used to eliminate invading trophozoites associted w/ E. histolytica?

A
  1. Metronidazole or
  2. Tinidazole
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10
Q

What 2 drug choices can be used to eradicate intestinal carriage of E. histolytica?

A
  1. Paromomycin (drug of choice) or
  2. Iodoquinol
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11
Q

If an individual with E. histolytica infection is an asymptomatic carrier (aka cyts or trophozoites w/ no internalized RBC’s) how are they treated?

A
  • Eradication of intestinal carriage of the organism (luminal amebicide)
  • Using either paromomycin or iodoquinol
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12
Q

What is the drug of choice for treating extraluminal E. histolytica?

Luminal amebicide of choice?

A
  • Metronidazole = extraluminal
  • Paromomycin (aminoglycoside) = luminal amebicide
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13
Q

What must be done when giving either metronidazole or tinidazole to treat extraluminal amebiasis associated w/ E. histolytica infection?

A

MUST be given w/ a luminal amebicide (paromomycin or iodoquinol) to ensure eradication

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14
Q

Why are Paromomycin and Iodoquinol useful for treating intraluminal E. histolytica?

Effect on extraintestinal organisms?

A
  • They are NOT absorbed in the GI
  • NO effect on extraintestinal organisms
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15
Q

Which antibiotic class does paromomycin belong to?

What are unique adverse effects of this class?

A
  • Aminoglycosides
  • Nephrotoxicity and ototoxicity!
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16
Q

What are the 2 steps to treatment of G. lamblia infections?

A
  1. Supportive = correct fluid and electrolyte imbalances
  2. Pharmacological = Tinidazole, Metronidazole, or Nitazoxanide
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17
Q

Which 3 antibiotics are indicated in treating G. lamblia infections?

Distinguish the first line treatment.

A
  1. Tinidazole = first-line agent
  2. Metronidazole = not FDA approved
  3. Nitazoxanide
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18
Q

What is the MOA of Nitazoxanide?

A

Inhibition of the pyruvate-ferredoxin oxioreductase enzyme

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19
Q

Is Nitazoxanide biologically active?

A
  • No, is a prodrug
  • Converted to active metabolite, Tizoxanide
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20
Q

What are unique adverse effects associated w/ Nitazoxanide?

A
  • Enlarged salivary glands
  • Yellow eyes
  • Dysuria
  • Bright yellow urine
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21
Q

Oocyst w/ 4 motile sporozoites describes which protozoa?

A

Cryptosporidium parvum

22
Q

What is the treatment of choice for Cryptosporidium infection in a patient with HIV as well as someone on immunosuppressive therapy?

A

- HIV = Antiretroviral therapy + nitazoxanide (if needed)

  • Other = Reduce dose of immunosuppressant + nitazoxanide
23
Q

What is the main goal in treating Cryptosporidium infection in an immunocompromised patient?

A

Restore immune function! So they can fight the bug.

24
Q

Which 2 antibiotics can be used for Cryptosporidium infection and what is the first line agent?

A
  1. Nitazoxanide (first line)
  2. Paromomycin
25
Q

Which nematodes are associated with intense itching at the site of penetration (i.e., in between the toes)?

A
  • Necator americanus
  • Ancylostoma duodenale

*The hookworms

26
Q

Which nematodes can be diagnosed based off on eggs in the stool?

A
  • Ancylostoma duodenale
  • Necator americanus
  • Ascaris lumbricoides
27
Q

How is the diagnosis of Strongyloides stercoralis made?

A

LARVAE in the stool (eggs are not passed in the stool!)

28
Q

Which nematode must you take caution with when prescribing immunosuppressive agents, such as prednisone for asthma?

A
    • Strongyloides stercoralis*
  • Immunosuppressive agents can cause severe autoinfection!
29
Q

Which 3 nematodes cause infection after ingestion of food w/ infective eggs?

A
  • Ascaris lumbricoides (roundworm)
  • Trichuris trichiura (whip worm)
  • Enterobius vermicularis (pinworm)
30
Q

What is the characteristic finding in the stool that can help with diagnosis of Trichuris trichiura (whip worm)?

A

Eggs in stool (FOOTBALL shaped)

31
Q

What is the MOA of the agents for nematodes: Albendazole and Mebendazole?

A

Inhibit microtubule synthesis, paralyze worms, worms passed in stool

32
Q

Which agents used for treatment of nematodes exist as a prodrug with an active metabolite only produced by first pass effect?

A
  • Albendazole
  • Mebendazole
33
Q

Why is Thiabendazole not used anymore for nematodes?

A

Much more toxic effects than albendazole and mebendazole

34
Q

What is the MOA of the agent for nematodes: Ivermectin?

A

Intesifies GABA-mediated transmission of signals in peripheral nerves of the nematodes = paralysis

35
Q

Which drug-drug interaction must be accounted for when prescribing Ivermectin for a nematode infection?

A

Do NOT combine w/ other GABA-enhancers (i.e., barbiturates, benzodiazepines, valproic acid)

36
Q

What is the MOA of the agent for nematodes: Pyrantel pamoate?

A

Neuromuscular blocking agent, causes release of ACh and inhibits AChE = paralysis and expulsion of nematode

37
Q

What is the drug of choice for N. americanus and A. duodenale?

Alternatives?

A
  • Albendazole (primary)
  • Mebendazole or Pyrantel Pamoate = alternatives
38
Q

What are the primary treatments for A. lumbricoides?

Alternative?

A
  • Albendazole and Mebendazole = primary
  • Ivermectin = alternative
39
Q

What is the primary treatment for S. stercoralis?

Alternative?

A
  • Ivermectin = primary
  • Albendazole = alternative
40
Q

What is the primary treatment for T. trichiura?

Alternative?

A
  • Mebendazole = primary
  • Albendazole = alternative
  • Ivermectin = 2nd alternative
41
Q

What is the primary treatment for E. vermicularis?

A
  • Albendazole
  • Mebendazole
  • Pyrantel pamoate

*ALL primary treatments!

42
Q

What are the clinical manifestations immediately, weeks, and years later following Schistosoma spp. infection?

A
  • Immediate = dermatitis
  • 4-8 weeks = Katayama fever –> hepatosplenomegaly, bronchospasm
  • Years = chronic fibrosis
43
Q

What is the drug of choice for Schistosoma infections?

A

Praziquantel

*Say it in japanese accent!

44
Q

What is the MOA of Praziquantel?

A

Increases permeability of the nematode and cestode cell membrane to Ca2+ —> paralysis and death!

45
Q

What are the immediate adverse effects and after several days of Praziquantel?

A
  • Immediate = headache, dizziness, drowsiness and lethargy
  • Several days = low-grade fever, pruritus, skin rash (effects of dying parasite)
46
Q

Which parasites can be diagnosed via proglottids in stool?

A
  • T. solium
  • T. saginata
  • D. latum
47
Q

What is special about the life cycle of Echinococcus granulosus?

Ingested how and what happens in humans?

A
  • Humans ingest eggs from dog feces
  • Eggs hatch in the intestine and larva form hydatid cysts!
48
Q

What are the 3 drugs of choice for Cestodes (i.e., T. solium/saginata, D. latum, and E. granulosus)?

A
  • Praziquantel = first-line
  • Albendazole = good choise
  • Niclosamide (not effective against hydatid cysts) = alternative tx for tape worms
49
Q

Niclosamide is not effective against which cestode?

A
  • Echinococcus granulosus
  • Not effective against hydatid cysts
50
Q

What is the MOA for Niclosamide?

Why is its use as a therapy limited?

A
  • Uncouples OxPhos, blocking uptake of glucose
  • Use limited by side effects, long duration, and limited availability