Lecture 14: Pharm. of GI Infections: Antibiotic and Anti-Parasitic Flashcards
What is the preferred tx for severe C. difficile infection?
i.e., first-line tx
Vancomycin (glycopeptide)
What is the preferred tx for mild C. difficile infection or if oral administration won’t work for the patient?
Metronidazole
What is the preferred tx for recurrent C. difficile infection?
Fidaxomicin (macrolide)
What are the adverse effects associated w/ Metronidazole?
- Metallic taste in mouth
- Disulfiram-like effect = vomiting if alcohol is ingested
What is the MOA (3 of them) of the macrolide: fidaxomicin used in the treatment of recurrent C. difficile infections?
- 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
What are 2 major adverse effects associated with Vancomycin?
- Red-man syndrome
- Nephrotoxicity (dose-dependent)
What is the MOA of Vancomycin?
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
What do you need to see to determine that a E. histolytica infection is pathogenic?
RBC’s in the cytoplasm of trophozoites (stool sample)
What 2 drugs can be used to eliminate invading trophozoites associted w/ E. histolytica?
- Metronidazole or
- Tinidazole
What 2 drug choices can be used to eradicate intestinal carriage of E. histolytica?
- Paromomycin (drug of choice) or
- Iodoquinol
If an individual with E. histolytica infection is an asymptomatic carrier (aka cyts or trophozoites w/ no internalized RBC’s) how are they treated?
- Eradication of intestinal carriage of the organism (luminal amebicide)
- Using either paromomycin or iodoquinol
What is the drug of choice for treating extraluminal E. histolytica?
Luminal amebicide of choice?
- Metronidazole = extraluminal
- Paromomycin (aminoglycoside) = luminal amebicide
What must be done when giving either metronidazole or tinidazole to treat extraluminal amebiasis associated w/ E. histolytica infection?
MUST be given w/ a luminal amebicide (paromomycin or iodoquinol) to ensure eradication
Why are Paromomycin and Iodoquinol useful for treating intraluminal E. histolytica?
Effect on extraintestinal organisms?
- They are NOT absorbed in the GI
- NO effect on extraintestinal organisms
Which antibiotic class does paromomycin belong to?
What are unique adverse effects of this class?
- Aminoglycosides
- Nephrotoxicity and ototoxicity!
What are the 2 steps to treatment of G. lamblia infections?
- Supportive = correct fluid and electrolyte imbalances
- Pharmacological = Tinidazole, Metronidazole, or Nitazoxanide
Which 3 antibiotics are indicated in treating G. lamblia infections?
Distinguish the first line treatment.
- Tinidazole = first-line agent
- Metronidazole = not FDA approved
- Nitazoxanide
What is the MOA of Nitazoxanide?
Inhibition of the pyruvate-ferredoxin oxioreductase enzyme
Is Nitazoxanide biologically active?
- No, is a prodrug
- Converted to active metabolite, Tizoxanide
What are unique adverse effects associated w/ Nitazoxanide?
- Enlarged salivary glands
- Yellow eyes
- Dysuria
- Bright yellow urine