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
Oocyst w/ 4 motile sporozoites describes which protozoa?
Cryptosporidium parvum
What is the treatment of choice for Cryptosporidium infection in a patient with HIV as well as someone on immunosuppressive therapy?
- HIV = Antiretroviral therapy + nitazoxanide (if needed)
- Other = Reduce dose of immunosuppressant + nitazoxanide
What is the main goal in treating Cryptosporidium infection in an immunocompromised patient?
Restore immune function! So they can fight the bug.
Which 2 antibiotics can be used for Cryptosporidium infection and what is the first line agent?
- Nitazoxanide (first line)
- Paromomycin
Which nematodes are associated with intense itching at the site of penetration (i.e., in between the toes)?
- Necator americanus
- Ancylostoma duodenale
*The hookworms
Which nematodes can be diagnosed based off on eggs in the stool?
- Ancylostoma duodenale
- Necator americanus
- Ascaris lumbricoides
How is the diagnosis of Strongyloides stercoralis made?
LARVAE in the stool (eggs are not passed in the stool!)
Which nematode must you take caution with when prescribing immunosuppressive agents, such as prednisone for asthma?
- Strongyloides stercoralis*
- Immunosuppressive agents can cause severe autoinfection!
Which 3 nematodes cause infection after ingestion of food w/ infective eggs?
- Ascaris lumbricoides (roundworm)
- Trichuris trichiura (whip worm)
- Enterobius vermicularis (pinworm)
What is the characteristic finding in the stool that can help with diagnosis of Trichuris trichiura (whip worm)?
Eggs in stool (FOOTBALL shaped)
What is the MOA of the agents for nematodes: Albendazole and Mebendazole?
Inhibit microtubule synthesis, paralyze worms, worms passed in stool
Which agents used for treatment of nematodes exist as a prodrug with an active metabolite only produced by first pass effect?
- Albendazole
- Mebendazole
Why is Thiabendazole not used anymore for nematodes?
Much more toxic effects than albendazole and mebendazole
What is the MOA of the agent for nematodes: Ivermectin?
Intesifies GABA-mediated transmission of signals in peripheral nerves of the nematodes = paralysis
Which drug-drug interaction must be accounted for when prescribing Ivermectin for a nematode infection?
Do NOT combine w/ other GABA-enhancers (i.e., barbiturates, benzodiazepines, valproic acid)
What is the MOA of the agent for nematodes: Pyrantel pamoate?
Neuromuscular blocking agent, causes release of ACh and inhibits AChE = paralysis and expulsion of nematode
What is the drug of choice for N. americanus and A. duodenale?
Alternatives?
- Albendazole (primary)
- Mebendazole or Pyrantel Pamoate = alternatives
What are the primary treatments for A. lumbricoides?
Alternative?
- Albendazole and Mebendazole = primary
- Ivermectin = alternative
What is the primary treatment for S. stercoralis?
Alternative?
- Ivermectin = primary
- Albendazole = alternative
What is the primary treatment for T. trichiura?
Alternative?
- Mebendazole = primary
- Albendazole = alternative
- Ivermectin = 2nd alternative
What is the primary treatment for E. vermicularis?
- Albendazole
- Mebendazole
- Pyrantel pamoate
*ALL primary treatments!
What are the clinical manifestations immediately, weeks, and years later following Schistosoma spp. infection?
- Immediate = dermatitis
- 4-8 weeks = Katayama fever –> hepatosplenomegaly, bronchospasm
- Years = chronic fibrosis
What is the drug of choice for Schistosoma infections?
Praziquantel
*Say it in japanese accent!
What is the MOA of Praziquantel?
Increases permeability of the nematode and cestode cell membrane to Ca2+ —> paralysis and death!
What are the immediate adverse effects and after several days of Praziquantel?
- Immediate = headache, dizziness, drowsiness and lethargy
- Several days = low-grade fever, pruritus, skin rash (effects of dying parasite)
Which parasites can be diagnosed via proglottids in stool?
- T. solium
- T. saginata
- D. latum
What is special about the life cycle of Echinococcus granulosus?
Ingested how and what happens in humans?
- Humans ingest eggs from dog feces
- Eggs hatch in the intestine and larva form hydatid cysts!
What are the 3 drugs of choice for Cestodes (i.e., T. solium/saginata, D. latum, and E. granulosus)?
- Praziquantel = first-line
- Albendazole = good choise
- Niclosamide (not effective against hydatid cysts) = alternative tx for tape worms
Niclosamide is not effective against which cestode?
- Echinococcus granulosus
- Not effective against hydatid cysts
What is the MOA for Niclosamide?
Why is its use as a therapy limited?
- Uncouples OxPhos, blocking uptake of glucose
- Use limited by side effects, long duration, and limited availability
