Pharmacology of GI Infections: Abx and Anti-parasite Drugs Flashcards
Antimicrobial agents that may induce C.diff diarrhea and colitis
Frequently associated drugs include:
Fluoroquinolones
Clindamycin
Cephalosporins (broad-spectrum)
Penicillins
[macrolides and TMX are occasionally associated; rarely associated are aminoglycosides, tetracylcines, metronidazole, and vancomycin
_____ is the preferred pharmacologic tx for severe C.diff infection
_____ is the equivalent which is utilized in mild C.diff infection, sometimes chosen if oral administration won’t work for the pt
Vancomycin; metronidazole
_____ is the agent of choice for recurrent C.diff infection because it spares many anaerobic colonic flora
Fidaxomicin (macrolide family)
Key drugs in tx of H.pylori
Omeprazole (PPI)
Metronidazole
Tetracycline
Bismuth subsalicylate
The therapeutic goals of entamoeba histolytica tx are to eliminate the invading trophozoites and eradicate intestinal carriage of the organism (luminal amebicides); what drugs are utilized to accomplish these goals?
To eliminate the invading trophozoites: metronidazole (drug of choice) or tinidazole (better tolerated)
Eradicate intestinal carriage of the organism: paromomycin or iodoquinol
Both metronidazole and tinidazole must be given with a luminal amebicide to ensure eradication of E.histolytica!
Asymptomatic carriers of entamoeba histolytica have cysts or trophozoites without internalized RBCs. How are these pts treated?
With luminal amebicide agents — paromomycin or iodoquinol
Iodoquinol is used as a luminal amebicide, it has no effect against extraintestinal organisms. It is a halogenated hydroxyquinoline with an unknown MOA.
What is unique about its pharmacokinetics and what are some adverse effects?
90% of the drug is retained in the intestine and excreted in feces
AEs = diarrhea, anorexia, N/V, abdominal pain, HA, rash, pruritis
What clinical feature differentiates G.lamblia from E.histolytica?
No blood in stool (no invasion of intestinal wall)
Pharmacologic agents utilized in G.lamblia
Tinidazole (first-line agent)
Nitazoxanide
Metronidazole (not FDA approved for this but sometimes used)
MOA of nitazoxanide
Inhibition of pyruvate-ferredoxin oxidoreductase enzyme (essential to anaerobic energy metab)
[prodrug of tizoxanide]
Adverse effects of nitazoxanide
Nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, yellow eyes, dysuria, bright yellow urine
Cryptosporidium parvum tx
Antidiarrheal agents: loperamide
Antimicrobial agents: nitazoxanide (preferred) or paromomycin
Fluid management
How does cryptosporidium parvum tx change depending on immune status?
The main goal in an immunocompromised pt is to restore immune function
HIV: antiretroviral therapy may need to be reduced, add nitazoxanide if needed
Other: reduce dose of immunosuppressant + nitazoxanide
How does infection with necator americanus and ancyclostoma duodenale initially begin? What are some clinical features?
Penetration of skin between toes — results in intense itching at site of penetration
Other effects: diarrhea, abdominal pain, weight loss, anemia
How does infection with ascaris lumbricoides initially begin? What are some clinical features?
Consumption of eggs in contaminated food
Clinical features = abdominal cramping, malnutrition, worm invasion
Most helminth infections are diagnosed by presence of eggs in stool. How is Strongyloides stercoralis diagnosed?
Since Strongyloides eggs are not passed in the stool, it is diagnosed by larvae in feces or by enterotest
How is strongyloides stercoralis infection started? What are some clinical features?
Larvae in soil penetrate human skin and travel to lungs —> coughed up and swallowed
Mature worms form in small intestine and release eggs
Clinical features: vomiting, abdominal bloating, diarrhea, anemia, weight loss
Why must you always check for strongyloides stercoralis in asthmatic patients when in endemic areas?
Patients with asthma may be on prednisone, which has immunosuppressive action that can lead to severe autoinfection with Strongyloides stercoralis
What is unique about the lifecycle of trichuris trichiuria (whipworm)?
No larvae, no transit through intestinal wall, no lung involvement, no eosinophilia, no autoinfection
Simple life cycle with ingestion of food with infective eggs
Diagnostic feature of trichuris trichiura
Football shaped eggs seen in feces
Life cycle and features of enterobius vermicularis (pinworm) infection
Eggs ingested, pinworms mature in cecum and ascending large intestine
Female migrates to perianal area to lay eggs —> severe perianal itching and potential for hand to mouth transmission
Dx by scotch tape test; do not cause eosinophilia
Drugs in general used to treat nematode infections
Albendazole Mebendazole Ivermectin Thiabendazole Pyrantel pamoate
MOA of albendazole and mebendazole
Inhibition of microtubule synthesis —> paralyzes worms which are then passed stool
Prodrug is turned into active metabolite after first pass effect
The MOA of thiabendazole is the same as albendazole and mebendazole, but what is different about this drug?
Rapidly absorbed after ingestion, largely excreted in urine, and can be absorbed from the skin
MUCH MORE TOXIC than albendazole and mebendazole —> dizziness, anorexia, nausea, vomiting
Less common effects include irreversible liver failure and fatal Stevens-Johnson syndrome
MOA of Ivermectin
Intensifies GABA-mediated transmission of signals in peripheral nerves of the nematode
Pharmacokinetics and adverse effects of ivermectin
Rapidly absorbed, oral only, wide distribution, excretion in feces
Adverse effects are uncommon; this drug should not be combined with other drugs that enhance GABA activity (barbiturates, benzodiazepines, valproic acid, etc)
MOA of pyrantel pamoate
Neuromuscular blocking agent, causes release of ACh and inhibits cholinesterase —> paralysis and expulsion of nematode
Pharmacokinetics and AEs of pyrantel pamoate
Poorly absorbed from GI tract, half of administered dose is recovered unchanged in feces
AEs are infrequent and transient
What is the primary drug of choice to treat infection with N.americanus or A.duodenale?
Albendazole
[alternate options: mebendazole, pyrantel pamoate]
What is the primary drug of choice to treat infection with A.lumbricoides?
Albendazole or Mebendazole
[alternate: ivermectin]
What is the primary drug of choice to treat infection with S.stercoralis?
Ivermectin
[alternate: albendazole]
What is the primary drug of choice to treat infection with T.trichiura?
Mebendazole
[alternate: albendazole then ivermectin]
What is the primary drug of choice to treat infection with E.vermicularis?
Albendazole OR Mebendazole OR Pyrantel Pamoate
[all considered primary options]
Which of the parasites invades the venous system through exposed skin and maintains the ability to survive and release eggs for years due to molecular mimicry?
Schistosoma spp. (blood flukes)
Considered Trematodes
Clinical manifestations of Schistosoma spp. infection
Dermatitis (immediate), Katayama fever including fever, hives, HSM, and bronchospasm (4-8 weeks in), chronic fibrosis (years)
Drug of choice for tx of Schistosoma spp. Infection
Praziquantal (effective against Schistosoma spp. and most other trematode and cestode infections)
MOA of Praziquantel
Increases permeability of nematode and cestode cell membranes to calcium —> paralysis, dislodgement, and death
Pharmacokinetics and AEs associated with praziquantel
Oral administration, rapid absorption, renal excretion
AEs: Immediate — headache, dizziness, drowsiness, lassitude; after several days — low-grade fever, pruritis, rash
Taenia solium and Taenia saginata are acquired by ingestion of undercooked meat containing larvae. What are some differences between the two?
T.solium = undercooked pork; attaches via hooks
T.saginata = undercooked beef; attaches via suckers
Both clinically manifest as weight loss and malnutrition
Which parasite is acquired by ingestion larvae in raw freshwater fish, exhibits few abdominal symptoms, and absorbes vitamin B12 causing anemia?
Diphyllobothrium latum
D.latum is dx by ___ and ___ in feces
Proglottids; eggs
Echinococcus granulosus is an extraintestinal tapeworm infection caused by ingestion of eggs from dog feces. What is the main clinical feature seen w/ E.granulosus?
Hydatid cysts in the intestines — formed by larvae
3 drugs used in tx of cestodes
Praziquantel
Niclosamide
Albendazole
_____ is an alternative durg used for tx of most tape worm infections because it is not effective against hydatid cysts; its MOA is uncoupling of oxphos and blocking uptake of glucose causing death of the parasite
Niclosamide
[note: use also limited by side effects, long duration of therapy, and limited availability]
Which parasites are considered Nematodes?
Necator americanus Ancyclostoma duodenale Ascaris lumbricoides Strongyloides stercoralis Trichuris trichiura Enterobius vermicularis
Which parasites are considered platyhelmintes?
Trematodes (blood flukes):
Schistosoma
Cestodes (tapeworms): Taenia solium Taenia saginata Diphyllobothrium latum Echinococcus granulosus
