Pharm - GI Parasites Flashcards
gram positive, spore forming, anaerobic rod
- antibiotic-associated pseudomembranous diarrhea and colitis
C. difficile
which C. diff toxin is an enterotoxin, causing diarrhea?
toxin A
which C. diff toxin is a cytotoxin -> cytotoxic to the colonic cells?
toxin B
what does C. diff infection in the colon lead to?
red inflamed mucosa with areas of white exudate (pseudomembranes on the surface) of the large intestine
what antibiotics are frequently associated with C. diff infection?
- fluoroquinolones
- clindamycin
- cephalosporins
- penicillins
what antibiotics are rarely associated with C. diff infection, and thus can be used as treatment?
- vancomycin
- metronidazole
- fidaxomicin
- NOTE: aminoglycosides, tetracyclines mentioned on table
what is the preferred treatment for severe C. diff infection?
vancomycin
what is the preferred treatment for mild C. diff infection?.
metronidazole
- has disulfrum-like effect (pt will throw up if taken with alcohol) KNOW THIS
- also causes metallic-taste in mouth
what is the preferred treatment for recurrent C. diff infection?
fidaxomicin
- spares many anaerobic colonic flora
what is the most common cause of duodenal ulcers ad chronic gastritis?
H. pylori
what are the key drugs used to treat H. pylori infection?
- omeprazole (PPI)
- metronidazole
- tetracycline
- bismuth subsalicylate
“classic amoeba”
- trophozoites invade intestinal mucosa -> portal blood circulation -> liver abscesses
Entamoeba histolytica
what is the life cycles of entamoeba histolytica?
trophozoite -> binucleated precyst -> tetranucleated cyst (what is pathogenic)
what drugs are used to eliminate the invading trophozoites?
metronidazole or tinidazole
what drugs are used to eradicate intestinal carriage of the organism (luminal amebicide)
- *paromomycin** or iodoquinol
- no effect on extraintestinal organisms
when would you use luminal amebicide agents?
for asymptomatic carriers (cysts or trophozoites without internalized red blood cells in the cytoplasm)
NOTE: both metronidazole and tinidazole still given with luminal amebicide, to ensure eradication of infection)
what luminal amebicide is contraindicated in a patient with an iodine allergy/sensitivity?
iodoquinol
- used as luminal amebicide, no effect against extraintestinal organisms
what is the MOA of iodoquinol?
halogenated hydroxyquinoline
- 90% is retained in the intestine and excreted in the feces
what are the adverse effects of iodoquinol?
diarrhea, anorexia, nausea, vomiting, abdominal pain, headache, rash, pruritis
kite-shaped trophozoite, 5% of US adults and infected (mostly asymptomatic)
- coat small intestine, interfering with fat absorption
- do NOT invade the intestinal wall -> do NOT cause bloody stool
- gassy, frothy diarrhea
- must examine stool for cytst
giardia lamblia
what are the pharmacological agents used to treat giardia lamblia?
tinidazole (first line agent)
- or nitazoxanide
this drug inhibits the pyruvate-ferredoxin oxidoreductase enzyme (which is essential to anaerobic energy metabolism)
- is a prodrug, what is it’s active metabolite?
nitazoxanide
- active metabolite is tizoxanide
- rapidly absorbed, excreted in urine and feces
what are the adverse effects of nitazoxanide?
nausea, anorexia, flatulence, increased appetite, enlarged salivary glands, yellow eyes, dysuria, bright yellow urine
oocyst with 4 motile sporozoites
- life cycle occurs within intestinal epithelial cells (causing diarrhea and abdominal pain)
- self limiting if immunocompetent
- can be life threatening if immunocompromised (3-17 L/day)
cryptosporidium parvum
what is the treatment for cryptosporidium parvum?
- antidiarrheal AND antimicrobial
- antidiarrheal: loperamide (Sheehy’s favorite, the failed opioid that’s just a diarrhea med now)
- antimicrobial: nitazoxanide (preferred), or paromomycin
what drug therapy is given for cryptosporidium parvum treatment in HIV patients?
antiretroviral therapy + nitazoxanide
- the main goal is to restore immune function
usually macroscopic helminth (dx requires visualization of microscopic eggs in feces)
- no immune response to worms, but response to dead worms and eggs (elevation of eosinophils)
nematodes
nematode that penetrates bare skin between toes
- larvae travel to lungs (alveoli) -> grow, are coughed up and swallowed -> adult worms dvlp in small intestine
necator americanus and ancylostoma duodenale (hook worms)
worm eggs excreted in feces -> larvae penetrate intestine and travel to lung -> larvae grown, are coughed up, and swallowed -> worms dvlp in small intestine -> release fertilized eggs in fecels
ascaris lumbricoides
larvae in soil, penetrates human skin, travels to lungs -> larvae grow in lungs -> coughed up and swallowed -> EGGS ARE NOT PASSED IN STOOL!!!
strongyloides stercoralis
- hatched larvae can autoinfect, extrete in feces -> infect, or excrete in feces, lay eggs, and new larvae -> infect
vomiting, abdominal bloating, diarrhea, anemia, wt loss
- immunospuuressive medications can lead to severe auto-infection
- dx: larvae in feces, enterotest
strongyloides stercoralis
simple life cycle: ingestion of food with infective eggs -> eggs hatch in small intestine, migration to cecum and ascending large intestine -> mature adult produces thousands of eggs per day for 1 year
- NO LARVAE, NO TRANSIT THROUGH INTESTINAL WALL, NO LUNG INVOLVEMENT, NO EOSINOPHILIA, NO AUTO-INFECTION!
trichuris trichiura (whip worm)
which worm has football shaped eggs?
trichuris trichura
eggs ingested, pinworms mature in cecum and ascending colon -> female migrates to perianal area (at night to lay eggs) -> eggs infectious 4-6 hours later
- severe perianal itching -> hand-mouth transmission
- no eosinophilia
enterobius vermicularis (pinworm) - SCOTCH TAPE TEST!
what are the two broad spectrum oral anti-heminthic agents?
albendazole and mebendazole
- (worms are bendy!)
what is the MOA of albendazole and mebendazole?
inhibit microtubule synthesis, paralyzing worms -> worms passed in stool
- are prodrugs, active metabolite produced after the first pass effect
what are the pharmacokinetics of thiabendazole?
rapidly absorbed after ingestion, largely excreted in urine, can be absorbed from the skin
- NOTE: same MOA as albendazole/mebendazole (just diff side groups)
what are the adverse effects of thiabendazole?
dizziness, anorexia, nausea, vomiting
- irreversible liver failure, fatal Stevens-Johnson syndrome
NOTE: much more toxic than albendazole/mebendazole (so it isn’t used much!)
what is the MOA of ivermectin?
intensifies y-aminobutyric acid (GABA)-mediated transmission of signals in peripheral nerves of the nematode
rapidly absorbed, oral only, wide distribution, excretion in feces
- adverse effects are uncommon
- should not be combined with other drugs that enhance GABA activity (barbituates, benzodiazepines, valproid acid)
ivermectin
neuromuscular blocking agent, causes release of acetylcholine and inhibits cholinesterase
- results in paralysis and expulsion of the nematode
- poorly absorved from GI tract, half administered dose recovered unchanged in feces
- infrequent/transient adverse effects
pyrantel pamoate
albendazole is the primary drug for which 3 worms?
- n. americanus/ a.duodenale
- a. lumbricoides
- e. vermicularis
mebendazole is the primary drug for which 3 worms?
- a. lumbricoides
- t. trichiura
- e. vermicularis
ivermectin is the drug of choice for which worm?
s. stercoralis
pyrantel pamoate in the drug of choice for which worm?
e. vermicularis
what are the 3 primary drugs used to treat e. vermicularis?
- albendazole
- mebendazole
- pyrantel pamoate
what are the 2 primary drugs used to treat a. lumbricoides?
- albendazole
- mebendazole
these worms are extremely common worldwide, found in fresh water
- invade venous system through exposed skin -> eggs must reach fresh water to hatch -> adult worms are able to survive and release eggs for years (NOT killed by immune system -> molecular mimicry)
schistosoma spp (blood flukes)
where are S. japonicum worms found?
- where do they reside?
- where do they deposit eggs?
Eastern Asia
- intestinal tract
- feces
where are S. mansoni worms found?
- where do they reside?
- where do they deposit eggs?
South America and Africa
- intestinal tract
- feces
where are S. haematobium worms found?
- where do they reside?
- where do they deposit eggs?
Africa
- bladder
- urine
eggs hatch in fresh water, larvae infect and mature within a snail -> infect humans (exposed skin) -> mate in intrahepatic portion of portal venous system -> migrate to veins surrounding intestine of bladder to lay eggs -> eggs enter the lumen of intestine or bladder to be excreted
schistosoma spp (blood flukes)
dermatitis (immediate), Katayama fever (fever, hives, bronchospasm, hepatosplenomegaly 4-8 weeks later), chronic fibrosis (d/t egg deposits that don’t make it to bladder)
schistosoma spp.
what is the treatment for schistosoma?
praziquantel
what is the MOA of praziquantel?
increases the permeability of nematode and cestode cell membrane to calcium -> paralysis, dislodgment, and death
what are the pharmackoinetics of praziquantel?
oral administration, rapidly absorbed, excreted mainly by the kidneys
what are the adverse effects of praziquantel?
headache, dissiness, drowsiness, fatigue (drug’s fault)
- after several days: low grade fever, pruritis, skin rash (dead worm’s fault, body clearing infection)
acquired by ingestion of undercooked pork containing larvae
- attaches via hooks
- diagnosed by proglottids and/or eggs in feces
taenia solium
acquired by ingestion of indercooked beef
- attaches via suckers
- diagnosed by proglottids and/or eggs in feces
taenia saginata
pigs/cows ingest eggs from field contaminated with human feces -> larvae disseminate through intestine into muscle of the aminal -> larvae develop into cysticerci -> humans inject undercooked meat -> tapeworm matures in intestine
taenia solium and taenia saginata
- clinically manifests as weight loss nad malnutrition
acquired by ingesting larvae in raw freshwater fish
- adult tape worm in human ingestion excretes gradis proglottids with eggs -> eggs hatch in water and convert to motile larvae -> ingested by human
- dx by proglottids and eggs in feces
diphyllobothrium latum
- few abdominal symptoms, worm absorbs vitamin B12 (anemia)
extra-intestinal tapeworm infection
- dogs and sheep perpetuate the life cycle with a human acting as a dead end: humans ingest eggs from dog feces -> eggs hatch in intestine and larva form hydatid cysts
echinoccus granulosus
what 3 drugs are used for cestode treatment?
- praziquantel
- niclosamide
- albendazole
what is unique about niclosamide?
it is the only drug that KILLS (rather than paralyzing) the worm
- but it isn’t used often d/t side effects, long duration of therapy, and limited availability
what is the MOA of niclosamide?
uncouples oxidative phosphorylation, blocking uptake of glucose
- not effective against hydatid cysts
