Pharm: GI Infections Flashcards
clostridium difficile (C. diff)
gram positive+, spore forming, anaerobic rod
caused by antibiotics, creates pseudomembranous layers that cause diarrhea, colitis (causes inflammation in the intestine)
what are signs of a CDI? (C. diff infection)
- severe diarrhea while on antibiotics
- abdominal cramping
- fever
- red inflamed intestinal mucosa with white pseudomembranous exudate (necrosis below that)
exotoxins found in C. diff?
- toxin A=enterotoxin (diarrhea)
- toxin B=cytotoxin (cytotoxic to colonic cells)
how to treat CDI?
- stop taking antibiotic
- supportive care (stop diarrhea, replace fluids)
- fecal transplantation
- give new antibiotics (vancomycin, metronidazole, fidaxomicin)
vancomycin
pharmacokinetics prevent it from entering GI if giving IV (if given PO, stays in GI)
- is cell wall synthesis inhibitor
- preferred tx for severe CDI, equivalent tx to metronidazole for mild CDI
metronidazole
- used for mild CDI
- can be used if oral administration won’t work for pt
- 2 main AE: disulfiram like effect (causes alcoholic to throw up if they ingest alcohol), and causes metallic taste in mouth
fidaxomicin
-tc for recurrent CDI,
spares many anaerobic colonic flora
Helicobacter pylori (H. pylori)
- MC cause of duodenal ulcers and chronic gastritis
- bismuth subsalicylate
- metronidazole
- tetracycline
- omeprazole (PPI)
Entamoeba histolytica (e. histolytica)
- “classic amoeba”
- life cycle: trophozoite, binucleated precyst, tetranucleated cyst (cyst=is how it is passed and diagnosed)
- trophozoites can invade intestinal mucosa (will see them having engulfed an RBC)
- can enter portal blood circulation, cause liver and pulmonary abscesses
Tx of E. Histolytica
- *must tx with drugs from both classes for full eradication
1. eliminate the invading trophozoites (body)- metronidazole or tinidazole
- eliminate intestinal carriage of organism (GI lumen)
- paromomycin or iodoquinol (stay just in GI lumen, doesn’t leave GI/affect other organs)
- metronidazole or tinidazole
- if pt is asymptomatic, can eliminate via luminal amebicide agents (bc they only exist in lumen of GI, not systemic)
Iodoquinol
- has 2 iodines in structure (don’t use in pts w/ iodine sensitivity)
- used as a luminal amebicide (stays in GI, excreted in feces)
- halogenated hydroxyquinoline, unknown MOA
- AE= d/n/v anorexia, abdominal pain, headache, rash, pruritus
Giardia Lamblia
- Trophozoite (kite shape) to cyst (dx by finding cysts in stool)
- *NO blood in stool
- coats wall of SI, preventing fat absorption (fat in diarrhea)
Tx of Giardia Lamblia
- supportive (correct fluid and electrolyte abnormalities from diarrhea)
- tinidazole (1st line tx)
- metronidazole (not fda approved for this use)
- nitazoxanide
Nitazoxanide
MOA: inhibits specific enzyme needed for anaerobic energy metabolism (pyruvate-ferredoxin oxidoreductase enzyme), is a prodrug (most be activated into tizoxanide)
- quickly absorbed, excreted in urine/feces
- AE= nausea, anorexia, flatulence, enlarged salivary glands, yellow eyes, bright yellow urine
Cryptosporidium parvum
- most of an issue with compromised immune system (severe/life threatening diarrhea), in healthy people, it is cleared by the immune system
- from contaminated water, day care, travelers,
- is an oocyst with 4 motile sporozoites, life cycle occurs within intestinal epithelial cells
Tx of cryptosporidium parvum
- stop the diarrhea with antidiarrheal agents
- loperamide (immodium, a “failed opioid”)
- fluid management
- antimicrobial agents
- nitazoxanide (preferred), or paromomycin
Tx of cryptosporidium in immunocomp pts
HIV= antiretroviral therapy+nitazoxanide (if needed)
Other= reduce dose of immunosuppressant+nitazoxanide
goal: restore immune fxn in immunocomp pts
Helminths: nematodes
- are usually macroscopic, dx requires visualization of eggs in feces
- nematodes=round worms
- no immune response to worms (can hide from immune system/mimicry), but there is response to dead worms and eggs, has elevation of eosinophils
Hook worms
-necator americanus, ancylostoma duodenale
Life cycle= penetrates skin between toes , larvae travel to lungs, are coughed up and swallowed, adult worms develop in SI, populate and release fertilized eggs, eggs excreted in feces** (eggs hatch and larvae live in soil)
=present with diarrhea, abdominal pain, weightloss, anemia, intense itching at penetration site
-adult worms attach/hook themselves to your intestine and get their nutrition from sucking your blood
ascaris lumbricoides
- consume eggs via contaminated food, larvae penetrate intestine and travel to lung, there larvae grow and are coughed up then swallowed, adult worms develop in SI, worms release fertilized eggs, **eggs excreted in feces, eggs hatch and larvae live in soil
- present with abdominal cramping, malnutrition, worm invasion
strongyloides stercoralis
- larvae in soil penetrates human skin, travels to lungs, larvae grow in lungs and are coughed up and swallowed into SI, mature worms grow in SI and release eggs,
- *eggs are NOT passed in stool!!** bc eggs hatch in intestine itself, hatched larvae can reinfect by penetrating GI, or be excreted in feces and have a direct (perianal) or indirect cycle
clinical strongyloides stercoralis
- present with v/d, abdominal bloating, anemia, weightloss
- immunosuppressive meds (prednisone in asthma) can lead to sever autoinfection
- dx: larvae in feces or enterotest (pt swallows string)
whip worm
- trichuris trichiura
- (simple life cycle) ingest eggs in contaminated food, eggs hatch in SI, migrate to cecum and LI, mature adult produces thousands of eggs/day, ***dx is eggs in feces (football shaped)
- no larvae, no transit thru intestinal wall, no lung involvement, no eosionophilia, no autoinfection
- presents with abdominal pain, diarrhea
pinworm
- enterobius vermicularis
- eggs are ingested, pinworms mature in cecum and ascending large intestine, females migrate to perianal area at night and lay eggs, eggs infectious 4-6hrs later, leads to severe perianal itching=hand to mouth transmission
- may use “scotch tape test”, has no eosinophilia
nematode tx: albendazole, mebendazole
- are broad spectrum oral anti-helminthic agents
- MOA: inhibits microtubule synthesis which paralyzes worms and worms are excreted in stool
- note: is a prodrug, activated after first pass effect
- AE= few with acute tx
nematode tx: thiabendazole
- same MOA as albendazole, mebendazole
- rapidly absorbed after ingestion, largely excreted in urine, can be absorbed from skin
- AE*= much more toxic than other “bend”
- dizziness, anorexia, n/v, irreversible liver failure, fatal stevens-johnson syndrome
nematode tx: ivermectin
MOA: intensifies GABA mediated transmission of signals in peripheral nerves of the nematode (paralyzes it)
- rapidly absorbed, only oral, wide distribution, excretion in feces
- AE= uncommon, should NOT combine with other drugs that enhance GABA activity (barbiturates, benxodiasepines, valproic acid)
nematode tx: pyrantel pamoate
MOA: neuromuscular blocking agent, causes release of ACh and inhibit of cholinesterase (paralysis and expulsion of nematode)
- poorly absorbed from GI tract
- AE=few/infrequent
platyhelminthes
flatworms
Trematodes
- Schistosoma spp. (blood flukes)
- female and male are found together
- found worldwide in freshwater
- invade the venous system thru exposed skin
- eggs must reach fresh water to hatch, adult worms can survive and release eggs for years (molecular mimicry-not killed by immune system)
schistosoma life cycle
- eggs hatch in fresh water, larvae infect and mature within a snail, mature larvae leave the snail and infect humans via exposed skin, they mature and mate in the intrahepatic portion of the portal venous system, the mating mature worms migrate to veins surrounding intestine of bladder to lay their eggs, eggs enter the lumens of intestine or bladder to be excreted
- clinically= immediate dermatitis, katayama fever (4-8 weeks- fever, hives, large liver/spleen), chronic fibrosis
Tx of schistosoma
praziquantel (also works agains most other trematodes and cestodes)
- MOA: increases permeability of nematode and cestode cell membranes to calcium, leading to paralysis, dislodgment and death
- oral administration, rapidly absorbed, mainly excreted by kidneys
- AE=immediate (due to drug): headache, dizziness, drowsiness, lassitude
- after several days (due to dead worms): low grade fever, pruritis, skin rash
Tapeworms
- cestodes (taenia solium[pork], taenia saginata[beef])
- lack a digestive tract, have a chain of segments, parts: scolex (head), immature proglottids, mature proglottids, gravid proglottids
- attach via hook (solium) or suckers (saginata)
- dx by finding proglottids or eggs in feces
- pigs/cows ingest egg from field contaminated with human feces, larvae disseminate through intestine into muscle of animal, develop into cysticerci, humans ingest undercooked meat, tapeworm matures in human intestine
- presents as weight loss, malnutrition
diphyllobothrium latum (d.latum)
- acquired by ingesting larvae in raw freshwater fish
- adult tapeworm in human ingestion excretes gravid proglottids with eggs, eggs hatch in water and convert to motile larvae, ingested by human (or fish)
- few abdominal symptoms, absorbs vit b12 (anemia)
- dx by proglottids, eggs in feces
echinococcus granulosus
- an extra intestinal tapeworm infection
- dogs and sheep perpetuate the life cycle with a human acting as a dead end
- human ingests eggs from dog feces
- eggs hatch in the intestine and larva form hyatid cysts in the humans muscles
cestode tx: niclosamide
-alternative drug for tx of most tape worm infections (won’t work against hydatid cysts)
MOA: uncouples oxidative phosphorylation, blocks uptake of glucose, results in DEATH of the parasite
-oral administration
-use if limited by AE, long duration of therapy, limited availabiltiy
other cestode tx
- niclosamide
- praziquantel
- albendazole
