GI_FINAL_Session 9

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GI_FINAL_Session 9
2011-03-12 18:51:11
GI gastrointestinal GI pharm

westernu GI final, session 9
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  1. what drugs can be used in the Tx of IBD?
    • 5-ASA-related agents (Sulfasalazine, Mesalamine, Olsalazine)
    • TNF inhibitors (Infliximab, Adalimumab)
    • Glucocorticoids (Budesonide, Prednisone)
    • Immunosuppressive Purine analogs (Azathioprine, Methotrexate)
  2. What drugs can be used in the Tx of IBS?
    • goal: relieve abd pain & improve bowel fn
    • mostly diarrhea:
    • anti-diarrheal agents--loperamide
    • mostly constipation:
    • fiber--bran or methylcellulose
    • *unresponsive to fiber --> milk of magnesia (osmotic laxative)
    • for chronic abd pain:
    • low dose tricyclic anti-depressants (amitriptyline or desipramine)
    • anticholinergics (dicyclomine)
    • Serotonin 5-HT3-R antag (Alosetron)
    • Cl-Channel Activators (Lubiprostone)
  3. For Sulfasalazine, describe
    clinical use
    adverse effects (unique 1st, common to others-last)
    name any related drugs and their unique characterisitcs.
    • MOA:
    • converted in colon to 5-ASA & Sulfapyridine
    • 5-ASA inhibits PG synthesis & migration of inflammatory cells (--> decreases inflammation)
    • Uses:
    • UC: Tx & maintenance; considered 1st line Rx's
    • Crohn's: adjunct
    • SE:
    • folate deficiency (recommend 1mg/d folic acid suppl.)
    • allergic rxn (fever, rash, hemolytic anemia)
    • N/V, HA, GI upset, malaise
    • related drugs:
    • *these are better tolerated than Sulfasalazine!!!
    • Mesalamine--extended release; as suppository or enema
    • Olsalazine -- prodrug, 2-ASA linked via "azo" (reduces absorption in SI, so can make it to colon)
  4. For Budesonide, describe:
    clinical use
    adverse effects
    • A glucocorticoid (also used: Prednisone):
    • MOA:
    • inhibit productio of inflammatory cytokines (TNF-a, IL1)
    • decrease gene expression of white-cell adhesion molecules
    • inhibit PLPA2 & COX
    • Uses: topical, oral, IV for IBD (both UC, Crohn's)
    • *NOT useful for maintaining dz remission
    • SE: assume usualy glucocorticoid SE's
  5. For Infliximab, describe:
    clinical use
    adverse effects (unique 1st, common to others-last)
    name any related drugs and their unique characterisitcs.
    • MOA:
    • anti-TNF ab's bind specifically to human TNF-a thus neutralizing that cytokine & inflammation in IBD
    • Uses:
    • acute & chronic maintenance of Crohn's
    • acute & chronic Tx of mod-severe UC
    • SE:
    • bacterial sepsis, reactivation of TB, fungus, pneumonia
    • Infusion Rxns: fever, HA, dizzy, uticaria, dyspnea, HoTN
    • other drug: Adalimumab
  6. For Azathioprine, describe:
    clinical use
    adverse effects (unique 1st, common to others-last)
    name any related drugs and their unique characterisitcs.
    • MOA:
    • inhibit purine nucleotide metabolism & DNA synthesis
    • -->inhibit cell division & proliferation
    • Uses:
    • UC & Crohn's: Tx & maintenance
    • SE:
    • bone marrow depression (leucopenia, anemia)
    • hepatitis
    • N/V
    • allergic rxns
    • other drugs: Methotrexate (inhibits DHF reductase...SE also include megaloblastic anemia, alopecia, & mucositis)
  7. what antidepressants would be effective in the tx of chronic abd pain in IBS?
    • tricyclic (e.g. amitriptyline)
    • --low doses appear to help
    • --may also have anticholinergic effects on GI motility & secretion--> decrease stool frequency & liquidity of stool
  8. For Dicyclomine, describe:
    clinical use
    adverse effects (unique 1st, common to others-last)
    • MOA:
    • an anticholinergic (antispasmodic)
    • inhibits muscarinic cholingergic receptors in enteric plexus on sm mm
    • Uses:
    • relief of abd pain/discomfort
    • SE:
    • anti-SLUD effects: dry mouth, visual disturbances, urinary retention, constipation
  9. For Alosetron, describe:
    clinical use
    adverse effects (unique 1st, common to others-last)
    • MOA:
    • blocks 5-HT3-receptors of enteric cholinergic neurons
    • --> inhibits colonic motility & increases colonic transit times
    • also blocks central 5-HT3-receptors which may decrease central response to visceral afferent stim
    • Uses:
    • reduce abd pain, cramps, urgency & diarrhea IN WOMEN (efficacy in men has not been established!!!!!)
    • SE:
    • ischemic colitis = serious (-->hosp, surg, death)
    • constipation = common SE of this drug
    • **note: according to Pum. this drug has been off/on the market & thus is probably last resort
  10. For Lubiprostone, describe:
    clinical use
    adverse effects (unique 1st, common to others-last)
    name any related drugs and their unique characterisitcs.
    • MOA:
    • a FA metabolite of PGE1 that stims type-2 Cl- Channels in intestine
    • -->increased liquid secretion & GI motlity
    • Uses:
    • chronic idiopathic constipation
    • Tx of women w/IBS+predom constipation
    • SE:
    • bloating & diarrhea
    • N, abd pain
    • dyspnea is a concern
    • is class C (risk can't be r/o) in pregos
  11. what's the definition of IBS?
    • Rome Criteria:
    • >/=3mo continuous or reccur abd pain that is:
    • --relieved by defecation and/or
    • --associated w/ change in frequency of stool and/or
    • --associated w/change in consistency of stool
    • AND >/=2 Sxs on >25% of occasions or days:
    • --altered stool frequency (>3bm/d or <3bm/wk)
    • --altered stool form (lumpy/hard or loose/watery)
    • --altered stool passage-straining, urgency or tenesmes
    • --passage of mucus
    • --bloating or feeling of abd distension

    • manning:
    • presence of abd pain & at least 2 of:
    • pain releif w/ defecation,
    • looser stools at pain onset,
    • more frequent stools at pain onset,
    • abd distention,
    • mucus,
    • tenesmes.
  12. describe image:
    • a view of postinfective IBS shows:
    • increased CD3, CD4, CD8 T lymphocytes, Macrophages & enteroendocrine cells
    • brown/red staining of enteroendocrine cells
    • from dan: enteroendocrine cells secrete 5-HT & histamine --> contributes to secretion & peristalsis
  13. what is the management of IBS?
    • Tx according to predominance (diarrhea or constipation):
    • IBS-Diarrhea:
    • --anti-diarrheal = loperamide
    • --abd pain meds
    • IBS-Constipation:
    • --fiber (bran, etc) OR milk of Mg
    • --abd pain meds
    • abd pain meds: low dose tricyclic anti-depressants, anticholinergics, serotonin 5-HT-R antag, Cl-Channel Activators

    • Tx according to Severity (from ppt slide):
    • Mild to Mod (altered gut physiology):
    • "gut-acting pharmacologic agents such as antispasmodics, antidiarrheals, fiber supplements, and gut serotonin modulators"
    • Severe (psychosocial issues):
    • "best managed with antidepressants and other psychosocial treatments"
  14. what is the major cause of acute colonic pseudo-obstruction?
    • electolyte imbalance--etiology:
    • trauma, infection, cardiac dz
    • **seen in admit's to hospital
  15. what is ogilvie's syndrome? presentation? etiology? diagnostics?
    • = acute colonic pseudo-obstruction w/o mechanical obstruction
    • M, >60yo
    • severe abd distention, constant adb pain, N/V
    • massivie dilation of cecum or right colon (often post op pt's)
    • **etiology unk--spontaneous massive dilation
    • Dxics via plain radiographs
  16. what are potential complications of Ogilvie's?
    • perforation--cecal diameter >10-20cm = increased risk
    • ischemia
  17. what is the management of Ogilvie's?
    • for pt w/o abd tenderness, fever, leukocytosis, cecal diameter <12cm:
    • --Treat underlying illness, correct electrolytes
    • --discontinue provoking meds (opioids, anti-Ch, CCB's)
    • --NG tube and rectal tube
    • --Ambulate pts or roll periodically from side to side and knee-chest position
    • --Judicious administration of enemas if large amt of stool on radigoraph
    • --Conservative tx successful in >80%

    • If not improve or deteriorate after 24-48hrs, cecal dilation >10cm for >3-4d, or cecal dilation >12cm:
    • --give Neostigmine injection if no contraindications
    • --Colonoscopic decompression in selected pts who
    • --don’t respond to neostigmine – successful in 70%; dilation recurs in 50%
  18. what are clinical manifestations of pseudomembranous colitis?
    • frequent, osmotic watery, occult blood diarrhea
    • low grade fever
    • lower abd pain
    • leukocytosis w/left shif
    • recent (w/in 10wks) ABX (clindamycin or amp or FQs)
    • pseudomembranes seen (raised yellowish-white plaques) on colonoscopy and creates wall thickening
  19. name & describe the organism & its pathogenesis.
    • C. difficile:
    • G+ rod, spore forming, toxins A, B
    • Pathogenesis:
    • exposure to abx establishes susceptibility
    • 2ndary contraction of C. diff (patho or nonpatho)
    • --> releases toxins A (entero) adn B (cyto) are clucosyltransferases that glucosylate a G protein called Rho GTPase
    • -----A: intestinal fluid secretion, chemotaxis, inflammation, pseudomembrane formation
    • -----B: more potent than toxin A in damaging colonic mucosa
    • -also have binary toxin, role unclear
    • =>cause proinflammatory & cytokine release that stim excess fluid secretion & attract PMNs
    • form spores: germinate in GI, acid & EtOH resistant
    • **Bleach 1:10 solution is sporicidal
  20. what are diagnostic tests for C. diff infecion?
    • cytotoxin assay of stool has greater specificity (75-100) than culture
    • If assay (-) can visualize on flexible sigmoidoscopy (NO colonoscopy b/c risk peforation)
  21. what is management of pseudomembranous colitis?
    • based on severity
    • Mild-Mod:

    • metronidazole 500mg oral/8hr
    • Severe (WBC >15,000 or <2000) w/ rising serum Cr or 1.5xbaseline):
    • vancomycin 125mg oral/6hr x 10-14d
    • Severe Complicated (HoTN, Ileus, Toxic megacolon, perforation, sepsis):
    • metronidazole 500mgIV/8hr
    • Vancomycin 500mg enteric/6hr
    • *colectomy before lactate >/=5
  22. describe image:
    Crohn's colitis: mixed acute & chronic inflammation, crypt atrophy, & multiple small epithelioid granulomas in mucosa
  23. what are the extraintestinal manifestations of Crohn's?
    • >in Crohn's:
    • Uveitis
    • Gallstones
    • Kidney Ca-oxalate stones
    • Arthritis
    • Common to both:
    • Erythema nodosum
    • more common in UC = pyoderma gangrenosum, although Pum showed slide w/Crohn' prob can't r/o
  24. what are potential complications for Crohn's?
    • Fistulas & strictures
    • malabsorption
    • anemia of chronic dz
    • sinus tracts
    • perforation
    • fibrosis
  25. Dx tests of Crohn's
    • flexible sigmoidoscopy --> cobblestoneing & rectal sparing
    • ASCA (+)
    • barium enema --> visualize rest of colon
    • -->see "string-sign" (strictures)
    • "fat wrapping"
  26. explain the pathophysiology of Crohn's? how is this related to Tx?
    • Th1 mediated, produce lymphokines (IFN-g) --> activate macrophages, which regulate Th1 cells by secreting more IL-12 and TNF-a (rx infliximab)
    • Drugs indicated in treatment aim to decrease inflammation & block these ck's.
  27. explain management of Crohns.
    • Ileoceacal Crohn's:
    • 5-ASA (1st line), sulfasalazine, azathioprine/mercaptopurine, budesonide, predisolone, infliximab, surgery
    • Crohn's Colitis:
    • Induction: sulfasalazine, 5ASA, prednisolone, infliximab, surgery
    • Remission: azathioprine/mercaptopurine, infliximab, methotrexate, (budesonide)
    • Fistulising Crohn's:
    • azathioprine/mercaptopurine, infliximab,metronidazole, ciproflaxacin, surgery

    ??1st line's first??
  28. describe features of Giardia.