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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)
-
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)
-
For Sulfasalazine, describe
MOA
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)
-
For Budesonide, describe:
MOA
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
-
For Infliximab, describe:
MOA
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
-
For Azathioprine, describe:
MOA
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)
-
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
-
For Dicyclomine, describe:
MOA
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
-
For Alosetron, describe:
MOA
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
-
For Lubiprostone, describe:
MOA
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 concernis class C (risk can't be r/o) in pregos
-
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.
-
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
-
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"
-
what is the major cause of acute colonic pseudo-obstruction?
- electolyte imbalance--etiology:
- trauma, infection, cardiac dz
- **seen in admit's to hospital
-
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
-
what are potential complications of Ogilvie's?
- perforation--cecal diameter >10-20cm = increased risk
- ischemia
-
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%
-
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
-
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
-
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)
-
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
-
describe image:
Crohn's colitis: mixed acute & chronic inflammation, crypt atrophy, & multiple small epithelioid granulomas in mucosa
-
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's...so prob can't r/o
-
what are potential complications for Crohn's?
- Fistulas & strictures
- malabsorption
- anemia of chronic dz
- sinus tracts
- perforation
- fibrosis
-
Dx tests of Crohn's
- flexible sigmoidoscopy --> cobblestoneing & rectal sparing
- ASCA (+)
- barium enema --> visualize rest of colon
- -->see "string-sign" (strictures)
- "fat wrapping"
-
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.
-
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??
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describe features of Giardia.
protozoa
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