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2012-01-31 21:43:43
HUSOP Diarrhea

Questions from lecture
Show Answers:

  1. name the three characteristics of Diarrhea
    abnormally liquid, unformed stool, increased frequency
  2. What are the time periods to be considered for acute, persistent and chronic diarrhea?
    Acute if < 2 weeks, Persistent if 2-4 weeks, Chronic if > 4 weeks
  3. When should pharmacotherapy of diarrhea in adult be administered?
    should be reserved for patients with significant or persistent symptoms.
  4. Name the four causes of diarrhea.
    Increased osmotic load within the intestine, resulting in retention of water within the lumen (Lactase deficiency), -Excessive secretion of electrolytes and water into the intestinal lumen � enterotoxins, -(Inflammatory) Exudation of protein and fluid from the mucosa - IBD, Shigellosis, -Altered intestinal motility resulting in rapid transit and decreased fluid absorption - postsurgical
  5. Some mechanisms of Bulk-Forming and hydroscopic agents are?
    may work as gels to modify stool texture, viscosity & decreased stool fluidity
  6. How do Clays (kaolin, a hydrated aluminum silicate) and attapulgite (magnesium aluminum disilicate (DIASORB) work?
    Bind water avidly (attapulgite absorbs 8 times its weight in water), May bind enterotoxins.
  7. Why is Pepto-Bismol effective? What is the metabolite responsible?
    antisecretory, anti-inflammatory, and antimicrobial effects, and bismuth subsalicylate reacts with HCl to form bismuth oxychloride
  8. Bismuth indications:
    Nausea and abdominal cramps also are relieved by bismuth. Diarrhea Acute gastroenteritis
  9. Name the three bile acid Sequestrants from lecture:
    Cholestyramine, colestipol, and colesevalam
  10. MOA of bile Sequestrants:
    Bind bile acids and some bacterial toxins
  11. Cholestyramine is useful in what condition?
    bile salt�induced diarrhea as in Pts with resection of distal ileum
  12. Partial interruption of normal enterohepatic circulation of bile salts, results in?
    excessive concentrations reaching the colon and stimulating water & electrolyte secretion
  13. Bile Salt depletion can cause?
    steatorrhea because of inadequate micellar formation required for fat absorption
  14. Describe enterohepatic circulation:
    95% bile acids are reabsorbed in the intestine (mainly in terminal ileum), returned to the liver, and then again secreted in bile
  15. How do opioids act to produce their antimotility and antisecretory effects? Effects of mu, d?
    either m- or d-opioid receptors on enteric nerves, epithelial cells, and muscle.,� Intestinal motility (m),� Intestinal secretion (d), Absorption (m and d)
  16. Name some commonly used opioid antidiarrheals, and where do they act?
    diphenoxylate, difenoxin, and loperamide act principally via peripheral m-opioid receptors
  17. Where are mu receptors located and what is it's role in anti-diarrhea?
    in GI tract, activation will reduce motility and secretions,
  18. Loperamide effects:
    ~50 times more potent than morphine as an antidiarrheal agent & penetrates CNS poorly., Increases small intestinal transit times. , Increases anal sphincter tone, Anti-secretory activity against cholera toxin (via Gi � � cAMP
  19. Which opioid is effective against traveler's diarrhea? MOA?
    Loperamide (IMODIUM), mu receptor agonist
  20. T/F: loperamide overdose can result in CNS depression.
  21. Why should you avoid giving Loperamide to children, 2 yrs old?
    The BBB is not fully developed and loperamide can penetrate into the Brain.
  22. What % of stool weight is water?
    70% to 85%
  23. What is left behind after the gut extract water, minerals, and nutrients from the luminal contents?
    a manageable pool of fluid for proper expulsion of waste material via the process of defecation.
  24. How many liters of water pass through the SI and how much leaves the colon?
    9 liters enters, only 100cc leaves
  25. Which ions are conserved in the colon? Which is lost?
    Na+, Cl-, CO2, are conserved, K+ is secreted from the colon
  26. Diphenoxylate & its active metabolite difenoxin (diphenoxylic acid) are _________ derivatives that are related structurally to _________?
    Piperidine derivatives, to meperidine
  27. How is Diphenoxylate metabolized to its metabolite? Name the metabolite:
    rapidly de-esterified to difenoxin
  28. Half life of Diphenoxylate and its metabolite are?
    Dihpenoxylate= 3hr, difenoxin= 12
  29. At what dosages can both Diphenoxylate and Difenoxin produce CNS effects?
    40 to 60 mg per day
  30. What is added to Diphenoxylate and Difenoxin to discourage abuse and deliberate overdosage and how much?
    Atropine (25mcg)
  31. What is an octapeptide analog of somatostatin?
    Octreotide (SANDOSTATIN)
  32. Why is Octreotide (SANDOSTATIN) a good choice in chemotherapy-induced diarrhea?
    Effective in inhibiting severe secretory diarrhea brought about by hormone-secreting tumors of the pancreas and the GI tract
  33. Indications of Octreotide (SANDOSTATIN)
    Chemotherapy-induced diarrhea, Diarrhea associated with HIV (AIDS enteropathy), Diabetes-associated diarrhea. ,Dumping syndrome seen in some patients after gastric surgery and pyloroplasty.
  34. MOA of Octreotide (Sandostatin)
    Octreotide inhibits the release of hormones (VIP, gastrin, secretin, 5HT, CCK, etc) triggered by passage of food into the SI that are responsible for distressing local and systemic effects,( inhibits intestinal secretion)
  35. SE of long term and short term of Octreotide?
    Short-term therapy: Transient nausea, bloating, or pain at sites of injection., Long-term therapy: Gallstone formation,
  36. Ulcerative colitis and Crohn's disease result from a combination of defects in?
    1) host interactions with intestinal microbiota, intestinal epithelial dysfunction, and 2) aberrant mucosal immune responses.
  37. What does NOD2 dysfunction cause?
    Crohn's, NOD2 doesn�t recognize the bacteria in gut as good and activates the Immune system. Including NFkB.
  38. What are the specific goals in treatment of IBD?
    Controlling acute exacerbations, maintaining remission, and treating specific complications such as fistulas.
  39. What is the problem with using steroids for the treatment of IBD?
    inappropriate for long-term use because of S/E and their inability to maintain remission
  40. Which immunosuppressant is preferred for long-term management of IBD?
  41. What is the first line therapy for mild-to-moderate ulcerative colitis?
    Mesalamine (5-ASA)
  42. Sulfasalazine (AZULFIDINE) consists of 5-ASA linked to sulfapyridine by what type of bond? What does the bond do?
    the azo linkage prevents absorption in the stomach and small intestine
  43. Sulfasalazine (AZULFIDINE) consists of 5-ASA linked to __________ by an azo bond.
  44. How is Sulfasalazine liberated for absorption?
    colonic bacteria cleave the azo bond
  45. MOA of Mesalamine and Sulfasalazine?
    Inhibition of the production of IL-1 and TNFa, Inhibition of the LOX (lipoxygenase) pathway, Scavenging of free radicals and oxidants, Inhibition of NFkB
  46. What % of sulfasalazine is absorbed in the SI, in the colon?
    30% of sulfasalazine, p.o. is absorbed in small intestine
  47. Where is sulfapyridine metabolized? How?
    hepatic metabolism, Acetylation and hydroxylation, Conjugation with glucuronic acid, and excretion in the urine, Rapid acetylators have lower systemic levels of drug, fewer adverse effects
  48. T/F: Fast acetylation and hydroxylation of sulfapyridine will less SE?
    False, just rapid acetylators
  49. What are the AE of sulfasalazine? What is the primary cause of the AEs?
    headache, nausea, and fatigue, rash, fever, Stevens-Johnson syndrome, hepatitis, pneumonitis, hemolytic anemia, BM suppression.
  50. Mesalamine has been associated with interstitial nephritis
    to the sulfa moiety
  51. What does sulfasalazine inhibit from being absorbed in the intestine? And how is this managed?
    folate, usually it is given with sulfasalazine
  52. What is the benefit of the 2nd generation mesalamine-based-therapy?
    replacement of the sulfapyridine with either another 5-ASA (olsalazine, DIPENTUM) or an inert compound (basalazide, COLAZIDE) devoids the Side Effects.
  53. Name the 5-ASA-based therapy drugs
    Mesalamine, Sulfasalazine, olsalazine, basalazide, PENTASA(DR), ASACOL(ph sensitive), CANASA (suppository), ROWASA(enama)
  54. Name the GC used for moderate-to-severe IBD with MOA:
    Hydrocortisone(distal proctits) and Budesonide(ileocecal Crohn's)- Inhibit NFkB, � inflammatory cytokines, -Suppress eicosanoid biosynthesis
  55. name the two Thiopurine derivatives that are used in severe IBD, steroid-resistant, or steroid-dependent patients:
    Mercaptopurine (6-MP, PURINETHOL) and azathioprine (IMMURAN)
  56. MOA of Thiopurine Derivatives:
    Thiopurine antimetabolites impair purine biosynthesis and inhibit cell proliferation
  57. Adverse Effects of Thiopurine Derivatives:
    Most serious idiosyncratic reaction is pancreatitis (5%), Fever, rash, arthralgias (occasionally), N/V more frequent, Bone marrow suppression, Cholestatic hepatitis is relatively rare.
  58. MOA of Methotrexate:
    inhibits DHFR, thereby blocking DNA synthesis & causing cell death. ,Causes apoptosis of activated CD4 and CD8, Inhibits Neutrophil adhesion
  59. Methotrexate is generally reserved for patients with what condition?
    when Crohn's disease is steroid-resistant
  60. MOA of Cyclosporine:
    Calcineurin inhibitor- inhibits IL-2 production by activated T cells
  61. Cyclosporine is effective in what condition?
    severe ulcerative colitis that has failed to respond adequately to glucocorticoid therapy
  62. MOA of Infliximab:
    a chimeric immunoglobulin (25% mouse, 75% human) that binds to and neutralizes TNFa.
  63. Why is infliximab effective in Crohn's Disease?
    neutralizes TNFa which is one of the principal cytokines mediating the TH1 immune response characteristic of Crohn's disease., TNFa stimulates vascular endothelium and vascular permeability
  64. AE of infliximab:
    increased incidence of respiratory infections, Of particular concern is potential reactivation of tuberculosis or other granulomatous infections
  65. Infliximab is contraindicated in patients with?? And what is the major concern (as with immunosuppressives)?
    severe CHF (New York Heart Association classes III and IV),- increased incidence of non-Hodgkin's lymphoma
  66. Before starting infliximab therapy, Patients should be tested for what condition? And if they test positive, what should be done?
    tuberculosis with purified protein derivative
  67. What roles do anti-biotics play in IBD?
    adjunctive treatment along with other medications for active inflammatory bowel disease, treatment for a specific complication of Crohn's disease, prophylaxis for recurrence in postoperative Crohn's disease.
  68. What are the three nost frequently used antibiotic in IBD?
    Metronidazole, ciprofloxacin, and clarithromycin
  69. Antibiotics are more beneficial in which type of Crohn's disease?
    in Crohn's disease involving the colon than in disease restricted to the ileum.
  70. What are some complications of Crohn's disease that may benefit from antibiotic treatment?
    intra-abdominal abscess and inflammatory masses, perianal disease (including fistulas and perirectal abscesses), small bowel bacterial overgrowth secondary to partial small bowel obstruction, secondary infections with organisms such as C. difficile, postoperative complications.
  71. Mild IBD is treated with?
    5 aminosalicylates, anti biotics, corticosteroids topically
  72. Moderate IBD is treated with?
    azathiopine, corticosteroids (p.o.), methotrexate, TNF antagonist
  73. Severe IBD is treated with?
    corticosteroids (IV), TNF antago, cyclosporine, surgery