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What is the epidemiology for IBD?
- Ulcerative colitis: 2-6/100,000 people per year
- Crohn's disease: 5-10/100,000 people per year
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What is the clinical presentation of Ulcerative colitis?
- Diffused inflammation limited to the surface of the colon
- Distal (confined to descending colon/sigmoideum) or Extensive (can include the transverse and ascending colon)
- Persistent bloody diarrhea
- Urgency
- Tenesmus (urgency accompanied by pain, cramping and involuntary straining efforts)
- Extra-gastrointestinal manifestations (joints, eyes, skin, etc)
- Growth failure/retardation and malnutrition (kids)
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What is the clinical presentation of Crohn's disease?
- Patchy, transmural inflammation in any part of the GI tract, including small intestines (30%) and stomach (5%)
- Classified by location and pattern (inflammatory, fistulating, stricturing)
- Intestinal obstruction (stricturing)
- Fistula (often perianal)
- Fissures (fistula from gut to other organs)
- Malnourished
- Malaise
- Anorexia
- Fever
- Extra-gastrointestinal manifestations (joints, eyes, skin, etc)
- Growth failure/retardation and malnutrition (kids)
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What is the etiology of IBD?
- Unknown
- Genetics play a role
- Luminal flora of the gut
- Smoking:
- increases risk of Crohn's
- decreases risk of ulcerative colitis
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What is the pathophysiology of IBD?
- Microflora in the GI tract inappropriately stimulate the immune system and trigger the inflammatory process
- Eventually T-cells are activated
- This process occurs both inside and outside the GI tract
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What are the risk factors/exacerbating factors for IBD?
- Smoking (Crohn's only)
- Infections (pulmonary or enteric)
- Use of NSAIDs
- Change in diet
- Psychological stress
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What ar the complications of IBD?
- Ulcerative colitis:
- fulminant colitis
- perforation of the colon
- toxic megacolon
- Crohn's:
- abscess formation
- intestinal obstruction
- fistulas
- strictures
- small intestinal bacterial overgrowth (SIBO)
- Others:
- arthrits/osteoporosis
- venothromboembolism (DVT, PE, clots)
- oral lesions (autoimmune mediated)
- anemia
- liver and pancreatic diseases
- eye disease (uveitis)
- erythema nodosum (tender, red bumps, usually on lower legs)
- pyoderma gangrenosum (ulceration of skin, usuall on lower legs)
- colorectal cancer
- toxic megacolon
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What is the non-pharmacologic therapy for IBD?
- Nutrition - maintain a steady diet void of triggers for exacerbation
- Surgery (colectomy) - for pts who fail or intolerant to drug therapy, or with toxic megacolon
- Aggressive fluid replacement
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What are the pharmacotherapies for IBD?
- Cipro + Metronidazole (Crohn's induction)
- 5-ASA and related (induction and maintenance - oral only if Crohn's)
- Oral corticosteroids (induction, except Budesonide for maintenance of mild-moderate Crohn's)
- IV corticosteroids (induction)
- Cyclosporine (Induction)
- Thiopurines (Maintenance)
- Methotrexate (Induction and Maintenance)
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What are the biologic agents used in IBD?
- Infliximab (Induction and Maintenance)
- Adalimumab (Induction and Maintenance of Crohn's)
- Certolizumab pegol (Induction and Maintenance of Crohn's)
- Natalizumab (Induction and Maintenance of Crohn's)
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What is the MOA of Metronidazole and Ciprofloxacin in IBD (Crohn's only)?
- Antibacterial (inhibition of bacterial DNA/RNA; Inhibition of Topo II DNA gyrase)
- Anti-inflammatory
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What are the SE of Metronidazole and Ciprofloxacin?
- NVD
- Disulfiram reaction
- Photosensitivity
- Furry tongue/metallic taste
- Urine discoloration
- Peripheral neuropathy
- Carcinogenic
- Pregnancy cat C
- Tendonitis/tendon rupture
- QT prolongation
- Dysglycemia
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What is the MOA of 5-ASA and related compounds in IBD?
Anti-inflammatory (exact mechanism unknown)
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What are the 5-ASA drugs used in IBD?
- Sulfasalazine
- Mesalamine, 5-ASA
- Olsalazine
- Balsalazide
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What are the SE of Sulfasalazine?
- Yellow/brown urine
- Photosensitivity
- Oligospermia
- NVD
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What are the special considerations for Sulfasalazine?
- Pro-drug converted to 5-ASA by bacteria in the gut
- Avoid in patients with hepatic insufficiency or G6PD
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What are the SE of Mesalamine, 5-ASA?
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What are the special considerations for Mesalamine, 5-ASA?
- Many oral and topical formulations
- Different sites of action
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What are the SE of Olsalazine and Balsalazide?
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What are the special considerations for Olasalazine and Balsalazide?
Pro-drugs converted to 5-ASA by bacteria in the gut
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What are the DI of 5-ASA?
- Thiopurines concurrent use increases risk of myelosuppression
- Warfarin - increases prothrombin time and INR
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Why can budesonide be used for maintenance therapy in IBD, unlike other corticosteroids?
It has high topical activity and a high rate of first-pass metabolism
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Which thiopurine is preferred d/t less hepatotoxicity?
Azathioprine
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Why are thiopurines only used for maintenance of IBD and not induction?
Typically takes several weeks, and up to 6 months, for onset
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Which Calcineurin inhibitor is used in IBD?
Cyclosporine (Induction only)
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