PHAR 255 > Inflammatory Bowel Conditions > Flashcards

Inflammatory Bowel Conditions Flashcards

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1
Q

What are the two main inflammatory bowel conditions?

A
  • Ulcerative colitis (UC)
  • Crohn’s disease (CD)
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2
Q

Describe inflammatory bowel disease

A

Idiopathic disease caused by immune response to intestinal microflora (antibodies form against parts of the GI tract)

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3
Q

What are the characteristics of ulcerative colitis?

A

It is a chronic inflammatory condition characterized by episodes of inflammation limited to the mucosal layer of the colon (starts in rectum and spreads proximally)

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4
Q

What are some characteristics of Crohn’s disease?

A

Chronic transmural (affects multiple layers of tissues that form the intestines) inflammation with skip lesions, affecting mouth to perianal area

Starts from proximal colon and spreads to the rest of the GI tract

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5
Q

Review slide 7 for comparison between Crohn’s disease and ulcerative colitis

A
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6
Q

What is the pathophysiology of inflammatory bowel conditions?

A
  • Immune system develops antibodies to intestinal normal flora and food antigens, inflammatory mediators are also involved
  • Initial trigger is often unknown
  • Genetic influence
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7
Q

What are some risk factors for inflammatory bowel disease?

A
  • Age (15-40 year olds, regardless of sex)
  • Genetic influence
  • Smoking (protective against ulcerative colitis due to nicotine’s anti-inflammatory effects)
  • Poor diet (processed food, high in saturated fat, sugar. Omega-3 can be beneficial due to anti-inflammatory effect)
  • Sedentary lifestyle (elevated risk)
  • Obesity (pro-inflammatory state that can trigger UC/Crohn’s disease)
  • Stress
    -Drugs (Antibiotics, NSAIDs)
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8
Q

What type of inflammatory bowel disease has the highest mortality rates?

A

1.4-5x higher mortality rates for CD vs. ulcerative colitis

CD increases risk for GI bleeds, obstrcuction, and cancer

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9
Q

What is the malignancy rate for CD?

A

7.6% at 30 years after diagnosis

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10
Q

What inflammatory bowel disease complication do most patients fear after diagnosis?

A

Colectomy

Only a single-digit percentage of patients need an ostomy bag (can calm down some patients)

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11
Q

What are some chronic symptoms asssociated with inflammatory bowel disease?

A
  • Abdominal pain
  • Diarrhea
  • Constipation
  • Mucousy stool (excess)
  • Bloody stool (if UC and closer to rectum then red streaks, if CD then more proximal and dark tarry stool
  • Weight loss
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12
Q

What are some flare symptoms associated with inflammatory bowel disease?

A
  • Fever
  • Sweats
  • Malaise
  • Arthralgia
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13
Q

Review slide 16 for a detailed severity classification for UC and CD

A
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14
Q

How are inflammatory bowel diseases diagnosed?

A
  • Physical exam
  • Lab exam (stool (blood or C. Diff) and blood testing (CRP or ESR))
  • Imaging and endoscopy (gold standard)
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15
Q

What are some things that should be monitored in inflammatory bowel disease?

A
  • Hemoglobin
  • Iron indices
  • Nutritional status
  • Growth
  • BMD (if using chronic corticosteroid for IBD)
  • Colonoscopy (within 8 years of onset and screen every 1-2 years if negative results)
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16
Q

What are the goals of treatment for inflammatory bowel disease?

A
  • Recognize disease early
  • Induce and sustain remission with least toxic therapy
  • Avoid complications
  • Maintain current daily life
  • Provide secondary care of symptoms
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17
Q

What are some non-pharm treatments for inflammatory bowel disease?

A
  • Bulk fiber to reduce diarrhea
  • Reduce fat intake (except Omega 3, has anti-inflammatory effect)
  • Elimination diet
  • Multivitamins to help prevent malnutrition (usually need more iron)
  • Probiotics (do not use alone)
  • Smoking cessation
  • Exercise
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18
Q

What are some principles of therapy for inflammatory bowel disease?

A
  • Induce remission of acute episode
  • Maintain remission
  • Minimize use of steroids
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19
Q

What is the definition of remission for inflammatory bowel disease?

A
  • Symptom free
  • No inflammatory consequences
  • Not steroid dependent
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20
Q

What is the role of corticosteroids in inflammatory bowel disease?

A
  • Highly effective agents for inducing remission
  • Orally for UC/CD
  • Topical foams and enemas in UC (because UC usually affects rectum, so more accessible)
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21
Q

What are some indications for corticosteroid use in ulcerative colitis?

A
  • Topical for mild-moderate ulcerative colitis
  • Oral for moderate-severe ulcerative colitis
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22
Q

What are some indications for corticosteroid use in Crohn’s Disease?

A

They are one of the few drugs used to acheive remisssion in CD

  • Oral for mild-severe Crohn’s disease induction
  • Budesonide can be used for short-term maintenance as well (less than 3 months)
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23
Q

How are corticosteroids dosed in inflammatory bowel diseases?

A

Prednisone 40-60mg daily (PO)

Budesonide (little systemic absorption (5%), runs through GI tract and released at a specific location in GI tract)

Hydrocortisone 10% enemas/foams QHS

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24
Q

What are some corticosteroid administration tips for inflammatory bowel disease?

A
  • Prednisone with food
  • Topicals (lie on left side)
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25
Should corticosteroids be used for maintenance therapy in inflammatory bowel disease?
No, corticosteroids should be bridged over to a more optimal maintenance therapy. Tapering is beneficial in preventing withdrawal Prednisone (max use for 4 weeks) Budesonide (max use for 8 weeks)
26
What are some common side effects associated with corticosteroids?
- GI intolerance - Appetite increase - Nervousness/anxiety - Insomnia - Tremors/heart palpitations
27
What are some serious side effects associated with corticosteroids?
- Cushingoid features - Blood glucose increase - Psychiatric side-effects - GI bleeds - Cataracts - Osteoporosis - Electrolyte imbalances
28
What are some monitoring tips for corticosteroid therapy?
- Annual eye exam - Blood glucose - CBC - Electrolytes - BMD
29
What are some drug interactions associated with corticosteroids?
- AChE-Inhibitors: steroids increase toxicity - Antacids (decrease absorption of steroids) - Diabetic meds: prednisone opposes effect - 3A4 induces/inhibitors (decrease/increases steroid) - Diuretics (more hypokalemia) - NSAIDs (mmore GI upset or ulceration risk) - Vaccines (steroids diminish efficacy) - Warfarin (steroids increase INR)
30
What is the clinical evidence for corticosteroid use in inflammatory bowel disease?
- Monotherapy to induce remission at first presentation of the disease - 60-80% of patients respond within 10-14 days (hopefully taper off within the next few years)
31
What are the most common used drug class in ulcerative colitis?
Aminosalicylates (5-ASA, SSZ, Olsalazine)
32
What is the most commonly used aminosalicylate in treatment of inflammatory bowel disease?
5-ASA (Mesalamine) is the most common aminosalicylate in UC treatment, not effective in CD
33
What is the main maintenance therapeutic agent in ulcerative colitis?
5-ASA
34
What are some contraindications for aminosalicylates?
- Hypersensitivity to salicylates - Hypersensitivity to sulfonamides (SSZ only) - Severe renal impairment (eGFR greater than 30) - Severe hepatic impairment - Existing gastric or duodenal ulcer
35
What is the mechanism of action for 5-ASA?
5-ASA controls inflammation by inhibiting COX pathways and blocks prostaglandins/leukotriene production in the colon SSZ is converted into 5-ASA in the colon
36
Review slides 38 to 39 for aminosalicylates
37
What are some qualities of aminosalicylate suppositories?
- Suppositories only reach rectum (not useful if UC extends proximally) - Enemas extend into distal colon - **Must be able to retain enema contents for at least 30 minutes** - Equal or more effective than oral agents - Better tolerated (results in lower healthcare costs) - Less dosing frequency
38
What are some common side effects associated with aminosalicylates?
- GI (NVD, pain) - Headache - Rash - Arthralgia - Urine discolouration
39
How can aminosalicylate GI effects be managed?
- Take with food - Consider an enteric-coated product - Restart at lower dose and slowly titrate - Divide dose BID-QID instead of once daily
40
What are some serious side effects associated with aminosalicylates?
- Hemotologic abnormalities (inc. thrombocytopenia) - Hepatoxicity - Photosensitivity (SSZ) - Bone marrow toxicity (SSZ)
41
What are some monitoring parameters associated with aminosalicylates?
- CBC - Renal function - Liver function
42
What are the characteristics of SSZ in treatment of UC?
Slightly more effective in induction and maintanence (more ADRs though vs. 5-ASA)
43
Are aminosalicylates useful in the treatment of CD?
No, corticosteroids are much more effective in managing CD
44
Review slide 47 for location of action for different aminosalicylate formulations
45
What is the role of immune modifiers in inflammatory bowel disease?
They are used when more conventional treatments (aminosalicylates and corticosteroids) are not effective
46
What are some examples of immune modifiers used to treat inflammatory bowel disease?
Immunosuppressants (**azathioprine, mercaptopurine**, methotrexate subcut) Biologics (TNF-inhibitors, integrin receptor blocker, interleukin inhinitors) Reserved for severe or unresponsive disease (can be steroid sparing)
47
What are some indications for immune modifiers for inflammatory bowel disease?
- 2 or more courses of steroids used in 12 months or more than 12 weeks of use per year - Relapse during steroid taper - Relapse within 6 months of stopping steroids - Non-response to steroids or 5-ASA - Frequent flares - Used earlier in course of CD vs. UC
48
How are immune modifiers for inflammatory bowel diseases administered?
Mercaptopurine/Azathioprine (oral dosing, once daily) Biologics (injected subcut)
49
What is the onset of action for immune modifiers in inflammatory bowel disease?
Mercaptopurine/Azathioprine (3-6 months) Most biologics (2-8 weeks) Vedolizumab (18-20 weeks, it is gut-selective in its immunosupression, reduced infections)
50
What is the duration of therapy for immune modifiers in inflammatory bowel disease?
Generally life-long (because patient has more severe form of IBD) Likely not possible to de-escalate therapy in most patients
51
What are some common side effects associated with mercaptopurine/azathioprine?
- Flu-like symptoms - GI symptoms
52
What are some common side effects associated with biologics in inflammatory bowel disease?
- Infection rate increase - Infusion reactions - Nausea - Headache - Malaise
53
What are some serious side effects associated with mercaptopurine/azathioprine in inflammatory bowel disease?
- Myelosuppression (2-5%) - Hepatoxicity (2%) - Infection increase (not to the same increase as methotrexate or the biologics products)
54
What are some serious side effects associated with TNF-inhibitors in inflammatory bowel disease?
- Reactivation of latent TB, Hep B/C, serious infections - Neutropenia - Malignancy increase - Antibody development (40% of patients become non-responders) - Hepatoxicity - HF - Autoimmune disease activation - Seizure risk
55
What are some serious side effects associated with Vedolizumab?
- Antibody development - Serious infection rates increase - Latent infection concern
56
Review slide 59 for monitoring tips for immune modifiers
57
What are some drug interactions with mercaptopurine/azathioprine?
Allopurinol and febuxostat (significantly increased risk of toxicity) Aminosalicylates (increased levels of Aza/mercapto.)
58
What are some drug interactions associated with biologics?
- Live vaccines - Other immunosuppressants
59
What biologics class is preferred in IBD treatment?
TNF-inhibitors are generally first line (inflixamab IV may have a slight advantage over others in the class) Vedolizumab is gut selective, but has slow onset of effect
60
Is maintenance therapy for ulcerative colitis recomended?
Yes, always provide maintenance (it follows frequent relapse/remissions schedules)
61
Is maintenance therapy for Crohn's disease recomended?
More difficult because higher dose corticosteroid is the only real treatment option Just treat flares (1-2 per year), consider maintenance if more than 2 flares/year
62
How are fistulas managed in inflammatory bowel disease?
Metronidazole +/- ciprofloxacin used for 2 weeks to prevent septic complications
63
What is the role of JAK inhibitors in inflammatory bowel disease?
Recently indicated for IBD (last line option after other biologics have been used unsuccessfully)
64
What are some secondary medications used in inflammatory bowel disease to manage side effects?
- Anti-diarrheals (loperamide preferred, can also use psyllium or methycellulose) - Pain medications (avoid NSAIDs and opiates, usually use TCAs or Buscopan) - Immunization (given before patient is immunosuppressed) - Anti-depressants/anxiety (TCAs preferred due to dual effect) - Nutrition
65
Review slide 77 for RxFiles guide to treating Ulcerative Colitis
66
Review slide 78 for RxFiles guide to treating Crohn's Disease
67
Review slides 68 to 76 for guidelines on IBD treatment
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