1
Q
What 2 parts make up the distal colon?
A
The descending and sigmoid
2
Q
What 2 parts make up the proximal colon?
A
The ascending and transverse colon
3
Q
What is ulcerative colitis (UC)?
A
Chronic inflammatory condition characterized by episodes of inflammation limited to the mucosal layer of the colon
4
Q
What is Crohn’s disease (CD)?
A
Chronic transmural inflammation with skip lesions, affecting mouth to perianal area.
5
Q
CD vs UC:
Skip areas
A
CD = common
UC = never
6
Q
CD vs UC:
Transmural involvement
A
CD = common
UC = occasional
7
Q
CD vs UC:
Rectal sparing
A
CD = common
UC = never
8
Q
CD vs UC:
Perianal involvement
A
CD = rare
UC = never
9
Q
CD vs UC:
Fistulas
A
CD = common
UC = never
10
Q
CD vs UC:
Strictures
A
CD = common
UC = never
11
Q
CD vs UC:
Granulomas
A
CD = common
UC = occasional
12
Q
What is the pathophysiology of IBD? (3)
A
- Initial trigger unknown
- Genetic influence
- Immune system creates antibodies to intestinal normal flora and food antigens; inflammatory mediators also involved
13
Q
UC begins in ______, while CD begins _______
A
rectum; anywhere
14
Q
What are 9 risk factors for IBD?
A
- Age and gender - 15-40, male = female
- Race and ethnicity - no direct link
- Genetic influence
- Smoking
- Poor diet
- Sedentary lifestyle
- Obesity
- Stress
- Medications
15
Q
What are 4 medication groups that are potentially risk factors for IBD? (2 big ones + 2 on the fence)
A
- Antibiotics
- NSAIDs
- Oral contraceptives - maybe?
- Isotretinoin - likely not
16
Q
In CD, mortality rates are x.y-z times higher
A
1.4-5
17
Q
What are the 2 most common causes of death in CD?
A
- Primary disease is the common cause of death
- Secondary infection is other leading cause
18
Q
In terms of frequent relapse, between CD and UC, which is more prone to it?
A
UC > CD
19
Q
In terms of lower quality of life, between UC and CD, which is worse?
A
CD > UC
20
Q
What are some other complications associated with IBD prognosis? (10, know the top one for sure)
A
- Colectomy*
- Osteoporosis
- Hypercoagulability –> VTE
- Anemia
- Gallstones
- Bladder/kidney stones
- Ulcers
- Uveitis
- Arthritis
- Malnutrition and electrolyte imbalance
21
Q
What are the symptoms of IBD? (10 - know top 2)
A
- Abdominal pain
- Diarrhea
- Constipation
- Mucousy stool
- Bloody stool
- Weight loss
- Fever
- Sweats
- Malaise
- Arthralgia
22
Q
How is mild UC classified? (3)
A
- +1-2 stools/day over baseline
- May be streaks of blood in stool (~50% of the time)
- No systemic involvement
23
Q
How is mild CD classified? (4)
A
- Can tolerate oral intake
- No dehydration
- Some abdominal pain/tenderness
- <10% weight loss
24
Q
How is moderate UC classified? (3)
A
- +3-4 stools/day over baseline
- Blood in stool most of the time
- Minimal systemic involvement
25
How is moderate CD classified? (6)
1. Unresponsive to treatment
2. Continuous fever
3. NVD
4. >10% weight loss
5. Anemia
6. Dehydration
26
How is severe UC classified? (3)
1. +5 stools/day over baseline
2. Blood alone passed
3. Systemic toxicity begins (fever, anemia, tachycardia)
27
How is severe CD classified? (4)
1. Symptoms persist despite steroid use
2. Obstruction
3. Persistent vomiting
4. High fever
28
How is fulminant UC classified? (3)
1. >6 stools/day over baseline
2. Systemic toxicity
3. Blood transfusion needed
29
What are the 3 diagnosis methods for IBD?
1. Physical exam
2. Lab exam
- Stool testing
- Blood tests
3. Imaging and endoscopy*
30
What should be monitored in IBD? (6)
1. Hemoglobin
2. Iron indices
3. Nutritional status
4. Growth
5. BMD if increased osteoporosis risk
6. Colonoscopy
- Within 8 years of onset
- Screen q1-3 years if 2 negative results
31
What are the goals of treatment for IBD? (5)
1. Recognize disease early
2. Induce and sustain remission with least toxic therapy
3. Avoid complications
4. Maintain current daily life
5. Provide secondary care of symptoms
32
The two main treatment groups for IBD are? (2+3)
1. Non-pharmacological treatments
2. Medications
- Corticosteroids
- Aminosalicylates (5-ASA)
- Immune modifiers --> Azathioprine/Mercaptoprine and Biologics
33
What are the 4 main non-pharm treatments for IBD?
1. Dietary
2. Probiotics
3. Smoking cessation
4. Exercise
34
What dietary counseling should be done regarding IBD? (4)
1. Bulk fiber to reduce diarrhea
2. Reduce fat intake (except Omega 3)
3. Consider trigger foods - "elimination diet"
4. Prevent malnutrition
- Calcium
- Fat soluble vitamins
- Zinc and magnesium
- Iron
- B12/folic acid
35
Probiotics in IBD. Yay or nay? (3+3)
1. Evidence lacking/conflicting (most data for UC)
2. Looks promising; very safe
3. Possible benefit:
- Induce remission
- Maintain remission
- Reduce diarrhea
Yay - just don't use in exclusion of other options
36
What is there to note about smoking cessation in CD and UC?
1. Definite improvement in CD and relapse rates
2. Possible risk increase in UC
37
What are the benefits of exercise in IBD? (2)
1. 50% RRR in reduction of flares
2. Likely reduces incidence as well
38
What are the principles of drug therapy in IBD? (3)
1. Induce remission of acute episodes
2. Maintain remission
3. Minimize steroid use
39
What is the definition of IBD remission? (3)
1. Symptom free; and,
2. No inflammatory consequences; and,
3. Not steroid-dependent
40
Corticosteroids are highly effective agents for inducing remission of IBD. What are the 2 formulations used?
1. Orally for UC/CD
2. Topical foams and enemas in UC - important option
41
What are the indications for corticosteroids in UC? (2)
1. Topical: Mild-moderate UC induction
2. Oral: Moderate-severe UC induction
42
What are the indications for corticosteroids in CD? (2)
1. Oral: Mild to severe CD induction
2. Budesonide can be used for short-term maintenance as well (< 3 months)
43
What is the dosing of prednisone in IBD induction?
40-60mg daily
44
Budesonide has 3 dosage forms for IBD. When are Entocort capsules used and what is the dosing?
Ileal/ascending colon - CD ONLY - 9mg daily
45
Budesonide has 3 dosage forms for IBD. When is Entocort enema used and what is the dosing?
Distal - UC ONLY - 2mg qHS
46
Budesonide has 3 dosage forms for IBD. When are Cortiment tablets used and what is the dosing?
UC ONLY - 9mg daily
47
True or False? Prednisone should be taken on an empty stomach
False - take with food
48
How should topical corticosteroids be administered?
Lie on left side. Retain contents for as long as possible
49
With corticosteroids, how long until there is symptom improvement?
How long until patient sees remission?
1. Symptom improvement as early as 2-3 days
2. Average 2-4 weeks to see remission
50
What is the duration of therapy for corticosteroids when being used for IBD induction?
What is the max length for prednisone?
What is the max length for budesonide oral or topical?
1. Use until remission
2. Prednisone ~4 weeks max recommended
3. Budesonide oral or topical ~8 weeks max
51
Corticosteroid taper is recommended mainly due to relapse with abrupt discontinuation. How should budesonide (oral) be tapered?
How should budesonide enema be tapered?
1. Taper budesonide 9-6-3-0 over 4 weeks
2. Likely no need to taper budesonide enema
52
When might we switch from prednisone to budesonide?
What should be considered in this situation (3)?
1. Done to reduce ADRs, HPA-axis suppression or reduce disease recurrence
2. Max dose of 6mg budesonide in this situation
3. Prednisone still needs to be tapered
4. Strongly consider also tapering budesonide when therapy complete
53
What are the common side effects of (oral) corticosteroids? (5)
1. GI intolerance
2. Appetite increase
3. Nervousness/anxiety
4. Insomnia
5. Tremors/heart palpitations
54
What are the serious side effects (long-term exposure) of (oral) corticosteroids? (7)
1. Cushingoid features
2. Blood glucose increase
3. Psychiatric side-effects
4. GI bleeds
5. Cataracts
6. Osteoporosis
7. Electrolyte imbalances
55
What are some things that should be monitored when on (oral) corticosteroids? (5)
1. Annual eye exam
2. Blood glucose
3. CBC
4. Electrolytes
5. BMD
56
Terry Tip: If systemic toxicity or drug interactions are a concern when using oral corticosteroids, what should be considered?
Consider budesonide or topicals if possible
57
What are some possible DIs seen with oral corticosteroids? (9 - know 4 or 5 perhaps)
1. AChE-Inhibitors
2. Antacids
3. Diabetic meds
4. 3A4 inducers/inhibitors
5. Fluroquinolones
6. Diuretics
7. NSAIDs
8. Vaccines
9. Warfarin
58
Can corticosteroids be used for maintenance therapy of IBD?
No - only to induce remission at first presentation of disease
59
What are the 3 aminosalicylate medications?
1. 5-ASA (Mesalamine - many forms)
2. Sulfasalazine (SSZ)
3. Olsalazine
60
The most commonly used agents in UC are?
Aminosalicylates
61
Aminosalicylates in CD. Yay or nay?
Nay - questionable efficacy; ineffective for maintenance
62
Aminosalicylates can be used for both induction and maintenace of UC and CD. What are the indications for induction? (3)
1. 5-ASA (oral +/- topical) therapy for mild UC
2. 5-ASA + prednisone for moderate and severe UC
3. SSZ for induction of mild-moderate CD
63
Aminosalicylates can be used for both induction and maintenance of UC. What is the indication for maintenance?
5-ASA (oral +/- topical) for maintenance of remission for mild-moderate UC
64
What are the CIs of aminosalicylates? (5)
1. Hypersensitivity to salicylates
2. Hypersensitivity to sulfonamides (SSZ only)
3. Severe renal impairment (eGFR <30)
4. Severe hepatic impairment
5. Existing gastric or duodenal ulcer
65
What is the MOA of 5-ASA?
How about SSZ?
1. 5-ASA controls inflammation by inhibiting COX pathways and blocks prostaglandin/leukotriene production in the colon
2. SSZ is converted into 5-ASA in the colon (where it does the same thing as the first point)
66
You don't need to know the doses of the aminosalicylates, but you should know how the dose differs between induction and maintenance
1. When using for induction - high dose
2. When using for maintenance - lower the dose to minimize side effects
67
Should know the brand name of the only aminosalicylate that is used once daily
Mezavant
68
What is the difference between suppositories and enemas?
Efficacy?
Tolerance?
How are aminosalicylate suppositories or enemas administered? (6 total points)
1. Suppositories reach rectum only
2. Enemas extend into distal colon
3. Equal or more effective than oral agents
4. Better tolerated
5. Less dosing frequency, lower cost
6. Must be able to retain enema contents for >30 minutes
69
How long on aminosalicylates until patient achieves remission?
2-4 weeks
70
What are the common side effects of oral aminosalicylates? (5)
What about SSZ specifics (2)?
1. GI (NVD, pain) - 20-30%
2. Headache - 14%
3. Rash
4. Arthralgia
5. Urine discoloration
SSZ Only:
1. Higher rates of above
2. Oligospermia - 33%, reversible
71
What are the serious side effects of oral aminosalicylates? (4, 2 are SSZ specific)
1. Hematologic abnormalities (inc. thrombocytopenia)
2. Hepatotoxicity
3. Photosensitivity (SSZ)
4. Bone marrow toxicity (SSZ)
72
What 3 things should be monitored when on sulfasalazine?
1. CBC
2. Renal function
3. Liver function
73
What are the DIs seen with 5-ASA? (3)
1. Antacids, PPIs, H2RAs
2. Digoxin decreased
3. Azathioprine/mercaptopurine toxicity increased
74
What are the DIs seen with SSZ? (4)
Same as 5-ASA, that is:
1. Antacids, PPIs, H2RAs
2. Digoxin decreased
3. Azathioprine/mercaptopurine toxicity increased; plus,
4. Phenytoin increased
75
What is the efficacy of aminosalicylates in UC? (5)
1. Induction achieved in 50% of patients
2. Maintains remission in 59% vs. 42% placebo
3. SSZ slightly more effective in induction and maintenance
4. All different formulations of oral 5-ASA are equal
5. Combining both oral and topical 5-ASA is superior to either agent alone
76
What is the efficacy of aminosalicylates in CD? (3)
1. SSZ inferior to corticosteroids for induction
2. SSZ superior to placebo for induction
3. Other 5-ASA preps: not superior to placebo for induction or maintenance
77
What are the immune modifier medication groups that may be used in IBD? (2)
1. Immunosuppressants
2. Biologics
78
When are the immune modifier medications used?
What is the key benefit?
1. Reserved for severe or unresponsive disease
2. Key benefit = steroid sparing
79
What are the immunosuppressant medications used in IBD? (2)
1. Azathioprine
2. Mercaptopurine
80
What are the TNF-inhibitors used in IBD? [ACE Got Incinerated, minus the E :( ]
1. Adalimumab
2. Certolizumab
3. Golimumab
4. Infliximab
81
What is the integrin receptor blocker medication used in IBD?
Vedolizumab
82
What is the interleukin-12 and 23 inhibitor medication used in IBD?
Ustekinumab
83
What are the indications for using immune modifiers in IBD? (6)
1. 2 or more courses of steroids used in 12 months; or >12 weeks of use per year
2. Relapse during steroid taper
3. Relapse within 6 months of stopping steroids
4. Non-response to steroids or 5-ASA
5. Frequent flares
6. Used earlier in course of CD vs. UC
84
Biologics specifically are indicated when in IBD?
For induction in moderate to severe UC or CD
85
Azathioprine/Mercaptopurine is specifically indicated when in IBD?
As part of induction regimen in CD, but not as monotherapy
86
What is the MOA of azathioprine/mercaptopurine?
Purine antagonists --> immune suppression
87
What is the MOA of vedolizumab?
Integrin receptor blocker
88
What is the MOA of ustekinumab?
Inhibits IL-12 and 23, disrupts T-lymphocytes
89
Azathioprine/Mercaptopurine both have ______-_____ dosing
weight-based
90
For the immune modifiers, there is no need to memorize the numbers, but what should you know about the dosing regimens?
Only need to know that for most of them, there are different protocols for UC and CD induction and maintenance therapies.
91
How should immune modifiers be titrated?
50mg, increase 25mg Q1-2 weeks
92
True or False? Both Azathioprine/Mercaptopurine need renal dosage adjustment
True:
Azathioprine - 10-50mL/min = 75% of lower end of target dose
Mercaptopurine - <50mL/min = use lower end of target dose
93
What is the route of administration and how often is Azathioprine/Mercaptopurine dosed?
Orally, once daily
94
What is the route of administration and how often is ustekinumab dosed?
SQ Q8W
95
What is the route of administration and how often is vedolizumab dosed?
IV infusion over 30 min for four initial doses, then SQ Q2W
96
How long is onset of Azathioprine/Mercaptopurine?
3-6 months
97
How long is onset of most biologics?
How about vedolizumab?
Most biologics = 2-8 weeks
Vedolizumab = 18-20 weeks
98
How long is duration of therapy for the immune modifiers?
Generally life-long
99
Common side effects of azathioprine/mercaptopurine are: (2)
1. Flu-like symptoms
2. GI symptoms
100
Common side effects of biologics are: (5)
1. Infection rate increase
2. Infusion reactions
3. Nausea
4. Headache
5. Malaise
101
What are the serious side effects of azathioprine/mercaptopurine? (3)
1. Myleosuppression (2-5%)
2. Hepatotoxicity (2%)
3. Infection increase
102
What are the serious side effects of TNF-inhibitors? (8)
1. Reactivation of latent TB, Hep B/C, serious infections
2. Neutropenia
3. Malignancy increase (non-melanoma skin cancer, lymphoma)
4. Antibody development
5. Hepatotoxicity
6. Heart failure
7. Autoimmune disease activation
8. Seizure risk
103
What are the serious side effects of vedolizumab/ustekinumab? (3)
1. Antibody development
2. Serious infection rates increase
- Vedolizumab may have less infection risk - gut selective
3. Latent infection concern
104
What should be monitored when on azathioprine/mercaptopurine? (3)
1. CBC baseline, every other week while titrating, then Q3M
2. LFTs baseline
3. Renal function
105
What should be monitored when on TNF-inhibitors/Vedolizumab/Ustekinumab? (4)
1. Baseline TB test and symptoms of bacterial or fungal infection
2. Hep B/C screening
3. Baseline and Q8-12 weeks: CrCl/urinalysis, CBCs, LFTs
4. Signs of infection
106
What are 3 DIs seen with azathioprine/mercaptopurine?
1. Allopurinol and febuxostat: significantly increased risk of toxicity with Aza/6MP
2. Aminosalicylates: increases levels of Aza/6MP
3. Live vaccines
107
What are the 2 DIs seen with biologics?
1. Live vaccines
2. Other immunosuppressants
108
Generally, which group of biologics is first-line for IBD?
TNF-inhibitors
109
Is maintenance therapy always indicated? (1 for UC, 1 for CD)
UC - always provide maintenance
CD
- For mild disease, may not need
- Consider if 2 or more exacerbations per year
110
When is combo therapy appropriate in UC? (More accurately, what are the combo therapies?) (4)
1. Corticosteroid (topical or oral) + SSZ or 5-ASA for induction has higher induction rates
2. 5-ASA oral + 5-ASA enemas improve induction rates
3. Biologics + ASA = improved induction/maintenance
4. Notably: little evidence for 5-ASA + immune modifiers
111
When is combo therapy appropriate in CD? (More accurately, what are the combo therapies?) (3)
1. Prednisone + SSZ possibly better for induction vs. monotherapy
2. Prednisone + Aza to speed time to induction
3. Biologics + Aza or 6MP = improved induction/maintenance rates, more steroid sparing, less antibody formation, but increased toxicity
112
How are IBD fistulas managed? (4)
1. Metronidazole +/- ciprofloxacin used to prevent septic complications of Crohn's
2. Often used if perianal fistulas or abscesses develop
3. Limited benefit during active disease
4. Combo used for 2 weeks
113
Last line options for IBD include: (3)
Il-23 inhibitors
- Mirikizumab
- Risankizumab
Janus Kinase Inhibitors
114
What are some secondary medications to be considered for IBD? (5)
1. Anti-diarrheals
2. Pain medications
3. Immunization
4. Anti-depressants/anxiety
5. Nutrition
115
When might anti-diarrheals be used in IBD?
Which agent preferred?
What does frequent use indicate?
1. May be used if mild diarrhea without systemic toxicity
2. Loperamide preferred
3. Frequent use indicates uncontrolled disease
116
When might pain medications be used in IBD?
What are the commonly used agents?
Which ones should be avoided?
1. May treat if no signs of systemic toxicity
2. Buscopan (hyoscine butylbromide) and Dicetel (pinaverium) commonly used
3. Avoid NSAIDs and opiates
117
Which anti-depressant class is preferred to use in IBD? Why?
1. TCAs
2. Seem to lower relapse rates, improve QoL, and reduce steroid use
