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Flashcards in Inflammatory Bowel Disease Deck (35)
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1

What are the two main diseases that come under Inflammatory Bowel Disease?

Ulcerative Colitis
Crohn’s Disease

2

What is the underlying pathogenesis of IBD diseases based on?

It boils down to a defective interaction between the mucosal immune system and gut flora- an autoimmune condition

3

What type of IBD is obesity a risk factor for?

Crohn’s Disease

4

Which T cell responses are involved in:
a. Ulcerative Colitis
b. Crohn's Disease

a. Ulcerative Colitis
Th2
b. Crohn's Disease
Th1

5

What are the main cytokines in:
a. Ulcerative Colitis
b. Crohn's Disease

a. Ulcerative Colitis
IL-5
IL-13
b. Crohn's Disease
TNF-alpha

6

Which layers of the gut are affected in:
a. Ulcerative Colitis
b. Crohn's Disease

a. Ulcerative Colitis
Mucosa + Submucosa
b. Crohn’s Disease
All Layers

7

Describe which regions of the gut are affected in:
a. Ulcerative Colitis
b. Crohn's Disease

a. Ulcerative Colitis
Starts at the rectum and proceeds proximally (continuous inflammation)
b. Crohn’s Disease
Can be anywhere on the GI tract (mouth to anus)
Patchy inflammation

8

Are abscesses, fissures and fistulae common in:
a. Ulcerative Colitis
b. Crohn's Disease

a. Ulcerative Colitis
No
b. Crohn’s Disease
Yes

9

Describe the effectiveness of surgery in:
a. Ulcerative
b. Crohn's Disease

a. Ulcerative Colitis
Curative
b. Crohn’s Disease
Not always curative, even if the affected area is cut out, it often reoccurs

10

Describe some supportive therapies that are given for IBD

Nutritional therapy
Fluid/electrolytes
Potentially even blood transfusions/oral iron

11

What are the three types of classic symptomatic treatment for IBD?

Aminosalicylates
Glucocorticoids
Immunosuppressants

12

What is the main aminosalicylate drug?

Mesalazine
AKA 5-aminosalicylic acid (5-ASA)

13

What is a slightly more complex aminosalicylate?

Olsalazine (this is 2 x 5-ASA)

14

What type of drug are aminosalicylates?

Anti-inflammatory

15

Describe the mechanism of anti-inflammatory action of aminosalicylates.

They inhibit IL-1, TNF-alpha and PAF
Decrease antibody secretion
Reduced cell migration (macrophages)
Localised inhibition of immune responses

16

Describe the activation of aminosalicylates.

Mesalazine does not have to be activated any further
Olsalazine must be activated by colonic flora

17

Describe the effectiveness of aminosalicylates in Ulcerative Colitis and Crohn’s Disease.

They are effective at inducing and maintaining remission in UC
They are better than steroids at inducing remission in UC
They are less effective in CD

18

Describe the use of glucocorticoids in IBD.

Use of glucocorticoids in UC is in decline because aminosalicylates are better
Glucocorticoids are still the drug of choice for inducing remission in CD
However, side effects are likely if they are used to maintain remission

19

What is an example of a glucocorticoid that has relatively few side effects?

Budesonide as tends to remain in gut

20

Describe the effectiveness of budesonide compared to other glucocorticoids.

Budesonide has fewer side effects than other glucocorticoids but it is less effective at inducing remission in CD

21

State three immunosuppressive agents that could be used in IBD.

Azathioprine
Methotrexate
Cyclosporin – only useful in severe UC

22

Describe the onset of action of azathioprine.

Slow onset – can take 3-4 months

23

Describe the activation of azathioprine.

Azathioprine needs to be metabolised by gut flora to 6-mercaptopurine

24

Describe the mechanism of action of azathioprine.

6-mercaptopurine is a purine antagonist
It interfered with DNA synthesis and cell replication
It impairs:
 Cell- and antibody-mediated immune responses
 Lymphocyte proliferation
 Mononuclear cell infiltration
 Synthesis of antibodies
It enhances:
 T cell apoptosis

25

What are the unwanted effects of azathioprine?

Nearly 10% of patients stop treatment because of the side effects
Pancreatitis
Bone marrow suppression
Hepatotoxicity
Increased risk (4 fold) of lymphoma and skin cancer

26

What is the mechanism of action of Methotrexate?

Folate antagonist
It reduces the production of thymidine and other purines
NOTE: not widely used because of significant side effects

27

What are the three potential mechanisms of manipulating the gut microbiome?

Nutrition based therapies – probiotics could be useful in UC
Faecal Microbiota Replacement Therapy (FMT) – could be useful in UC
Antibiotics – Rifaximin
 Interferes with bacterial transcription by binding to RNA polymerase
 Induces and sustains remission in moderate CD
 Potentially beneficial in UC

28

Give 2 examples of anti-TNF-alpha antibodies.

Infliximab (IV)
Adalimumab (SC)

29

Describe the effectiveness of anti-TNF- antibodies in Crohn’s Disease.

60% of patients will respond within 6 weeks are it is potentially curative

30

Describe the mechanism of action of anti-TNF-alpha antibodies.

Knocking out TNF-alpha leads to general downregulation of other inflammatory cytokines downstream
Induced cytolysis of cells expressing TNF-alpha
Promotes apoptosis of activated T cells