Inflammatory Bowel Disease NOTFINISHED

Question 1

What are the two main disease of IBD?

Answer 1

Crohn’s disease

Ulcerative colitis

Question 2

Describe the layers of the GIT that Crohn’s and ulcerative colitis affect.

Answer 2

Crohn’s disease has transmural pathogenesis.

Ulcerative colitis is limited to the mucosa.

Question 3

Which of the two IBD’s holds greater risk of colorectal cancer and primary sclerosing cholangitis?

Answer 3

Ulcerative colitis is more likely to progress to colorectal cancer and PSC than Crohn’s.

Question 4

Describe the anatomical locations that ulcerative colitis and Crohn’s affects.

Answer 4

Ulcerative colitis usually begins in the distal large bowel, and progresses proximally.

Crohn’s can affect any part of the bowel, particularly the terminal ileum.

Question 5

What role do aminosalicylates play in management of IBD?

Give two examples

Answer 5

Main role is to maintain remission in ulcerative colitis

• Sulphasalazine
• Mesalazine

Question 6

What are the adverse effects of aminosalicylates?

Answer 6

Headache, nausea, diarrhoea and epigastric pain.

Severe side effects with sulphasalazine = SJS, pancreatitis

Question 7

How are corticosteroids used in the management of IBD?

Give two examples.

Answer 7

Corticosteroids act as inflammatory agents used for short term therapy in relapses of both UC and Crohn’s

Examples:

• IV hydrocortisone
• PO prenisolone / budesonide

Question 8

What are the short term and long term adverse effects of using corticosteroids?

Answer 8

Short term:

• HTN
• Raised blood sugar

Long term:

• Osteoporosis
• Thinning of skin
• Steroid-induced diabetes mellitus

Question 9

What is the action of thiopurines in management of IBD?

Give an example (Hint: prodrug)

Answer 9

Thiopurines immunosuppress T cells to prevent inappropriate reaction to antigens.

Azathiopurine is a prodrug that is metabolised to form 6-mecaptopurine

• 6 mercaptopurine is metabolised into thioguanine, which has RAC-1 inhibition and causes apoptosis of T-cells

Question 10

What are the adverse effects of azathiopurine?

Answer 10

Since it suppresses T cells, it can cause immunosuppression.

Also: bone marrow failure, hepatotoxicity.

Question 11

What are the enzyme-related risks of azathiopurine

Answer 11

TPMT metabolises 6-mercaptopurine into 6-MMP

If TPMT activity is low, more of the 6-MP is converted into other products, such as 6-thioguanine

• Too much thioguanine = increased risk of myelosuppression and other side effects

Question 12

How are anti-TNF-α agents used in the management of IBD?

Give two examples and the nomenclature rule.

Answer 12

TNF-α regulates immune cells, produced mainly by macrophages. Blocking TNF-α is useful for UC and Crohn’s

Examples

• Inflixmab
• Adalimumab
• Anything that ends in -mab

Question 13

What are the adverse effects of anti-TNF-α agents

Answer 13

• Immune suppression
• Increased rate of malignancy
• Drug induced lupus

Question 14

What do the stems -xi-, -zu- and -u- mean?

Answer 14

• xi- = chimeric
• zu- = humanised
• u- = human

Question 15

What is the action of anti-integrin antibodies?

Give an example (Hint - targets a4b7 integrin)

Answer 15

Integrin-mediated adhesion allows leukocytes to attach to tissues and enter them. Blocking the ability for white cells to enter tissues reduces the inflammation they cause.

Example: Vedolizumab - targets a4b7 integrin

Question 16

What are the actions of anti-IL-12/23 antibodies?

Give an example:

Answer 16

IL-12 promotes TH1 response (intracellular killing)

IL-23 promotes TH17 response (produces IL-17, highly inflammatory cytokine)

Example: Ustekinumab

Question 17

What is the action of JAK inhibitors?

Example:

Answer 17

Janus kinase associated with cytokine receptors, involved in signalling of inflammatory cells.

Example: Tofacitinib

Useful in ulcerative colitis.