IBD Pathophys and Pharm

Question 1

Review: What gene to people really like to talk about in IBD?

Answer 1

NOD2 - intracellular bacteria sensing and Paneth cell function
(apparently this is more for CD than UC)

Question 2

4 processes involving bacteria that when dysregulated may contribute to IBD?

Answer 2

Pathogenic bacteria
Abnormal microbial composition
Defective host containment of commensals
Defective host immunoregulation

Question 3

What kind of T cells are thought to be involved in UC and CD?

Answer 3

Th17

Question 4

Weird relationship between CD, UC, and smoking?

Answer 4

CD: smoking -> increased risk of CD flare.
UC: smoking may be protective.

Question 5

“Skip lesions” and “cobblestoning” are buzzwords for…

Answer 5

Gross appearance of CD.

Question 6

What does the transmural inflammation of CD often lead to?

Answer 6

Fistulae and strictures.

Question 7

Strictures in CD might be driven by…?

Answer 7

An attempt to heal, mediated by TGF-beta -> fibrosis.

Question 8

Is perianal disease more common in CD or UC?

Answer 8

CD

Question 9

Big picture about extra intestinal manifestations of IBD?

Answer 9

Lots of systems.
Lots of inflammatory things.
Some things are products of impaired absorption?

Question 10

How can IBD contribute to kidney stones?

Answer 10

More oxalate gets absorbed. Secretion in kidneys -> kidney stones.

Question 11

2 derm manifestations related to IBD?

Answer 11

Pyoderma Gangrenosum (purulent, autoimmune skin lesion)
Erythema Nodosum (red, itchy skin rash)

Question 12

What’s primary sclerosing cholangitis? Is it more commonly associated with CD or UC?
Why is it bad?

Answer 12

Inflammation of biliary tree -> stricturing / beading irregularity.
Iincreases risk of colorectal cancer and cholangiocarcinoma.

Question 13

How can you cure UC?

Answer 13

Colectomy (usually not the best option though)

Question 14

4 treatments for mild IBD?

Answer 14

Short-course glucocorticoids..
5-aminosalicylates (5-ASAs) - for UC
Budesonide - for CD
Topical steroids - (hydrocortisone enema).

Question 15

3 types of medical therapies in more severe IBD?

Answer 15

Immunomodulators (thiopurines, methotrexate)
Anti-TNF agents
Anti-alpha4 agents

Question 16

What’s the MoA of aminosalicylates? (4 things)

Is it more useful in CD or UC?

Answer 16

Inhibit T cell prolifeation.
Inhibit Ag presentation.
Inhibit adhesion (of immune cells?)
Decrease TNF production.
Seems to be more useful in UC than CD.

Question 17

2 adverse effects of 5-ASAs?

Answer 17

Paradoxical diarrhea

Interstitial nephritis.

Question 18

Main utility of corticosteroids in IBD?

Answer 18

Induction of remission - they don’t seem to be useful for maintenance.

Question 19

What is budesonide?

Which IBD is it more for?

Answer 19

A glucocorticoid formulation designed to be released in the colon.
Meant for CD.

Question 20

How do azathioprine and 6MP work?

Answer 20

Inhibition of DNA synthesis.

Question 21

Is cyclosporin used for IBD much anymore?

Answer 21

No.

Question 22

Effects of TNF inhibition?

Answer 22

Anti-inflammatory

Apoptosis of T cells and lymphocytes (only if the mAb includes the Fc portion)

Question 23

3 anti-TNF drugs?

Answer 23

Infliximab
Adalimumab
Certolizumab (PEGylated Fab’)

Question 24

What’s one reason antibody-based drugs can stop working?

Answer 24

Patients develop antibodies that neutralize the antibodies.

Question 25

How do anti-alpha4 drugs work? Drug that does this?

Answer 25

Blocking integrins and thus adhesion of leukocytes.

Natalizumab does this.

Question 26

What’s the major adverse effect of anti-alpha4 Abs? How can it be avoided?

Answer 26

Progressive multifocal leukoencephalopathy (PML) - Caused by JC Virus.
Screen people for JCV Abs in serum prior to giving natalizumab.

Question 27

Why are ABx more useful for CD than UC?

Answer 27

ABx help with the complications of transmural inflammation - abscesses, fistulae present in CD.
These don’t happen in UC.

Question 28

What’s the first-line therapy for CD?

Answer 28

Budesonide

Question 29

What’s the first-line therapy for UC?

Answer 29

5-ASAs