IBD Pathophysiology and Pharmacology

Question 1

UC/Crohn’s difference in epi

Answer 1

UC has smaller peak in elderly peopulation, but have similar geographic, gender proprtions

Question 2

To what degree does Crohn’s run in families?

Answer 2

15x increased risk for family members, monozygotic twins = 67% concordance (but 5-15% in US twins)

Question 3

What is the main gene implicated in IBD?

Answer 3

NOD2

Question 4

Which GWAS pathways appear involved in both UC and CD?

Answer 4

IL23 and IL12 –> involved in Th17 cells

Question 5

Will IBD develop in a germ-free environment?

Answer 5

no –> need bacteria

Question 6

Most common locations of CD

Answer 6

ileum and colon –> lots of bacteria

Question 7

Th17 cells are activated by….

Answer 7

IL6, 21,23 and TGFbeta

Question 8

What Ig is secreted in UC?

Answer 8

IgG1 and IgG3

Question 9

What Ig is secreted in CD?

Answer 9

IgG2

Question 10

Does smoking increase risk of CD?

Answer 10

yes

Question 11

Does smoking increase risk of UC?

Answer 11

protective

Question 12

primary sclerosing cholangitis is more common in UC or CD?

Answer 12

UC –> chronic inflammation of intra/extra hepatic ducts of biliary tree

Question 13

Risk of PSC

Answer 13

higher risk of colorectal cancer and cholangiocarcinoma

Question 14

5 classes of pharma agents in IBD

Answer 14

5-ASA, steroids, immunomodulators, anti-TNF, anti-alpha4 inhibitors

Question 15

Is CD curable?

Answer 15

no

Question 16

Is UC curable?

Answer 16

yes –> surgery/colectomy

Question 17

Etiologic factors for more aggressive IBD

Answer 17

tobacco in CD, perianal/penetrating disease, age<40, low albumin/anemia

Question 18

Tx of mild IBD

Answer 18

short course of steroids, 5 aminosalicylates for UC, budesonide for CD, topical steroid for distal disease

Question 19

Tx of moderate IBD

Answer 19

immune suppression: thiopurine antimetabolites, methotrexate, anti-tnf, anti-alpha 4 inhibitors

Question 20

MOA of aminosalicylates

Answer 20

inhibition of T cell proliferation, inhibition of antigen presentation, inhibition of adhesion, decreased TNF production

Question 21

Indication for aminosalicylates

Answer 21

UC

Question 22

Adverse events in aminosalicylate use

Answer 22

paradoxical diarrhea, interstitial nephritis

Question 23

Indication for steroids

Answer 23

induction of remission in moderate/severe UC and CD

Question 24

Indication for budesonide

Answer 24

induction of remission in CD, standard initial tx for mild CD

Question 25

Benefit of budesonide

Answer 25

high degree of first pass metabolism reduces side effects

Question 26

How are immunomodulators Azathioprine and 6MP cleared?

Answer 26

TPMT enzyme --> common mutation can lead to markedly increased active metabolite --> bone marrow suppression

Question 27

Indication for AZA/6MP

Answer 27

induction and maintenance of remission of CD

Question 28

How fast do AZA/6MP work?

Answer 28

several months required for full benefit

Question 29

Adverse effects of AZA/6MP

Answer 29

leukopenia, pancreatitis, hepatitis, infection, malignancy (NHL)

Question 30

Indication for methotrexate

Answer 30

induction/maintenance of CD remission

Question 31

Adverse effects of methotrexate

Answer 31

nausea, hepatic fibrosis, teratogenic, ppneumonitis, leukopenia

Question 32

Indication for cyclosporin A

Answer 32

bridge while waiting for onset of action of AZA/6MP

Question 33

Adverse effects of cyclosporin A

Answer 33

nephrotoxicity, hypertrichosis, gingival hyperplasia, ht, seizures, liver, etc

Question 34

3 main anti-TNFs

Answer 34

infliximab, adalimumab, certolizumab pegol

Question 35

MOA of anti-TNFs

Answer 35

induction of apoptosis of T cells/lymphocytes in lamina propria, cytokine changes/reduction in secretion

Question 36

Indication for anti-TNFs

Answer 36

induction and maintenance of remission in CD ...also, infliximab and adalimumab for UC

Question 37

Adverse effects of anti-TNFs

Answer 37

transfusion reactions, hypersensitivity, lupus, infection, lymphoma, HSCTL

Question 38

Are combination anti-TNFs/immunomodulator effective?

Answer 38

yes

Question 39

MOA natalizumab

Answer 39

block alpha4 integrin --> no binding of leukocytes to wall of blood vessel --> less leukocyte trafficking in gut

Question 40

Indication for natalizumab

Answer 40

induction/maintenance of CD

Question 41

Adverse effects for natalizumab

Answer 41

progressive multifocal leukoencephalopathy by reactivation of JC

Question 42

Are Ab's useful in CD, UC?

Answer 42

only in CD for complications like fistulae and abscesses

Question 43

1st line therapy for CD

Answer 43

budesonide

Question 44

1st line therapy for UC

Answer 44

5asa