IBD Pathophysiology and Pharmacology Flashcards

1
Q

UC/Crohn’s difference in epi

A

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

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2
Q

To what degree does Crohn’s run in families?

A

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

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3
Q

What is the main gene implicated in IBD?

A

NOD2

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4
Q

Which GWAS pathways appear involved in both UC and CD?

A

IL23 and IL12 –> involved in Th17 cells

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5
Q

Will IBD develop in a germ-free environment?

A

no –> need bacteria

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6
Q

Most common locations of CD

A

ileum and colon –> lots of bacteria

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7
Q

Th17 cells are activated by….

A

IL6, 21,23 and TGFbeta

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8
Q

What Ig is secreted in UC?

A

IgG1 and IgG3

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9
Q

What Ig is secreted in CD?

A

IgG2

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10
Q

Does smoking increase risk of CD?

A

yes

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11
Q

Does smoking increase risk of UC?

A

protective

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12
Q

primary sclerosing cholangitis is more common in UC or CD?

A

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

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13
Q

Risk of PSC

A

higher risk of colorectal cancer and cholangiocarcinoma

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14
Q

5 classes of pharma agents in IBD

A

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

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15
Q

Is CD curable?

A

no

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16
Q

Is UC curable?

A

yes –> surgery/colectomy

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17
Q

Etiologic factors for more aggressive IBD

A

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

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18
Q

Tx of mild IBD

A

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

19
Q

Tx of moderate IBD

A

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

20
Q

MOA of aminosalicylates

A

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

21
Q

Indication for aminosalicylates

A

UC

22
Q

Adverse events in aminosalicylate use

A

paradoxical diarrhea, interstitial nephritis

23
Q

Indication for steroids

A

induction of remission in moderate/severe UC and CD

24
Q

Indication for budesonide

A

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

25
Q

Benefit of budesonide

A

high degree of first pass metabolism reduces side effects

26
Q

How are immunomodulators Azathioprine and 6MP cleared?

A

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

27
Q

Indication for AZA/6MP

A

induction and maintenance of remission of CD

28
Q

How fast do AZA/6MP work?

A

several months required for full benefit

29
Q

Adverse effects of AZA/6MP

A

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

30
Q

Indication for methotrexate

A

induction/maintenance of CD remission

31
Q

Adverse effects of methotrexate

A

nausea, hepatic fibrosis, teratogenic, ppneumonitis, leukopenia

32
Q

Indication for cyclosporin A

A

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

33
Q

Adverse effects of cyclosporin A

A

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

34
Q

3 main anti-TNFs

A

infliximab, adalimumab, certolizumab pegol

35
Q

MOA of anti-TNFs

A

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

36
Q

Indication for anti-TNFs

A

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

37
Q

Adverse effects of anti-TNFs

A

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

38
Q

Are combination anti-TNFs/immunomodulator effective?

A

yes

39
Q

MOA natalizumab

A

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

40
Q

Indication for natalizumab

A

induction/maintenance of CD

41
Q

Adverse effects for natalizumab

A

progressive multifocal leukoencephalopathy by reactivation of JC

42
Q

Are Ab’s useful in CD, UC?

A

only in CD for complications like fistulae and abscesses

43
Q

1st line therapy for CD

A

budesonide

44
Q

1st line therapy for UC

A

5asa