IBD

Question 1

What are the two distinct disorders seen in inflammatory bowel disease?

Answer 1

Ulcerative colitis: a mucosal inflammatory condition confined to the rectum and colon

Crohn’s disease: a transmural inflammation of the GI tract that can affect any part, from the mouth to the anus

Question 2

Clinical features of crohn’s disease?

Answer 2

fever, malaise

rectal bleeding,

abd tenderness, abd mass, a wall and internal fistulas

aphthous or linear ulcers

DISCONTINUOUS distribution

Question 3

clinical features of UC?

Answer 3

rectal bleeding

+/- abd tenderness

CONTINUOUS distribution

Question 4

Tx of IBD?

Answer 4

agents used to relieve inflammatory process and induce disease remission

• Aminosalicylates
• Corticosteroids
• Antimicrobials
• Immunosuppressive
• Biologic TNF alpha
• Anti-intefrins

Question 5

MOA Aminosalicylate?

Answer 5

goes through the bowel and released at a specific spot to cause a localized (not systemic) effect

Question 6

What is considered low risk crohn’s disease?

Answer 6

no or mild sxs

norma/mild elevated CRP and/or fecal calprotectin levels

dx >30yrs

limited distribution of bowel disease

no prior intestinal resection

Question 7

1st line tx fr mild crohn’s disease in adults?

Answer 7

Budesonde

Question 8

What are some aminosalicylates?

Answer 8

Sulfasalazine

Olsalazine

Balsalazide

Mesalamine-various forms

Question 9

What are Mesalamine Compounds?

Answer 9

5-ASA packaged in various ways to deliver it to different segments of the small or large bowel

ex. Pentasa, Asacol and Apriso, Lialda, Rowasa (enema) & Canasa (suppositories)

Question 10

MOA of Pentasa?

Answer 10

contains timed-release microgranules that release 5-ASA throughout the small intestine

Question 11

MOA of Asacol and Apriso?

Answer 11

5-ASA coated in a pH-sensitive resin that dissolves at pH 6-7

pH of the distal ileum and proximal colon

Question 12

MOA of Lialda?

Answer 12

pH-dependent resin that encases a multimatrix core

on dissolution of the pH-sensitive resin in the colon, water slowly penetrates its hydrophilic and lipophilic core, leading to slow release of mesalamine throughout the colon

Question 13

MOA of Rowasa and Canasa?

Answer 13

5-ASA delivered in high concentrations to the rectum and sigmoid colon

Question 14

Clinical uses of 5-ASA drugs?

Answer 14

UC: induce & maintain remission in tx of mild-mod (1st line)

Crohn’s: efficacy unproved (1st line in mild-mod disease)

Question 15

ASEs of Sulfasalazine?

Answer 15

20

Question 16

ADEs of Olsalazine?

Answer 16

secretory diarrhea

Question 17

ADEs of Mesalamine?

Answer 17

20

Question 18

What should be monitored in pts given Sulfasalazine?

Answer 18

20

Question 19

MOA of glucocorticoids?

Answer 19

Inhibits production of inflammatory cytokines (TNF-α, IL-1) and chemokines (IL-8)

Reduces expression of inflammatory cell adhesion molecules

inhibits gene transcription of nitric oxide synthase, phospholipase A, cox 2, etc.

Question 20

What is Budesonide?

Answer 20

potent synthetic analog of prednisolone

Question 21

PK of budesonide?

Answer 21

rapid first pass hepatic metabolism > low oral bioavailability

Question 22

In a pt with moderate to severe active inflammatory bowel disease, should you give a higher dose of glucocorticoids?

Answer 22

NO

• not more efficacious
• more ADEs

in severely ill > admin IV

Question 23

MOA of methotrexate?

Answer 23

inhibition of dihydrofolate reductase enzyme important in the production of thymidine and purines

may: interfere w/ interleukin, stimulate release of adenosine, stimulate apoptosis and death activated T lymphocytes

Question 24

Use of Methotrexate?

Answer 24

Crohn’s disease

also: RA, CA

Question 25

ADEs of Methotrexate?

Answer 25

bone marrow depression, alopecia, mucosities

permanent peripheral neuropathy when used for prolonged periods

Question 26

What can be used to reduce risk of ADEs in pt taking Methotrexate?

Answer 26

folate supplementation

Question 27

What is common among psoriasis pts taking Methotrexate?

Answer 27

hepatic damage

> renal insufficiency may increase risk of hepatic accumulation and toxicity