L24- GI Drugs II (inflammatory bowel disease)

Question 1

IBD pharmological treatment is based on….

Answer 1

• Sx severity and responsiveness
• anatomic distribution of disease
• drug toxicity

Question 2

list the drugs used to treat mild IBD

Answer 2

• 5-ASA
• antibiotics
• topical corticosteroids
• budesonide

Question 3

list the drugs used to treat moderate IBD

Answer 3

• azathiopurine
• MTX
• oral corticosteroids
• TNF antagonist

Question 4

list the drugs used to treat severe IBD

Answer 4

• IV corticosteroids
• TNF antagonists
• cyclosporine
• natalizumab
• surgery

Question 5

list the aminosalicyclates (+ active ingredient)

Answer 5

• sulfasalazine
• balsalazide
• mesalamine

5-ASA is active ingredient (unknown mechanism)

Question 6

describe action of 5-ASA in terms of route of administration and affected segments in GIT

Answer 6

Oral –> complete absorption in jejunum (NO effect beyond: ileum, colon, rectum)

Suppository / Enema –> patients with isolated sigmoid colon or rectal disease

Question 7

Sulfasalazine:

• (1) type drug + composition (including purpose)
• (2) first step after oral administration
• (3) is the second active step

Answer 7

1- (aminosalicyclates) 5-ASA -(azo bond)- sulfapyridine [dec 5-ASA absorption in jejunum]

2- most passes into colon –> reduced by bacterial enzyme (azoreductase) –> sulfapyridine + 5-ASA

3- 5-ASA therapeutic actions in colon + backwash into terminal ileum

Question 8

Sulfasalazine AEs

Answer 8

(aminosalicylates)

• 40% patients unable to tolerate
• upset GI, HAs, arthralgias, myalgias, BM suppression, hypersensitivity reactions (mostly due to sulfapyridine)

Question 9

Balsalazide is a (1) type drug with (2) formulation in order to have (3) effect. (4) are the AEs.

Answer 9

1- aminosalicylates

2- 5-ASA + unabsorbed carrier molecule

3- delivery to colon (+ terminal ileum)

4- generally well tolerated

Question 10

Mesalamine is a (1) type drug with (2) formulation in order to have (3) effect. (4) are the AEs.

Answer 10

1- aminosalicyclates

2- 5-ASA in timed release or pH sensitive micrgranules

3- release active drug in desired / affected GIT segment

4- generally well-tolerated

Question 11

list the glucocorticoids for IBD

Answer 11

• prednisone
• prednisolone
• budesonide

Question 12

describe purpose of glucocorticoid therapy for IBD

Answer 12

• induces remission of acute exacerbations of IBD

- NOT for maintaining remission

Question 13

Prednisone and Prednisolone are administered in (1) fashion

Hydrocortisone is administered in (2) fashion

(3) are the AEs for all the glucocorticoids

Answer 13

1- oral, once daily

2- enema (for sigmoid / rectal IBD flares)

3- adrenal suppression, hypoglycemia, immunosuppression, osteoporosis

Question 14

Budesonide is a (1) type drug used for its (2) effects and has (3) benefit over other similar drugs

Answer 14

1- glucocorticoid

2- topical effects on luminal surface of inflamed bowel wall

3- has very strong 1st pass effect –> dec rate of systemic adverse effects (compared to prednisolone)

Question 15

list the immunosuppressants used to treat IBD

Answer 15

• mercaptopurine (6-MP)
• asathiopurine
• MTX

Question 16

describe the MOA and advantage of IBD immunosuppressants

Answer 16

• purine inhibition
• induces and maintains IBD remission
• steroid sparing effect

Question 17

list immunosuppressant AEs (include drug to avoid in combination)

Answer 17

• n/v
• hepatotoxicity
• BM depression

-avoid with Allopurinol (inc 6-thioguanine nucleotide concentration –> life-threatening leukopenia)

Question 18

MTX:

• (1) MOA
• (2) AEs, which are reduced by (3)

Answer 18

1- DHF-reductase inhibition (thymidine, purines) –> reduces IL-1 inflammatory actions (given at low doses)

2- BM depression, megaloblastic anemia, mucositis

3- folate supplementation (doesn’t reduce anti-inflammatory effects)

Question 19

list the anti-TNFα drugs

Answer 19

• infliximab

- adalimumab

Question 20

TNF is a key mediator of….

Answer 20

• pro-inflammatory CK release
• stimulates acute phase hepatic proteins
• upregulates endothelial adhesion molecules –> promotes leukocyte migration

Question 21

anti-TNFα MOA and indications

Answer 21

• binds and inactivates TNF

- indicated for acute / chronic IBD

Question 22

list AEs for anti-TNFα drugs

Answer 22

• Th1 activity suppression (inc fungal infections, reactivation of latent TB)
• Igs against drug
• inc risk of lymphoma, acute hepatic failure, CHF

Question 23

(1) is the main Anti-Integrin, with (2) MOA and (3) as indications

Answer 23

1- Natalizumab

2- Ig against several integrins on circulating inflammatory cells –> disrupts leukcyte adhesion / migration

3- moderate to severe unresponsive CD

Question 24

Anti-integrin AEs

Answer 24

(natalizumab)

• infusion reactions
• opportunistic infections
• reactivation of JC virus (human polymavirus) –> multifocal leukoencephalopathy