IBD

Question 1

Mesalamine (General)

Answer 1

5-ASA

MOA:
* Inhibits prostaglandin production
* May inhibit NFĸB activity

Use:
– Mild to moderate UC (first-line)
* Used for induction and maintenance of remission
– off-label CD

PK: 5-ASA absorbed from SI; does not reach distal colon
Different formulations:
* Azo structure: ↓absorption in the small
intestine
* Distal GI tract: azo-bond cleaved by
resident bacteria

Question 2

Sulfasalazine

Answer 2

Type: 5-ASA

MOA:
* Inhibits prostaglandin production
* May inhibit NFĸB activity

Use:
– Mild to moderate UC (first-line)
* Used for induction and maintenance of remission
– off-label CD

PK: Absorption
– 30% in small intestine –> taken up by
the liver and excreted unmetabolized in the bile
– 70%: reach colon –> cleaved by bacterial
enzymes

AES: high incidence (systemic effects of
sulfapyridine –> sulfa moiety)
Pruritus, rash
Abdominal pain, loss of appetite,
nausea, vomiting
Impairs folate absorption

Question 3

Olsalazine and Balsalazide

Answer 3

5-ASA

MOA:
* Inhibits prostaglandin production
* May inhibit NFĸB activity

Use:
– Mild to moderate UC (first-line)
* Used for induction and maintenance of remission
– off-label CD

AES: (well tolerated)
– Secretory diarrhea

Question 4

Prednisone, budesonide, hydrocortisone

Answer 4

Glucosteroids

MOA: Inhibition of PLA2 –> decreased synthesis of PG and LT
– decreased gene transcription (NOS, COX-2, NFkB), decreased inflammatory cytokines and chemokines

Use: Moderate to severe active UC and CD

Formulations: many

AES: Cushings Syndrome (moon face, hyperglycemia, osteoporosis, increase infection)

Question 5

6-MP and azathioprine

Answer 5

Thiopurine derivatives (Immunosuppressants)

Prodrugs

MOA: false nucleotides into dna –> strand breaks –> inhibits cell proliferation (inflammatory cells)

Use: MR of UC and CD

AES:
Bone marrow suppression
Alopecia, rash
N/V
– Hepatotoxicity
– Hypersensitivity reactions (pancreatitis)
– Increased risk of infections
– Increased risk of malignancies (BBW)

Monitering: CBCs and Liver function test required/ low TPMT –> BM depression

DDI: allopurinol –> severe leukopenia

Question 6

Methotrexate

Answer 6

Folic acid antagonist/ immunosuppressant

MOA: Competitive inhibitor of DHT reductase –> impair DNA synthesis

Usde: MR of UC and CD

PK: excretion –> renal

AEs:
Alopecia, photosensitivity, rash (BBW)
Diarrhea (BBW), nausea and vomiting
Hepatotoxicity (BBW)/ Renal Impairment
Bone marrow suppression (BBW)

DDI: salicylates, NSAIDs, penicillin (drugs the inhibit renal secretion of MTX)

CI: Pregnancy, hepatic disease

Monitering: Testing q1-3 months

Question 7

Infliximab, Adalimumab, Golimumab, Certolizumab

Answer 7

Anti-TNF Therapy

MOA: blocks TNF from binding to receptor

Use: MR of UC and CD (DOC for fissures)
- UC = IAG
- CD = IAC

AES:
increased infection –> TB tests
Antibody to antibody (Infliximab)
Acute adverse infusion reaction (fever, headache, SOB, etc)
severe hepatic reaction (rare)
New primary malignancy (BBW) /lymphomas

Question 8

Natalizumab and Vedolizumab

Answer 8

MOA: antibody to integrin –> decrease extravasation of lymphocytes

Use: MR of CD and UC

AEs:

N = PML (BBW), hepatotoxicity
Z = Similar to N, but less PML