Drugs used for IBD

Question 1

Sulfasalazine

Answer 1

Anti-inflammatory drug
- inhibits IL-1 and TNF-a
- inhibits lipoxygenase pathway
- inhibits PPAR-y
- inhibits NF-kB (transcription factor needed for inflammatory mediator production)

not absorbed my intestine because of azo linkage

Question 2

Prednisolone (glucocorticoid)

Answer 2

Anti-inflammatory Drug

MOA: binds to receptor, forms homodimer that translocates to nucleus and binds to glucocorticoid responsive element
- transactivation: annexin-1 (lipocortin-1) formation –> inhibits phospholipase 2 (anti-inflammatory effect)

Question 3

Thiopurine derivatives: Azathioprine, 6-mercaptopurine

Answer 3

IMMUNOSUPPRESSANT
MOA: impairs biosynthesis, inhibits cell proliferation, suppress immune system, reduce inflammation

if genetic polymorphism in TMPT
- minimal TMPT activity: bone marrow suppression
- increase TMPT activity: hepatotoxicity, reduced therapeutic effect

Question 4

Methotrexate

Answer 4

IMMUNOSUPPRESSANT
MOA: inhibits DNA synthesis, suppressing immune responses, reduces inflammation
- irreversibly binds to DHFR
- reversibly binds to thymidylate synthetase

Question 5

Cyclosporine

Answer 5

IMMUNOSUPPRESSANT
- inhibits calcineurin and a potent immunomodulator

Question 6

Infliximab

Answer 6

Anti-TNF-a (monoclonal antibody)
MOA: neutralize soluble and membrane-bound TNF-a, less immune response in Crohn’s disease and ulcerative colitis