IBD IBD Pharmacotherapy 1 — Questions and Answers
Question 1: What is the mechanism of action of mesalamine (5-ASA) in treating ulcerative colitis?
- Blocking TNF-α receptor binding
- Local anti-inflammatory effect via inhibition of arachidonic acid metabolites and NF-κB in colonic mucosa (Correct answer)
- Inhibiting JAK1/JAK3 kinases
- Suppressing T-cell activation via calcineurin inhibition
Correct answer: Local anti-inflammatory effect via inhibition of arachidonic acid metabolites and NF-κB in colonic mucosa
Mesalamine exerts topical anti-inflammatory effects in the colonic mucosa by inhibiting NF-κB, COX pathways, and arachidonic acid metabolites independently of systemic absorption.
Question 2: Which anti-TNF biologic is available as both IV infusion and subcutaneous formulation for IBD treatment?
- Certolizumab pegol
- Adalimumab
- Infliximab (Correct answer)
- Golimumab
Correct answer: Infliximab
Infliximab (Remicade) is primarily administered IV, but biosimilars and newer formulations now allow subcutaneous administration (infliximab SC).
Question 3: Thiopurine medications (azathioprine, 6-mercaptopurine) work primarily by which mechanism in IBD?
- Blocking TNF-α synthesis
- Inhibiting de novo purine synthesis, leading to T and B lymphocyte suppression (Correct answer)
- Blocking IL-12/IL-23 signaling
- Inhibiting dihydrofolate reductase
Correct answer: Inhibiting de novo purine synthesis, leading to T and B lymphocyte suppression
Thiopurines are converted to 6-thioguanine nucleotides that inhibit de novo purine synthesis and T-lymphocyte proliferation, causing immunosuppression.
Question 4: Before initiating thiopurine therapy, testing for which enzyme deficiency is recommended to prevent severe toxicity?
- Glucose-6-phosphate dehydrogenase (G6PD)
- Thiopurine methyltransferase (TPMT) or NUDT15 (Correct answer)
- Dihydropyrimidine dehydrogenase (DPD)
- Uridine diphosphate glucuronosyltransferase (UGT)
Correct answer: Thiopurine methyltransferase (TPMT) or NUDT15
TPMT and NUDT15 enzyme deficiencies impair thiopurine metabolism, leading to accumulation of toxic metabolites causing severe myelosuppression.
Question 5: Vedolizumab (Entyvio) is considered 'gut-selective' because it specifically blocks which interaction?
- TNF-α binding to its receptor on intestinal epithelial cells
- α4β7 integrin on lymphocytes from binding MAdCAM-1 on gut endothelium (Correct answer)
- IL-6 receptor signaling in the colon
- JAK1 signaling in mesenteric lymph nodes
Correct answer: α4β7 integrin on lymphocytes from binding MAdCAM-1 on gut endothelium
By blocking α4β7/MAdCAM-1 interaction, vedolizumab selectively prevents gut-homing lymphocytes from entering intestinal tissue without systemic immunosuppression.
Question 6: Which corticosteroid formulation for IBD is designed to minimize systemic side effects through extensive first-pass hepatic metabolism?
- Prednisone
- Methylprednisolone IV
- Budesonide (Correct answer)
- Hydrocortisone enema
Correct answer: Budesonide
Budesonide undergoes >90% first-pass hepatic metabolism, resulting in high local anti-inflammatory potency with significantly fewer systemic corticosteroid side effects.
IBD IBD Pharmacotherapy 1
What is the mechanism of action of mesalamine (5-ASA) in treating ulcerative colitis?