Drugs for Inflammatory Bowel Disease

IBD & Aminosalicylates - Gut Soothers

• Inflammatory Bowel Disease (IBD): Chronic gut inflammation; Ulcerative Colitis (UC) & Crohn's Disease (CD).
  • UC: Colon, continuous lesions. CD: Any GI part, skip lesions, transmural.
  • Goals: Induce & maintain remission, improve QoL.
• Aminosalicylates (5-ASA): First-line for mild-moderate IBD.
  • MOA: ↓ local inflammatory mediators (prostaglandins, leukotrienes, ROS, NF-κB).
  • Sulfasalazine: 5-ASA + sulfapyridine (carrier, causes most ADRs).
  • Mesalamine (5-ASA): Various formulations (pH-dependent, delayed-release, topical) for targeted delivery.
  • ADRs: GI upset, rash. Sulfasalazine: Hemolysis (G6PD deficiency), hepatitis. Mesalamine: Rare interstitial nephritis.

⭐ Sulfasalazine can cause reversible oligospermia and folate malabsorption.

Corticosteroids & Immunomodulators - Flare Rescuers

• Corticosteroids (Acute Flares):

  • MOA: Broad anti-inflammatory; ↓ cytokines.
  • Prednisolone: Systemic; moderate-severe flares.
  • Budesonide: Controlled-release; high first-pass metabolism → ↓ systemic ADRs. Mild-moderate ileocecal Crohn's/UC.
  • ADRs: Hyperglycemia, osteoporosis, infections, Cushingoid. Short-term use.

• Immunomodulators (Maintenance, Steroid-Sparing):

  • Azathioprine (AZA) / 6-Mercaptopurine (6-MP):
    • MOA: Prodrugs → 6-thioguanine; ↓ purine synthesis, ↓ T-cell proliferation.
    • Onset: Slow (3-6 months).
    • ADRs: Myelosuppression, pancreatitis, hepatotoxicity.
    • ⭐ > Thiopurine methyltransferase (TPMT) enzyme level testing is crucial before initiating Azathioprine or 6-Mercaptopurine to predict risk of myelosuppression.
  • Methotrexate (MTX):
    • MOA: DHFR inhibitor; anti-inflammatory.
    • Role: Crohn's maintenance.
    • ADRs: Myelosuppression, hepatotoxicity, pneumonitis, teratogenic. Folate advised.

Biologic Therapies - Targeted Titans

Advanced options for moderate-to-severe or refractory Crohn's Disease (CD) & Ulcerative Colitis (UC). Pre-treatment screening crucial.

Awaiting image generation for "Mechanisms of action for biologic therapies in IBD: Anti-TNF, Vedolizumab, Ustekinumab"...

JAK Inhibitors & Algorithm - New Waves & Game Plans

• Tofacitinib (Xeljanz): Oral Janus Kinase (JAK) inhibitor.
  • MOA: Blocks JAK-STAT pathway → ↓ pro-inflammatory cytokine signaling.
  • Use: Moderate-severe Ulcerative Colitis (refractory to biologics/other therapies).
  • ⚠️ Key ADRs (BBW components):
    • Serious infections (TB, bacterial, fungal, viral).
    • Malignancy (e.g., lymphoma).
    • Major Adverse Cardiovascular Events (MACE).
    • Thrombosis (PE, DVT, arterial).
  • Other: ↑ Lipids (cholesterol), ↑ LFTs, cytopenias, GI perforation risk.

⭐ Tofacitinib, an oral Janus Kinase (JAK) inhibitor, carries a Black Box Warning for serious infections, malignancy, major adverse cardiovascular events, and thrombosis.

Simplified IBD Treatment Algorithm:

High‑Yield Points - ⚡ Biggest Takeaways

• Mesalamine (5-ASA) is mainstay for mild-moderate Ulcerative Colitis (UC); less effective in Crohn's.
• Sulfasalazine (5-ASA + sulfapyridine) has more side effects (e.g., folate deficiency, rash).
• Corticosteroids (Budesonide, Prednisolone) for acute flares; not for maintenance.
• Immunomodulators (Azathioprine, MTX) are steroid-sparing and used for maintenance.
• Anti-TNF agents (Infliximab, Adalimumab) treat moderate-severe IBD refractory to others.
• Vedolizumab is a gut-specific anti-integrin for refractory IBD.
• Ustekinumab (anti-IL-12/23) is effective for both Crohn's disease and UC.