Drugs for Inflammatory Bowel Disease

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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. Current vs. Novel 5-ASA Formulations for IBD Treatment

⭐ 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.

Biologic Class / AgentPrimary Target(s)RouteKey Considerations & Adverse Drug Reactions (ADRs)
Anti-TNF-α Agents
Infliximab, Adalimumab, Golimumab, CertolizumabTNF-α (pro-inflammatory cytokine)IV/SCRisk of serious infections (TB reactivation), infusion/injection site reactions, demyelination, drug-induced lupus, worsening HF, loss of response.
Anti-Integrin
Vedolizumabα4β7 integrin (gut-specific)IV/SCGut-selective; nasopharyngitis, headache, arthralgia. Rare: Progressive Multifocal Leukoencephalopathy (PML).
Anti-IL-12/23
UstekinumabIL-12 & IL-23IV/SCUpper respiratory infections, headache, fatigue. Also for psoriasis. Rare: Reversible Posterior Leukoencephalopathy Syndrome (RPLS).

Biologic therapies for IBD: Mechanisms of action 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.

Practice Questions: Drugs for Inflammatory Bowel Disease

Test your understanding with these related questions

The drug used in steroid-refractory acute severe ulcerative colitis is:

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Flashcards: Drugs for Inflammatory Bowel Disease

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Sulfasalazine is metabolized by _____ into the active component (mesalamine) which is used to treat the colitis aspects of IBD

TAP TO REVEAL ANSWER

Sulfasalazine is metabolized by _____ into the active component (mesalamine) which is used to treat the colitis aspects of IBD

colonic Bacteria

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