PH6.5 | PH6.5 | Chronic Lower-GI Symptom Pharmacotherapy — SDL Guide — Summary & Reflection

KEY TAKEAWAYS

IBD and IBS Pharmacotherapy — Key Points:

Critical distinction: IBD = organic inflammation (UC: mucosal/continuous/colon; CD: transmural/segmental/any site) → requires anti-inflammatory/immunosuppressive drugs. IBS = functional disorder (no inflammation, normal endoscopy) → symptom-targeted drugs only; NO immunosuppression.

IBD drug classes:
- 5-ASA (aminosalicylates): mesalazine (UC first-line, well tolerated); sulfasalazine (prodrug + sulphapyridine carrier → ADRs: haemolysis, male infertility, nausea; folic acid 5 mg/day supplementation required).
- Corticosteroids: prednisolone (acute flares, taper over 8–12 weeks, NOT maintenance); budesonide (high first-pass, ileal/right-colonic CD).
- Thiopurines (azathioprine/6-MP): Maintenance; slow onset 3–6 months. TPMT testing mandatory before starting — TPMT-deficient patients → fatal myelosuppression. ADRs: myelosuppression, hepatotoxicity, pancreatitis, lymphoma. Allopurinol interaction → reduce AZA dose by 75%.
- Methotrexate: CD maintenance; SC weekly; teratogenic → contraception required; folic acid supplementation required.
- Anti-TNF (infliximab IV, adalimumab SC): Moderate-severe IBD; screen for latent TB (IGRA) + hepatitis B before starting; TB prophylaxis with isoniazid if IGRA+.
- Vedolizumab (anti-α4β7): Gut-selective; lower systemic infection risk than anti-TNF.
- JAKi (tofacitinib, upadacitinib): Oral; rapid onset; herpes zoster risk (vaccinate before starting).

IBS pharmacotherapy by subtype:
- IBS-D: loperamide + mebeverine (first-line antispasmodic); low-dose amitriptyline (pain + motility); rifaximin (bloating/SIBO).
- IBS-C: linaclotide (preferred — pain + constipation), lubiprostone.
- IBS pain: mebeverine (first-line), hyoscine butylbromide, peppermint oil.

REFLECT

You are reviewing a 32-year-old man with Crohn's disease who has been on azathioprine 2 mg/kg/day for 6 months. He now requires infliximab for ongoing disease activity (steroid-dependent, inadequate thiopurine response). He asks: 'Do I have to keep taking the azathioprine after starting the drip, or can I stop?' Think through: (a) why is combination azathioprine + infliximab sometimes recommended rather than infliximab monotherapy? (Hint: anti-drug antibody formation); (b) what are the additional infection risks of combination immunosuppression, and how would you monitor? (c) how would you counsel him about the TB screening that is required before his first infliximab infusion? This scenario integrates drug interaction pharmacology, safety monitoring, and patient communication — reflecting the real complexity of managing moderate-severe IBD in a resource-conscious Indian healthcare setting.