Inflammatory Bowel Disease – Dr.

Tagle
Mesalamine (5-ASA) based therapy
-Chronic Disease  First-line therapy for mild to moderate ulcerative colitis
- Idiopathic  Archetype is sulfasalazine (Azulfidine) which is 5-ASA
- Inflammatory Intestinal Condition linked to sulfapyridine with an azo bond
 Azo bond prevents absorption of drug in upper GI
Signs and Symptoms  Although a salicylate , doeas not produce
 Diarrhea cyclooxygenase inhibition as aspririn
 Abdominal Pain  Sulfapyridine is responsible to side-effects of
 Bleeding sulfasalazine
 Anemia  Advantage of 2nd generation drugs
 Weight Loss  Olsalazine (Dipentum) , Balsalazide (Colazide)

Extraintestinal Signs and symptoms  Delayed release mechanism – decreased side effects
 Arthritis  Pentasa
 Ankylosing Spondylitis  Asacol
 Sclerosing cholangitis
 Uveitis Pharmacokinetics
 Iritis  20 – 30% absorbed in small intestine
 Pyoderma gangrenosum  70% in colon
 Erythema nodosum
Adverse Effects
Major Subtypes  Headache , nausea , fatigue
1. Ulcerative Colitis  Allergic reactions
 Characterized by confluent mucosal inflammation  Inhibits folate absorption
of the colon
 Starts at anus and spreads proximally Glucocorticoids
 Effective in acute exacerbations
2. Crohn’s Disease  Responsive divided in 3 classes:
 Characterized by transmural inflammation of any
part of GI o Steroid responsive – improves clinically within 1 –
 Most common area – Ileocecal valve 2 weeks and remains in remission as the steroids
 Non-confluent area of inflammation are tapered
 “skip areas”
 Lead to fibrosis , strictures and fistula formation o Steroid dependent – response to steroids but
experience a relapse of symptoms as the steroid
Goals for Therapy dose tapered
 Control acute exacerbation
 Maintain remission o Steroid unresponsive - patients do not improve
 Treat specific complication like fistula even with prolonged high-dose glucocorticoids

Crohn’s Disease Glucocorticoids are not effective in maintaining remission in

 marked infiltration of lymphocytes , macrophages , IBD’s
granuloma formation and submucosal fibrosis
 Cytokine profile: increase interleukin-12 , interferon Y ,
TNF
 T-helper mediated inflammatory process

Ulcerative colitis
 Lymphocytic and neutrophilic infiltrates
 Mediated by T2 pathway
Immunosuppressive agents

Thiopurine derivatinces
 Mercaptopurine (6-MP Purinethol)
 Azathioprine (Imuran)
 Used to treat severe IBD or those are steroid –resistant
or steroid –dependent
 Impair purine byosynthesis and inhibit cell proliferation

Methotrexate
 Induces and maintains remission , with more rapid
response
 Higher doses compared to autoimmune disease

Cyclosporine
 For severe ulcerative colitis
 Long-term therapy NEORAL , a microemulsion form
with increased oral bioavailability
 Used to treat fistula complications

Anti-TNF therapy
 Infliximab (remicade) , a chimeric immunoglobulin
(25% mouse , 75% human) binds and neutralize TNF-a ,
one of the principal cytokines mediating the T1
immune response in Crohn’s

Antibiotics
 May either initiate or perpetuate the inflammation of
IBD
 Used as adjunctive therapy
 Treatment of specific complication of Crohn’s disease
 Prophylaxis for recurrence

Metronidazole , Ciprofloxacin , Clarithromycin

 Effective for complications like intra – abdominal
abscesses , infections like C. difficile

Supportive therapy in IBD

 Analgesics
 Anticholinergics – Dicyclomine
 Antidiarrheal – loperamide , diphenoxylate
 Cholestyramine
 Oral iron folates , Vit B12

Therapy of IBD in pregnancy

 Category B – used frequently in pregnancy and
considered safe
 Mesalamine
 Glucocorticoids