Objectives
1.
Review the pathologenesis of inflammatory bowel disease. 2. Discuss the drugs used in the treatment of IBD, their pharmacokinetics, pharmacodynamics, adverse effects and toxicity. 3. Discuss the novel drugs used for IBD.
intestinal conditions
Gastrointestinal symptoms
Diarrhea Abdominal Bleeing Anemia Weight
pain
loss
Extraintestinal symptoms
Arthritis Ankylosing
Major Subtypes
Ulcerative
Ulcerative Colitis
Characterized
by confluent mucosal inflammation of the colon Starts at anus and spreads proximally
Crohns disease
Characterized
by transmural inflammation of any part of GI Most common area - ileocecal valve Non-confluent area of inflammation skip areas Lead to fibrosis ,strictures and fistula formation
acute exacerbation Maintain remission Treat specific complication like fistula Glucocorticoids remain the treatment of choice for moderate-to-severe flares but inappropriate for long-term use because of side effects and inability to maintain remission
Mainstay
Pathogenesis of IBD
Crohns
disease -
Transmural
marked infiltration of lymphocyes, macrophages,granuloma formation, and submucosal fibrosis profile: increase interleukins 12, interferon Y, tumor necrosis factor mediated inflammatory process
Cytokine
T-helper
Ulcerative Superficial
colitis
Mediated
therapy for mild to moderate ulcerative colitis is sulfasalazine (Azulfidine) which is 5-ASA linked to sulfapyridine with an azo bond
Archetype
Azo bond prevents absorption of drug in upper GI Although a salicylate, does not produce cyclooxygenase inhibition as aspirin
Sulfapyridine
Advantage
of 2nd generation drugs 1. Not linked to sulfapyridine Olsalazine ( Dipentum) Balsalazide ( Colazide)
2.
Pharmacokinetics
20-30%
of release of mesalamine in GIT Colon: sulfazalazine olsalazine Ileum, colon: Asacol - mesalamine pH sensitive release tablets Stomach, jejunum, ileum, colon: Pentasa
Adverse Effects
Headache,
Glucocorticoids
Effective
in acute exacerbations Response divided in 3 classes: Steroid responsive Steroid dependent Steroid unresponsive
Steroid
responsive Improves clinically within 1-2 weeks and remains in remission as the steroids are tapered Steroid dependent - response to steroids but experience a relapse of symptoms as the steroid dose is tapered
Steroid
Glucocorticoids
Immunosuppresive Agents
Thiopurine derivatives Mercaptopurine (6-MP Purinethol) Azathioprine (Imuran) Used to treat severe IBD or those who are steroid-resistant or steroiddependent Impair purine biosynthesis 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 Crohns
Antibiotics
May
either initiate or perpetuate the inflammation of IBD Used as adjunctive treatment Treatment of specific complication of Crohns disease Prophylaxis for recurrence in postoperative Crohns disease
Dicyclomine Antidiarrheal- Loperamide, Diphenoxylate Cholestyramine Oral iron, folates, Vit B12
END GOOD
AFTERNOON!