PHARMACOTHERAPY OF INFLAMMATORY BOWEL DISEASES BY l a

PHARMACOTHERAPY OF INFLAMMATORY BOWEL DISEASES BY l a m a K a i l a D. r D y g lo o c a m r a h P f o Assistant Professor

Learning objectives Classify drugs used in management of IBD according to their mechanism of action. Distinguish the different derivatives of 5 ASA, characterize the site of activity of their different formulations. Discuss the role of CSs and immunosuppressants in management of IBDs Discuss the mechanism of action , uses and adverse effects of Anti. TNF-α in IBD. Outline the pharmacologic option for induction and maintenance of remission for both UC, and CD

Course of IBD Remission Relapse

Aim of Therapy of IBD Induction of remission Maintenance of remission Relieve symptoms Decrease complications

Pathogenesis of IBD IL 3, 5, 10, 13 UC CD

Pathogenesis of IBD Luminal microbial Antigens Environmental. Anti- Genetic triggers inflammatoryfactors IBD Immune response

General Approach to treatment Aminosalisylate Corticosteroids Immunosuppressant Anti-diarrheals Antimicrobials Anti-spasmodic Iron Anti-TNF-α (Biological therapy) Symptomatic treatment

Pharmacotherapy of IBDs AMINOSALISYLATE DERIVATIVES By reaching the affected area In sufficient concentration

AMINOSALISYLATE DERIVATIVES Sulfasalazine: Azo -bond 5 -aminosalisylic acid (5 -ASA) (Mesalamine) Sulfapyridine

AMINOSALISYLATE DERIVATIVES Sulfasalazine H 2

AMINOSALISYLATE DERIVATIVES Sulfasalazine Induction & Maintenance of remission in mild to moderate ↓ PG & leukotrienes ↓neutrophil chemotaxis ↓NF-k. B Free radicle scavenger

AMINOSALISYLATE DERIVATIVES Sulfasalazine v - Headache nausea, fatigue 5 -aminosalisylic acid (Mesalamine) (mild to severe) Therapeutic - ↓Folate absorption benefitsoligospermia - Reversible Sulfapyridine Adverse effects

AMINOSALISYLATE DERIVATIVES Sulfasalazine 5 -aminosalisylic acid Sulfapyridine Olsalazine 5 -aminosalisylic acid 5 -aminosalisylic Sulfapyridine acid Balsalazide 5 -aminosalisylic acid Inert Sulfapyridine molecule

AMINOSALISYLATE DERIVATIVES Mesalamine Jejunum Ileum Colon Rectum Slow release (time dependent) p. H- dependent Enema Supp.

AMINOSALISYLATE DERIVATIVES 5 -aminosalisylic acid derivatives Jejunum Ileum Colon Rectum Sulfapyr. Sulfasalazine 5 -ASA Olsalazine 5 -ASA Inert molecule Balsalazide Slow release (time dependent) p. H dependent Enema Supp 5 -ASA

Corticosteroids Lipocortin A which inhibit PLA ↓Inflammatory Cytokines

Corticosteroids Induction of remission moderate to severe s y a d 0 l a or Prednisone Methylprednisolone Budesonide y Re 3 a d fra 0 1 ct 7 or y V I s Hydrocortisone and methylprednisolone Hydrocortisone enema and suppository

Immunosuppressants Azathioprine Induction &Maintenance of remission Steroid sparing DNA

Immunosuppressants Methotrexate Folic acid Induction & Maintenance of remission in CD DNA

Immunosuppressants Cyclosporine CS Induction of remission in severe fulminant UC NF-AT IL-2 R IL-2 Calcinurine Proliferation

Antimicrobials Metronidazole & Ciprofloxacin Altering Perianal and colonic CD After surgery

Probiotics

Biological therapy Anti-TNF-α

Biological therapy Anti-TNF-α Infliximab Adalimumab Chimeric Antibody formation Allergic reaction Fully humanized No Antibody Less Adverse effects Adalimumab

Biological therapy Anti-TNF-α Refractory CD (also in UC) Fistulizing CD

Therapeutic strategy Step up Severe Moderate Mild Surgery CS IV Steroids Anti TNF-α Oral Steroids AZA, MTX Budesonide Topical steroids Antibiotics ASA Top down Anti-TNF-α Immunosuppressants Immunosuppressant Steroids ASA Early Antibiotics Steroids ASA Late

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