Chronic inflammatory bowel diseases
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Chronic inflammatory Bowel Diseases. By Prof. Abdulqader Alhaider 1434H. Chronic inflammatory bowel diseases (IBD) IBD is a group of auto-immune disorders in which the intestines become inflamed. are chronic inflammatory bowel disease which have relapsing and limiting course.

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Chronic inflammatory bowel diseases
Chronic inflammatory Bowel Diseases


Prof. AbdulqaderAlhaider


Chronic inflammatory bowel diseases


  • IBD is a group of auto-immune disorders in which the intestines become inflamed.

  • are chronic inflammatory bowel disease which have relapsing and limiting course.

  • The major types of IBD are Crohn's disease and ulcerative colitis (UC).

Differences between Crohn's disease and UC

  • Symptoms of UC:

    -Abdominal pain; Diarrhea and bleeding.

    Complications: Anemia ; megacolon, fever, abdominal pain, dehydration, colon cancer.

Treatment of IBD

  • 5-amino salicylic acid compounds (5-ASA).

  • Glucocorticoids

  • Immunomodulators

  • Biological therapy (TNF-α inhibitors).

  • Surgery in severe condition

Drugs Used for Rx and maintenance of I.B.D

I) Anti-inflammatory Drugs

  • A. 5-Aminosalicylic Acid:

    MOA:inhibit prostaglandins and leukotriens synthesis; decreases neutrophilchemotaxisand decreases free radicles production. scavenging free radical production

    Note: since it is irritant to GIT, this drug should not be given orally as such.


    a)Sulpha containing 5-Aminosalicylic Acid

    (e.g: Sulphasalazine)

    Sulphasalazine is a Prodrug (20-30 %) absorbed by intestine, secreted in the bile and hydrolysed in ileum and colon by isoreductase.

    Sulfapyridine + 5- ASA Hydrolysed in

    bacteria in ileum

    Linked by Azo group and colon

    Which part is active and is it absorbed?

Sulphasalazine continue
Sulphasalazine (Continue…)

Prodrug used in maintenance therapy less effective in acute attack;

Use for U.colitis; Crohn’s colitis but not Crohn’s of small intestine Why?.

Note: Nowadays it is seldom to be used for Crohn’s disease (new 5-ASA are preferred but still use for UC).

  • Side Effects :

    • Muscular pain 29% , N/V, Diarrhea

    • Crystalluria and interstitial nephritis

  • Hypersensitivity reactions as: skin rash, fever, aplastic anemia. Why?

  • Inhibit absorption of folic acid ` (megaloplastic anemia)

  • Infertility in man (decrease sperm counts). However, it is save in pregnancy.

  • B. Non-sulpha containing 5-Aminosalicylic Acid

    1. Mesalamines Compounds

    • Formulations that have been designed to deliver 5-ASA in small & large colon.

    • e.g. pentasa (orally): time release microgranules that release 5-ASA through the small intestine

      e.g. Asacol 5-ASA coated in pH sensitive resin that dissolved at pH 7

    • e.g. Rowasa (enema) or Canasa (suppositories)

    • Treat and maintain remission in mild to moderate ulcerative colitis.

    • Well tolerated, less side effects (sulfa free).

    2. Azo compounds

    Compounds contain 5-ASA and connected by azo bond to another molecule of 5-ASA or to inert compound

    Azo structure (N=N)

    reduces absorption in small intestine

    Bacteria cleave the azo dye and release 5-ASA in terminal ileum and colon


    Olsalazine(Two molecules (dimer) of 5-ASA linked together by diazo bond which pass small intestine to ilium and colon))

    Balsalazide5-ASA + inert carrier (Colazal).


    Small Intestine

    Large Intestine


    w/ eudragit-S



    Oral 5-ASA Release Sites

    Mechanism of action

    • Block PGs, LTs & cytokine production / NF-kB activation

    • Inhibit bacterial peptide–induced neutrophilchemotaxis & adenosine-induced secretion,

    • Scavenge reactive oxygen metabolites

    Mesalamine in microgranules

    Clinical uses of 5-amino salicylic acid compounds

    Induction and maintenance of remission

    in mild to moderate ulcerative colitis & Crohn’s disease (First line of treatment).

    Are NOT USEFUL in actual attack or severe forms of IBD.

    Rheumatoid arthritis (Sulfasalazine only)

    Rectal formulations are used in ulcerative proctitisand proctosigmoiditis.

    2. Corticosteroid


    • Inhibits phospholipase A2, inhibit gene expression of NO synthase, COX-2

    • Inhibit inflammatory cytokines (TNF-a)


    • Treat moderate – severe ulcerative colitis

      (prednisone P.O. 40-60 mg/day for 2 weeks

    • Less effective as prophylactic (maintaining remission).

    • Budesonide as controlled release oral (9 mg/day) formulation (Entocort).

    • Hydrocortisone enema or suppository for rectum or sigmiod colon

    • used also for extracolonic manifestations such as ocular lesion, skin disease and peripheral arthritis


    II. Immunomodulators

    Are used to induce remission in IBD in active

    or severe conditions or steroid dependent or

    steroid resistant patients.

    Immunomodulators include:

    • Methotrexate

    • Purine analogs:

      (azathioprine & 6-mercaptopurine).

    II) Immunomosuppressive Agents :

    • 1) Azathioprine; is pro-drug of 6-mercaptopurine that Inhibit purine synthesis

      M.O.A.:Suppress the body’s immune system

      Clinical indications: for Rx and maintenance of remission of severe conditions and steroids dependent or resistant (ulcerative and Cronn’s disease)

      Side Effects:

      - N/V and bone marrow depression; LFT changes

      - Hypersensitivity reactions Why?

    • 2. Methotrexate:

    • MOA:dihydrofolatereductase inhibitor works as antimetabolite.

      • Uses:Cronn’s disease (to induce and maintain remission); Rheumatoid Arthratis and cancer.

    • Side effects:

      • Bone marrow suppresion.

    Monoclonal antibodies used in ibd tnf inhibitors
    Monoclonal antibodies used in IBD(TNF-α inhibitors)





    • Is a monoclonal IgG antibodies.

    • 25% murine – 75% human.

    • Anti-TNF-α: Inhibits soluble or membrane –bound TNF-α located on activated T lymphocytes and

    • Given as infusion (5-10 mg/kg).

    • has long half life (8-10 days)

    • 2 weeks to give clinical response


    • Severe crohn’s disease.

    • Patients not responding to Immunomodulators or glucocorticoids.

    • Treatment of rheumatoid arthritis

    • Psoriasis

    Side effects

    Acute or early adverse infusion reactions (Allergic reactions or anaphylaxis in 10% of patients).

    Delayed infusion reaction (serum sickness-like reaction, in 5% of patients).

    Pretreatment with diphenhydramine, acetaminophen, corticosteroids is recommended.

    Side effects (Cont.)

    Infection complication (Latent tuberculosis, sepsis, hepatitis B).

    Loss of response to infliximab over time due to the development of antibodies to infliximab

    Severe hepatic failure.

    Rare risk of lymphoma.

    Adalimumab humira
    Adalimumab (HUMIRA)

    Fully humanized IgG antibody to TNF-α

    Adalimumab is TNFα inhibitor

    It binds to TNFα, preventing it from activating TNF receptors

    Has an advantage that it is given by subcutaneous injection

    is approved for treatment of, moderate to severe Crohn’s disease, rheumatoid arthritis, psoriasis.

    Certolizumab pegol cimzia
    Certolizumabpegol (Cimzia)

    Fab fragment of a humanized antibody directed against TNF-α

    Certolizumab is attached to polyethylene glycol to increase its half-life in circulation.

    Given subcutaneously for the treatment of Crohn's disease & rheumatoid arthritis

    Summary for drugs used in IBD

    5-aminosalicylic acid compounds

    Azo compounds:

    sulfasalazine, olsalazine, balsalazide


    Pentasa, Asacol, Rowasa, Canasa


    prednisone, prednisolone, hydrocortisone, budesonide



    Purine analogues: Azathioprine&6mercaptopurine

    TNF-alpha inhibitors (monoclonal antibodies)

    Infliximab – Adalimumab - Cetrolizumab

    Inductive Therapies

    Maintenance Therapies

    • For UC

    • Aminosalicylates

    • Corticosteroids

    • Cyclosporin >

    • For CD

    • Aminosalicylates

    • Corticosteroids

    • Antibiotics

    • Infliximab >

    • Immunosupressors

    • Azathioprine

    • 6-MP

    • Methotrexate

    • Aminosalicylates

    • Infliximab

    • NO corticosteroids







    Systemic Corticosteroids


    Oral Steroids