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.
Chronic inflammatory bowel diseases
Differences between Crohn's disease and UC
-Abdominal pain; Diarrhea and bleeding.
Complications: Anemia ; megacolon, fever, abdominal pain, dehydration, colon cancer.
Treatment of IBD
Drugs Used for Rx and maintenance of I.B.D
I) Anti-inflammatory Drugs
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
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?
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).
B. Non-sulpha containing 5-Aminosalicylic Acid
1. Mesalamines Compounds
e.g. Asacol 5-ASA coated in pH sensitive resin that dissolved at pH 7
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).
Oral 5-ASA Release Sites
Mechanism of action
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.
(prednisone P.O. 40-60 mg/day for 2 weeks
Are used to induce remission in IBD in active
or severe conditions or steroid dependent or
steroid resistant patients.
(azathioprine & 6-mercaptopurine).
II) Immunomosuppressive Agents :
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)
- N/V and bone marrow depression; LFT changes
- Hypersensitivity reactions Why?
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.
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.
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
sulfasalazine, olsalazine, balsalazide
Pentasa, Asacol, Rowasa, Canasa
prednisone, prednisolone, hydrocortisone, budesonide
Purine analogues: Azathioprine&6mercaptopurine
TNF-alpha inhibitors (monoclonal antibodies)
Infliximab – Adalimumab - Cetrolizumab