College of Pharmacy pharmacology of GIT Inflammatory bowel disease by Dr. sherzad Kh RASHID

Inflammatory bowel disease Inflammatory bowel diseases are chronic inflammatory conditions of gut. This include Crohn’s disease and ulcerative colitis .

Crohn’s disease -CD CD takes its name from one of three physicians who first described the disease in 1932. CD may affect any part of GIT from the lips to the anal margin, but ileocolic disease remains the commonest presentation.

Ulcerative colitis -UC UC is a chronic relapsing inflammatory disorder affecting colonic and rectal mucosa. If UC affects only the rectal mucosa it is termed proctitis. If it involves the rectum and the sigmoid colon it is known as proctosigmoiditis. Involvment of other parts of colon is termed colitis.

Treatment of inflammatory bowel disease A wide assortment of drugs and nutritional supplements are available to maintain the patient in long periods of remission in both CD and UC. However, surgical intervention will eventually become necessary when the patient relapses and fails to respond to drug therapy.

Drug treatment Aminosalicylates Corticosteroids , and immunosuppressive agents are routenly used. Others : cyclosporin, sodium cromoglycate, bismuth salts, arsenic salts, thalidomide , antibiotic , cholestyramine , fish oil, nicotine and metronidazol are helpful in some cases.

1. Aminosalicylates E.g. sulfasalazine , mesalamine are used to treat mild or moderate UC and CD. Sulphasalazine is the most effective in maintaining remission in ulcerative colitis. Sulphasalzine consists of sulphapyridine diazotized + 5-aminosalicylic acid (mesalazine ) which is active form.

Actions of sulfasalazine Sulfasalazine is metabolized by intestinal bacteria into two compound (five- aminosalicylic acid( 5-ASA ) and sulfpyridine ). 5-ASA is the compound responsible for reducing inflammation, whereas sulfpyridine is responsible for adverse effects. Mechanism :Possible , mechanism by which 5-ASA reduces inflammation include , suppression of prostaglandin synthesis and suppression of migration of inflammatory cell into affected region.

Side effects Approximately 30% of patients using sulfasalazine discontinue the drug because of toxicity. The most common problems are dose-related and include nausea, gastrointestinal upset, headaches, arthralgias, myalgias, bone marrow suppression, and malaise reversible infertility occurs in men, but sulfasalazine does not affect fertility in women. The drug does not appear to be teratogenic

2. Corticosteroids The preferred steroid is prednisolone, administered orally or rectally and parentrally in emergency situations. Glucocorticoids are indicated primarily for induction of remission and not for long term maintenance. Side effects: adrenal suppression, osteoporosis, peptic ulcer and hyperglycemia.

3. Immunomodulators Immunosuppressants e.g. azathioprine, mercaptopurine, Cyclosporine and methotrexate are used for long term therapy. Azathioprim by it self is inactive once in the body it is converted to mercaptopurine a compound with pharmacologic activity.

Adverse Effects Dose-related toxicities of azathioprine or 6-mercaptopurine include nausea, vomiting, bone marrow depression (leading to leukopenia, macrocytosis, anemia, or thrombocytopenia), and hepatic toxicity

4. Anti-TNF-Alpha Therapy: Infliximab Infliximab ( Remecade )is a new and unique drug for Crohn’s disease . This highly effective agent is a monoclonal antibody that bind with and thereby inactivates tumor necrosis factor-alpha , a key immunoinflammatory modulator.

Adverse effects Infliximab infusions result in acute adverse infusion reactions in > 10% of patients, but discontinuation of the infusion is required in only 1%. Early reactions include : fever, chills, pruritus, urticaria, or cardiopulmonary symptoms that include chest pain, dyspnea, or hemodynamic instability

Drugs Used In The Treatment Of Irritable Bowel Syndrome

Irritable Bowel Syndrome ( IBS ) Irritable Bowel Syndrome ( IBS ) is an idiopathic chronic, relapsing disorder characterized by abdominal discomfort (pain, bloating, distention, or cramps) in association with alterations in bowel habits (diarrhea, constipation, or both). With episodes of abdominal pain or discomfort, patients note a change in the frequency or consistency of their bowel movements.

Treatment of IBS Pharmacologic therapies for IBS are directed at relieving abdominal pain and discomfort and improving bowel function. For patients with predominant diarrhea, antidiarrheal agents, especially loperamide, are helpful in reducing stool frequency and fecal urgency. Antispasmodics (Anticholinergics) Commonly used medications in this class include dicyclomine and hyoscyamine

Serotonin 5-HT3-receptor Antagonists Alosetron is a 5-HT3 antagonist that has been approved for the treatment of patients with severe IBS with diarrhea. Four other 5-HT3 antagonists (Ondansetron, Granisetron, Dolasetron, And Palonosetron) have been approved for the prevention and treatment of nausea and vomiting ; however, their efficacy in the treatment of IBS has not been determined