INFLAMMATORY BOWEL DISEASE

1. Salahadin A. (B.Pharm.)
Department of Pharmacy
Haramaya University
Ethiopia.
Inflammatory Bowel Disease

2. DEFINITION
 There are two forms of idiopathic inflammatory
bowel disease (IBD):
 ulcerative colitis, a mucosal inflammatory
condition confined to the rectum and colon, and
 Crohn’s disease, a transmural inflammation of
GI mucosa that may occur in any part of the GI
tract.
 The etiologies of both conditions are unknown, but
they may have a common pathogenetic mechanism

3. PATHOPHYSIOLOGY
 The major theories of the cause of IBD involve
a combination of infectious, genetic, and
immunologic causes.
 The inflammatory response with IBD may
indicate abnormal regulation of the normal
immune response or an autoimmune reaction
to self-antigens.
 Microflora of the GI tract may provide a trigger

4.  Crohn’s disease may involve a T lymphocyte
disorder that arises in genetically susceptible
individuals as a result of a breakdown in the
regulatory constraints on mucosal immune
responses to enteric bacteria.
 Proposed etiologies for IBD are
 Smoking appears to be protective for
ulcerative colitis but associated with increased
frequency of Crohn’s disease.

5.  Ulcerative colitis and Crohn’s disease differ in
two general respects:
 anatomic sites and depth of involvement
within the bowel wall.
 There is, however, overlap between the two
conditions, with a small fraction of patients
showing features of both diseases

6. Proposed Etiologies for Inflammatory
Bowel Disease

7. ULCERATIVE COLITIS
 Ulcerative colitis is confined to the colon and
rectum and affects primarily the mucosa and the
submucosa.
 The primary lesion occurs in the crypts of the
mucosa (crypts of Lieberkühn) in the form of a
crypt abscess.
 Local complications (involving the colon)
occur in the majority of ulcerative colitis patients.
 Relatively minor complications include

8.  A major complication is toxic megacolon,
 a severe condition that occurs in up to 7.9%
of ulcerative colitis patients admitted to
hospitals.
 The patient with toxic megacolon usually has
a high fever, tachycardia, distended
abdomen, elevated white blood cell count,
and a dilated colon.
 The risk of colonic carcinoma is much
greater in patients with ulcerative colitis as

9.  Approximately 11% of patients with ulcerative
colitis have hepatobiliary complications
including fatty liver, pericholangitis, chronic active
hepatitis, cirrhosis, sclerosing cholangitis,
cholangiocarcinoma, and gallstones.
 Arthritis commonly occurs in IBD patients and is
typically asymptomatic and migratory.
 Arthritis typically involves one or a few large
joints such as the knees, hips, ankles, wrists,
and elbows.

10.  Ocular complications (iritis, episcleritis,
and conjunctivitis) occur in up to 10% of
patients.
 Five percent to 10% of patients
experience dermatologic or mucosal
complications (erythema nodosum,
pyoderma gangrenosum, aphthous
stomatitis).

11. Aphthous Ulcers

12. CROHN’S DISEASE
 Crohn’s disease is a transmural inflammatory
process.
 The terminal ileum is the most common site of
the disorder but it may occur in any part of the
GI tract.
 About two-thirds of patients have some colonic
involvement, and 15% to 25% of patients have
only colonic disease.

13.  Complications of Crohn’s disease may involve the
intestinal tract or organs unrelated to it.
 Small-bowel stricture and subsequent obstruction is a
complication that may require surgery.
 Fistula formation is common and occurs much more
frequently than with ulcerative colitis.
 Systemic complications of Crohn’s disease are
common and similar to those found with ulcerative colitis.
 Arthritis, iritis, skin lesions, and liver disease often
accompany Crohn’s disease.
 Nutritional deficiencies are common with Crohn’s

14. Clinical Presentation of Ulcerative
Colitis

15. Clinical Presentation of Crohn’s
Disease

16. Comparison of the Clinical and Pathologic Features
of Crohn’s Disease and Ulcerative Colitis

17. DESIRED OUTCOME
 Goals of treatment include
 resolution of acute inflammatory processes,
 resolution of attendant complications (e.g., fistulas,
abscesses),
 Alleviation of systemic manifestations (e.g.,
arthritis),
 maintenance of remission from acute inflammation,
or surgical palliation or cure.

18. TREATMENT
 GENERAL APPROACH
 Treatment of IBD centers on agents used to relieve the
inflammatory process.
 Salicylates, glucocorticoids, antimicrobials, and
immunosuppressive agents are commonly used to treat
active disease and, for some agents, to lengthen the time
of disease remission.
 In addition to the use of drugs, surgical procedures are
sometimes performed when active disease is not
adequately controlled or when the required drug dosages

19. NONPHARMACOLOGIC
TREATMENT
 Nutritional Support
 Patients with moderate to severe IBD are often
malnourished.
 The nutritional needs of the majority of patients
can be adequately addressed with enteral
supplementation.
 Patients who have severe disease may require a
course of parenteral nutrition.
 Probiotic formulas have been effective in

20. Surgery
 For ulcerative colitis, colectomy may be performed
when the patient has disease uncontrolled by
maximum medical therapy or when there are
complications of the disease such as colonic
perforation, toxic dilatation (megacolon),
uncontrolled colonic hemorrhage, or colonic
strictures.
 The indications for surgery with Crohn’s disease are
not as well established as they are for ulcerative
colitis, and surgery is usually reserved for the

21. PHARMACOLOGIC THERAPY
 The major types of drug therapy used in IBD include
 aminosalicylates,
 glucocorticoids,
 immunosuppressive agents (azathioprine,
mercaptopurine, cyclosporine, and methotrexate),
 antimicrobials (metronidazole and ciprofloxacin), and
 agents to inhibit tumor necrosis factor-α (TNF- α)
(anti–TNF-α antibodies).

22.  Sulfasalazine, an agent that combines a
sulfonamide (sulfapyridine) antibiotic and
mesalamine (5-aminosalicylic acid) in the same
molecule, has been used for many years to treat
IBD.
 Corticosteroids and adrenocorticotropic hormone
have been widely used for the treatment of
ulcerative colitis and Crohn’s disease and are used
in moderate to severe disease.
 Prednisone is most commonly used.

23. Mesalamine Derivatives for
Treatment
of Inflammatory Bowel Disease

24.  Immunosuppressive agents such as azathioprine
and mercaptopurine (a metabolite of
azathioprine) are sometimes used for the
treatment of IBD.
 These agents are generally reserved for cases
that are refractory to steroids and may be
associated with serious adverse effects such as
lymphomas, pancreatitis, or nephrotoxicity.
 Cyclosporine has been of short-term benefit in
acute, severe ulcerative colitis when used in a

25.  Methotrexate given 15 to 25 mg intramuscularly
once weekly is useful for treatment and
maintenance of Crohn’s disease.
 Antimicrobial agents, particularly metronidazole,
are frequently used in attempts to control Crohn’s
disease, particularly when it involves the perineal
area or fistulas.
 Infliximab is an anti-TNF antibody that is useful in
moderate to severe active disease and steroid-
dependent or fistulizing disease but the cost far

26.  Steroids and sulfasalazine appear to be equally
efficacious; however, the response to steroids
may be evident sooner.
 Rectally administered steroids or mesalamine
can be used as initial therapy for patients with
ulcerative proctitis or distal colitis.
 Transdermal nicotine improved symptoms of
patients with mild to moderate active ulcerative
colitis in daily doses of 15 to 25 mg.

27. Severe or Intractable Disease
 Patients with uncontrolled severe colitis or
incapacitating symptoms require hospitalization for
effective management.
 Most medication is given by the parenteral route.
 With severe colitis, there is a much greater reliance
on parenteral steroids and surgical procedures.
 Sulfasalazine or mesalamine derivatives have not
been proven beneficial for treatment of severe

28.  Steroids have been valuable in the treatment of
severe disease because the use of these agents may
allow some patients to avoid colectomy.
 A trial of steroids is warranted in most patients before
proceeding to colectomy, unless the condition is
grave or rapidly deteriorating.
 Continuous IV infusion of cyclosporine (4 mg/kg/day)
is recommended for patients with acute severe
ulcerative colitis refractory to steroids.

29. Maintenance of Remission
 Once remission from active disease has been
achieved, the goal of therapy is to maintain the
remission.
 The major agents used for maintenance of
remission are sulfasalazine (2 g/day) and the
mesalamine derivatives, although mesalamine is not
as effective as sulfasalazine.
 Steroids do not have a role in the maintenance of
remission with ulcerative colitis because they are
ineffective.

30.  If they are continued, the patient will be exposed
to steroid side effects without likelihood of
benefits.
 Azathioprine is effective in preventing relapse of
ulcerative colitis for periods exceeding 4 years.
However, 3 to 6 months may be required for
beneficial effect.
 For patients who initially respond to infliximab,
continued administration of 5 mg/kg every 8
weeks as maintenance therapy is an alternative

31. SELECTED COMPLICATIONS
 Toxic Megacolon
 The treatment required for toxic megacolon includes
general supportive measures to maintain vital
functions, consideration for early surgical intervention,
and antimicrobials.
 Aggressive fluid and electrolyte management are
required for dehydration.
 When the patient has lost significant amounts of
blood (through the rectum), blood replacement is also
necessary.
 Steroids in high dosages (hydrocortisone 100 mg
every 8 hours) should be administered intravenously
to reduce acute inflammation.
 Antimicrobial regimens that are effective against
enteric aerobes and anaerobes should be

32.  Systemic Manifestations
 • The common systemic manifestations of IBD
include arthritis, anemia, skin manifestations
such as erythema nodosum and pyoderma
gangrenosum, uveitis, and liver disease.
 Anemia may be a common problem where there
is significant blood loss from the GI tract. When
the patient can consume oral medication, ferrous
sulfate should be administered. Vitamin B12 or
folic acid may also be required

33. EVALUATION OF THERAPEUTIC
OUTCOMES
 The success of therapeutic regimens to treat
IBDs can be measured by patient-reported
complaints, signs and symptoms, direct
physician examination (including endoscopy),
history and physical examination, selected
laboratory tests, and quality of life measures.
 • To create more objective measures, disease-
rating scales or indices have been created.

34.  The Crohn’s Disease Activity Index is a commonly used scale,
particularly for evaluation of patients during clinical trials. The
scale incorporates eight elements:
 (1) number of stools in the past 7 days;
 (2) sum of abdominal pain ratings from the past 7 days;
 (3) rating of general well-being in the past 7 days;
 (4) use of antidiarrheals;
 (5) body weight;
 (6) hematocrit;
 (7) finding of abdominal mass; and
 (8) a sum of symptoms present in the past week.
 Elements of this index provide a guide for those measures that
may be useful in assessing the effectiveness of treatment
regimens.

35.  Standardized assessment tools have also been
constructed for ulcerative colitis.
 Elements in these scales include
 (1) stool frequency;
 (2) presence of blood in the stool;
 (3) mucosal appearance (from endoscopy); and
 (4) physician’s global assessment based on
physical examination, endoscopy, and laboratory
data.

36. References
1. Marie A. Chisholm-Burns.Pharmacotherapy
Principles & Practice. Chisholm-burns Ma,
editor: The McGraw-Hill Companies, Inc. ; 2008.
2. Joseph T. DiPiro P, Executive Dean and
Professor, South Carolina College of
Pharmacy, University of South Carolina.
Pharmacotherapy A Pathophysiologic
Approach. Seventh Edition ed.: McGraw-Hill;
2008.
3. Koda-Kimble MAY, Lloyd Yee. Applied
Therapeutics: The Clinical Use Of Drugs, 9th
Edition. Koda-Kimble MAY, Lloyd Yee, editor:
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