This document provides an overview of the pharmacotherapy of inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). It defines IBD and IBS, discusses their pathophysiology and clinical presentation. For treatment, it outlines the general approaches including medications used to induce and maintain remission for IBD such as aminosalicylates, corticosteroids, immunosuppressants, antibiotics, biologics and surgery. It also discusses managing IBD complications. For IBS, it discusses treatments based on predominant symptoms including fiber, laxatives, antispasmodics, antidiarrheals, 5-HT3/5-HT4 agents and psychotherapy. The document concludes by evaluating

1. Pharmacotherapy of irritable bowel
syndrome and inflammatory bowel
disease
By
solomon weldegebreal(B.pharm,
Msc)
1

2. Pharmacotherapy of inflammatory
bowel disease
Out line
Introduction
Pathophysiology
clinical presentation
Treatment
Evaluationg out comes
2

3. Introduction(1)
Definition
• Inflammatory bowel disease (IBD) is an immune-
mediated chronic intestinal condition.
• There are two forms of idiopathic inflammatory
bowel disease (IBD).
• Ulcerative colitis-a mucosal inflammatory condition
confined to the rectum and colon.
• Crohn’s disease - a chronic disease of unknown causes that
mainly presents as granulomatous inflammatory lesions of
the gastroentestinal tract.
3

4. Introduction(2)
Epidemiology
The incidence of IBD varies within different
geographic areas.
CD and UC both occur at the highest incidence
in Europe, the United Kingdom, and North
America
Crohn's disease (CD) in united states has
• an incidence of 3.6 to 8.8 per 100,000 persons
• prevalence of 20 to 40 per 100,000 people
4

5. Introduction(3)
• Ulcerative colitis (UC) incidence ranges from 3
to 15 cases per 100,000 persons per year
among the white population with a
prevalence of 80 to 120 per 100,000.
• Both sexes are affected equally with IBD,
although some studies show slightly greater
numbers of women with CD and males with
UC.
5

6. Introduction(4)
• The peak incidence occurs in the second or
third decades of life, with a second peak
occurring between 60 and 80 years of age.
6

7. Introduction(5)
Etiology
The etiologies of both conditions are
unknown, but they may have a common
pathogenic mechanism.
The cause of IBD involve a combination of
infectious, genetic, and immunologic factors.
7

8. Introduction(6)
Proposed etiologies of IBD
 Infectious agents-Viruses (e.g., measles),
Mycobacteria,Chlamydia
 Genetics-Metabolic defects-Connective tissue disorders,
Select genes and single nucleotide polymorphisms
 Enviromental factors- diet, smoking(CD)
 Psychological factors-stress, occupation, emotional or
physical trauma
 Immune defects-immune mediated mucosal damage
8

9. Pathopysiology(1)
• UC and CD differ in two general respects:
anatomic sites and depth of involvement
within the bowel wall.
• 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 to activate inflammation.
9

10. Pathophysiology(2)
• 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.
• Smoking appears to be protective for
ulcerative colitis but associated with increased
frequency of Crohn’s disease.
10

11. Pathophysiology(3)
• Ulcerative colitis
• It is confined to the colon and rectum
• affects primarily the mucosa and the submucosa.
• The primary lesion occurs in the crypts of the mucosa in
the form of a crypt abscess.
• Involve Local complications
• Relatively minor complications include
hemorrhoids,anal fissures, or perirectal abscesses.
11

12. Pathophysiology(4)
• A major complication is toxic megacolon-occur
in 7.9% of UC patients admitted to hospital
• Greater risk of colonic carcinoma
• Hepatobiliary complications(10%)-fatty liver,
pericholangitis, chronic active
hepatitis,cirrhosis, sclerosing cholangitis,
cholangiocarcinoma, and gallstones.
12

13. Pathophysiology(5)
• Arthritis-is usually asymptopatic and
migratory
• Ocular complications (iritis, episcleritis, and
conjunctivitis) occur in up to10% of patients.
• 5% to 10% of patients experience
dermatologic or mucosal complications
(erythema nodosum, pyoderma gangrenosum,
aphthous stomatitis).
13

14. Pathophysiology(6)
• Crohn’s disease
it 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
14

15. Pathophysiology(7)
• Patients often have normal bowel separating
segments of diseased bowel; that is, the
disease is often discontinuous.
• Complications of crohn’s diseasea
Small bowel stricture
Obstruction
Nutritional deficiency
Iritis,arthritis,liver disease,skin lesion
15

16. Clinical presentation(1)
• Ulcerative colitis
Sign & symptoms
• Abdominal cramping
• Frequent bowel movements, often with blood in the stool
• Weight loss
• Fever and tachycardia in severe disease
• Blurred vision, eye pain, and photophobia with ocular
involvement
• Arthritis
• Raised, red, tender nodules that vary in size from 1 cm to
several centimeters
16

17. Clinical presentation(2)
Physical examination
• Hemorrhoids, fissures, or perirectal abscesses may be
present
• Iritis, uveitis, episcleritis, and conjunctivitis with ocular
involvement
• Dermatologic findings with erythema nodosum,
pyoderma gangrenosum, or aphthous ulceration
17

18. Clinical presentation(3)
Laboratory tests
• Decreased hematocrit/hemoglobin
• Increased erythrocyte sedimentation rate
• Leukocytosis and hypoalbuminemia with severe disease
18

19. Clinical presentation(4)
• Patients with moderate disease have more
than four stools per day but with minimal
systemic disturbance.
• With severe disease, the patient has more
than six stools per day with blood, with
evidence of systemic disturbance as shown by
fever, tachycardia,anemia, or erythrocyte
sedimentation rate greater than 30.
19

20. Clinical presentation..CD….
Crohn’s disease
• Clinical symptoms
diarrhea(80%) and abdominal pain(70%)
Hematochezia is observed in 30 % of patients, but
is usually not massive.
 a perirectal or perianal lesion(50%).
 fistulas and abscesses(15%)
20

21. Clinical presentation…CD..
• Systemic symptoms
weight loss and fever(40-70%)
Extra-intestinal complications such as lesions in
the joints, skin, and eyes are observed in
approximately 2–10 % of patients.
21

22. Clinical presentation…CD..
As with ulcerative colitis, the presentation of
Crohn’s disease is highly variable. A single
episode may not be followed by further episodes,
or the patient may experience continuous,
unremitting disease.
The course of Crohn’s disease is characterized by
periods of remission and exacerbation. Some
patients may be free of symptoms for years,
while others experience chronic problems in spite
of medical therapy.
22

23. Treatment
• Desired outcome
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
23

24. Treatment..
• General approach
 Salsilates
 glucocorticoids
 Antimicrobials
 Immunosuppressive agents
 surgery
24

25. Treatment..
• Non pharmacologic treatment
Nutritional support
surgery
• Pharmacologic treatment
The major types of drug therapy used in IBD
I. Aminosalsilates - mild IBD
II. Glucocorticoids(predinsolone) – moderate to
sever
25

26. Treatment…
III. immunosuppressive agents(azathioprine and
mercaptopurine)-reserved for cases that are
refractory to steroids and may be associated
with serious adverse effects such as
lymphomas, pancreatitis, or nephrotoxicity.
IV. Methotrexate given 15 to 25 mg
intramuscularly once weekly is useful for
treatment and maintenance of Crohn’s
disease.
26

27. Treatment…
V. Antimicrobial agents, particularly
metronidazole, are frequently used in
attempts to control Crohn’s disease,
particularly when it involves the perineal area
or fistulas.
VII. anti-TNF antibody(Infliximab)- moderate to
sever active disease and steroid-dependent or
fistulizing disease but expensive.
27

28. Treatment….
I. ulcerative colitis
 Management of ulcerative colitis depends on the
severity of the disease.
 Rectally administered steroids or mesalamine
can be used as initial therapy for patients with
ulcerative proctitis or distal colitis.
28

29. Treatment…
29

30. Treatment…
1. Croh’s disease
I. Active CD
• The goal of treatment for active Crohn’s
disease is to achieve remission;however, in
many patients, reduction of symptoms so that
the patient may carry out normal activities or
reduction of the steroid dose required for
control is a significant accomplishment.
30

31. 31

32. Treatment…
• Cyclosporine is not recommended for Crohn’s
disease except for patients with symptomatic
and severe perianal or cutaneous fistulas.
32

33. Treatment…
II. Maintenance of remission
 Prevention of recurrence of disease is clearly
more difficult with Crohn’s disease than with
ulcerative colitis.
 Sulfasalazine and oral mesalamine derivatives
are effective in preventing acute recurrences
in quiescent Crohn’s disease.
 Steroids have no place
33

34. Treatment…
III. Management of complications
Toxic Megacolon
o When the patient has lost significant amounts of
blood (through the rectum), blood replacement is
also necessary.
o Dehydration
o antimicrobials
Anemia-ferious sulphate inddition folic acid
and vitamin B 12
34

35. Treatment..
• Special considerations for pregnancy
Drug therapy for IBD is not a contraindication for
pregnancy
If a patient has an initial bout of IBD during , a
standard approach to treatment with sulfasalazine
or steroids should be initiated.
Folic acid supplimmentation-1mg BID
Metronidazole,methotrexate, shuold not be used
Azathioprine and mercaptopurine-fetal deformity
35

36. Treatment….
• Evaluation of therapeutic out comes
patient-reported complaints
 signs and symptoms
direct physician examination(including endoscopy)
 history and physical examination
 selected laboratory tests, and quality of life
measures.
36

37. Irritable bowel syndrome
• Out line
Introduction
Pathophysiology
Clinical presentation
Treatment
Evaluating out come
37

38. Introduction
definition
• IBS is a gastrointestinal syndrome
characterized by chronic abdominal pain and
altered bowel habits in the absence of any
organic cause.
• It is the most commonly diagnosed
gastrointestinal condition.
38

39. Introduction…
• Epidemiology
The prevalence of IBS is approximately 10% to
15% based on North American and European
population-based studies.
younger patients and women are more likely to be
diagnosed with IBS.
39

40. Pathophysiology(1)
• IBS results from altered somatovisceral and
motor dysfunction of the intestine from a
variety of causes.
• Abnormal central nervous system processing
of afferent signals may lead to visceral
hypersensitivity, with the specific nerve
pathway affected determining the exact
symptomatology expressed.
40

41. Pathophysiology(2)
• Factors known to contribute to these
alterations include
genetics,
motility factors
Inflammation
colonic infections
mechanical irritation to local nerves, stress, and
other psychological factors.
41

42. Pathophysiology(3)
• Two types of serotonin exist within the gut:
serotonin type 3 (HT3) and serotonin type 4
(HT4), which are responsible for secretion,
sensitization, and motility.
• There is an increase in the postprandial levels
of 5-HT in those who suffer from diarrhea-
predominant IBS when compared with
nonsufferers.
42

43. Clinical presentation
• Sign & symptoms
• Lower abdominal pain
• Abdominal bloating and distension
• Diarrhea symptoms, >3 stools/day
• Extreme urgency
• Passage of mucus
• Constipation symptoms, <3 stools/wk, straining,
incomplete evacuation
• Psychological symptoms such as depression and anxiety
43

44. Clinical presentation…
• Nongastrointestinal symptoms
Urinary symptoms
Fatigue
Dyspareunia
• Other concurrent conditions
o Fibromyalgia
o Functional dyspepsia
o Chronic fatigue syndrome
44

45. Treatment
• General approach
 The treatment approach to IBS is based upon the
predominant symptoms and their severity.
a. Milder, less frequent episodes - dietary restrictions
and a higher-fiber diet, with addition of bulk-forming
laxatives, if necessary.
b. More persistent disease - antispasmodic or
antidiarrheal agents such as loperamide.
c. the most-severe - the 5-HT 4 agonists (e.g.,
tegaserod), or the 5-HT3 receptor antagonists (e.g.,
alosetron).
45

46. Treatment…
• Constipation predominant disease
I. Dietary fiber
II. Bulking agents e.g psyllum
III. 5-HT4 receptors agonists(Tegaseride) – increase
GI motility & decrease viseral sensation
• Diarrhea predominant disease
Avoid Caffeine, alcohol, and artificial sweeteners
(sorbitol, fructose, and mannitol)
46

47. Treatment..
 Loperamide - decreases intestinal transit, enhances
water and electrolyte absorption, and strengthens
rectal sphincter tone.
 5-HT 3 receptor antagonist (Alosetron )
 Pain in IBS - tricyclic antidepressants and serotonin
reuptake inhibitors
 Tricyclic antidepressants should be avoided in patients
with pain and constipation.
 In addition, psychotherapy, including cognitive
behavioral therapy, relaxation therapy, and
hypnotherapy, has been shown to decrease IBS
symptoms.
47

48. Treatment..
• Evaluation of therapeutic out come
Therapeutic goals in IBS should focus on the
patient's primary complaint.
relieve abdominal pain - antispasmodic drugs
Improved disturbed bowel habits - antidiarrheals
and bulk-forming agents.
central nervous system dysregulation -
antidepressants, psychotherapy,
48

49. Thank you
49