IRRITABLE BOWEL SYNDROME

• characterized by chronic abdominal

pain and altered bowel habits in the
absence of any organic cause.
• the most commonly diagnosed
gastrointestinal condition

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 EPIDEMIOLOGY

• The prevalence 5% to 15% based on North

American and European population-based studies
• IBS affects men and women, young patients, and
the elderly.
• However, younger patients and women are more
likely to be diagnosed with IBS.
• A systematic review estimated that there is an
overall 2:1 female predominance in North
America.
• Although only 15% of those affected actually seek
medical attention, IBS is the cause of between
25% and 50% of all referrals to gastroenterologists
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 PATHOPHYSIOLOGY

• altered somatovisceral and motor dysfunction of the

intestine from a variety of causes.
• Abnormal CNS processing of afferent signals may lead
to visceral hypersensitivity, with the specific nerve
pathway affected determining the exact
symptomatology expressed
• This visceral hypersensitivity is a neuroenteric
phenomenon that is independent of motility and
psychological disturbances
• Factors known to contribute to these alterations include
genetics, motility factors, inflammation, colonic
infections, mechanical irritation to local nerves, stress,
and other psychological factors.
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• Serotonin-Type Receptors
• Two types of serotonin exists within the gut:
serotonin type 3 (HT3) and serotonin type 4
(HT4), which are responsible for secretion,
sensitization, and motility.
• Previous studies show that there is an increase in
the postprandial levels of 5-HT in those who
suffer from diarrhea predominant IBS when
compared with non-sufferers.
• Therefore, stimulation and antagonism of these
serotonin receptors has become a focused area
for research on new drug therapies for both
diarrhea- and constipation-predominant disease. 4
 CLINICAL PRESENTATION

• presents as either diarrhea-predominant

or constipation-predominant disease and
• can be defined as lower abdominal pain,
disturbed defecation (constipation,
diarrhea, or an alternating pattern of
both), and bloating in the absence of
structural or biochemical factors that
might explain these symptoms

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Clinical Presentation of Irritable Bowel Syndrome

Signs and 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
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Non-GI symptoms
• Urinary symptoms
• Fatigue
• Dyspareunia
Other concurrent conditions
• Fibromyalgia
• Functional dyspepsia
• Chronic fatigue syndrome
Reduced health-related quality of life
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 Symptom-Based Criteria for Irritable Bowel Syndrome

The Manning criteria

• Chronic or recurrent abdominal pain for at least
6 months and two or more of the following:
1. Abdominal pain relieved with defecation
2. Abdominal pain associated with more frequent
stools
3. Abdominal pain associated with looser stools
4. Abdominal distension
5. Feeling of incomplete evacuation after
defecation
6. Mucus in stools
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 Symptom-Based Criteria for Irritable Bowel Syndrome

Rome III diagnostic criteria for irritable

bowel syndrome
• Recurrent abdominal pain or discomfort at
least 3 days per month in the last 3 months
associated with two or more of the following:
1. Relieved with defecation
2. Onset associated with a change in
frequency of stool
3. Onset associated with a change in form
(appearance) of stool
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• Additional diagnostic steps that can
be taken include
– sigmoidoscopy or colonoscopy
– examination of the stool for occult blood
and ova and parasites
– complete blood cell count
– Erythrocyte sedimentation rate, and
– serum electrolytes

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 TREATMENT

Irritable Bowel Syndrome

GENERAL APPROACH TO TREATMENT
• Milder, less frequent episodes can be managed with
dietary restrictions and a higher-fiber diet, with addition
of bulk-forming laxatives, if necessary.
• More persistent disease may require as-needed uses of
various antispasmodic or antidiarrheal agents such as
loperamide
• Lastly, the most severe forms of this disease may call
for pharmacologic agents directed specifically at the
underlying neurohormonal imbalance, such as the 5-
HT4 agonists, such as tegaserod, or the 5-HT3 receptor
antagonists, such as alosetron.
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Treatment algorithm for irritable bowel syndrome

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Treatment algorithm for irritable bowel syndrome

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CLINICAL CONTROVERSY
• The newer serotonin receptor agonists and antagonists
tegaserod and alosetron act on GI-specific serotonin
receptors to treat constipation-predominant and diarrhea
predominant IBS, respectively.
• However, both drugs are currently only indicated for
women.
• Efficacy and safety in men has not been established
because the initial manufacturer’s sponsored clinical trials
contained insufficient numbers of men with IBS to provide
the necessary statistical power to prove efficacy and safety.
• Ongoing studies should determine if these drugs are
indicated in men.

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• Alosetron, a 5-HT3 receptor antagonist, was
withdrawn from the U.S. market in 2000 as a
result of serious adverse effects, including
severe constipation and ischemic colitis that did
not appear in the initial clinical trials.
• It was reintroduced in 2002 and is now limited
to an FDA-approved restricted-use program in
lower initial doses, and requires extensive
postmarketing surveillance.
• Results of these trials are necessary to
definitively determine alosetron’s true safety
profile, especially with regard to its association
with or causation of fatal ischemic colitis. 15
 CONSTIPATION-PREDOMINANT DISEASE

• dietary fiber may be beneficial

• Patients should be instructed to begin with 1
tablespoonful of fiber with 1 meal daily and
• gradually increase the dose to include fiber with 2 and
3 meals a day until the desired outcome is achieved.
• End points: bulkier and more easily passed stools.
• If unable to tolerate dietarybran, bulking agents such
as psyllium may be substituted
• Laxative use is not encouraged in these patients, and
it should only be used in the smallest dose for the
least amount of time in cases of severe constipation

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Tegaserod
• is a serotonin derivative that activates 5-HT4
receptors on the neurons in the gastrointestinal
tract
• increases GI motility and decreases visceral
sensations.
• approved as 2-mg or 6-mg doses given twice daily
30 minutes prior to a meal with water for up to 12
weeks.
• Stimulation of the 5-HT4 receptors by tegaserod
increases gastric secretions and promotes motility,
with improvement in symptoms generally occurring 17
• Currently this therapy is only approved for use in
women, as efficacy and safety in men has not
been established because of inadequate
numbers of men enrolled in clinical trials to date.
• In addition, length of effective therapy has only
been approved for 12 weeks; however,
tegaserod may provide safe and effective
therapy for up to 12 months.
• Diarrhea was the most common adverse effect,
resulting in drug discontinuation in 1.6% of study
subjects.

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 DIARRHEA-PREDOMINANT DISEASE

• Caffeine, alcohol, and artificial

sweeteners (sorbitol, fructose, and
mannitol) are known to irritate the gut
and produce a laxative effect.
• Lactose intolerance should be considered
in certain patients; however, the
prevalence of this condition may be
exaggerated.
• Herbal medicines or teas often contain
senna, which may produce diarrhea.
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loperamide
• used for episodic management of urgent diarrhea,
• Decreases intestinal transit, enhances water and
electrolyte absorption, and strengthens rectal
sphincter tone.
• careful dosage titration can usually be undertaken
to prevent the development of constipation.
• Bile acid sequestrants such as cholestyramine
may be useful in patients with diarrhea related to
idiopathic bile acid malabsorption or following
cholecystectomy

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Alosetron
• the first truly effective treatment for diarrhea-
predominant IBS.
• However, in November 2000 it was voluntarily withdrawn
from the market
– because of severe GI adverse effects, constipation and 8 cases
of possible ischemic colitis and death.
• Because this drug was highly effective in many patients,
the FDA approved restricted use of alosetron in June 2002.
• lower initial doses of 0.5 mg twice daily, for women with
diarrhea-predominant symptoms of longer than 6 months’
duration that are not relieved by conventional therapy.

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• Use of Antidepressants in IBS
• Tricyclic antidepressants :have shown
some benefit in treatment of
diarrhea-predominant IBS associated
with moderate to severe abdominal
pain, by modulating perception of
visceral pain, altering GI transit time,
and treating underlying
comorbidities.
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 PAIN IN IBS

• Both TCAs and SSRIs produce analgesia, and may

relieve depressive symptoms if present.
• Preprandial doses of drugs containing
anticholinergic properties may suppress pain
(and/or diarrhea) associated with an overactive
postprandial gastrocolonic response.
• TCAs 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
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• DRUG CLASSES CURRENTLY UNDER
INVESTIGATION FOR THE TREATMENT OF IBS
• Probiotics such as Lactobacillus and
Bifidobacterium reduced IBS symptoms in
several investigation trials.
• Another 5-HT3 antagonist, cilansetron, has
demonstrated similar efficacy to that of
alosetron in phase II trials and enrolled
enough male patients to show benefit in
males as well.
• This drug is currently in phase III trials.
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 EVALUATION OF THERAPEUTIC OUTCOMES

• IBS is usually classified as constipation-predominant, diarrhea

predominant, or IBS with abdominal pain and bloating.
• Therapeutic goals in IBS should focus on the patient’s primary
complaint.
• Dietary and drug therapy goals should focus on end-organ
treatment to relieve abdominal pain (antispasmodic drugs) or
disturbed bowel habits (antidiarrheals and bulk-forming agents).
• Additionally, severe symptoms from central nervous system
dysregulation should be treated with antidepressants,
psychotherapy, relaxation/stress management, cognitive behavior
treatment, and/or hypnosis aimed at specific affective disorders.
• Lastly, the serotonin receptor agonists and antagonists can be
used in carefully selected patients whose symptoms are not
adequately controlled with other agents.
• patients with severe IBS consider psychological treatments such as
psychotherapy, relaxation/stress management, and/or cognitive 25
Thank you!

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• Current procedures used in the diagnosis of
irritable bowel syndrome include:
A. Manning or Rome III criteria
B. Sigmoidoscopy or colonoscopy
C. Occult blood test and examination for
parasites
D. CBC and erythrocyte sedimentation rate
E. All of the above
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• Which of the following statements about
irritable bowel syndrome (IBS) is/are true?
A. It affects up to 80% of adults worldwide
B. It is equally prevalent in both men and women
C. It is characterized by abdominal pain,
disturbed defecation, and bloating
D. It is known to be of viral origin
E. All of the above

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• The major pathophysiologic cause of irritable
bowel syndrome is believed to be:
A. Bipolar disorder
B. Norwalk and rotavirus
C. Laxative abuse
D. Visceral hypersensitivity
E. E. coli

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• Which of the following treatment measures is
recommended in constipation-predominant
IBS?
A. Saline cathartics
B. Loperamide
C. Mineral oil
D. Dietary fiber

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