Irritable Bowel
Syndrome
Case
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A 34-year-old woman who presents to her physician with the
chief complaint of a 4-month history of hard pellet-like stools
and difficulty when passing stools
She states that she constantly feels bloated and has taken to
wearing loose-fitting clothing because she cannot tolerate
anything tight around her abdomen
She states that she was diagnosed with “spastic colon” in
college and thinks she remembers hearing the physician
talking about IBS as a diagnosis
She has been able to tolerate the minimal symptoms until
about 6 months ago when she began to notice some bloating
and a decrease in the number of bowel movements per week
Contd.
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She attributes the worsening symptoms to increased stress at
work and her recent enrollment in an evening MBA program.
Prior to 6 months ago, she states that she averaged about
five stools a week. She estimates that she has had one or two
bowel movements a week for the past month.
She complains of straining to pass her stools and states that
she has to get up 30 minutes earlier in the morning to allow
for an attempt to pass a stool.
She also states that the abdominal pain is not limited to when
she passes a stool. She complains of abdominal pain and
bloating almost continuously throughout the day for the past 2
months, although her symptoms are somewhat alleviated by
passing a “good stool
Contd.
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She also states that the symptoms are worse when she has
midterms or finals or when she needs to complete a major
college writing assignment.
She does not remember having any gastroenteritis symptoms
in the past year, and she has never eaten yogurt.
She resumed taking psyllium powder 3 months ago but could
not stand the taste and wasn’t sure how much it was helping.
She thought about trying FiberCon but didn’t know if it would
help her symptoms since both psyllium and FiberCon are
laxatives.
She switched to sorbitol solution, but she says it tastes too
sweet and doesn’t seem to help
Assessment
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IBS associated with:
 abdominal
discomfort
 Bloating
 constipation
What is Irritable Bowel Syndrome(IBS)?
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A group of functional bowel disorders
Chronic abdominal complaints without a structural or
biochemical cause
Constitutes a major health problem with
gastrointestinal (GI) symptoms
The cause of IBS is unknown.
Affects up to ~20 % adults in the industrialized
world
The condition is more frequent in women.
The direct medical costs of IBS are ~ $ US 8 billion
in the US each year.
Symptoms of IBS
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Abdominal discomfort and pain
Bloating, mucous in stools, diarrhea, constipation, or
alternating diarrhea and constipation
Depression, anxiety or stress
IBS can be subdivided into
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Diarrhea-predominant (IBS-D)
Constipation-predominant (IBS-C)
Alternating diarrhea and constipation
Treatment
Patient Counseling and Dietary
Alterations
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Reassurance and careful explanation of
the functional nature of the disorder
how to avoid obvious food precipitants
are important first steps
Antispasmodics
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anticholinergic drugs may provide temporary
relief for symptoms such as painful cramps
related to intestinal spasm
postprandial pain is best managed by giving
antispasmodics 30 min before meals
belladonna alkaloids
Some physicians prefer to use synthetic
anticholinergics such as dicyclomine that have
less effect on mucous membrane secretions
and therefore produce fewer undesirable side
effects
Mebeverin (colofac®)
an antispasmodic with a direct action on
the smooth muscle of the
gastrointestinal tract
 135 mg three times daily by mouth
before meals
 100 mg three times daily has also been
used
 A modified-release preparation is also
available, taken as 200 mg twice daily
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Continuing…
25 mg for those aged 3 to 4 years
 50 mg for those 4 to 8 years
 100 mg for those 8 to 10 years
 135 to 150 mg for those over 10 years
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Adverse Effects and
Precautions
adverse effects appear rare
 gastrointestinal disturbances
 dizziness, headache, insomnia, anorexia,
and decreased heart rate have been
reported
 rash, urticaria, and angioedema
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CONSTIPATIONPREDOMINANT DISEASE
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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
For patients unable to tolerate dietary bran, 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
The 5-HT4 agonist tegaserod is the first therapy
approved by the FDA specifically for the treatment
of constipation-predominant form
Serotonin is important in gut function
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GI disorders may be related to
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an imbalance of serotonin in the gut
an improper reaction of the digestive system to serotonin
a faulty communication network between serotonin in the gut
and the brain and spinal cord.
Serotonin plays a major role in modulating intestinal
movement and perception of pain. Helps to soften
stools by releasing water.
Serotonin (5-hydroxytryptamine, 5HT)
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A monoamine neurotransmitter
Found in cardiovascular tissue, the
peripheral nervous system, blood cells,
and the CNS
HO
95 % resides in the GI tract
Serotonergic neurons secrete 5HT
The function of serotonin is exerted upon
its interaction with specific receptors.
14 distinct families of 5HTreceptors;
5HT1, 5HT2, 5HT3 and ….
NH2
N
H
5HT3 receptors and its antagonists
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5HT3 receptors
 A ligand-gated cation channel
 Present in the GI tract
 Control sensation, contraction of intestinal muscle
 Release of fluid into the intestines
5HT3 antagonists
 Slow intestinal transit
 Decrease intestinal secretions
 Decrease the water content of stool
 Diminish colonic pain
5HT4 receptors and its agonists
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5HT4 receptors
 G-protein-coupled receptor
 Present in the GI tract
 Mediate both relaxation and contraction of circular
smooth-muscle strips
 Induces small bowel and to a lesser extent colonic fluid
secretion
5HT4 agonists
 Accelerate gastric emptying
 Accelerate small and large bowel transit
 Increase stool water content
Tegaserod in IBS-C
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The first selective serotonin 5HT4 receptor partial
agonist approved by FDA for the treatment of
abdominal pain and constipation predominent IBS
patients
Brand name is ZelnormTM by Novartis Pharmceu. Corp.
How does tegaserod work?
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The exact mechanism of tegaserod’s action is not yet
understood completely.
Tegaserod binds with high affinity at 5HT4 receptors.
The activation of 5HT4 receptors in GI tract stimulates the
peristaltic reflex and intestinal secretion
As a result, contractions increase and the increased
contractions speed the transit of digesting food and reverse
constipation.
Reduces the sensitivity of the intestinal pain-sensing nerves
and reduces pain by inhibiting visceral sensitivity
Tegaserod –a Promising Option
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Tegaserod is rapidly absorbed and metabolized.
Effective in increasing the frequency of stools,
relieving abdominal pain and discomfort, and
decreasing the sensations of bloating
Diarrhea is an occasional side effect
Is approved only for women
Should be prescribed under the guidance of a
specialist
DIARRHEA-PREDOMINANT
DISEASE
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Avoidance of certain food products may be necessary
Caffeine, alcohol, and artificial sweeteners (sorbitol,
fructose, and mannitol) are known to irritate the gut
and produce a laxative effect
Herbal medicines or teas often contain senna, which
may produce diarrhea
In patients with disease persistence following dietary
modification, loperamide may be used for episodic
management of urgent diarrhea
or in situations in which the patient wishes to avoid
the possibility of an acute onset of symptoms
Continuing…
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Loperamide decreases intestinal transit,
enhances water and electrolyte absorption,
and strengthens rectal sphincter tone
Cholestyramine may be useful in patients
with diarrhea related to idiopathic bile
acid malabsorption or following
cholecystectomy
Diarrhea-predominant IBS caused by
excessive stimulation of the 5-HT3
receptor can be relieved by the drug
alosetron
Alosetron in IBS-D
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The first drug is approved for female patients by
FDA
Brand name is Lotronex® by Glaxo Smith Kline
A potent and selective antagonist of the 5HT3
receptors
How does alosetron works?
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The exact mechanism how alosetron relieves the
symptoms of IBS-D is unknown.
Serotonin in the intestines controls how pain is felt,
contraction of intestinal muscle, and release of fluid
into the intestines. An excessive release of or an
excessive response to serotonin causes a pain and
diarrhea.
By blocking 5HT3 receptors, alosetron reduced pain
and motor responses.
Alosetron-New Drug for IBS
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Alosetron is rapidly absorbed and extensively
metabolized.
Effective in relieving pain, normalizing bowel
frequency, and reducing urgency
In November 2000 it was voluntarily withdrawn from the market
due to severe GI adverse effects, including 113 reported cases
of serious 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
Alosetron is now available via an FDA-approved restricted use
program
It is now indicated, in lower initial doses of 1 mg daily, for
women with diarrhea-predominant symptoms of greater than 6
months’ duration that are not relieved by conventional therapy
Antidepressant Drugs
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In addition to their mood-elevating effects,
antidepressent medications have several physiologic
effects that may be beneficial in IBS
In a 2-month study of desipramine, abdominal pain
improved in 86% of patients compared to 59% given a
placebo
Another study of desipramine in 28 IBS patients
showed improvement in stool frequency, diarrhea, pain,
and depression
Improvements were observed mainly in diarrheapredominant patients
The beneficial effects of the tricyclic compounds in the
treatment of IBS appear to be independent of their
antidepression actions
The therapeutic benefits for the bowel symptoms occur
faster and at a lower dosage
Cotinuing…
paroxetine may be useful in
constipation-predominant patients
 A small placebo-controlled study of
citalopram in IBS patients reported
reductions in pain
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Antiflatulence
Therapy