1. Irritable Bowel Syndrome

2. Case
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

3. Contd.
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

4. Contd.
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

5. Assessment IBS associated with: abdominal discomfort Bloating
constipation

6. What is Irritable Bowel Syndrome(IBS)?
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.

8. Symptoms of IBS Abdominal discomfort and pain
Bloating, mucous in stools, diarrhea, constipation, or alternating diarrhea and constipation
Depression, anxiety or stress
IBS can be subdivided into
Diarrhea-predominant (IBS-D)
Constipation-predominant (IBS-C)
Alternating diarrhea and constipation

10. Treatment

12. Patient Counseling and Dietary Alterations
Reassurance and careful explanation of the functional nature of the disorder
how to avoid obvious food precipitants are important first steps

13. Antispasmodics
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

14. 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

15. 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

16. 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

17. 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
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

18. Serotonin is important in gut function
GI disorders may be related to
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.

19. Serotonin (5-hydroxytryptamine, 5HT)
A monoamine neurotransmitter
Found in cardiovascular tissue, the peripheral nervous system, blood cells, and the CNS
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 ….

21. 5HT3 receptors and its antagonists
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

22. 5HT4 receptors and its agonists
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

23. Tegaserod in IBS-C
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.

24. How does tegaserod work?
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

25. Tegaserod –a Promising Option
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

26. DIARRHEA-PREDOMINANT DISEASE
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

27. Continuing…
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

28. Alosetron in IBS-D
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

29. How does alosetron works?
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.

30. Alosetron-New Drug for IBS
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

31. Antidepressant Drugs
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 diarrhea-predominant 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

32. Cotinuing…
paroxetine may be useful in constipation-predominant patients
A small placebo-controlled study of citalopram in IBS patients reported reductions in pain

33. Antiflatulence Therapy