Functional GI Disorders

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Functional GI Disorders

• Yousif A. Qari MD,FRCPC

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Functional GI Disorders

• Irritable Bowel Syndrome
• Functional Dyspepsia

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Irritable Bowel Syndrome
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Definition

• Irritable bowel syndrome (IBS)
• is a chronic medical disorder characterized by
  abdominal pain and altered bowel function

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World Prevalence of IBS

• 10 and 20 around the globe.
• 20 -50 of GI referrals

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Prevalence of IBS Diagnosis in Primary Care and
Gastroenterology Practices
IBS
IBS
Other diagnosis
Other GI diagnsis
Prevalence in Gastroenterology
Prevalence in general practice
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Prevalence in the US of IBS Compared to Other
Chronic Diseases
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Rates of Self-Reported IBS in the USA by Sex and
Age
lt
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The "Rome Diagnostic Criteria for IBS

• At least 3 months of abdominal pain
• 1. Relieved with defecation
• 2. Associated with a change in the frequency
  of stool
• Or
• 3. Associated with a change in consistency
  of stool
• AND
• Two or more of the following for at least 25 of
  days
• 1. Disturbed defecation
• 2. Altered stool form
• 3. Altered stool passage
• 4. Passage of mucus
• 5. Bloating or feeling of abdominal
  distention

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IBS A Chronic Condition
No change in diagnosis 97
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Pathophysiology
Pathogenesis of IBS remains obscure
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Pathophysiology

• deregulation of the gut's serotonin transporter
• Post-enteritis IBS

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IBS is a "real" gut disease

• Constipation

• Diarrhea

chemical or mechanical stimulation of the gut
Serotonin release
reduced capacity to reuptake serotonin
serotonin uptake is normal
excess free serotonin
desensitization of the receptors
reducing motor function
Moses PL et al. Am J Gastroenterol. 200297240.
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Patients concerns

• Too much pain
• Nothing works
• Helpless
• Worried
• Frustrated
• Depressed
• Socially isolated
• Can't work

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Physicians concerns

• Listen
• Main symptom
• Alarming symptoms
• Medications
• Worried ?
• Depressed ?
• Wants a sick leave ?
• Hypochondriac ?
• Social problems ?

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Alarm symptoms

• Hematochezia,
• Weight loss gt 10 pounds
• Family history of colon cancer OR IBD
• Recurrent fever
• Anemia
• Chronic severe unrelenting diarrhea
• Nocturnal symptoms

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Always do

• Proper examination
• Reassurance
• Explain the nature of the disease
• Set a clear prospective therapeutic goal with the
  patient
• Lower the expectations of the patient
• Encourage active participation by the patient in
  her/his well being.

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Diagnosis

• Good history and physical
• CBC
• ESR
• Stoolanalysis
• Sigmoidoscopy
• Spastic colon
• Inflammation
• Tumors
• Melanosis coli
• Scybala
• Colonoscopy or Barium enema

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Therapy

• Constipation predominant
• Diarrhea predominant

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Key Clinical Implications

• Treatment of individuals with IBS is indicated if
  the patient and physician believe that the IBS
  symptoms diminish the patient's quality of life.
• Most diagnostic tests are unnecessary in patients
  with IBS who do not have "alarm" symptoms. such
  an individual has lt 1 likelihood of being
  diagnosed with an organic gastrointestinal
  disorder.

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bulking agent in IBS

• Thirteen trials were conducted
• 7 were high quality
• 3 showed a benefit
• Benefit limited to constipation only
• Can be useful placebos
• Gradual increase of dose

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Dietary Advice

• Patients often say certain foods upset them
• Two large studies reported remission in patients
  on elimination diets
• 48 response

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Anticholinergics

• Dicyclomine
• Efficacy supported by only 1 trial
• Global improvement
• Improvement in abdominal pain and constipation.
• 64 anticholinergic side effects vs 16 in
  controls
• hyoscyamine.
• 2 combination trials reported global improvement
  without measuring improvement in specific
  symptoms

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Smooth Muscle Relaxants

• Mebeverine (Duspataline)
• Improvement in abdominal pain
• Short term benefit
• Heterogeneous ?
• publication bias ?

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Antidepressants

• Metaanalysis
• 14 Randomized control trials, 1970 1999
• 849 patients
• 19 TCAs, 4 others
• Effective for primary, global, and pain control
  measures ( p lt0.001 )

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Low-Dose Tricyclic Antidepressants

• 7 trials 1 met high quality criteria¹
• 4 out of the 7 trials, showed significant
  improvement in
• Abdominal pain
• Diarreah¹
• The number needed to treat (NNT) for the TCAs is
  3, This means that if you treat 3 people, 1 will
  get a benefit. ²

¹Jailwala et al, Ann Interrn Med 2000133136
²Jackson et al, Am J Med 2000 108 65
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Drugs for the Treatment of Bloating

• We have little to offer here
• Eliminating dietary factors including excess
  sorbitol, fructose, and lactose-containing foods
  if patients are lactase-deficient helps a few .
• Simethicone (Disflatyl), charcoal, or beanase are
  probably useless.
• Prokinetics / Alosetron useless
• No proven treatment for bloating

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Loperamide for IBS With Diarrhea

• Improves diarrhea, urgency, and borborygmi²
• Increases frequency of bowel movements, and
  improves stools consistency³
• Does not affect abdominal pain or distention³

² Cann et al, Dig Dis SCI 1984 29239
³ ailwala et al, Ann Interrn Med 2000133136
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5HT3 Receptor Antagonist Therapy

• IBS with diarrhea
• Five randomized, controlled trials (1mg given
  twice/D)
• Improves
• stool frequency
• stool consistency
• abdominal discomfort
• and global IBS symptoms
• ?? Ischemic colitis

Alosetron
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5HT4 Receptor Agonist Therapy

• Four randomized, controlled trials in female
  patients with IBS with constipation
• Significant improvement in
• Global IBS symptoms
• Individual IBS symptoms of abdominal pain,
  bloating, and constipation
• Diarrhea (9 vs 4.5 in plaebo)
• usually occurred in the first week of treatment
• transient
• 2 discontinue medication
• Tegaserod is effective for the treatment of IBS
  in female patients with constipation

Tegaserod
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celiac sprue Prevalence in IBS

• prevalence (5)
• it may be appropriate to obtain endomysial and
  antigliadin antibodies in IBS patients with
  diarrhea

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Functional Dyspepsia

• Definition Poorly understood
• Abdominal pain or discomfort that occurs in
  relation to meals
• Episodic or persistent pain or discomfort
  localized to the epigastrium or upper abdomen
• Chronic or recurrent upper abdominal pain or
  nausea that may not be related to meals.

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Pathophysiology of Dyspepsia

• Purely speculative
• Motor abnormality
• Delayed gastric emptying 30 -80
• Antral hypomotility in 25
• ? Abnormal function or abnormal perception.
• H.pylori role??
• High acid production??
• Billiary dysmotility
• Esophageal spasm
• Psychological background

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Diagnosis of Dyspepsia

• Good history physical
• Alarming symptoms
• Wt loss
• Dysphagia
• Anemia
• Nocturnal pain
• Endoscopy
• Serology for H.pylori
• Trial of therapy
• Motility-like dyspepsia
• Reflux-like dyspepsiaq
• Ulcer-like Dyspepsia

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Therapy for Dyspepsia

• Reassurance
• Change in life style
• Trial of therapy
• Anti-acid
• PPI
• Prokinetics
• Antideppressants
• Psychotherapy

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conclusion

• Although bulking agents are effective for the
  treatment of constipation and loperamide is
  effective for the treatment of diarrhea, neither
  agent is effective for the treatment of IBS,
  Therefore, these medications cannot be
  recommended as first-line therapy for IBS
• These agents have not been shown to be effective
  for improvement in individual IBS symptoms of
  abdominal discomfort or bloating.
• These agents were ineffective for improvement in
  global IBS symptom

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Conclusion contd

• Tegaserod is the only currently available US Food
  and Drug Administration-approved agent for the
  treatment of IBS with constipation
• TCAs may be beneficial for the improvement of
  abdominal discomfort
• Patients with IBS who do not have alarm symptoms
  should not undergo multiple diagnostic tests.
• Alosetron is approved by the FDA for the
  treatment of women with severe IBS with diarrhea
  that has failed to respond to conventional
  therapy

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Therapy of IBS

• Antispasmodic Agents
• Only 3 randomized, controlled trials
• (dicyclomine and hyoscyamine)
• Only 1 of these trials demonstrated beneficial
  effects
• side effects in 80
• available evidence does not support the efficacy
  of antispasmodic agents for the management of
  IBS.

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Thankyou
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Bulking Agents

• Good treatments for constipation
• Improve the frequency and form of bowel movements
  in constipated patients
• Do not improve global IBS symptoms, abdominal
  discomfort or bloating

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Antidiarrheal Therapy

• 3 poorly designed randomized, controlled trials
  examining the efficacy of loperamide for the
  treatment of IBS.
• loperamide is a very effective therapy for
  diarrhea,
• no effect on the abdominal discomfort and
  bloating
• No effects on global IBS symptoms

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Antidepressant Agents

• Six randomized, controlled trials examining the
  efficacy of tricyclic antidepressants (TCAs) at
  low dose
• not well designed
• conflicting evidence for improvement of abdominal
  pain
• No efficacy of these agents for global IBS
  symptom improvement.
• should be used with extreme caution in patients
  with IBS with constipation.