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Drugs for the treatment of irritable
bowel syndrome (IBS)
Domina Petric, MD
IBS is an idiopathic, chronic,
relapsing disorder characterized by:
• abdominal discomfort (pain,
bloating, distention, cramps)
• in association with alterations in
bowel habits
(diarrhea,constipation)
Introduction
Introduction
Pharmacotherapy goals:
• relieving abdominal pain and discomfort
• improving bowel function
For patients with predominant diarrhea,
antidiarrheal agents (loperamide especially)
are helpful in reducing stool frequency and
fecal urgency.
For patients with predominant constipation,
fiber supplements may lead to softening of
stools and reduced straining.
Increased gas production may exacerbate
bloating and abdominal discomfort.
Introduction
• Osmotic laxatives, especially
milk of magnesia, are used to
soften stools and promote
increased stool frequency.
• For chronic abdominal pain,
low doses of tricyclic
antidepressants (amitriptyline
or desipramine, 10-15 mg/d)
appear to be helpful.
Introduction
• Low doses of tricyclic
antidperessants have no effect on
mood, but may alter central
processing of visceral afferent
information.
• The anticholinergic properties of
these agents may have effects on
gastrointestinal motility and
secretion, reducing stool frequency
and liquidity.
Introduction
• Tricyclic antidepressants
may alter receptors for
enteric neurotransmitters
such as serotonin, affecting
visceral afferent sensation.
Antispasmodics (anticholinergics)
• Antispasmodics work primarily
through anticholinergic
activities.
• Dicyclomine, hyoscyamine:
inhibit muscarinic cholinergic
receptors in the enteric plexus
and on smooth muscle.
• At low doses, they have
minimal autonomic effects.
Antispasmodics (anticholinergics)
• At higher doses these agents
exibit significant additional
anticholinergic effects: dry
mouth, visual disturbances,
urinary retention and
constipation.
Serotonin 5-HT3 receptor antagonists
• 5-HT3 receptors in the
gastrointestinal tract activate
visceral afferent pain sensation via
extrinsic sensory neurons from the
gut to the spinal cord and CNS.
• Inhibition of afferent
gastrointestinal 5-HT3 receptors
may reduce unpleasant visceral
afferent sensation: nausea,
bloating and pain.
Serotonin 5-HT3 receptor antagonists
• Blockade of central 5-HT3
receptors also reduces the central
response to visceral afferent
stimulation.
• 5-HT3 receptor blockade on the
terminals of enteric cholinergic
neurons inhibits colonic motility,
especially in the left colon,
increasing total colonic transit
time.
Alosetron
• 5-HT3 receptor antagonist for the
treatment of patients with severe
IBS with diarrhea.
• Alosetron is highly potent and
selective antagonist.
• It is rapidly absorbed from the GI
tract.
• Bioavailability is 50-60%.
• Plasma half-life is 1,5 hours.
Alosetron
• It undergoes extensive hepatic
cytochrome P450 metabolism
with renal excretion of most
metabolites.
• Binds with higher affinity and
dissociates more slowly from
5-HT3 receptors than other 5-
HT3 antagonists.
Clinical use
• Alosetron is approved for the
treatment of women with severe
IBS with predominant diarrhea.
• Dosage is 1 mg 1-2 daily.
• It reduces IBS-related lower
abdominal pain, cramps, urgency
and diarrhea.
• Reduces the mean number of
bowel movements per day and
improves stool consistency.
Adverse events
• Alosetron is associated with rare,
but serious gastrointestinal toxicity.
• Constipation occurs in up to 30%
of patients with diarrhea-
predominant IBS.
• Serious complications of
constipation requiring
hospitalization (with or without
surgery) and episodes of ischemic
colitis have been reported.
Adverse events
• Alosetron is restricted to
women with severe diarrhea
predominant IBS who have not
responded to conventional
therapies.
• It is important to educate
patients about relative risks
and benefits.
Chloride channel activator
• Lubiprostone is a prostanoic acid
derivative that stimulates the type
2 chloride channel (CIC-2) in the
small intestine.
• It is used in the treatment of
chronic constipation.
• It is approved for the treatment of
women with IBS with predominant
constipation.
Chloride channel activator
• Dose for IBS is 8 mcg
twice daily.
• It should be avoided in
pregnant women and
women of child-bearing
age.
Literature
• Katzung, Masters, Trevor.
Basic and clinical
pharmacology.

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Drugs for the treatment of irritable bowel syndrome

  • 1. Drugs for the treatment of irritable bowel syndrome (IBS) Domina Petric, MD
  • 2. IBS is an idiopathic, chronic, relapsing disorder characterized by: • abdominal discomfort (pain, bloating, distention, cramps) • in association with alterations in bowel habits (diarrhea,constipation) Introduction
  • 3. Introduction Pharmacotherapy goals: • relieving abdominal pain and discomfort • improving bowel function For patients with predominant diarrhea, antidiarrheal agents (loperamide especially) are helpful in reducing stool frequency and fecal urgency. For patients with predominant constipation, fiber supplements may lead to softening of stools and reduced straining. Increased gas production may exacerbate bloating and abdominal discomfort.
  • 4. Introduction • Osmotic laxatives, especially milk of magnesia, are used to soften stools and promote increased stool frequency. • For chronic abdominal pain, low doses of tricyclic antidepressants (amitriptyline or desipramine, 10-15 mg/d) appear to be helpful.
  • 5. Introduction • Low doses of tricyclic antidperessants have no effect on mood, but may alter central processing of visceral afferent information. • The anticholinergic properties of these agents may have effects on gastrointestinal motility and secretion, reducing stool frequency and liquidity.
  • 6. Introduction • Tricyclic antidepressants may alter receptors for enteric neurotransmitters such as serotonin, affecting visceral afferent sensation.
  • 7. Antispasmodics (anticholinergics) • Antispasmodics work primarily through anticholinergic activities. • Dicyclomine, hyoscyamine: inhibit muscarinic cholinergic receptors in the enteric plexus and on smooth muscle. • At low doses, they have minimal autonomic effects.
  • 8. Antispasmodics (anticholinergics) • At higher doses these agents exibit significant additional anticholinergic effects: dry mouth, visual disturbances, urinary retention and constipation.
  • 9. Serotonin 5-HT3 receptor antagonists • 5-HT3 receptors in the gastrointestinal tract activate visceral afferent pain sensation via extrinsic sensory neurons from the gut to the spinal cord and CNS. • Inhibition of afferent gastrointestinal 5-HT3 receptors may reduce unpleasant visceral afferent sensation: nausea, bloating and pain.
  • 10. Serotonin 5-HT3 receptor antagonists • Blockade of central 5-HT3 receptors also reduces the central response to visceral afferent stimulation. • 5-HT3 receptor blockade on the terminals of enteric cholinergic neurons inhibits colonic motility, especially in the left colon, increasing total colonic transit time.
  • 11. Alosetron • 5-HT3 receptor antagonist for the treatment of patients with severe IBS with diarrhea. • Alosetron is highly potent and selective antagonist. • It is rapidly absorbed from the GI tract. • Bioavailability is 50-60%. • Plasma half-life is 1,5 hours.
  • 12. Alosetron • It undergoes extensive hepatic cytochrome P450 metabolism with renal excretion of most metabolites. • Binds with higher affinity and dissociates more slowly from 5-HT3 receptors than other 5- HT3 antagonists.
  • 13. Clinical use • Alosetron is approved for the treatment of women with severe IBS with predominant diarrhea. • Dosage is 1 mg 1-2 daily. • It reduces IBS-related lower abdominal pain, cramps, urgency and diarrhea. • Reduces the mean number of bowel movements per day and improves stool consistency.
  • 14. Adverse events • Alosetron is associated with rare, but serious gastrointestinal toxicity. • Constipation occurs in up to 30% of patients with diarrhea- predominant IBS. • Serious complications of constipation requiring hospitalization (with or without surgery) and episodes of ischemic colitis have been reported.
  • 15. Adverse events • Alosetron is restricted to women with severe diarrhea predominant IBS who have not responded to conventional therapies. • It is important to educate patients about relative risks and benefits.
  • 16. Chloride channel activator • Lubiprostone is a prostanoic acid derivative that stimulates the type 2 chloride channel (CIC-2) in the small intestine. • It is used in the treatment of chronic constipation. • It is approved for the treatment of women with IBS with predominant constipation.
  • 17. Chloride channel activator • Dose for IBS is 8 mcg twice daily. • It should be avoided in pregnant women and women of child-bearing age.
  • 18. Literature • Katzung, Masters, Trevor. Basic and clinical pharmacology.