Constipation and IBS and drugs used in their treatment

Constipation and IBS

1. Drugs used in treating Drugs used in treating
constipation and IBSconstipation and IBS
Prof. Hanan HagarProf. Hanan Hagar
Pharmacology DepartmentPharmacology Department
Medical College, KSUMedical College, KSU

2. What is constipation?What is constipation?
infrequent defecation, often with straining
and the passage of hard, uncomfortable stools.


May be accompanied by other symptoms: May be accompanied by other symptoms:
Abdominal and Rectal pain
Flatulence
Loss of appetite
Lethargy
Depression

3. Causes of constipations Causes of constipations

Decreased motility in colon: Decreased motility in colon:
Decrease in water and fiber contents of diet.

Difficulty in evacuation:Difficulty in evacuation:
Local painful conditions: Anal fissures, piles
Lack of muscular exercise

Drug-induced: Drug-induced:
Anticholinergic agents
Opioids
Antipsychotics
 Iron

4. Treatment of Constipation Treatment of Constipation
General Measures :General Measures :
1. Adequate fluid intake.1. Adequate fluid intake.
2. High fiber contents in diet.2. High fiber contents in diet.
3. Regular exercise3. Regular exercise
4. Regulation of bowel habit.4. Regulation of bowel habit.
5. Avoid drugs causing constipation.5. Avoid drugs causing constipation.
6. Use drugs (laxatives or purgatives)6. Use drugs (laxatives or purgatives)

5. Medications used in constipations Medications used in constipations
Drugs that hasten the transit of food throughDrugs that hasten the transit of food through
the gastrointestinal tract are called the gastrointestinal tract are called laxativeslaxatives
or purgatives.or purgatives.
Classification of laxatives:Classification of laxatives:
1.1.Bulk forming laxativesBulk forming laxatives
2.2.Osmotic laxatives Osmotic laxatives
3.3.Stimulant laxativesStimulant laxatives
4.4.Stool softeners (lubricants)Stool softeners (lubricants)

6. Classification of laxatives or purgativesClassification of laxatives or purgatives
Bulk forming laxatives:Bulk forming laxatives:
Increase volume of non absorbable solidIncrease volume of non absorbable solid
residue.residue.
Osmotic laxatives:Osmotic laxatives:
Increase water content in large intestine.Increase water content in large intestine.

7. Classification of laxatives or purgativesClassification of laxatives or purgatives
Stimulant or irritant laxatives:Stimulant or irritant laxatives:
Act by direct stimulation of nerve endings in Act by direct stimulation of nerve endings in
colonic mucosacolonic mucosa
Stool softeners (lubricants):Stool softeners (lubricants):
Alter the consistency of feces Alter the consistency of feces  easier to pass easier to pass

8. Bulk (fiber) LaxativesBulk (fiber) Laxatives
Include:Include:
Insoluble dietary fibers:Insoluble dietary fibers:

Indigestible parts of vegetables & fruitsIndigestible parts of vegetables & fruits

Bran powderBran powder
Hydrophilic colloidsHydrophilic colloids

Psyllium seedPsyllium seed

Methyl celluloseMethyl cellulose

Carboxymethyl cellulose (CMC)Carboxymethyl cellulose (CMC)

9. Mechanism of Action Mechanism of Action
Hydrophilic colloids are non absorbed Hydrophilic colloids are non absorbed 
Increase the Increase the bulk of intestinal contentsbulk of intestinal contents by by
water retentionwater retention   mechanical pressure mechanical pressure
on the walls of intestine on the walls of intestine  stimulation stimulation
of stretch receptors of stretch receptors   peristalsis peristalsis 
evacuation of evacuation of soft soft stool.stool.

10. Side Effects Side Effects
•Delayed onset of action (1-3 days).Delayed onset of action (1-3 days).
•Intestinal obstruction Intestinal obstruction (should be taken with (should be taken with
enough water).enough water).
•Bloating, flatulence, distensionBloating, flatulence, distension
•Interfere with other drug absorption e.g. iron, Interfere with other drug absorption e.g. iron,
cardiac glycosides. cardiac glycosides.

11. Osmotic LaxativesOsmotic Laxatives

are soluble, poorly absorbable compounds are soluble, poorly absorbable compounds
((salts or sugarssalts or sugars).).

They remain in the bowel, attract and retain They remain in the bowel, attract and retain
water by water by osmosis osmosis thereby increasing the thereby increasing the
volume of feces volume of feces   peristalsis peristalsis  evacuation evacuation
of of watery watery stool.stool.

12. Osmotic Osmotic LaxativesLaxatives
Include:Include:
1.1.Sugars :Sugars : e.g. lactulose e.g. lactulose
2.2.Salts (Saline laxatives)Salts (Saline laxatives)
•Magnesium sulphate or hydroxideMagnesium sulphate or hydroxide
•Sodium or potassium phosphate.Sodium or potassium phosphate.
3.3.Polyethylene glycol (PEG)Polyethylene glycol (PEG)

13. LactuloseLactulose

Non absorbable disaccharide Non absorbable disaccharide

Metabolized by bacteria Metabolized by bacteria in colonin colon into into
fructose and galactose. fructose and galactose.

These sugars are fermented into lactic acid These sugars are fermented into lactic acid
and acetic acid that function as osmotic and acetic acid that function as osmotic
laxatives.laxatives.
UsesUses
Prevention of chronic constipationPrevention of chronic constipation
Hepatic encephalopathy (Hyperammonemia)Hepatic encephalopathy (Hyperammonemia)
  Hemorrhoids Hemorrhoids

14. Lactulose increases the H+
 concentration in
Lactulose increases the H+
 concentration in
the gut, This favors the formation of the non-the gut, This favors the formation of the non-
absorbable NH4+
 from NH3, trapping
absorbable NH4+
 from NH3, trapping
NH3
 in the colon and reducing its back
NH3
 in the colon and reducing its back
diffusion into blood. diffusion into blood.

Side EffectsSide Effects
1.1.Delayed onset of action (2-3 days) Delayed onset of action (2-3 days)
2.2.Abdominal cramps and flatulence.Abdominal cramps and flatulence.
3.3.Electrolyte disturbances. Electrolyte disturbances.

15. Saline LaxativesSaline Laxatives
Include drugs asInclude drugs as

Magnesium sulphate (Epson’s salt ).Magnesium sulphate (Epson’s salt ).

Magnesium hydroxide (milk of magnesia).Magnesium hydroxide (milk of magnesia).

Sodium phosphate or potassium phosphate.Sodium phosphate or potassium phosphate.

have rapid effect have rapid effect (within 1-3 h ).(within 1-3 h ).

Isotonic or hypotonic solution should be used.Isotonic or hypotonic solution should be used.
UsesUses
Treatment of acute constipation Treatment of acute constipation

16. Side Effects Side Effects

Disturbance of fluid and electrolyte balanceDisturbance of fluid and electrolyte balance

May have systemic effects.May have systemic effects.
ContraindicationsContraindications
Sodium salts # in cardiac patients.Sodium salts # in cardiac patients.
Magnesium salts are contraindicated in: Magnesium salts are contraindicated in:

Renal failureRenal failure

Heart blockHeart block

CNS depressionCNS depression

Neuromuscular blockNeuromuscular block

17. Balanced Polyethylene Glycol (PEG)Balanced Polyethylene Glycol (PEG)

Isotonic solution of polyethylene glycol & Isotonic solution of polyethylene glycol &
electrolytes (NaCl, KCl, Na bicarbonate).electrolytes (NaCl, KCl, Na bicarbonate).

Colonic lavage solutionColonic lavage solution

Used for whole bowel irrigation prior to Used for whole bowel irrigation prior to
colonoscopy or surgery (4L over 2-4 hours).colonoscopy or surgery (4L over 2-4 hours).
AdvantagesAdvantages

Limited fluid or electrolyte imbalance (iso-Limited fluid or electrolyte imbalance (iso-
osmotic).osmotic).

less flatulence and crampsless flatulence and cramps

18. Stimulant Laxatives Stimulant Laxatives
are the most powerful among laxatives andare the most powerful among laxatives and
should be used with care.should be used with care.
Mechanism of Action:Mechanism of Action:
act via direct stimulation of enteric nervous act via direct stimulation of enteric nervous
system system  increased peristalsis & purgation. increased peristalsis & purgation.
DrugsDrugs

BisacodylBisacodyl

Castor oilCastor oil

Anthraquinone derivatives Anthraquinone derivatives (senna, cascara, (senna, cascara,
aloes)aloes)

19. Bisacodyl Bisacodyl
-Acts on colonActs on colon
-Onset of action = Onset of action =
orally (6-12 h)/ per rectum (1 h)orally (6-12 h)/ per rectum (1 h)
Castor Oil Castor Oil

Acts in small intestine Acts in small intestine

Vegetable oil degraded by lipase Vegetable oil degraded by lipase  ricinoleic ricinoleic
acid + glycerin acid + glycerin

Ricinoleic acid is very irritating to mucosa.Ricinoleic acid is very irritating to mucosa.

Onset of action = 2-6 h.Onset of action = 2-6 h.

20. Anthraquinone glycosidesAnthraquinone glycosides
e.g. senna, cascara, aloee.g. senna, cascara, aloe

Act in colonAct in colon

Hydrolyzed by bacterial colon into sugarHydrolyzed by bacterial colon into sugar
+ emodin + emodin ((The absorbed emodin has direct The absorbed emodin has direct
stimulant actionstimulant action).).

Emodin may pass into milk.Emodin may pass into milk.

Delayed onset of action (8-12 h).Delayed onset of action (8-12 h).

21. Common stimulant purgatives
DrugsType Site of ActionOnset of Action
Cascara
Anthraquinone
colon8-12 hours
Senna Anthraquinonecolon8- 12 hours
Aloe veraAnthraquinonecolon8-12 hours
BisacodylDiphenylmethanecolon6-8 hours
Castor Oilricinoleic acidsmall intestine 2-6 hours

22. Side EffectsSide Effects
1.1.Abdominal cramps may occur.Abdominal cramps may occur.
2.2.Prolonged use Prolonged use  atonic colon due to atonic colon due to
dependence & destruction of myenteric dependence & destruction of myenteric
plexus.plexus.

ContraindicationsContraindications

Senna is contraindicated in lactationSenna is contraindicated in lactation

Castor oil # in pregnancy Castor oil # in pregnancy  reflex reflex
contraction of uterus contraction of uterus  abortion. abortion.

23. Fecal Softeners Fecal Softeners
(Lubricants)/surfactants(Lubricants)/surfactants

Are non absorbed drugs Are non absorbed drugs

Act by either decreasing surface tension or byAct by either decreasing surface tension or by
softening the feces thus promoting defecation.softening the feces thus promoting defecation.

Treat constipation in patients with hard stool Treat constipation in patients with hard stool
or specific conditions and for people who or specific conditions and for people who
should avoid straining . should avoid straining .

24. Fecal Softeners Fecal Softeners
(Lubricants)/surfactants(Lubricants)/surfactants
Drugs Drugs

Docusate Docusate

Glycerin Glycerin

Paraffin oilParaffin oil

25. Docusate Docusate
•sodium dioctyl sulfosuccinatesodium dioctyl sulfosuccinate
•One type of Surfactants One type of Surfactants

Act by decreasing surface tension of fecesAct by decreasing surface tension of feces

is given orally (1-3 days) or enema (5-20 min).is given orally (1-3 days) or enema (5-20 min).

26. Paraffin oilParaffin oil

Mineral oil, lubricantMineral oil, lubricant

Not palatableNot palatable

impairs absorption of fat soluble vitamins.impairs absorption of fat soluble vitamins.
GlycerinGlycerin

Lubricant Lubricant

Given rectally (suppository)Given rectally (suppository)

27. PurgativesSite of actionOnset time
Bulk purgativesSmall & large
intestine
12-72 h
Saline purgativesSmall & large
intestine
1-3 h
Lactulosecolon12-72 h
Mineral oilcolon6 – 8 hours
DocusateSmall and large
intestine
12 – 72 hours
StimulantsSmall intestine
Colon
colon
Castor oil
Bisacodyl
anthraquinones

28. Irritable bowel syndrome (IBS)Irritable bowel syndrome (IBS)
Chronic bowel disorder characterized byChronic bowel disorder characterized by
abdominal discomfortabdominal discomfort (bloating, pain, distention, (bloating, pain, distention,
cramps) associated with cramps) associated with alteration in bowelalteration in bowel
habitshabits (diarrhea or constipation or both). (diarrhea or constipation or both).

29. Symptomatic treatment of IBSSymptomatic treatment of IBS

Antispasmodics e.g. mebeverineAntispasmodics e.g. mebeverine

Low doses of tricyclic antidepressants Low doses of tricyclic antidepressants
(amitriptyline)(amitriptyline)

Anticholinergic action Anticholinergic action

reduce visceral afferent sensationreduce visceral afferent sensation

Laxatives in IBS-Constipation Laxatives in IBS-Constipation

antidiarrheals in IBS-Dantidiarrheals in IBS-D

Alosetron (IBS-D)Alosetron (IBS-D)

Tegaserod (IBS-C) Tegaserod (IBS-C)

30. Alosetron Alosetron

Selective 5HT-3 antagonist Selective 5HT-3 antagonist

block 5-HT3 receptors of the enteric nervous block 5-HT3 receptors of the enteric nervous
system of the gastrointestinal tractsystem of the gastrointestinal tract

inhibition of colon motility.inhibition of colon motility.

inhibition of unpleasant visceral afferent pain inhibition of unpleasant visceral afferent pain
sensation (nausea, pain, bloating).sensation (nausea, pain, bloating).

32. Uses of Alosetron Uses of Alosetron
Used in severe IBS with diarrhea in womenUsed in severe IBS with diarrhea in women
Adverse effectsAdverse effects
Constipation and ischemic colitis may occur.Constipation and ischemic colitis may occur.

33. Tegaserod Tegaserod
5HT-5HT-
4 4 agonist. agonist.

Stimulation of 5HT-4 of enteric nervous system Stimulation of 5HT-4 of enteric nervous system
of GIT of GIT  increases peristalsis increases peristalsis

Short term treatment of IBS-associated with Short term treatment of IBS-associated with
constipation in womenconstipation in women

Restricted to special patients that require Restricted to special patients that require
hospitalization.hospitalization.

34. Bulking agentsOral, 48–72
 hours
acute & chronic constipation
stool softenersoral, 24–72
 hours;
rectal, 5 --20
 minutes
prevention of straining after
rectal surgery and in acute
perianal disease
Osmotic laxatives
(lactulose)
oral, 24–72
 hours
- chronic constipation
-hepatic encephalopathy
- opioid constipation
Saline laxativesoral, 0.5–3
 hours;
rectal, 30
 minutes
short term treatment of
moderate-to-severe
constipation; chronic
constipation; bowel preparation
SummarySummary