LOGO

DRUG THERAPY
FOR CONSTIPATION
Dr. Jatin Dhanani

Causes of constipation

Consequences of chronic constipation

Piles
Anal fissures
Prolapse of rectum
UTI
Stomatitis

Treatment
Non pharmacological

Onset of Action 1-3 hrs

Pharmacological

Osmotic laxatives Mag.

hydroxide, Mag. sulphate,
Mag. citrate, Polyethylene
Glycol (PEG)
Stimulant laxative castor
oil

Onset of Action 1-3

days

Onset of Action 6-8 hrs

Stimulant laxatives
Diphenylmethane
Bisacodyl,
phenolphthalein
Anthraquinone senna,
cascara sagrada

Bulk-forming laxatives
Bran and dietary fibers,
psyllium (ispaghula husk)
methylcellulose,
carboxymethylcellulose
Surfactant and emollients
docusates, mineral oil
(liquid paraffin)
Lactulose

Non - pharmacological
Fiber rich diet
Plenty of fluid
Bowel habit
Plenty
of fluid
Physical
Increase
water
activity
content
of stool

Fiber rich diet

Resistant to enz
degradation and so
present to colon
Non-polysaccharide
lignin, cellulose
Noncellulose
polysaccharide
hemicellulose, mucilage,
gum, pectin
Less fermentable and
less water soluble fibers
are best lignin and
celllulose

Bowel habit

Running for work

Avoidance of
defecation reflex

Physical activity

Require for normal

movement of
bowel

Pharmacological Therapy
Laxatives (aperients)
(cathartics)
Mechanism of action

Purgatives

Direct increase propulsive movement

Osmotic or hydrophilic action increase colonic
content
By acting on intestinal mucosa decrease
absorption of water and electrolyte
Inhibition of Na+K+ATPase of villous cells
impairing electrolyte and water absorption
Stimulation of adenylyl cyclase in crypt cells
Enhance PG synthesis
Intestinal mucosal cell injuries

Bulk forming Laxatives

Bran/dietary fiber

Bran and dietary fibers,

psyllium (ispaghula hus
methylcellulose,
carboxymethylcellulose

Byproduct of flour industry

Bran of wheat high lignin content (nonpolysaccharide and non-fermentable)
Dietary fibers unabsorbable cell wall and
other constituents of vegetables and fruits
cellulose, pectin, glycoproteins,
polysaccharides
Acts by absorbs water directly as well as by
degradation of pectin by bacteria
Gums, lignin, pectin binds to bile acids and
prevent further absorption degradation of
cholesterol in liver decrease plasma LDL
cholesterol

Use
Prevention of functional constipation
Irritable bowel syndrome (IBS)
Problems
Large quantity require (20-40 gm/day)
Takes time for action
Can be use as prevention only
Cannot be use in patients with ulcerations,
adhesions, stenosis, chances of fecal
impaction (megacolon, megarectum)

Psyllium

Derived from
plantago seeds
Contain natural
colloidal mucilage
absorb water
Fermentation in colon
increase mass of
colonic bacteria
May be allergic
Dose: 2 -4 gm

Ispaghula Husk

Contain mucilage
and hemicellulose
Acts similarly to
psyllium
Dose: 8 12 gm

Methylcellulose

Semisynthetic,

colloidal, highly

hydrophilic
Swells upto 20 -25
Adequate amount of fluid should
times be taken
with all the bulk forming agents

Stool softener
Docusates

docusates,
mineral oil (liquid para

Anionic detergent emulsifies colonic content

and increase penetration of water in feces
Increase mucosal cAMP water secretion
Three salts available sod., pot., cal.
Problems
Bitter in taste
Abdominal pain and cramps
Liver damage on longer use

Liquid paraffin

Mixture of petroleum hydrocarbons

Indigestible, minimally absorb,
pharmacologically inert
Onset of action takes 2-3 days
Acts by soften the stool and coating of hard
scybali
Dose: 15-30 ml/day
Problems:
Unpleasant swallowing
Leakage per anum physical and social
embarrassment
Pass through gi mucosa to lymph produce
foreign body granuloma

Lactulose

Semisynthetic disaccharide of fructose and

lactose
Not digested or absorb retain water
Breakdown in colon to produce osmotically
active product
Onset of action takes 1-2 days time
Use in constipation due to drugs (opioid,
vincristin), elderly, idiopathic chronic
constipation
Problems:
abdominal distension, cramps, flatulence
electrolyte disturbance
Also use in hepatic coma detoxify ammonia
of blood

Stimulant Purgatives
Powerful purgatives

Mechanism of action:

Irritate intestinal mucosa stimulate myenteric

plexuses
Inhibits basolateral Na+ K+ ATPase of villous
cells
Increase cAMP in crypt cells and PG synthesis

Adverse Effects:

Hypokalemia
Large dose cathartic effect
Long term use colonic atony and abuse
Stimulate gravid uterus abortion

Diphenylmethanes
Phenolphthalein

Not use - Carcinogenic potential

Bisacodyl

Most commonly use

Prodrug acetylate in intestine
Enterohepatic circulation
Irritate colonic mucosa, inflammation,
secretion
Action after 6-8 hrs
Suppository 30 min 1 hr
Dose: 5 -15 mg

Sodium picosulfate

Anthraquinone

Aloe, cascara, senna

Plant purgatives (emodins)
Inactive colonic bacteria activate and liberate
active anthrol
Enterohepatic circulation (6 -8 hrs)
Acts similarly as diphenylmethane

Problems

Secrets in milk purge in infant

Skin rashes, FDE
Long term use colonic atony and mucosal
pigmentation (melanosis)

Tegaserod

5-HT4 receptor agonist increase release of

Ach and CGRP
Increase peristalsis (colon, stomach and ileum)
Secretion of fluid and electrolyte
Only small amount absorb through GIT

Indication

Constipation predominant irritable bowel

syndrome
Chronic constipation

Side effects

Loose motion, flatulence, headache

Dose 2 -6 mg BD

Castor oil

One of the oldest purgatives

Obtain from seeds of Ricinus communis
Hydrolyzed in ileum to recinoleic acid and
glycerol
Ricinoleic acid decrease intestinal absorption
and increase secretion of fluid
Also increase peristalsis by irritating mucosa
Purgation in 2 -3 hrs

Side effects

Unpalatable, frequent cramping

Villous tip damage
Dehydration
After constipation

Dose 5 15 ml

Osmotic laxatives
Mechanism

Saline
sugar
distendNondigestible
bowel
PEG & electrolyte sol.

Retain water osmotically

increase peristalsis
Mg salts release cholecystokinin

Salts available

Mag. sulfate (epsom salt) 5 - 15 g

Mag. hydroxide (milk of magnesia) 8% w/w 3 0
ml
Sol. sulfate (glaubers salt) 10 15 gm
Sod. pot. tartrate (rochelle salt)
All salts dissolved in 150 200 ml of water

Indication

Preparation of bowel for surgery and

colonoscopy
Food/drug poisoning
After-purge in treatment of tapeworm surgery

Contraindication

Mg salts renal insufficiency

Na salts CHF and other cardiac conditions
Repetition

Polyethylene Glycol with electrolyte

sol.

Osmotically accumulate fluid in lumen

Use for preparation of gut for surgery

Purgative abuse
Self medication for longer time

Mostly psychological
Complete evacuation of colon

Dangers of purgative abuse

Fluid electrolyte imbalance (hypokalamia)

Steatorrhoea
Malabsorption syndrome
Protein losing enteropathy
Flaring of intestinal pathology
Rupture of appendix

Contraindications of laxatives
Constipation due to mechanical
obstruction

Stricture, adhesions

Acute undiagnosed abdominal pain

Other disease like cretinism,
carcinoma
Drug induced constipation

Choice of purgatives
Physiological conditions

Pregnancy and elderly

Plenty of water, simple walk,
Dietary fibers, bulk forming agents
Resistant cases senna, bisacodyl

Functional constipation

Spastic
dietary fibers and bulk forming agents
Stimulatory agents are c/I
Atonic due to age, debility and laxative abuse
Non-drug measures like plenty of fluid,
exercise, reassurance
Bulk forming agents, dietary fibers

Bedridden patients (MI, stroke, postoperative,

fracture)
Prevention bulk forming, lactulose,
docusates
Treatment- enema, bisacodyl, senna
Preparation of bowel for surgery and diagnostic
procedure
One day before bisacodyl or senna orally
at night
On the day bisacodyl suppository or
enema
After surgical procedure
After hernia surgery or ocular surgery
Piles and fissure surgery
Bulk forming and surfactant laxatives

Constipation related to drug

Drug / food poisoning

Saline purgatives

Drug induce constipation

Laxative should be avoided

Laxative use in selective cases opioid induce
Specific antagonist

LOGO

Thank You