Pharmacology Lecture Slides on Therapy of Constipation by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College

1. Therapy of Constipation
Sanjaya Mani Dixit
Assistant Prof of Pharmacology

2. Clinical scenario
A 24-year-old female named Ms. Johnson comes to your clinic complaining
of constipation. She reports having fewer than three bowel movements
per week and experiencing difficulty passing stools that are often hard and
dry.
Ms. Johnson also reports feeling bloated and experiencing abdominal
discomfort. She leads a sedentary lifestyle and does not engage in regular
physical activity. Upon taking a thorough history, it is learnt that Ms.
Johnson's diet primarily consists of processed foods and lacks fiber. She
also reports consuming large amounts of dairy products and not drinking
enough water.
How do you manage her condition?

3. Phenolpthalein
to
Bisacodyl
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4. Introduction
Its Causes
Laxatives/ Purgatives
Drug Classification
Details on Drugs
Obsolete agents
Clinical uses of Laxatives
Adverse effects of Laxatives
Non-drug treatment
Constipation

5. One of the least talked topics
Almost everyone gets constipated sometime
during life
Trend is on the rise with people resorting to
eat processed fiber-less foods rather than the
whole grain meals.
Most commonly affected:
◦ Women
◦ Elderly
◦ Bed ridden patients
Constipation

6. Constipation is the functional impairment in the
inherent capacity of the colon to produce normally
formed stools at regular intervals.
The normal length of time between bowel
movements ranges widely from person to person.
Some people have bowel movements three times a
day; others, up to three times a week. Going longer
than three days without a bowel movement is too
long. After three days, the stool or feces become
harder and more difficult to pass.
Definition

7. CONSTIPATION
Hard and
small volume
of stool
Feeling of
incomplete
evacuation
Difficulty in
passage
Excessive
straining
Decreased
frequency of
evacuation
Patient’s view of Constipation

8. Not enough fiber in the diet
Lack of physical activity (especially in the elderly, bed ridden
patients)
Milk (in some people)
Irritable bowel syndrome
Hormonal disorders (Hypothyroidism)
Abuse of laxatives
Changes in life or routine such as pregnancy, aging, and travel
Ignoring the urge to have a bowel movement
Specific diseases or conditions, such as stroke (most common)
Problems with the colon and rectum
Problems with intestinal function (chronic idiopathic
constipation)
Causes of constipation
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9. Drugs that cause constipation
Pain medications (especially narcotics-opium)
NSAIDs – Prostaglandin synthesis inhibitors
Antacids that contain aluminum and calcium-
Al(OH)3 and CaCO3
Drugs with anticholinergic action
◦ Antiparkinson drugs-Orphenadine
◦ Antispasmodics-Hyoscine (Buscopan)
◦ Antidepressants-TCA-Amitriptyline, Imipramine,
Iron supplements
Causes of constipation

10. Mouth
Stomach
5-6d
18-24h
5-6h
0.5-2.5h
SI
Caecum
Excretion starts
Complete clearance
Juice Secretion
Daily Fluid intake
Absorption of fluid
Liquid in formed
feces
1-1.5L
8-9L
100ml
Food and fluids in gut
SI, Caecum & Colon

11. ANS effect on GIT
Relaxation
of
Gut
and
Sphincter
closure
Increased
tone
and
peristalsis
+
-

12. Laxatives are drugs that loosen the bowel, and promote
evacuation of the intestine.
A distinction may sometimes be made according to the intensity
of action.
Laxative or aperients: Produces milder action, elimination of
soft but formed stools.
Purgative or cathartic: Produce stronger action resulting in more
fluid evacuation.
Many drugs in low doses act as laxatives and in larger doses as
purgatives.
Laxatives & Purgatives

13. Bulk-forming purgatives:
◦ Dietary fibers; Bran; Ispaghula; Psyllium.
Stool softeners:
◦ Docusate sodium; Liquid paraffin; Glycerol
Irritant/Stimulant purgatives
◦ Bisacodyl; Senna
Osmotic purgatives:
◦ Magnesium sulphate; Lactulose.
CLASSIFICATION OF DRUGS

14. Laxative Classification based on time of effect
G&G
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15. ◦ Inhibition of Na+/K+ ATPase in the intestinal villi
 Decreases water and electrolyte absorption
◦ Stimulation of adenyl cyclase in intestinal crypts
 Increases water and electrolyte secretion
◦ Enhancing PG synthesis in mucosa which increases
secretion
◦ Structural injury to absorbing intestinal cells
Fluid accumulation mechanisms
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16. Bisacodyl (EDL)
Lactulose (EDL)
Magnesium sulphate (EDL)
Liquid paraffin
Ispaghula
Psyllium seeds
Senna Leaves
Commonly used laxatives
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17. Class: Stimulant/Irritant laxative
Mechanism of action
Bisacodyl, is a prodrug, it is converted to its active
desacetyl metabolite by intestinal brush border enzymes
and colonic bacteria (Deacetylation).
It is not absorbed from the GIT and acts basically in the
large intestine hence less loss of fluid and electrolytes.
Small amounts are known to undergo enterohepatic
circulation.
Tablet-5mg PO (Dulcolax)
Suppository 10mg (evacuation in 15-60 mins)
Bisacodyl (Dulcolax)
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18. Adverse effects
Prolonged use is known to cause local irritation and
may even lead to colonic atony.
They are main agents involved in laxative dependence.
Stimulant purgatives are known to have powerful
action and may cause griping (associated digestive
discomfort).
Since irritant purgatives may reflexly stimulate gravid
uterus is contraindicated in pregnancy.
Cramps, allergy, Steven Johnson’s syndrome (deadly
skin disease) may also occur.
Bisacodyl
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19. Class: Osmotic/Saline laxative
Mechanism of action
They are unabsorbed from the GIT, and due to their
osmotic effect, they retain water and electrolytes, thus
increasing the intestinal bulk and augmenting persistalsis
indirectly, helping to cause laxation.
Apart from this the magnesium salts are also known to
cause release of cholecystokinin-pancreozymin, which
stimulate the intestinal secretory and motor activity.
Site of Action (SOA) - SI and LI-produce watery stools in 3-6
hrs
Advice- Drink plenty of water to avoid dehydration
Magnesium sulphate
Aka Epsom salt
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20. Adverse Effects
Systemic toxicity may occur following absorption
especially in kidney disease when clearance is impaired.
Mg salts- CNS Depression
Prolonged use may result in fluid and electrolyte
imbalance and volume depletion (exacerbation of
hypovolemic shock)
Dose: 5-10 gm
Other Magnesium Salts
Milk of Magnesia
Magnesium Oxide
Magnesium Citrate
Magnesium Carbonate
Magnesium sulphate
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21. Class: Osmotic/Saline laxative
Mechanism of action
Synthetic non-absorbable disaccharide of galactose and
fructose that resists intestinal disaccharidase activity; and due to
their osmotic effect, they retain water and electrolytes, thus
increasing the intestinal bulk and augmenting persistalsis
indirectly, helping to cause laxation.
Metabolized to lactic acid in the gut, which acidifies the gut
contents and binds to ammonia as ammonium ions thus
expelling them from the body which is useful in treatment of
hepatic coma.
Also small amounts of acetic acid and formic acid are formed
thus adding to the osmotic effect.
Lactulose
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22. Uses
Constipation
Hepatic Coma
Adverse Effects
Prolonged use may result in fluid and
electrolyte imbalance.
Dose: 30-50ml (3.5 gm/ 5ml) at night
Lactitol is the new palatable derivative of
Lactulose
Lactulose
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23. These include high residue foods that contain a
high proportion of indigestible matter.
Mechanism of action
These purgatives act by their physical property of
swelling and providing the bulk, thus enhancing
natural evacuation.
Some of them are known to have lubricating
properties.
They form solid or semisolid stools without irritation
and griping.
Since they are not absorbed they are devoid of any
systemic effects.
Bulk Purgatives
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24. Paradoxically, they also can be used for the
treatment of diarrhoea-however it is not
much desired.
Adverse effects
Cause flatulence, owing to the fermentation,
however, this is reduced after some period
They are the treatment of choice for chronic
constipation.
Bulk Purgatives

25. Fiber is defined as that part of food that resists
enzymatic digestion and reaches the colon largely
unchanged.
Fermentation of fiber has two important effects:
(1) it produces short-chain fatty acids –prokinetic effect
(2) it increases bacterial mass– increases mass of stool
Fiber

26. In the past was k/a residue or roughage and was
slowly eliminated from diet.
It consists of cellulose, hemicelluloses, pectin and
lignin.
Fruits and vegetables contain more pectins &
hemicelluloses which are more readily fermentable
and produce less effect on stool transit.
The pectins in bran following bacterial degradation
gives osmotically active products.
Fiber

27. Lignins, pectins and gums bind to bile acid and promote its
excretion. This causes higher consumption of cholesterol in liver
and thus help in decreasing plasma cholesterol. It is also said to
decrease blood glucose levels.
They hold water, form gel and bind to bile acids, which on
reaching the colon are broken down into small chain fatty acids
thus helping in the formation of bulkier and softer stool.
Uses
They are useful in Spastic colon, Irritable bowel syndrome,
Colonic diverticular disease, Anal fissures, Piles
They are also known to decrease the colonic cancer by
decreasing the duration of contact with the locally formed
carcinogens, by enhancing excretion.
Fiber

28. DOSS (Dioctyl sodium sulfosuccinate/ Docussate sodium)
It is an anionic surfactant and promotes softening of already
formed hardened feces that are pose difficulty in excretion.
Adverse effects
Bitter taste can cause nausea.
Cramps and abdominal pain
Hepatotoxicity might occur on prolonged use.
Animal studies have shown interference with wound healing.
Disrupts mucosal barrier and enhances absorption of drugs
which otherwise would not be absorbed.
Do not combine with liquid paraffin, since it enhances the
absorption.
Stool Softners

29. Most widely used emollient laxative, a hydrocarbon
mixture
Not significantly absorbed, pharmacologically inert
Exerts a softening and lubricating effect on feces
Lubricates hard scybali by coating them
Decreases straining while defecation, finds use
occasionally post-operatively.
Adverse Effects
If during swallowing, it trickles into lungs- lipoid
pneumonia
Chronic use- deficiency of fat soluble vitamins
Leakage of oil through the anal sphincter-social
discomfort
Liquid paraffin

30. Phenolpthalein -caused colorful lesion of skin lasting for
months or years or sometimes permanent.
Newer derivative with similar structure which is much used
now is Bisacodyl.
Calomel (Mercurous chloride) - major cause of Pink disease in
children which occurs as a result of mercury poisoning
Castor oil-One of the oldest purgative –in SI breaks to glycerol
and Ricinoleic acid -pugative action
Regular use-damage to intestinal mucosa
Pregnancy-Uterine contraction
Unpalatibility, frequent cramping, possibility of dehydration
following complete colonic evacuation-No longer preferred
Obsolete Agents

31. Constipation
◦ Atonic constipation: Bulk purgatives, if not useful then
Bisacodyl or Senna
◦ Spastic constipation: Fiber or bulk purgatives; stimulant
purgatives should be avoided.
Poisoning (food/drug)- flushing the GIT- saline purgatives
Anthelminthic therapy adjunct- parasite elimination
(tapeworm)-Saline purgatives
Pre-operative abdominal surgery/radiological examination-
Saline purgative, Bisacodyl, Senna
Anal fissure, piles, typhoid, cardiac disease, pregnant women-
lubricant purgative, to decrease straining during defecation-
Bisacodyl, senna, enema or liquid paraffin.
Clinical Uses of laxatives

32. Lactulose and sorbitol are equally efficacious in
the treatment of constipation caused by opioids
and vincristine, of constipation in the elderly,
and of idiopathic chronic constipation. They are
available as 70% solutions, which are given in
doses of 15 to 30 ml at night.
Osmotic purgatives are preferred agents for
preparing the bowel before surgery and
colonoscopy; in poisoning and as after-purge in
treatment of worm infestation.
Clinical Uses

33. Bloating, griping (associated digestive discomfort )
Loss of fluids and electrolytes- with prolonged use of
saline purgatives
Problem with absorption of lipid soluble vitamins
with prolonged use of lubricant purgatives
Cathartic colon with overuse of stimulant laxatives
DOSS- surfectant causes hepatotoxicity on
prolonged use
Prolonged use of bisacodyl is known to cause
colonic atony. Cramps, allergy, Steven Johnson’s
syndrome may also occur.
Adverse reactions of laxatives
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34. Non-drug treatment

35. Alteration of diet: Adding fiber to diet
Ample hydration
Indulgence in physical activity
Bowel training regimen-developing habit of
not suppressing the call for evacuation
Solving the psychosocial issues involved
If constipation is due to any medications
being taken, try decreasing the dose or
changing to another medication which does
not cause constipation.
Non-drug treatment

36. The constipation cycle
http://www.constipationadvice.co.uk/achieving_inner_health/dr_porter_constipation_article_6.php

37. Bulk Purgatives
◦ Increase bulk, to induce natural peristalsis
Saline Purgatives
◦ Cause purgation by the osmotic effect of the
unabsorbed salts from the colon
Stimulant purgatives
◦ Cause local irritation in the lumen to induce
peristalsis or increase motility by acting on
myenteric plexus
Stool Softners
◦ Surfectants and oils coat the feces and soften them,
thus causing laxation
Mechanism of Axn at a glance

38. An increase in intrathoracic (chest cavity)
pressure which can lead to a reduction in
coronary (heart), cerebral (brain) and peripheral
circulation.
development of hernias,
worsening of symptoms of gastro-esophageal
reflux disease (GERD),
transient ischaemic attacks (mini-strokes) and
syncope (fainting) in patients with neurological
disease
Hemorrhoids may develop due to straining.
Straining to defecate causes

39. Stevens-Johnson Syndrome is a potentially deadly skin disease
that usually results from a drug reaction.
Drugs linked to Stevens-Johnson Syndrome:
◦ Valdecoxib
◦ NSAIDS (non-steroid anti-inflammatory drugs), Allopurinol,
Phenytoin, Carbamazepine, barbiturates, anticonvulsants, and sulfa
antibiotics.
The condition can sometimes – although not very often – be
attributed to a bacterial infection, and in some cases there is no
known cause for the onset of Stevens-Johnson Syndrome or
Toxic Epidermal Necrolysis. However, the most common cause is
through drug related reaction.
Both forms of the disease can be deadly as well as very painful
and distressing.
Stevens-Johnson Syndrome

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