Drugs for constipation

1. DRUGS FOR
CONSTIPATION
Presenter: Ananya
Moderator: Dr. Sadhana Holla

2. CONTENTS
• Definition
• Causes
• Symptoms
• Classification
• Mechanism of action
• Choice and use of purgatives
• Purgative abuse

3. WHAT IS CONSTIPATION?
• Constipation means delayed passage of
faeces through the intestine with
defaecation process remaining normal.
• Evacuation associated with straining and
usually incomplete.

4. • If more than three days pass without a bowel movement, the intestinal contents may
harden, and a person may have difficulty or even pain during elimination.
• Straining during bowel movements or the feeling of incomplete evacuation may also
be reported as constipation.
• Normal range: From 3 times daily to 3 times per week.

5. CAUSES:
• Ignoring the urge to pass the stools
• Dehydration
• Lack of exercise
• Lack of dietary fiber.
• Hormonal disturbances.
• Neurogenic disorders.
• Systemic illnesses.

6. Symptom
s
Pain or
bloating
headach
e
anorexia
lethargy
Straining bowel
movements
Lumpy or
hard stools
Feeling of
blockade in
intestine/rectum

7. LAXATIVES
(Aperients, Purgatives, Cathartics)
o Drugs that promote evacuation of bowel.
a) Laxative or aperients: milder action, elimination of soft but
formed stools.
b) Purgative or cathartic: stronger action, more fluid and
forceful evacuation.

8. CLASSIFICATION:
Bulk forming
agents
Dietary fiber: bran
Psyllium( plantago)
Ispaghula
Methyl cellulose
Stool softner
Docusates(DOSS)
Liquid paraffin
Osmotic
purgatives
Mag. sulfate
Mag. Hydroxide
Sod.sulfate
Sod. Phosphate
Lactulose
Lactitol

9. STIMULANT PURGATIVES
Diphenylmethanes
Bisacodyl
Sod.picosulfate
Anthraquinones(emodins)
Senna
Cascara
sagrada
5-HT4 agonist
Prucalopride
PG analogue
Lubiprostone

10. MECHANISM
OF ACTION
Hydrophilic or osmotic
action
Decrease absorption of
water and electrolytes.
Increasing propulsive
activity

11. BULK PURGATIVES
1. DIETARY FIBRE: BRAN
Residual product of flour industry which
consist of 40% of dietary fiber.
Consist of un- absorbable cellulose, lignin,
pectin, glycoproteins & other
polysaccharides.

12. •MECHANISM OF ACTION:-
•Absorbs water in the intestines, swells, increases water
content of feces-softens it and facilitates colonic transit.
•Dietary fiber supports bacterial growth in colon which
contribute to faecal mass
•First line approach for most patients of simple constipation.
•Reduces recto sigmoid intraluminal pressure.
•Relieves symptoms of
Irritable bowel syndrome (IBS) including pain, constipation as
well as diarrhea.

13. DRAWBACKS
 Unpalatable
 Large quantity (20-40 g/day) needs.
 Does not soften faeces already present in colon or rectum.
 Should not be used in patients with gut ulcerations, adhesions.

14. 2.PSYLLIUM & ISPAGHULA
• Contain natural colloidal mucilage.
• Forms a bulky gelatinous
mass by absorbing by water.
• Largely fermented in colon increase
bacterial mass & softens the faeces.

15. STOOL SOFTENER
1.Docusates(dioctyl sodium sulfosuccinate):
Anionic detergent
Softens stools by net water accumulation in the lumen by
an action on intestinal mucosa.
Emulsifies the colonic content and increases penetration
of water into the faeces.
100-400mg/day.
Indicated when straining at stools must be avoided.

16. DRAWBACKS
• Disrupt the mucosal barrier and enhance absorption of many non-
absorbable drugs.
Eg: Liquid paraffin- should not be combined with DOSS.
• Cramps and abdominal pain.
• Liquid preparations cause nausea

17. 2. LIQUID PARAFFIN
Introduced in 19th century.
Viscous liquid.
Mixture of petroleum hydrocarbon.
Pharmacologically inert.
Soften stools and is said to lubricate by coating
them.

18. DISADVANTAGES
• Unpleasant to swallow
• Small amount passes into intestinal mucosa produce foreign body
granuloma.
• Swallowing it may trickle in lungs lipid pneumonia.
• Carries away fat soluble vitamins with it into the stools; deficiency
may occur on chronic use.
• Interfere with healing in anorectal region, use occasionally.

19. STIMULANT PURGATIVES
• Powerful purgatives.
• Produce griping.

20. 1. DIPHENYLMETHANES
• BISACODYL:
Partly absorbed and excreted in bile.
Activated in intestine by deacetylation.
Irritates colonic mucosa, produce inflammation &
increase secretion.
Effects appears within 6-8 hrs.

21. 2.ANTHRAQUINONES (EMODINS)
• SENNA & CASCARA SAGRADA:
 Obtained from leaves and pods of cassia sp., most popularly
used as traditional therapy for constipation.
 After administration, colonic flora converts them to
the active form anthrol, acts locally and enterohepatic
circulation.
 Side effects: skin rashes, prolonged use causes mucosal
pigmentation, colonic atony.
 Lactating mothers.

22. 3. 5-HT4 agonist
• PRUCALOPRIDE
 Facilitates cholinergic neurotransmission.
 Increases colonic transit without affecting gastric emptying.
 Improves colonic transit & stool frequency in patients - chronic
idiopathic constipation.
 Marketed in Europe, Canada, and UK for treatment in females.

23.  Given in dose of 2-4mg orally OD.
 Low affinity for cardiac potassium channels &does not prolong Q-T.
 Side effects: abdominal pain ,headache, dizziness, and fatigue.

24. LUBIPROSTONE
 PG analogue (EP4 receptor agonist).
 Stimulating mucosal Cl¯ channels and increasing
intestinal secretion.
 Used in the treatment of constipation-predominant
IBS and chronic constipation.

25. OSMOTIC PURGATIVES
Solutes, not absorbed in the intestine.
Increases peristalsis indirectly, retain water osmotically and
distend the bowel.
Preferred for preparation of bowel before surgery and colonoscopy.
Magnesium salt release cholecystokinin which augments motility and
secretion.
 All Organic salts used as osmotic purgatives – similar action but
differ in dose.

26. DOSES OF VARIOUS OSMOTIC
PURGATIVES
• Mag. Sulfate (Epsom salt): 5-15 g.
• Sod. Sulfate (Glauber's salt): 10-15 g.
• Sod.phosphate :6-12 g.
• Mag. Hydroxide( Milk of magnesia): 8% W/W suspension of 30ml.
• Sod.pot. Tartrate (Rochelle salt): 8-15 g.

27. LACTULOSE
Non absorbable sugar used to prevent or
treat acute as well as chronic
constipation.
Metabolized by colonic bacteria.
Used to treat and prevent constipation in
pregnant and lactating mothers.
In addition to purgative
effect, reduces blood ammonia level
in patients with hepatic encephalopathy
by following mechanism.
Reduces luminal pH in the colon
(Breakdown product of lactulose is
acidic)
lactulose
Ammonia converted to ammonium
ion (not absorbed from gut)
Decreases blood ammonia
level.

28. Common side effcets – flatus and abdominal cramps.
For purgative action, it is given in a dose of 10 gm BD with
plenty of water.
 In hepatic encephalopathy, 20 gm TDS is given but causes
loose motions.

29. LACTITOL
Disaccharide sugar alcohol.
Fermented by colonic bacteria into osmotically active and
weakly acidic products.
Increased water content and lowered pH.
Helpful in hepatic encephalopathy
Side effects – distention ,flatulence, cramps, dyspepsia,
nausea and vomiting.

30. CHOICE AND
USE OF
PURGATIVES

31. • Indication of laxatives is prevention and treatment of acute as well as
chronic constipation.
• Contraindicated in:
i. Undiagnosed abdominal pain, colic or vomiting.
ii. Organic constipation: obstruction in bowel, hypothyroidism,
hypercalcemia, malignancies, and certain drugs.
Eg: opiates, sedatives, antiparkinsonian, antidepressants etc.

32. INDICATIONS OF LAXATIVES
1. Functional constipation
 Stool frequency: 2days to 2-3 times/day.
 Constipation may be spastic and atonic.
i. Spastic constipation (irritable bowel):
• Stools are hard, rounded, stone like & difficult to pass.
• First choice laxative: ispaghula or soluble fibres.
• Stimulant purgatives are contraindicated.

33. ii. Atonic constipation (sluggish bowel)
• Advanced age , debility or laxatives
abuse.
• Non drug measures: fluids, exercise,
regular habits and reassurance.
• Bulk forming agents or osmotic
laxatives like lactulose or
mag.hydroxide.
• Poor compliance: bisacodyl or senna.

34. 2. Bedridden patients
Bowel movement may be sluggish, and constipation anticipated.
Prevention: bulk forming agents; docusates, lactulose, and liquid
paraffin.
Treatment: enema (soap water/glycerine); bisacodyl or senna orally.
Methylnaltrexon:
• opioid antagonist acting on opiod receptors in the gut.
• Counteract opioid analgesic induced constipation in cancer/palliative
care patients without blocking the analgesic action.

35. 3. To avoid straining at stools:
• To keep the faeces soft.
4. Preparation of bowel for surgery, colonoscopy, abdominal X-ray.
• Bowel needs to be emptied of the contents including gas.
• Saline purgative, bisacodyl or senna.
5. After certain anthelmintics
• Saline purgative or senna- flush out the worm and drug.
6. Food/drug poisoning
• To drive out the unabsorbed irritant/poisonous material from intestines.

36. MISCONCEPTION ABOUT
CONSTIPATION?
• That a bowel movements every day is
necessary.
• Wastes stored in the body are absorbed
and are dangerous to health or shorten the
life span.
These misconceptions
have led to a marked
overuse and abuse of
laxatives.

37. PURGATIVE ABUSE
• Some individuals are obsessed with using purgatives
regularly.
• This may be the reflection of psychological problem.
• Others use a purgative casually, obtain through bowel
evacuation, and by the time colon fills up for a proper
motion(2-3 days) they get convinced that they are
constipated and start taking the drugs regularly.

38. • Chronic use of purgatives must be discouraged. Once the purgative
habit forms, it is difficult to break.
 Drawbacks of purgative abuse:
 Fluid and electrolyte imbalance, hypokalemia.
 Steatorrhea, malabsorption syndrome.
 Protein loosing enteropathy.
 Spastic colitis.

39. REFERENCE
• KD Tripathi, Essentials Of Medical Pharmacology, 8th edition, Jaypee medical
publishers(Ltd) New Delhi 2019, drugs for constipation and diarrhea, Pg. 721-
726.
• HL, KK Sharma, Sharma & Sharma’s principle of pharmacology, 3rd edition,
Paras medical publishers 2017,drugs for constipation, Hyderabad, Pg. 411-414 .
• Satoskar R.S, Rege N. Nirmal, Bhandarkar S.D, Pharmacology and
pharmacotherapeutics, elsevier,24th edition 2015, pharmacotherapy of
constipation, pg.610-620.

40. Thank you