Laxatives

1. LAXATIVES

2. Drugs promoting evacuation of bowels.
Based on the intensity of action:
(a)Laxative or aperient:Milder action, elimination of soft
but formed stools
(b)Purgative or cathartic:Stronger action resulting in more
fluid and forceful evacuation

3. CLASSIFICATION OF LAXATIVES
1.Bulk forming agents
Dietary fibre:Bran,Psyllium(plantago),Isphagulla,Methyl Cellulose
2.Stool Softner
Docusates(DOSS), Liquid Paraffin
3.Stimulant Purgatives
(a)Diphenylmethanes:Bicodyl, Sod.picosulfate,
(b) Anthraquinones(Emodins) :Senna, Cascara sagrada
(c) 5-HT4 agonist:Prucalopride
(d) PG analogue:Lubiprostone
4.Osmotic Purgatives
Mag. sulfate, Mag.hydroxide, Sod.sulfate, Sod. phosphate
Sod.pot.tartrate, Lactulose, Lactitol

4. MECHANISM OF ACTION
A laxatives increase the water content of the faeces by
(a) A hydrophilic or osmotic action, retaining water and
electrolytes in the intestinal lumen-increase volume of
colonic content and make it easily propelled.
(b) Acting on intestinal mucosa, decrease net absorption of
water and electrolyte;intestinal transit is enhanced
indirectly by the fluid bulk.
(c) Increasing propulsive activity as primary action-allowing
less time for absorption of salt and water as a secondary
effect.

5. Laxatives modify the fluid dynamics of the mucosal cell and may
cause fluid accumulation in gut lumen by one or more of following
mechanisms:
(a) Inhibiting Na+K+ATPase of villous cells-impairing electrolyte and
water absorption
(b) Stimulating adenylyl cyclase in crypt cells-increasing water and
electrolyte secretion
(c) Enhancing PG synthesis in mucosa which increases secretion
(d) Increasing NO synthesis which enhances secretion and inhibits
non-prpulsive contractions in colon
(e) Structural injury to the absorbing intestinal mucosal cells

6. BULK FORMING LAXATIVES
MOA

7. Dietary fibre:Wheat bran consists of 40% of dietary
fibre
It absorbs water in the intestine, swells, increases
water content of faeces
Stimulate local peristalsis and defecation reflexes by
increasing faecal bulk
Increased intake of dietary fibre most appropriate
method for prevention of functiinla constipation
It is the first line approach for most patients of simple
constipation
Dose:20-40g/day
Side effect:Bloating
C/E:GIT ulceration, adhesions, stenosis

8. Psyllium(Plantago) and Ispaghula
Contain natural colloidal mucilage
Largely fermented in colon:increase bacterial mass
and softens the faeces
Refined isaphagula husk 3-8g is freshly mixed with
cold milk, fruit juice or water and taken once or
twice daily
Acts in 1-3 days
It should not be swallowed dry(may cause
esophageal impaction)

9. STOOL SOFTNER MOA

10. Docusates(Dicotyl Sodium sulfosuccinate:DOSS)
It is anionic detergent
Softens the stools by net water accumulation in the
lumen by action on the intestinal mucosa.
It emulsifies the colonic contents and increases
penetration of water into the faeces
Dose:100-400mg/day;acts in 1-3 days
Side effects:Cramps, Abdominal pain, Nausea.
Prolonged use leads to Hepatotoxicity.

11. Liquid Paraffin
•Viscous liquid
•Mixture of petroleum hydrocarbons.
•Pharmacologically inert.
•Dose:15-30ml/day-oil as such or in emulsified form.
Side effects
•It is not palatable
•Frequent use leads to the deficiency of fat soluble vitamins.
•Leakage of the oil past anal sphincter.
•While swallowing it may trickle to lungs-cause lipid pneumonia.
•Delays healing in anorectal region
•Foreign body granuloma in intestine.

12. OSMOTIC PURGATIVES MOA

13. Solutes not absorbed in the intestine retain water osmotically,
increase fluidity of stools and distend the bowel-increase
peristalsis indirectly.
Magnesium ions release cholecystokini which augments motility
and secretion, contributing to purgative action of Mag.salts.
Mag.sulfate(Epsom salt):5-15g;bitter in taste, may nauseate
Mag.hydroxide(8%W/W suspension) 30ml;bland in taste, also
used as an antacid
Sod.sulfate(Glauber’s salt):10-15g;bad in taste.
Sod.phosphate:6-12g, taste not unpleasant.
Sod.pot.tartrate(Rochelle salt):8-15g, relatively pleasant tasting.

14. Mag.salts are contraindicated in renal insufficiency
Sod.salts should not be given to patients of CHF and other
Sod.retaining states
Repeated use of saline purgatives can cause fluid and electrolyte
imbalance.
Saline purgatives are not used now for the treatment of constipation
because they are inconvenient/unpleasant, produce watery stools and
after constipation.

16. Lactulose
 Semisynthetic disaccharide of fructose and lactose
 Neither digested, nor absorbed in the small intestine therefore
retains water.
 Broken down in the colon by bacteria to osmotically more
active product.
 Dose:10-30g taken with plenty of water.
 It produce soft formed stools in 8-24hours.
Side effect
 Flatulence, cramps
 Lactulose cause reduction of blood NH3 concentration by
20-50% in patients of hepatic encephalopathy.
Doe:20g TDS

17. STIMULANT PURGATIVES
MOA

18. Diphenylmethanes:Bisacodyl
Activated in the intestine by deactylation.
In the colon it irritate the mucosa, produce mild inflammation
and secretion.
Dose:5-10mg oral at bed time;10mg (adult), 5mg (child)
suppository in morning.
Side effects:Abdominal cramps and skin rashes.
Higher dose can cause mucosal damage.

19. Anthraquinones:Senna, Cascara sagrada
Plant purgatives contain anthraquinone glycoside(emodins)
Active principle “anthrol” which acts locally or is absorbed
into circulation
Acts on the myentric plexus to increase peristalsis and
decrease segmentation
Senna dose:12-25mg hs, effect come within 6-8hours.
Side effects:Produce abdominal cramps and nausea.
Senna glycosides are secreted through milk.
 Chronic use leads to brown pigmentation of the colon
known as melanosis coli.

20. All laxatives are contraindicated in:
Undiagnosed abdominal pain,colicor vomitting.
Stricture or obstruction in bowel, hypothyroidism, hypercalcemia,
malignancies
Drugs which can cause constipation:
Opiods
Anticholinergics
Antiparkinsonian
Antidepressants and Antihistaminics
Aluminium and calcium groups of antacids
Oral iron, Clonidine,Verampil,Laxative abuse

21. CHOICE AND USE OF
PURGATIVES
1.Functional constipation
 Spastic constipation:Dietary fibre, bulk forming agents taken
over weeks. Stimulant purgatives are contraindicated
Atonic constipation(Sluggish bowel):Due to old age, debility or
laxative abuse. Bulk forming agent, bisacodyl or senna given
once or twice a week.
2.Bedridden patients
(MI, stroke, fractures, postoperative)
Prevent constipation:Give bulk forming agents, docusates,
lactulose,liquid paraffin

22. 3.To avoid straining at stools
(Hernia, cardiovascular diseases, eye surgery) and in perianal
afflictions(piles, fissures, anal surgery)
Bulk forming agents, lactulose or docusates
4.Preparation of bowel for surgery, colonoscopy,abdominal X-ray
Saline purgative,bisacodyl or senna
5.After certain antihelmintics
Saline purgatives or senna
6.Food/drug poisoning
Saline purgatives