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Drugs Acting On GIT Laxatives & Purgatives: Dr. Syed Muneeb Anjum (PH.D.) Ips, Uvas
Drugs Acting On GIT Laxatives & Purgatives: Dr. Syed Muneeb Anjum (PH.D.) Ips, Uvas
By
Dr. Muneeb
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Constipation
Constipation
Unsatisfactory defecation
Infrequent stools, difficult stool passage, or seemingly incomplete
defaecation
Can occur at any age
Commonly seen in women, the elderly, and during pregnancy
It happens most often due to changes in diet or routine, or due to
inadequate intake of fiber
Bowel habit
Bowel habit can vary considerably in frequency without doing harm
Not having a bowel movement daily is NOT constipation
Constipation and risk of malignancy or other serious bowel
disorder
New onset constipation at age over 50
Accompanying symptoms such as anaemia, abdominal pain, weight loss,
or overt or occult blood in the stool
Needs detailed investigations 3
Constipation
General Management
Balanced diet with whole grains, fruits and vegetables
Increased dietary fibre content, adequate fluid intake and exercise
Fibre intake should be increased gradually (to minimise flatulence and bloating)
The effects of a high-fibre diet may be seen in a few days although it can take as long as 4 weeks
Adequate fluid intake is important (particularly with a high-fibre diet or fibre supplements), but can be difficult for some
people (for example, the frail or elderly).
Fruits high in fibre and sorbitol, and fruit juices high in sorbitol, can help prevent and treat constipation.
Misconceptions
Bowel habits may lead to excessive laxative use
Laxative abuse may lead to hypokalaemia
Before prescribing laxatives it is important to be sure that the patient is constipated and that the constipation is not
secondary to an underlying undiagnosed complaint
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Laxatives and Purgatives
Drugs that promote evacuation of bowels. Classified based on the intensity of action.
Laxative or aperient
Milder action, elimination of soft but formed stools
Purgative or cathartic
Stronger action resulting in more fluid evacuation
Many drugs in low doses act as laxative and in larger doses as purgative
Classification Classification
Bulk forming laxatives Stool softeners
Dietary fibre: Bran, Psyllium Docusates (DOSS), Liquid paraffin, Glycerol
(Plantago),Ispaghula, Methylcellulose suppositories
Stimulant laxatives/purgatives Osmotic laxatives/purgatives
Diphenylmethanes Magnesium sulphate, Magnesium hydroxide
Phenolphthalein, Bisacodyl, Sodium picosulfate Sodium sulphate, Sodium phosphate
Anthraquinones (Emodins) Sodium potassium Tartrate
Senna, Cascara sagrada, co-danthramer Lactulose
5-HT4 agonist
Others
Tegaserod
Linaclotide, Prucalopride 5
Laxatives and Purgatives
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Mechanism of action
All purgatives increase the water content of faeces by:
A hydrophilic or osmotic action
Retaining water and electrolytes in the intestinal lumen—increase volume of colonic content and make it easily propelled.
Decrease in net absorption of water and electrolyte
Acting on intestinal mucosa, decrease net absorption of water and electrolyte; intestinal transit is enhanced indirectly by the
fluid bulk.
Increasing propulsive activity as primary action
Allowing less time for absorption of salt and water as a secondary effect
Increased water content of stools as the primary action or it is a consequence of increased motility
Laxatives modify the fluid dynamics of the mucosal cell and may cause fluid accumulation in gut lumen by one or
more of following mechanisms:
Inhibiting Na+/K+ATPase of villous cells— impairing electrolyte and water absorption.
Stimulating adenylyl cyclase in crypt cells— increasing water and electrolyte secretion.
Enhancing PG synthesis in mucosa which increases secretion.
Structural injury to the absorbing intestinal mucosal cells
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Laxatives and Purgatives
Bulk forming laxatives Indications Contra-indications Adverse Effects
Bran
A by-product of flour industry consists of 40% dietary fibre
Absorbs water in the intestines, swells, increases water content of faeces and facilitates its
colonic transit, 20-40 g/day for 3- 4 days
Methylcellulose
A semi-synthetic, colloidal hydrophilic derivative of cellulose; 4-6 g / day is satisfactory
in most individuals
Psyllium seed (ispaghula husk)
Contains natural colloidal mucilage that absorbs water and makes a gelatinous mass
3-12 g of refined husk freshly mixed with water or milk, taken daily-acts in 1-3 days
Generous amounts of water must be taken, with all bulk forming agents
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Laxatives and Purgatives
Stimulant Laxatives/purgatives
Some of them primarily increase motility by acting on myenteric plexuses
More important mechanism of action is accumulation of water and electrolytes in the lumen by altering
absorptive and secretory activity of the mucosal cells
They inhibit Na/K-ATPase at the basolateral membrane of villous cells
Transport of Na+ and accompanying water into the interstitium is reduced
Activation of c-AMP in crypt cells
Secretion is enhanced by activation of c-AMP in crypt cells and by increased PG synthesis
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Laxatives and Purgatives
Diphenylmethanes
Phenolphthalein
An indicator and in use as purgative from the beginning of the 20th century. It turns urine pink if alkaline
Dose: 60-130 mg, to be taken at bedtime
Bisacodyl (DULCOLAX)
Bisacodyl is activated in the intestine by deacetylation. Primary site of action is in the colon: irritate the mucosa, produce
mild inflammation and secretion. One or two semi-formed motions occur after 6-8 hours. Optimum doses vary considerably
among individuals.
Dose: 5-15 mg, q 24h
Sadium picosulfate (LAXOBERON, SKILAX)
Hydrolysed by colonic bacteria to the active form acts locally to irritate the mucosa and activate myenteric neurones.
Bowel movement generally occurs after 6-72 hours of oral dose.
Together with Mag. Citrate solution Colon evacuation for colonoscopy or surgery
Dose Adults: 5-15 mg , Child dose: 0.25mg/kg , q 24h
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Laxatives and Purgatives
Anthraquinones (Emodins)
Senna ()سنامیک
Obtained from leaves of cassia sp., Cascara sagrada is the powdered bark of the buck-thorn tree
Contain anthraquinone glycosides, also called emodins
The active principle acts on the myenteric plexus to increase peristalsis and decrease segmentation.
They also promote secretion and inhibit salt and water absorption in the colon.
Senna anthraquinone has been found to stimulate PGE2 production in rat intestine
Indications
5HT4 Agonists
! Prucalupride
Prucalupride
• Chronic Constipation
It is a new selective 5HT4 receptor agonist with no action on other receptors • Constipation – predominant IBS
Activates pre-junctional 5-HT4 receptors on intrinsic enteric afferent nerves
Enhances release of excitatory transmitter Ach and calcitonin gene related peptide (CGRP)
Both promote peristaltic reflex and colonic secretion (by enhancing cAMP mediated CI- efflux)
Propulsive activity is increased in the stomach, ileum and most prominently in colon
Enteric neurons stimulate proximal bowel contraction (via acetylcholine and substance P)
and distal bowel relaxation (via nitric oxide and vasoactive intestinal peptide)
Tegaserod (withdrawn now)
5HT4 receptor partial agonist
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Laxatives and Purgatives
Osmotic Purgatives Indications Adverse Effects
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