Drug Therapy for Constipation
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Transcript of Drug Therapy for Constipation
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LOGO
Dr. Jatin Dhanani
DRUG THERAPY FOR CONSTIPATION
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Causes of constipation
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Consequences of chronic constipation
Piles Anal fissures Prolapse of rectum UTIStomatitis
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Treatment
Non - pharmacological
Onset of Action 1-3 hrs Osmotic laxatives – Mag.
hydroxide, Mag. sulphate, Mag. citrate, Polyethylene Glycol (PEG)
Stimulant laxative – castor oil
Onset of Action 6-8 hrsStimulant laxatives
Diphenylmethane – Bisacodyl, phenolphthalein
Anthraquinone – senna, cascara sagrada
Onset of Action 1-3 days Bulk-forming laxatives –
Bran and dietary fibers, psyllium (ispaghula husk), methylcellulose, carboxymethylcellulose
Surfactant and emollients – docusates, mineral oil (liquid paraffin)
Lactulose
Pharmacological
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Non - pharmacological
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
Plenty of fluid Increase water
content of stoolBowel habit
Running for work Avoidance of
defecation reflex Physical activity
Require for normal movement of bowel
Fiber rich diet Plenty of fluid Bowel habit Physical
activity
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Pharmacological Therapy
Laxatives (aperients) Purgatives (cathartics)Mechanism of action
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
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Bulk forming Laxatives
Bran/dietary fiber Byproduct of flour industry Bran of wheat – high lignin content (non-
polysaccharide 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
Bran and dietary fibers, psyllium (ispaghula husk), methylcellulose, carboxymethylcellulose
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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)
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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 times Adequate amount of fluid should be taken
with all the bulk forming agents
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Stool softener
Docusates 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
docusates,mineral oil (liquid paraffin)
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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 Aspiration – lipoidal pneumonia Deficiency of lipid soluble vitamins
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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
Dose: in constipation – 10 gm BDhepatic coma – 20 gm TDS
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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
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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
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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)
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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
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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
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Osmotic laxatives Mechanism
Retain water osmotically – distend bowel – 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 (glauber’s salt) – 10 – 15 gm Sod. pot. tartrate (rochelle salt) All salts dissolved in 150 – 200 ml of water
SalineNondigestible sugarPEG & electrolyte sol.
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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
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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
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Contraindications of laxatives
Constipation due to mechanical obstruction Stricture, adhesions
Acute undiagnosed abdominal painOther disease like cretinism,
carcinoma Drug induced constipation
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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
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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
After antihelminthic saline purgatives and senna
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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
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LOGO
Thank You