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Dr. Jatin Dhanani

DRUG THERAPY FOR CONSTIPATION

Causes of constipation

Consequences of chronic constipation

Piles Anal fissures Prolapse of rectum UTIStomatitis

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

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

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

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

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)

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

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)

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

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

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

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

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)

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

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

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.

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

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

Contraindications of laxatives

Constipation due to mechanical obstruction Stricture, adhesions

Acute undiagnosed abdominal painOther disease like cretinism,

carcinoma Drug induced constipation

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

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

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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