Drugs for Constipation

Stool Softener
Doccusates (Dioctyl sodium sulfosuccinate): Anionic detergent, softens stool by water accumulation in lumen. Emulsifies colonic contents, increases penetration of water in faeces. Mild laxative. Detergent action disrupt mucosal barrier, enhance absorption of nonabsorbable drugs. Side effects: Cramps and abdominal pain. Bitter---nausea. Hepatotoxicityprolonged use.

Stimulant Purgatives
Powerful purgatives---gripping. Accumulation of water and electrolytes in lumen. Inhibit sodium pot ATPase at basolateral membrane of villous cells. Secretion is enhanced by activation of cAMP in crypt cells and increased PG synthesis. Large doses---fluid and electrolyte imbalance. Hypokalaemia on regular use. Contraindicated in pregnancy. Subacute or chronic intestinal obstruction.

Diphenylmethanes: Bisacodyl: Partly absorbed and re-excreted in bile. Activated in intestine by deacetylation. Site of actioncolon: irritate mucosa, produce mild inflammation and secretion. Phenolphthalein 60-130 mg. Bisacodyl 5-15 mg. Ineffective in some individuals. Produce fluid evacuations and cramps in others. Allergic reactions: skin rashes, fixed drug eruption, StevenJohnson syndrome. Bisacodyl: 5 mg (infant) and 10 mg (adult) suppository: acts by irritating anal and rectal mucosa---reflex increase in motility--evacuation occurs 20-40 min. Cause inflammation and mucosal damage.

Anthraquinones: Senna---leaves and pods of Cassia sp. Cascara sagrada---powdered bark of buckthorn tree. Anthraquinone glycosidesemodin. Unabsorbed in small intestine----colon-----bacteria liberate anthrol--locally or enters circulation---excreted in bile to act on small intestine. 6-8 h to produce action. Increases peristalsis. Purgation in suckling infant. Taken at bed time. Cramps and excessive purging in some cases. Promotes secretion and inhibits salt and water reabsorption in colon. Side effects: skin rashes. Regular use 4-12 months----colonic atony and melanosis.

Tegaserod: Selective 5-HT4 receptor partial agonist. Enhances release of ACh and calcitonin gene related peptide--promote peristaltic reflex and colonic secretion. Propulsive activity increased in stomach, ileum, colon. Constipation-predominant IBS: increase in stool frequency, relief of abdominal pain. Chronic constipation. Small fraction absorbed. Excreted unchanged in faces. Half life: 11 h. Side effects: loose motion, flatulence, headache.

Osmotic Purgatives
Solutes not absorbed intestine retain water osmotically and distend the bowel---increasing peristalsis. Mg ions---cholecystokinin---purgative action Mg salts. Mg sulfate, Mg hydroxide, Sod. Sulphate, Sod pot tartarate. Salts dissolved in 150-200 ml water: produce 1-2 fluid evacuations within 1-3h with mild cramping and nearly complete emptying of bowels. Mg salts contraindicated renal insufficiency and sodium contraindicated in CHF. Preparing bowel for surgery and colonoscopy. Food and drug poisoning.

Choice and Use of Purgatives

1. Functional constipation: Spastic constipation: Tegaserod. Atonic constipation: Bisacodyl or Senna once or twice a week. 2. Bedridden patients: Prevent constipation: bulk forming agents on a regular schedule, docustaes, lactulose, liquid paraffin. Treat constipation: enema, bisacodyl or senna. 3. To Avoid Straining At Stools: Hernia, CV disease, eye surgery, piles. 4. Preparation of bowel for surgery, colonoscopy, abdominal X-ray: saline purgative, bisacodyl, senna. 5. After certain anthelmintics: saline purgative, bisacodyl, sennaflush out worms. 6. Food/ drug poisoning