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CONSTIPATION Laxatives: Laxatives are milder in action and deal with evacuation of rectum. With use of laxatives, there is elimination of formed stools. Cathartics/purgatives: Purgatives are drugs which promote defecation and they are used in the treatment of constipation. Cathartics are severe in action and deal with evacuation of colon. With their use, liquid form of stool is eliminated. Functions of Colon: Modification of consistency Maintenance of consistency of stool through reabsorption of water. More water is reabsorbed, stool will harder. Storage of fecal material Evacuation takes place only when it is convenient for person. Factors affecting function of colon: Diet: Diet rich in fiber content will produce a softer consistency of stool Water intake Causes of constipation: Diet: Diet lacking fiber content will lead to constipation Structural abnormalities: Hemorrhoids and anal fissure. In these, patient is reluctant to pass stool. Tumors of colon can cause constipation Intestinal obstruction Management of constipation: To remove the cause Diet changes Use of drugs Purgatives: Bulk Purgatives: Hydrophilic colloids, Ispaghula Husk, Bran, Methylcellulose, Psyllium seed Anthraquinone derivatives: Aloe, Senna, Cascara. Diphyenyl methane derivatives: Bisacodyl Irritant oil: Castor oil Lubricant purgative: Liquid paraffin Osmotic Purgatives: Magnesium sulfate, Magnesium Hydroxide Saline purgatives: Sodium Phosphate Non-absorbable Sugars: Lactulose, Sorbitol Stool Softeners: Glycerin, Sodium docusate, Calcium docusate, Potassium docusate. 5 HT4 Receptor Agonist: Tegaserod Bulk Forming Purgatives: Mechanism of Action: Fiber in our diet is partly fermented and unfermented Fermented portion is converted into short chain fatty acids which have got prokinetic activity (they increase motility and secretion) Unfermented portion imbibes water and increases bulk of stool due to this there is distention and increase in peristalsis. Adverse Effects: Allergic reaction with psyllium seeds, abdominal discomfort Uses: Mainly constipation, Irritable bowel syndrome, Stimulant Purgatives, Powerful purgatives Anthraquinone Purgatives: Mechanism of Action: Anthraquinone contains an active principle EMODIN which is a glycoside. It is passed into colon where it is acted upon by bacteria and they liberate ANTHROL which has prokinetic activity. Adverse Effects: Cathartic colon, Melanosis coli. Diphenylyl methane Derivatives: Bisacodyl: Mechanism of Action: This agent is hydrolyzed in gut through deacetylation and converted to active form which produces low grade inflammation as a result of which motility and secretions are increased. Adverse Effects: Abdominal pain/discomfort, few allergic reactions. Castor Oil: Oldest purgative largely used by quacks. Triglyceride component is acted upon by pancreatic lipases as result of which glycerol and ricinoleic acid is formed. Ricinoleic acid has prokinetic activity. Prolonged use is prohibited; it can damage intestinal mucosa as well as intestinal neurons. Liquid Paraffin: A viscous mixture of petroleum hydrocarbons with a lubricant action helps in relieving constipation as it coats the stool. Docusate: Cause accumulation of water in the lumen of colon because of which they soften the stool, Motility of gut, Increased by stimulating cAMP, Disrupts mucosal barrier. Adverse effects: Abdominal Cramps, Pain, Nausea, Bitter in Taste, Hepatotoxicity Osmotic Purgatives: These are not absorbed in small intestine & retain water due to osmolar action by absorbing water, increase the bulk of stool because of which there is distention of colon and increase in motility. Magnesium salts can increase secretion of CCK, which aids in purgative action of Mg. Uses: Preparation of bowel before colonoscopy in food and drug poisoning, Preparation of bowel before surgery. Glycerin: Given in form of suppository. Acts as Osmotic action and Lubricant action Lactulose: It is converted into organic acid, decrease pH of colon, converts ammonium into nonabsorbable ammonium ion and thus decreases ammonia absorption. Uses: Hepatic encephalopathy Tegaserod: It is a Partial agonist at serotonin 4 receptors and has high affinity for these receptors as compared with 5HT3 receptors. It resembles serotonin and increases release of Acetylcholine and calcitonin Gene Related Peptides by acting on pre-junctional serotonin 4 receptors. Increases cAMP dependent chloride efflux thus increases secretion, motility Prokinetic activity is seen in stomach and small/large intestine. Uses: Gastropharesis, in chronic constipation when all other remedies fail, Irritable bowel syndrome Adverse Effects: Diarrhea, Abdominal discomfort, Flatulence, Headache.