Dr. RAGHU PRASADA M S MBBS,MD ASSISTANT PROFESSOR DEPT. OF PHARMACOLOGY SSIMS & RC.

Constipation has many reversible or secondary causes, including lack of dietary fiber, drugs, hormonal disturbances, neurogenic disorders, and systemic illnesses. In most cases of chronic constipation, no specific cause is found. Up to 60% of patients presenting with constipation have normal colonic transit.

Laxatives or aperient- milder action, elimantion of soft, formed stools Purgatives or cathartic- stronger action resulting in more fluid evacuation

Bulk forming- dietary fibre: BRAN, PSYLLIUM, ISPAGHULA, METHYLCELLULLOSE Stool softener-DOCUSATES (DOSS), LIQUID PARAFFIN Stimulant purgatives- Diphenyl methanes-PHENOLPHTHALEIN, BISACODYL, SODIUM PICOSULFATE Anthraquinones-emodins SENNA, CASCARA SAGRADA 5-HT4 agonist- PRUCALOPRIDE Fixed oil-CASTOR OIL

Osmotic purgatives-MAGNESIUM SALTS: SULFATE, HYDROXIDE Sodium salts- SULFATE, PHOSPHATE SODIUM POTASSIUM TARTARATE, LACTULOSE

All purgatives increase the water content of faeces by Hydrophilic or osmotic action, retaining water and electrolytes in the intestinal lumen-increase volume of colonic content They decrease the net absorption of water and electrolyte Increasing propulsive activity as primary action allowing less time for absorption

Modification of fluid dynamics Inhibiting Na+K+ ATPase of villlous cells impairing electrolyte and water absorption Stimulate adenylyl cyclase in crypt cells increasing water and electrolyte secretion Enhances PG synthesis in mucosa Increasing NO synthesis increases secretion

Bulk stimulants-cellulose, lignins, gums, pectins and polysaccharides Absorb water in intestine swells, increase water Content of the fecal matter to increase in bulk, Stimulate peristalsis by increasing bulk in stool through absorption of water in the colon Osmotically active products may be formed in colon bacterial degradation of cholesterol in liver

Demerits Unpalatable, large quantity 3-4 days for full effect Doesn’t soften already formed Better for prevention Cannot be used in patients with gut ulceration, adhesions and stenosis

Ducosates-DOSS-dioctyl Sodium Sulfosuccinate Faecal softening agent, detergent like properties acts by holding water to the feacal matter, thus rendering it softer and easier to pass It emulsifies the colonic contents and increases the penetration of water into the faeces ADR-cramps and abdominal pain Poloxamer: Coloxyl. Also act on intestinal wall to inhibit water reabsorption, these are used to ease bowel movements and work over several days.

liquid paraffin Mixture of petroleum hydrocarbons Has a detergent action on the surface of the intestinal bolus, making a softer stool Pharmacologically inert and lubricate hard scybali by coating them Disadvantages Bland unpleasant Foreign body granuloma in intestinal mucosa Lipid pneumonia Vitamin deficiency Post anal leakage and interfere healing

Glycerin Hyperosmolar laxative used to gently evacuate the rectum without systemic effects higher in the GI tract Mineral oil Forms a slippery coat on the contents of the intestinal tract

Bisacodyl (Dulcolax) Partly absorbed and reexcreted in bole It is activated in intestine by deacetylation They produce mild inflammation and irritate mucosa increase secretion Very popular OTC laxative Enteric coated to dissolve in small intestine and produces stimulating effect on colon. Can irritate stomach hence enteric coated. 5-15mg Evacuation 6-12 hours after oral and 15-60 mins suppository Sodium picosulfate-

Senna : Reliable drug, similar to cascara Produces bowel action in 6-12 hours Castor oil : Old standby for thorough evacuation of the intestine

Magnesium sulfate (Epsom Salts) Sodium phosphate, sodium salts Glycerol, Lactulose, Sorbitol Contents are hypertonic, causing water to be retained and if the osmotic pressure is great enough, can pull water from the gut capillaries back in to the bowel lumen. Leading to a stimulation in the defecation process

Actions: Forms a slippery coat on the contents of the intestinal tract; less water is absorbed out of the bolus; bolus is less likely to become hard or impacted Pharmacokinetics: Not absorbed systemically Indications: Short-term relief of constipation; prevent straining; remove ingested poisons; an adjunct in anthelmintic (treatment of worms) therapy

Actions: Directly stimulates the nerve plexus in the intestinal wall, causing increased movement and the stimulation of local reflexes Pharmacokinetics: Not absorbed systemically Indications: Evacuate the bowel for diagnostic procedures; remove ingested poisons from the lower GI tract; adjunct in anthelmintic therapy

Actions: Increases motility of the GI tract by increasing the fluid in intestinal contents; enlarges bulk; stimulates local stretch receptors; activates local activity Pharmacokinetics: Not absorbed systemically Indications: Short-term relief of constipation; prevent straining; evacuate the bowel for diagnostic procedures; remove ingested poisons; adjunct in anthelmintic therapy

Functional constipation Short-term relief of constipation Bed ridden patients Prevent straining when it is clinically undesirable Evacuate the bowel for diagnostic procedures Remove ingested poisons from the lower GI tract As an adjunct in anthelmintic therapy Food poisoning and drug poisoning