Pharma laxative

• Laxatives


  Commonly used for constipation to accelerate the movement of food through the GI tract
• Laxatives increase the potential for loss of pharmacologic effect of poorly absorbed, delayed-acting, and extended-release oral preparations by accelerating their transit through the intestines
• Laxatives may cause electrolyte imbalances when used chronically
• Many laxatives have a risk of dependency for the user
• General indications of laxatives

  • Constipation
  • To increase excretion of toxic substances from the GIT
  • To prepare the bowel before X-ray or colonoscopy
  • Painful anal conditions e.g. anal fissure or piles
  • Postoperative: e.g. after hemorrhoids (piles) to avoid strain
• Contraindications of laxatives


  • Undiagnosed abdominal pain or inflammatory bowel disease (may lead to intestinal perforation)
  • Organic obstruction of the GIT
• Classification of laxatives according to mechanism of action

  • Irritants and stimulants
  • Bulk laxatives
  • Saline and osmotic laxatives
  • Stool softeners (emollient laxatives or surfactants)
  • Lubricant laxatives
  • Chloride channel activators

  
• Senna


  • Widely used stimulant laxative
  • Taken orally, causes evacuation of the bowels within 8 to 10 hours
  • Causes water and electrolyte secretion into the bowel
• Bisacodyl


  • Available as suppositories and enteric-coated tablets
  • Potent stimulant of the colon
  • Acts directly on nerve fibers in the mucosa of the colon
• Castor oil


  • Broken down in the small intestine to ricinoleic acid, which is a very irritating substance and promptly increases peristalsis
  • Pregnant patients should avoid castor oil because it may stimulate uterine contractions
• Bulk laxatives


  • Include hydrophilic colloids (from indigestible parts of fruits and vegetables)
  • Form gels in the large intestine, causing water retention and intestinal distension, thereby increasing peristaltic activity
  • Similar actions are produced by methylcellulose, psyllium seeds, and bran
  • Should be used cautiously in patients who are immobile because of their potential for causing intestinal obstruction

  
• Saline and osmotic laxatives


  • Saline cathartics, such as magnesium citrate and magnesium hydroxide, are nonabsorbable salts that hold water in the intestine by osmosis
  • Distend the bowel, increasing intestinal activity and producing defecation in a few hours
  • Electrolyte solutions containing polyethylene glycol (PEG) are used as colonic lavage solutions to prepare the gut for radiologic or endoscopic procedures
  • Lactulose is a semisynthetic disaccharide sugar that acts as an osmotic laxative, cannot be hydrolyzed by GI enzymes but is degraded by colonic bacteria into lactic, formic, and acetic acids, increasing osmotic pressure, causing fluid accumulation, colon distension, soft stools, and defecation

  
• Stool softeners (emollient laxatives or surfactants)


  • Surface-active agents that become emulsified with the stool produce softer feces and ease passage
  • Include docusate sodium and docusate calcium
  • May take days to become effective and are often used for prophylaxis rather than acute treatment

  
• Lubricant laxatives


  • Mineral oil and glycerin suppositories are lubricants and act by facilitating the passage of hard stools
  • Mineral oil should be taken orally in an upright position to avoid its aspiration and potential for lipid pneumonia

  
• Chloride channel activators


  • Lubiprostone, currently the only agent in this class, works by activating chloride channels to increase fluid secretion in the intestinal lumen
  • Eases the passage of stools and causes little change in electrolyte balance
  • Used in the treatment of chronic constipation, particularly because tolerance or dependency has not been associated with this drug
  • Drug-drug interactions appear minimal because metabolism occurs quickly in the stomach and jejunum
• Approaches to the treatment of severe acute diarrhoea

  • Maintenance of fluid and electrolyte balance
  • Use of anti-infective agents
  • Use of spasmolytic or other antidiarrhoeal agents
• Antimotility agents


  • Two drugs that are widely used to control diarrhoea are diphenoxylate and loperamide
  • Both are analogs of meperidine and have opioid-like actions on the gut
  • They activate presynaptic opioid receptors in the enteric nervous system to inhibit acetylcholine release and decrease peristalsis
  • At the usual doses, they lack analgesic effects
  • Because these drugs can contribute to toxic megacolon, they should not be used in young children or in patients with severe colitis
• Adsorbents


  • Adsorbent agents, such as aluminum hydroxide, activated charcoal and methylcellulose, are used to control diarrhoea
  • Presumably, these agents act by adsorbing intestinal toxins or microorganisms and/or by coating or protecting the intestinal mucosa
  • They are much less effective than antimotility agents, and they can interfere with the absorption of other drugs

  
• Agents that modify fluid and electrolyte transport


  • Bismuth subsalicylate, used for traveler's diarrhoea, decreases fluid secretion in the bowel
  • Its action may be due to its salicylate component as well as its coating action
  • Adverse effects may include black tongue and black stools