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antidiarrheal agents



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  • 2. Diarrhea  Abnormal frequent passage of loose stool or  Abnormal passage of stools with increased frequency, fluidity, and weight, or with increased stool water excretion.
  • 3.  Diarrhea is the condition of having three  or more loose or liquid bowel movements  per day. 
  • 4.  For adults on a typical Western diet, stool weight >200 g/d can generally be considered diarrheal.
  • 5. Acute diarrhea  Sudden onset in a previously healthy person  Lasts from 3 days to 2 weeks  Self-limiting  Resolves without sequelae
  • 6. Chronic diarrhea  Lasts for more than 3 weeks  Associated with recurring passage of diarrheal stools, fever, loss of appetite, nausea, vomiting, weight loss, and chronic weakness
  • 7.  Diarrhea can be caused by  An increased osmotic load within the intestine (resulting in retention of water within the lumen)  Excessive secretion of electrolytes and water into the intestinal lumen.  Exudation of protein and fluid from the mucosa.  Altered intestinal motility resulting in rapid transit (and decreased fluid absorption).
  • 8.  Pharmacotherapy of diarrhea should be reserved for patients with significant or persistent symptoms.  Nonspecific antidiarrheal agents typically do not address the underlying pathophysiology responsible for the diarrhea; their principal utility is to provide symptomatic relief in mild cases of acute diarrhea.
  • 9. ORS  Composition of ORS : HOME WORK
  • 10. Mechanism of Action Adsorbents  Coat the walls of the GI tract  Bind to the causative bacteria or toxin, which is then eliminated through the stool.  Examples: bismuth subsalicylate (Pepto- Bismol), kaolin-pectin, attapulgite.
  • 11.  Clays such as kaolin (a hydrated aluminum silicate) and other silicates such as attapulgite (magnesium aluminum disilicate) bind water avidly and also may bind enterotoxins.  However, this effect is not selective and may involve other drugs and nutrients; hence, these agents are best avoided within 2–3 hours of taking other medications.  A mixture of kaolin and pectin (a plant polysaccharide) is a popular over-the-counter remedy (kaolin-pectin) and may provide useful symptomatic relief of mild diarrhea.
  • 12. Side Effects Adsorbents  Constipation, dark stools  Confusion, twitching  Hearing loss, tinnitus, metallic taste, blue gums
  • 13. Mechanism of Action Anticholinergics  Decrease intestinal muscle tone and peristalsis of GI tract  Result: slowing the movement of fecal matter through the GI tract  Examples: Atropine
  • 14. Side Effects Anticholinergics  Urinary retention, hesitancy, impotence  Headache, dizziness, confusion, anxiety, drowsiness  Dry skin, rash, flushing  Blurred vision, photophobia, increased intraocular pressure
  • 15. Antimotility and Antisecretory Agents OPIOIDS  Opioids continue to be widely used in the treatment of diarrhea.  They act principally through either µ- or δ- opioid receptors on enteric nerves, epithelial cells, and muscle.  These mechanisms include effects on intestinal motility (µ receptors), intestinal secretion (δ receptors), or absorption (µ and d receptors).  Commonly used antidiarrheals such as Diphenoxylate, and Loperamide act principally via peripheral µ-opioid receptors and are preferred over opioids that penetrate the CNS.
  • 16. Loperamide  Loperamide a Piperidine butyramide derivative with µ- receptor activity, is an orally active antidiarrheal agent.  The drug is 40–50 times more potent than morphine as an antidiarrheal agent and penetrates the CNS poorly.  It increases small intestinal and mouth-to-cecum transit times.  Loperamide also increases anal sphincter tone, an effect that may be of therapeutic value in some patients who suffer from anal incontinence.  In addition, loperamide has antisecretory activity against cholera toxin and some forms of Escherichia coli toxin
  • 17. Diphenoxylate and Difenoxin  Diphenoxylate and its active metabolite Difenoxin (diphenoxylic acid) are related structurally to meperidine.  As antidiarrheal agents, diphenoxylate and difenoxin are somewhat more potent than morphine.  Both compounds are extensively absorbed after oral administration, with peak levels achieved within 1–2 hours.  Both drugs can produce CNS effects when used in higher doses (40–60 mg/day) and thus have potential for abuse and/or addiction.
  • 18. A/E  They are available in preparations containing small doses of atropine (considered subtherapeutic) to discourage abuse and deliberate overdosage.  With excessive use or overdose, constipation and (in inflammatory conditions of the colon) toxic megacolon may develop.  In high doses, these drugs cause CNS effects as well as anticholinergic effects from the atropine (e.g., dry mouth, blurred vision)
  • 19. BULK-FORMING AGENTS  Hydrophilic and poorly fermentable colloids or polymers such as Carboxymethyl cellulose and Calcium Polycarbophil absorb water and increase stool bulk.  They usually are used for constipation but are sometimes useful in mild chronic diarrhea in patients suffering with Irritable Bowel Syndrome (IBS-A).
  • 20. Antidiarrheal Agents: Interactions  Adsorbents decrease the absorption of many agents, including digoxin, clindamycin, quinidine, and hypoglycemic agents.
  • 21. Nursing Implications  Obtain thorough history of bowel patterns, general state of health, and recent history of illness or dietary changes, and assess for allergies  DO NOT give bismuth subsalicylate to children younger than age 16 or teenagers with chickenpox because of the risk of Reye’s syndrome.
  • 22.  Anticholinergics should not be administered to patients with a history of glaucoma, urinary retention, cardiac problems, myasthenia gravis.
  • 23. Constipation
  • 24. Constipation  Difficult, incomplete sensation, or infrequent evacuation of dry hardened feces from the bowels  It is symptom, not a disease  Disorder of movement through the colon and/or rectum  Can be caused by a variety of diseases or drugs
  • 25.  Constipation can be corrected by adherence to a fiber- rich (20–30 g daily) diet, adequate fluid intake, appropriate bowel habits and training, and avoidance of constipating drugs.  Constipation related to medications can be corrected by use of alternative drugs where possible, or adjustment of dosage.  If nonpharmacological measures alone are inadequate, they may be supplemented with bulk- forming agents or osmotic laxatives.
  • 26.  When stimulant laxatives are used, they should be administered at the lowest effective dosage and for the shortest period of time to avoid abuse.  Habitual use of laxatives may lead to excessive loss of water and electrolytes; secondary aldosteronism may occur if volume depletion is prominent.
  • 27.  The terms laxatives, cathartics, purgatives, and evacuants often are used inter changeably.  There is a distinction, however, between laxation (the evacuation of formed fecal material from the rectum) and catharsis (the evacuation of unformed, usually watery fecal material from the entire colon).  Laxatives are employed before surgical, radiological, and endoscopic procedures where an empty colon is desirable.
  • 28. Laxatives  1)Bulk laxatives: by increasing the volume of non-absorbable solid residues  Eg: Hydrophilic Colloids, Bran, Methylcellulose, Psyllium, Ispaghula  2)Osmotic laxative: by increasing the water content  Eg: Saline purgatives:MgSo4 (Epsom salts), Mg(OH)2 (MOM), Lactulose
  • 29.  3)Fecal Softners: by altering the consistency of feces  Eg: DOSS (dioctyl sodium sulfosuccinate), Mineral oils, Glycerin suppositories  4)Stimulant/Irritant Purgative/laxative: by increasing the motility and secretion  Eg: Senna, Cascara, Castor oil, Bisacodyl. Phenolphthalein
  • 30. Bulk laxatives  Include hydrophilic colloids(prepared from indigestible parts of fruits, vegetables and seeds)  Forms gel in large intestinecause water retention and intestinal distension increase peristaltic activity  Are first line approach for most pts of simple constipation  Uses:  Habitual constipation in elderly pts  hemorrhoids pts
  • 31. Osmotic laxatives  Saline purgatives: Laxatives containing magnesium cations or phosphate anions commonly are called saline laxatives: magnesium sulfate, magnesium hydroxide, magnesium citrate,sodium phosphate  Solutes that are not absorbed in intestineretain more water osmoticallydistend the bowelincrease peristalsisleads purgation about an hour later
  • 32.  Abd. cramps can occur  Quick onset of action  Advised to take plenty of water administration of hypertonic sol may cause dehydration
  • 33.  Uses:  For preparation of bowel before surgery and colonoscopy  In food/drug poisoning
  • 34. Lactulose  Semisynthetic disaccharide of fructose and galactosenot digested or absorbed in small intestineretains water  In colonbacteria convert it into two component sugarfermentationlactic acid and acetic acidfunction as osmotic laxative  After lactulose administration, gut contents have low pH than normaldecrease activity of ammonia producing organismhence used in treatment of hepatic encephalopathy
  • 35. Fecal softeners  Promote more water and fat in the stools  Lubricate the fecal material and intestinal walls  Emulsifying effect on fecesmake them retain more watersofter stooleasier to pass out  Abd cramps can occur  Uses: condition where straining at stool has to be avoided like hernia, piles, fissures, anal surgery
  • 36. Stimulant laxative  They increase the peristalsis by stimulation of gut mucosa  Causes abd cramps, prolonged use cause atonic colon(sluggish bowel)  Used mainly for preparation of bowel for surgery, colonoscopy and abd X-rays
  • 37.  Bisacodyl: given orally and also as suppositorydefecation in 15-30min  Phenolphthalein: given orally  A/E:allergic rashes in skin
  • 38. Laxatives: Side Effects  Bulk forming  Impaction  Fluid overload  Emollient (stool softener)  Skin rashes  Decreased absorption of vitamins  Hyperosmotic  Abdominal bloating  Rectal irritation
  • 39.  Saline  Magnesium toxicity (with renal insufficiency)  Cramping  Diarrhea  Increased thirst  Stimulant  Nutrient malabsorption  Skin rashes  Gastric irritation  Rectal irritation All laxatives causes electrolyte imbalance
  • 40. Laxatives: Nursing Implications  Assess fluid and electrolytes before initiating therapy  Patients should not take a laxative if they are experiencing nausea, vomiting.
  • 41.  A healthy, high-fiber diet and increased fluid intake should be encouraged as an alternative to laxative use  Long-term use of laxatives often results in decreased bowel tone and may lead to dependency
  • 42. Abuse and danger of laxative  Repeated administration may produce:  GI disturbaces like spastic colitis, dyspepsia, anorexia and nausea  Nutritional deficiencies of calories, vitamins, minerals  Loss of fluids and electrolytes  Complete dependency on drugs
  • 43. The End…..