7. Laxative, Purgatives & Anti-diarrhea agents

• what type of laxatives is the safest?

  bulk-forming
• Laxative abuse can lead to hypokalemia
• synthetic fibers such as polycarbophil is a bulk forming laxative
• Bulk forming MOA

  • indigestible hydrophilic substance
  • induce retention of water and increase bulk of stool
  • cause distension of intestinal wall
  • stimulate peristalsis
• Bulk forming is treatment of choice for chronic constipation
• stool softener MOA

  • contain
  • detergent - reduce surface tension in intestinal lumen
  • lubricant
• Stool Surfactant Agents - facilitate incorporation of water and fat into the stools thereby softening it
• Stool softeners uses

  • laxative in hemorrhoids
  • prevent female impaction
• Mineral oil in stool softener should not be used in bedridden
• Docusate (stool softener) useful in mild constipation and safe in pregnancy
• Osmotic laxative & Stimulants laxative MOA

  • increase NO synthase & NO
  • stimulate intestinal secretion
  • Biosynthesis of PAF - stimulate colonic secretion and GI motility
• Osmotic agents - attract and retain the water

  • increase intraluminal pressure and peristalsis
• Long term use of osmotic agents - causes excessive loss of fluid and electrolytes
• Osmotic agents such as magnesium

  • poorly absorbed from gut
  • osmotically active solutes act by retaining water in colonic lumen
• Magnesium laxative stimulate CCK release - which

  • increasing intestinal secretion
  • enhance colonic motility
• Osmotic laxative - C/I

  • critically ill patients - lead to hypovolemic shock
  • due to depletion of intravascular volume
• Mg2+ containing Osmotic laxative C/I

  • renal insufficiency due to retention of Mg2+ & hypermagnesemia
• Lactulose is osmotic laxatives
• Lactulose - not affected by intestinal disaccharidases

  • hence not digested and absorbed
• Lactulose

  • retains water cause distension and increase peristalsis
• colonic bacteria degrade lactulose into organic acids

  • which are osmotically active compounds
• Lactulose is use in hepatic encephalopathy
• Lactulose

  • reduce pH of colon by forming lactic acid
  • acidic pH of colon make NH4
  • NH4+ is polar - not absorbed and secreted
  • reduce ammonium level in the blood
• Polyethylene glycol (PEG) is nonabsorbable

  • induce secretion of fluid into GIT lumen to produce watery stool
• PEG does not produce significant cramps or farts unlike lactulose
• PEG is used

  • complete GIT or colonic cleansing
  • whole bowel irrigation due to poison
  • treatment of prevention of chronic constipation
• Stimulant laxative names

  • senna
  • -bisacodyl
• Castor oil (stimulant laxatives) - not used in pregnancy
• Stimulant laxatives

  • decrease water absorption
  • stimulate intestinal secretion
  • stimulate enteric nerve
  • directly stimulate peristalsis
• Senna can lead to brown discoloration of colon due to lipofuscin macrophages
• ** senna can cause melanosis coli

  • confused with bowel ischemia
• Chloride secretion Activators name

  • -tide
• Chloride secretion activators MOA

  • Guanylate cyclase-C (GC-C) agonists
  • increase cGMP and activate cGMP PKGII and CFTR
  • enhance secretion of chloride and HCO3
• (methyna) Methylnaltrexone is approved for opioid-induced constipation.
• Naloxegol – used in opioid-induced constipation (OIC) in adults
• (alvi) Alvimopan - Useful in the management of postoperative ileus secondary to abdominal surgery.
• Alvimopan (alvi) - increased myocardial infarction
• Opioid receptor anatagonist MOA

  • They don't cross BBB
  • block intestinal mu (μ) opioid receptors without affecting the analgesic effects of opioids in CNS.
• Antibiotic are not used in EHEC due to risk for hemolytic uremic syndrome
• Antibiotics are indicated in diarrhea with

  • abdominal pain
  • blood in the stool
  • fever >7 days