PHM101: Pharmacology of Laxatives and Constipation Therapies
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Questions and Answers

What is the primary mechanism by which bulk forming laxatives increase fecal mass?

  • Stimulation of peristalsis through increased water retention
  • Inhibition of water absorption in the colon
  • Fermentation of fiber in the colon to produce short chain fatty acids (correct)
  • Decreased gut motility

    • Which of the following osmotic laxatives is contraindicated in the elderly and individuals with renal disease?

  • Lactulose
  • Phosphate salts (correct)
  • Magnesium salts
  • Polyethylene glycol

    • What is the primary effect of lactulose on the gut?

  • Increased water retention in the colon (correct)
  • Decreased gut blood flow
  • Increased gut motility
  • Inhibition of gut motility

    • What is the primary mechanism of action of lubricant-type laxatives, such as Fleet enema?

    <p>Coating the gut wall to prevent water reabsorption and dehydration of fecal mass</p> Signup and view all the answers

    Which of the following is a characteristic of polyethylene glycol (PEG)?

    <p>High osmotic pressure</p> Signup and view all the answers

    What is the primary mechanism of action of mineral oil as a stool softener?

    <p>Emollient effect on the gut mucosa</p> Signup and view all the answers

    What is a potential side effect of glycerin suppositories?

    <p>Local discomfort and sensation of burning</p> Signup and view all the answers

    What is the primary difference between bulk forming laxatives and osmotic laxatives?

    <p>Mechanism of action</p> Signup and view all the answers

    What is the mechanism of action of stimulant laxatives, such as bisacodyl and cascara?

    <p>Producing a low-grade inflammation in the intestines that promotes water and salt accumulation</p> Signup and view all the answers

    Why does bisacodyl require hydrolysis by esterases for activity?

    <p>To delay the onset of action</p> Signup and view all the answers

    What is a potential complication of using bisacodyl for more than 10 days?

    <p>Damage to the intestinal mucosa</p> Signup and view all the answers

    What is the mechanism of action of docusate, a stool wetting-agent?

    <p>Decreasing the surface tension of stool</p> Signup and view all the answers

    What is the mechanism of action of Senna and Cascara in the large intestine?

    <p>Inhibit colonic mucosal Na+/K+ ATPase, resulting in the accumulation of salt and water in the colon lumen</p> Signup and view all the answers

    What is the adverse effect of laxatives on the kidneys?

    <p>Increased sodium reabsorption and potassium excretion</p> Signup and view all the answers

    What is the primary receptor subtype involved in controlling GI motility and secretion?

    <p>5-HT-4</p> Signup and view all the answers

    What is the mechanism of action of Prucalopride?

    <p>Activation of 5-HT-4 receptor</p> Signup and view all the answers

    What is the mechanism of action of Linaclotide?

    <p>Agonist of guanylate cyclase C receptor</p> Signup and view all the answers

    What is the primary route of elimination of Prucalopride?

    <p>Renal elimination</p> Signup and view all the answers

    What is the effect of Castor oil on the gut lumen?

    <p>Stimulates water and electrolyte secretion</p> Signup and view all the answers

    What is the adverse effect of laxatives on the colon?

    <p>All of the above</p> Signup and view all the answers

    What is the primary function of bulk-forming laxatives?

    <p>To increase the bulk of stool by absorbing water</p> Signup and view all the answers

    Which of the following is a potential contraindication for the use of laxatives?

    <p>Abdominal pain</p> Signup and view all the answers

    What is the primary goal of a balanced diet in relation to bowel movements?

    <p>To ensure regular bowel movements without the need for laxatives</p> Signup and view all the answers

    What is the mechanism of action of osmotic laxatives?

    <p>They retain luminal fluid by osmotic mechanisms</p> Signup and view all the answers

    What type of laxative is characterized by their ability to stimulate propulsive contractions in the gut?

    <p>Stimulants (irritants)</p> Signup and view all the answers

    What is the primary function of pro-kinetic agents in relation to constipation?

    <p>To stimulate propulsive contractions in the gut</p> Signup and view all the answers

    What is the net stool fluid content a balance of?

    <p>Ingested or secreted fluids and salts, and fluids absorbed along the GI tract</p> Signup and view all the answers

    What type of laxative is characterized by their ability to decrease absorption of fluid by targeting transport processes?

    <p>Osmotic laxatives</p> Signup and view all the answers

    What is the primary mechanism of lubiprostone in increasing chloride conductance?

    <p>Agonist at prostaglandin E4 receptor which secondarily activates CFTR</p> Signup and view all the answers

    What is the primary mechanism of opioids in causing constipation?

    <p>Mechanism distinct from their analgesic effects in the CNS</p> Signup and view all the answers

    What is the route of administration of methylnaltrexone?

    <p>Subcutaneous administration</p> Signup and view all the answers

    What is the primary mechanism of prosecretory agents in increasing chloride flux?

    <p>Activation of the ClC-2 channel and agonist activity at the prostaglandin E4 receptor</p> Signup and view all the answers

    What is the primary mechanism of peripherally acting μ-opioid receptor antagonists in treating opioid-induced constipation?

    <p>Blocking the effect of opioids on the gut, without affecting analgesia</p> Signup and view all the answers

    What is the primary mechanism of lubiprostone in increasing chloride flux?

    <p>Activation of the ClC-2 channel and agonist activity at the prostaglandin E4 receptor</p> Signup and view all the answers

    What is the primary mechanism of prokinetic agents in increasing gut motility?

    <p>Targeting specific receptors in the gut such as 5HT4 and stimulating motor activity</p> Signup and view all the answers

    What is the primary mechanism of lubiprostone in increasing chloride conductance?

    <p>Activation of the ClC-2 channel and agonist activity at the prostaglandin E4 receptor</p> Signup and view all the answers

    Study Notes

    Physiology of GI Water and Salt Balance

    • Net stool fluid content is a balance of ingested or secreted fluids and salts, and fluids absorbed along the GI tract

    Laxatives

    • Do not use in the presence of (especially persistent) abdominal pain because there may be an obstruction
    • A balanced diet should contain enough fiber and water to ensure regular bowel movements, making laxatives unnecessary

    Mechanism of Action of Laxatives

    • Retain luminal fluid by osmotic or bulk mechanisms
    • Decrease absorption of fluid by targeting transport processes
    • Alter motility by inhibiting non-propulsive contractions or by stimulating propulsive contractions

    Bulk and Osmotic Laxatives

    • Bulk laxatives (hydrophilic colloids) increase fecal mass and distend the colon, stimulating peristalsis
    • Examples: Agar, bran, psyllium, methylcellulose, sodium carboxymethylcellulose
    • Must be taken with fluids to prevent obstruction formation

    Osmotic Laxatives

    • Favor water retention, which stimulates peristalsis
    • Examples: Magnesium salts, phosphate salts, lactulose, polyethylene glycol (PEG)

    Magnesium Salts

    • Slowly absorbed, increasing the amount of water in the lumen
    • Distend the colon and stimulate catharsis

    Phosphate Salts

    • Examples: Fleet Phospho-Soda
    • More absorption than magnesium salts, requiring higher concentrations
    • High concentrations may pose a risk of electrolyte imbalances
    • Contraindicated in the elderly, renal disease, and individuals on ACE inhibitors, ARBs, NSAIDs, and diuretics

    Lactulose

    • Disaccharide that is resistant to hydrolysis in the intestine
    • Increased water retention leads to increased volume of fluid in the colon
    • Metabolized into lactic acid and fatty acids in the colon, which have an osmotic effect

    Polyethylene Glycol (PEG)

    • Long-chains that are poorly absorbed and retain water due to their high osmotic pressure

    Stool Softeners

    • Mineral oil: lubricates the fecal mass, coats the gut wall to prevent water reabsorption, and prevents dehydration of the fecal mass
    • Interferes with the absorption of fat-soluble vitamins
    • May cause leakage

    Stool Softeners/Irritant

    • Glycerin suppository: hygroscopic agent that draws water into the fecal matter, increases peristalsis, and acts as a lubricant
    • May cause local discomfort and a sensation of burning

    Stool Wetting-Agents

    • Docusate: surfactant that decreases the surface tension of stool, allowing for mixing of water and fatty substances
    • Softens stool and may stimulate intestinal fluid secretion

    Stimulant (Irritant) Laxatives

    • Examples: Bisacodyl, cascara, senna
    • Produce a low-grade inflammation in the intestines, promoting water and salt accumulation and stimulating peristalsis
    • Molecular mechanisms may involve prostaglandins, NO, PAF, and Na+/K+ ATPase

    Diphenylmethanes

    • Bisacodyl: requires hydrolysis by esterases for activity, resulting in a delayed onset of >6 hours (rectal administration can produce effects as soon as 20 minutes)
    • Na+/K+ inhibitor
    • Can damage the intestinal mucosa; should not be used for more than 10 days

    Anthraquinones

    • Examples: Senna, cascara
    • Requires actions by bacteria in the large intestine, causing a delayed onset of action (6-12 hours)
    • Inhibit colonic mucosal Na+/K+ ATPase, resulting in the accumulation of salt and water in the colon lumen
    • May directly stimulate colonic contractions

    Ricinoleic Acid

    • Castor oil: hydrolyzed to form ricinoleic acid, which stimulates water and electrolyte secretion and increases peristalsis
    • Has an unpleasant taste

    Adverse Effects of Laxatives

    • Diarrhea
    • Abdominal pain
    • Cramping
    • Dilated colon
    • Mucosal inflammation
    • Hypokalemia: increases the loss of sodium and decreases plasma sodium levels, activates the renin-aldosterone system, and leads to kidney increase sodium reabsorption and increase potassium excretion

    Prokinetic Agents

    • 5-HT has an essential role in GI motility and secretion
    • 5-HT-4 is the receptor subtype most involved in controlling motility
    • Prucalopride: a highly selective 5HT-4 agonist used in the treatment of chronic constipation
    • Mainly renal elimination, with minimal potential for drug-drug interaction

    Pro-Secretory Agents

    • Stimulate electrolyte secretion into the gut lumen, increasing the bulk of intestinal contents
    • Linaclotide: agonist of guanylate cyclase C receptor (GC-C), activating guanylate cyclase and subsequently activating CFTR, leading to secretion of chloride and bicarbonate into the lumen
    • Lubiprostone: mechanism may involve activation of ClC-2 channel with resultant increase in chloride flux and likely also involves agonist at prostaglandin E4 receptor, which secondarily activates CFTR to increase chloride conductance

    Opioid Antagonists

    • Opioids can cause constipation by a mechanism distinct from their analgesic effects in the CNS
    • Peripherally acting μ-opioid receptor antagonists are effective at treating drug-induced constipation without affecting the analgesia
    • Methylnatrexone: a μ-opioid receptor antagonist requiring subcutaneous administration
    • Naloxegol: orally available, heavily metabolized and inactivated by CYP3A4, with potential for interaction with other foods and drugs

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    Pharmacology of Laxatives 2024 PDF

    Description

    This quiz covers the pharmacology of laxatives and therapies for constipation, including physiology of GI water and salt transport, different types of laxatives, and pro-kinetic and prosecretory agents.

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