What are the different classifications of laxatives?

Classification of Laxatives

Laxatives are classified into five main categories based on their mechanisms of action: osmotic laxatives, stimulant laxatives, stool softeners/surfactants, lubricants, and specialized agents for opioid-induced constipation. 1

Osmotic Laxatives

Osmotic laxatives work by drawing water into the intestine to hydrate and soften stool.

• Polyethylene glycol (PEG):

  • Sequestrates fluid in the bowel
  • Virtually no net gain or loss of electrolytes
  • FDA-approved as an osmotic laxative 2
  • Considered first-line for many constipation types, especially in elderly patients 1

• Lactulose:

  • Not absorbed in small bowel
  • Has 2-3 day latency before effect
  • May cause bloating, nausea, and abdominal discomfort

• Magnesium salts (magnesium citrate, magnesium hydroxide):

  • Rapid onset of action
  • Caution: Can cause hypermagnesemia, especially in renal impairment 1

• Sulfate salts:

  • Similar osmotic mechanism
  • Use with caution in renal impairment

Stimulant Laxatives

Stimulant laxatives work by irritating sensory nerve endings, stimulating colonic motility, and reducing colonic water absorption.

• Anthranoid compounds:

  • Senna, cascara
  • Hydrolyzed by colonic bacteria to yield active molecules
  • Best taken in evening for morning effect
  • Wide variation in effectiveness

• Diphenylmethane derivatives:

  • Bisacodyl (FDA-approved as stimulant laxative) 3
  • Sodium picosulfate
  • Act on proximal colon to increase sodium and water movement into colonic lumen

• Polyphenolic compounds:

  • Similar mechanism to anthranoids
  • Short-term use recommended for refractory constipation

Stool Softeners/Surfactants

• Docusate sodium:
  • Allows water and lipids to penetrate stool
  • Hydrates and softens fecal material
  • Limited experimental evidence supporting efficacy 1

Lubricant Laxatives

• Mineral oil:
  • Softens and lubricates stool
  • Lubricates intestinal lining to facilitate defecation
  • Caution: Risk of aspiration lipoid pneumonia in bed-bound patients and those with swallowing disorders 1
  • Generally considered obsolete in general medicine but still used in palliative care 4

Specialized Agents for Opioid-Induced Constipation (OIC)

• Peripherally Acting μ-Opioid Receptor Antagonists (PAMORAs):

  • Naldemedine, naloxegol, methylnaltrexone
  • Block μ-opioid receptors in gut without affecting central analgesia
  • Used for laxative-refractory OIC 1

• Combined opioid/naloxone medications:

  • Reduce risk of OIC 1

Other Categories

• Bulk-forming laxatives:

  • Psyllium, methylcellulose, ispaghula, sterculia
  • Increase stool volume
  • Not recommended for opioid-induced constipation 1
  • Require adequate fluid intake
  • Contraindicated in non-ambulatory patients with low fluid intake due to risk of mechanical obstruction 1

• Intestinal secretagogues:

  • Lubiprostone
  • Act on chloride channels to stimulate fluid secretion into intestinal lumen 1

• Selective 5-HT agonists:

  • Prucalopride
  • Activate 5-HT4 receptor to increase colonic motility and accelerate transit 1

Clinical Application Considerations

1. First-line treatment for constipation: Osmotic laxatives (PEG, lactulose) or stimulant laxatives (senna, bisacodyl) 1

2. Opioid-induced constipation:

   • Prophylactic laxative therapy recommended
   • Osmotic or stimulant laxatives preferred
   • Bulk laxatives contraindicated 1
   • PAMORAs for laxative-refractory cases 1

3. Elderly patients:

   • PEG (17g/day) offers efficacious and tolerable solution with good safety profile 1
   • Avoid liquid paraffin in bed-bound patients
   • Use saline laxatives cautiously due to risk of hypermagnesemia 1

4. Safety considerations:

   • Despite historical concerns, recent evidence suggests stimulant laxatives do not cause long-term colonic damage or increase cancer risk 5
   • Most clinical trials on stimulant laxatives are limited to 4 weeks duration 6
   • Magnesium salts should be used cautiously in renal impairment 1

Common Pitfalls

1. Inadequate fluid intake when using bulk-forming laxatives, which can worsen constipation

2. Overuse of stimulant laxatives causing diarrhea and electrolyte imbalances, particularly hypokalemia

3. Using bulk laxatives for OIC, which is ineffective and potentially harmful

4. Failing to consider renal function when prescribing magnesium-based osmotic laxatives

5. Not accounting for drug interactions and comorbidities, especially in elderly patients

6. Inappropriate use of enemas in patients with neutropenia, thrombocytopenia, or recent colorectal surgery 1

Understanding the different classifications of laxatives and their mechanisms of action allows for appropriate selection based on the specific constipation etiology, patient characteristics, and clinical context.