What are anthraquinone laxatives, such as senna and cascara sagrada?

Anthraquinone Laxatives: Mechanism, Uses, and Safety Considerations

Anthraquinone laxatives are stimulant laxatives derived from plants that function by stimulating the myenteric plexus in the colon and inhibiting colonic water absorption, with their principal effect in the descending and sigmoid colon. 1

Mechanism of Action

Anthraquinone laxatives work through a unique mechanism:

• They contain glycosides that remain unabsorbed in the small intestine and are carried to the large bowel
• In the colon, intestinal bacteria metabolize them to their active forms (aglycones)
• These active compounds have both motor and secretory effects on the colon 1
• They stimulate the myenteric plexus and inhibit water absorption in the colon 1
• Their effect is primarily local and depends on sufficient intestinal motility to present them to the colon for bacterial degradation 1

Common Examples

The main anthraquinone laxatives include:

• Senna (Cassia angustifolia/alexandrina)
• Cascara sagrada (from buckthorn bark)
• Aloe (contains anthraquinone derivatives)
• Dantron (rarely used due to potential carcinogenicity concerns) 1

Clinical Use

Anthraquinone laxatives are commonly used for:

• Treatment of constipation, particularly when other laxatives have failed
• Best taken in the evening or at bedtime, aiming to produce a normal stool the next morning 1
• Often used in combination with osmotic laxatives for more severe constipation
• May be particularly useful in opioid-induced constipation when combined with other agents 1

Administration and Dosing

• Senna is available in various forms including tablets, syrup, and tea
• FDA labeling for senna indicates a dose of 8.8mg/5mL for the syrup formulation 2
• Should not be used for longer than one week unless directed by a doctor 2
• Best taken at bedtime for morning bowel movement 1

Safety Considerations and Side Effects

Anthraquinone laxatives require careful consideration:

• Short-term use is generally safe but long-term use requires caution 3
• Common side effects include abdominal cramping, diarrhea, and nausea 4
• May cause perineal blistering in some patients, especially with higher doses and prolonged stool-to-skin contact 4
• Long-term use can lead to pseudomelanosis coli (pigmentation of the colonic mucosa) 3
• Historical concerns about carcinogenicity have been raised, but more recent evidence suggests senna is not carcinogenic when used appropriately 5
• Contrary to previous beliefs, there is no clinical or animal evidence that long-term use damages intestinal muscle or myenteric neurons 1
• Should be avoided in patients with intestinal obstruction 1

Contraindications

Anthraquinone laxatives should not be used in:

• Patients with intestinal obstruction
• Undiagnosed abdominal pain
• Pregnancy (unless specifically directed by a physician)
• Children under 12 years without medical supervision
• Patients with inflammatory bowel conditions during acute flares

Place in Treatment Algorithm

For constipation management:

1. First-line options: Osmotic laxatives (PEG, lactulose, magnesium salts)
2. Second-line options: Stimulant laxatives including anthraquinones (senna, cascara)
3. For opioid-induced constipation: Osmotic or stimulant laxatives are generally preferred 1

Key Differences from Other Laxative Classes

• Bulk-forming laxatives (psyllium, methylcellulose): Increase stool volume; not recommended for opioid-induced constipation 1
• Osmotic laxatives (PEG, lactulose): Draw water into bowel; generally preferred as first-line 1
• Stool softeners (docusate): Limited evidence for efficacy 6
• Lubricants (mineral oil): Less effective than modern alternatives 1

Monitoring

When using anthraquinone laxatives:

• Monitor for abdominal pain, nausea, or vomiting
• Discontinue if rectal bleeding occurs 2
• Watch for changes in bowel habits lasting over two weeks
• Be alert for signs of electrolyte disturbances with prolonged use

Despite historical concerns about carcinogenicity and damage to enteric nerves, more recent evidence suggests that appropriate use of anthraquinone laxatives is safe and effective for short-term management of constipation 5.