Mechanism of Action of Senna in Chronic Constipation
Senna works by bacterial conversion of sennosides A and B into active metabolites (rheinanthrone and rhein) that stimulate prostaglandin E2 production and chloride secretion, resulting in increased colonic peristalsis and luminal water content. 1
Detailed Pharmacological Mechanism
Bacterial-Dependent Activation:
- Sennosides A and B require sequential metabolism by colonic bacteria (specifically glycosidases) to produce the active metabolites rheinanthrone and rhein 1
- This bacterial dependency means that antibiotic use can potentially decrease senna's efficacy by affecting the colonic bacteria needed for drug activation 1
- Over 90% of sennosides and their metabolites are excreted in the feces 1
Dual Mechanism of Action:
- Motor effects: The active metabolites directly stimulate colonic peristalsis, producing propulsive contractions that move stool through the colon 1
- Secretory effects: Stimulation of prostaglandin E2 production leads to chloride ion secretion, which draws water into the colonic lumen and increases stool water content 1
Clinical Pharmacology
Timing and Dosing:
- Best taken in the evening or at bedtime, with the aim of producing a normal stool the next morning 1
- Trial dosing was 1 g daily, though this is higher than commonly used in clinical practice 1
- The guideline panel suggests starting at a lower dose and increasing if there is no response 1
Clinical Efficacy:
- Senna significantly increases complete spontaneous bowel movements per week (mean difference 7.60,95% CI 5.90–9.30) compared to placebo 1
- Response rates are substantially higher with senna versus placebo (RR 5.25,95% CI 2.05–13.47) 1
- Quality of life scores improve significantly with senna treatment (MD 7.80,95% CI 1.40–14.20) 1
Important Clinical Considerations
Common Side Effects:
- Abdominal pain and cramping may occur, particularly with higher doses 1
- Wide variation in clinical effectiveness exists among patients 1
- The stimulating effect may be too great for overtly weak or debilitated patients 1
Duration of Use:
- While trials were conducted for 4 weeks, longer-term use is probably appropriate, though data are needed to better understand tolerance and side effects 1
- No evidence of tolerance development has been found in pediatric literature reviews 2
Special Populations:
- In patients with advanced cancer or debilitated states, the strong stimulant effect may not be well-tolerated 1
- For opioid-induced constipation, senna is recommended as part of prophylactic laxative regimens 3
Comparison to Other Laxatives
Senna differs from other stimulant laxatives in its mechanism: bisacodyl and sodium picosulfate are converted to the same active metabolite (BHPM) through different pathways (mucosal deacetylase enzymes for bisacodyl, bacterial desulfate enzymes for sodium picosulfate), whereas senna's unique pathway produces rheinanthrone and rhein 1