What is the mechanism of action of bisacodyl (stimulant laxative)?

Mechanism of Action of Bisacodyl

Bisacodyl is a diphenylmethane stimulant laxative that must be converted to its active metabolite bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) in the gut, which then acts directly on the colonic mucosa to stimulate colonic peristalsis and increase sodium and water movement into the colonic lumen. 1

Metabolic Activation

• Bisacodyl is a prodrug that requires enzymatic conversion to become pharmacologically active 1, 2
• The conversion occurs via small bowel and colonic mucosal deacetylase enzymes that transform bisacodyl into BHPM 1
• This differs from sodium picosulfate (SPS), which is converted to the same active metabolite (BHPM) but by colonic bacterial desulfate enzymes instead 1

Dual Mechanism: Motility and Secretion

Stimulation of Colonic Motility

• BHPM stimulates sensory nerves in the proximal colon, directly enhancing colonic peristalsis and reducing transit time 1, 2
• The drug accelerates ascending colon emptying (median 6.5 hours vs 11.0 hours with placebo), which contributes significantly to its efficacy 3
• This prokinetic effect works by stimulating the myenteric plexus in the colon 1

Enhancement of Fluid Secretion

• BHPM increases sodium and water movement into the colonic lumen, increasing stool water content 1, 2
• This secretory action may contribute more to bisacodyl's laxative effect compared to other stimulant laxatives like senna 4
• The mechanism involves direct action on colonic mucosa rather than systemic effects 2

Clinical Pharmacology

Onset and Duration

• Oral tablets work within 6-12 hours, while rectal suppositories act within 30-60 minutes 1
• Bisacodyl demonstrates a prolonged action compared to sennosides, likely due to different pharmacokinetics 4

Local vs Systemic Action

• Bisacodyl acts locally in the large bowel with minimal systemic absorption 2
• The poorly absorbed diphenylmethane structure ensures the drug remains in the gastrointestinal tract 1

Important Clinical Considerations

Antibiotic interactions are less relevant for bisacodyl compared to sodium picosulfate, since bisacodyl's conversion depends on mucosal enzymes rather than colonic bacteria 1

The mechanism produces both benefits and adverse effects: the same stimulation of sensory nerves and fluid secretion that relieves constipation also causes abdominal cramping and diarrhea in 53.4% of patients at 10 mg dosing 1

Starting at 5 mg orally is preferable to the 10 mg dose used in clinical trials, as this reduces adverse effects while maintaining efficacy 1