Lactulose, Macrogol (PEG) and Bisacodyl

Mechanism

💧 Osmotic Laxatives

• Representatives: Lactulose (Duphalac) and Macrogol/PEG (Movicol).
• Mechanism: They retain water in the intestinal lumen by gastric osmotic gradient.
• They soften the stool, increase the intrabolus volume and passively distend the colon wall, stimulating the peristaltic myenteric reflex.

⚡ Stimulant Laxatives

• Representatives: Bisacodyl (Dulcolaxo) and sennosides.
• Mechanism: Direct irritation of the Auerbach plexus.
• They actively stimulate fluid secretion and colonic smooth muscle contraction, causing rapid evacuation.

Mechanism of action

Lactulose: It is a synthetic disaccharide (galactose-fructose) that is not absorbed in the small intestine because it lacks specific lactulase. Upon reaching the colon unchanged, it is metabolized by anaerobic sacrolytic bacteria into short-chain fatty acids (lactic, acetic and formic acid).

This acid fermentation markedly decreases the pH of the colonic lumen (from ≈ 7.0 to < 5.0) and generates an active osmotic gradient that draws water into the gastric colon.

Macrogol (PEG 3350/4000): It is a high molecular weight ethylene oxide polymer that is not absorbed and is resistant to bacterial degradation. Its ether groups covalently retain water molecules through hydrogen bonds, increasing the liquid mass of the colon and proportionally increasing the fecal bolus.

Bisacodyl: It is a prodrug hydrolyzed by intestinal esterases to its active metabolite phenol dipyramidyl. This irritates the sensory nerve endings of the colonic mucosa, stimulating the myenteric reflex arc and increasing the secretion of mucus and electrolytes into the lumen by inhibiting the Na⁺/K⁺-ATPase of the enterocytes.

Mechanism of Ammonium Trapping in Hepatic Encephalopathy

In patients with decompensated liver cirrhosis and severe hyperammonemia, lactulose is a key therapeutic pillar. When acidifying the colonic lumen through the production of short-chain fatty acids (pH ≈ 5.0), free ammonia (NH₃, diffusible and neurotoxic gas) is immediately protonated into ammonium ion (NH₄⁺, charged molecule, non-diffusible and insoluble in membranes):

NH₃ (diffusible) + H⁺ leftharpoons NH₄⁺ (not diffusible)

The ammonium ion is irreversibly trapped in the lumen of the colon ("ionic trapping") and is rapidly excreted by laxative evacuations induced by the same sugar, preventing its cerebral systemic diffusion.

Indicators and dose

Approved indications

• Chronic functional constipation of any cause in adults and children.
• Lactulose: Prevention and treatment of porto-systemic / hepatic encephalopathy.
• Bisacodyl: Symptomatic relief of occasional acute constipation and preparation of the colon prior to colonoscopy or radiology studies (rectal route).

Dosage and Clinical Adjustment

Adults:

• Chronic constipation: 15 mL to 30 mL of lactulose orally per day, or 1 to 2 sachets of Macrogol (PEG 3350) daily dissolved in water.
• Hepatic encephalopathy: 30 mL to 45 mL orally every 8-12 hours of lactulose, dynamically adjusting the dose to achieve 2 to 3 soft stools per day. In the acute phase it can be administered by retention enemas (300 mL in 700 mL of distilled water).
• Bisacodyl: 5 mg to 10 mg orally at night before bedtime. Do not exceed 10 continuous days.

Adjustment in Renal / Hepatic Failure: Does not require dose modifications (Macrogol and lactulose are not absorbed in a relevant systemic manner).

Security

Contraindications

• Absolute (Common): Mechanical obstruction of the colon, active intestinal perforation, severe decompensated ulcerative colitis, toxic megacolon. Active severe Crohn's disease. Abdominal pain of unknown etiology.
• Lactulose (Additional): Congenital galactosemia (patients do not metabolize the free galactose present in the solution).

Adverse effects (ADRs)

• Lactulose: Marked flatulence and meteorism extremely common at the beginning of treatment (up to 20%, due to the gas generated in bacteroid bacterial fermentation), intestinal colic, nausea.
• Macrogol: Mild nausea, watery diarrhea, mild abdominal distension.
• Bisacodyl: Severe abdominal cramping pain, rapid dehydration, electrolyte imbalances in continuous use (severe hypokalemia), colonic atonality in prolonged use due to injury induced in the myenteric plexuses ("cathartic colon").

Lactose and Safety in Diabetes

Despite its intensely sweet taste, lactulose is not absorbed systemically and its metabolism by the microflora does not raise plasma glucose. However, because commercial oral solutions contain unavoidable traces of free sugars from industrial synthesis (free lactose and galactose), glycemic control should be carefully monitored in patients with poorly controlled severe diabetes mellitus.