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1/25/2021
Lactulose is a disaccharide (sugar molecule composed of two smaller sugar molecules bonded together, in this case
fructose and galactose).
Lactulose is a solid substance that is very soluble in water and has a sweet taste. Lactulose is a chronic acidifier
which promotes laxation.
Chemically lactulose is known as 4-O-β-D-galactopyranosyl-D-fructofuranose. The molecular formula is C 12H22O11.
Pharmacokinetics
Lactulose may take up to 48 hours to act. (BNF-80)
Lactulose is poorly absorbed from the gastrointestinal tract.
Following administration by mouth, lactulose passes essentially unchanged into the large intestine where it is
metabolized by saccharolytic bacteria with the formation of simple organic acids, mainly lactic acids and small
amounts of acetic acids and formic acids.
The small amount of absorbed lactulose is subsequently excreted unchanged in the urine.
Urinary excretion has been determined to be 3% or less and is essentially complete within 24 hours.
Therapeutic Indications
Lactulose is indicated for the treatment of
Constipation
Hepatic Encephalopathy (Hepatic encephalopathy (portal systemic encephalopathy)
Mechanism of Action
For Constipation
There are two proposed mechanisms
1) Metabolism of lactulose by bacteria results in reduced colonic pH, which stimulates peristalsis and decreases
stool transit time. In turn, decreased water reabsorption from the feces further facilitates the passage of soft,
well-formed stools.
2) Increased osmotic pressure of fecal material secondary to an increase in colonic organic acids results in
accumulation of fluid from surrounding tissues, helping to soften stool mass.
Lactulose also is used to treat hepatic encephalopathy. Patients with severe liver disease have an impaired capacity
to detoxify ammonia coming from the colon, where it is produced by bacterial metabolism of fecal urea. The drop in
luminal pH that accompanies hydrolysis to short-chain fatty acids in the colon results in “trapping” of the ammonia
by its conversion to the polar ammonium ion. Combined with the increases in colonic transit, this therapy
significantly lowers circulating ammonia levels. The therapeutic goal in this condition is to give sufficient amounts
of lactulose (usually 20–30 g three to four times per day) to produce two to three soft stools a day with a pH of 5–
5.5.
Administration
Hepatic Encephalopathy-
Adult: Adjusted according to response to 30–50 mL 3 times a day, subsequently adjusted to produce 2–3
soft stools per day.
SIDE-EFFECTS
CONTRA-INDICATIONS
Galactosaemia,
Gastro-intestinal obstruction
Gastro-intestinal perforation
Risk of gastrointestinal perforation
BNF 80 (British National Formulary) September 2020-March 2021 (2020, Pharmaceutical Press)
Laurence Brunton, Bjorn Knollmann, Randa Hilal-Dandan - Goodman and Gilman’s The
Pharmacological Basis of Therapeutics (2017, McGraw-Hill Education)