Lactulose is effective in hepatic encephalopathy, but does not improve mortality rate [MEDLINE]
Pharmacology
Lactulose (Disaccharide of Galactose + Fructose = Beta-Galactosidofructose) is Poorly Absorbed from the Gastrointestinal Tract and is Converted by Colonic Bacteria to Lactic Acid (and to a lesser degree, to acetic acid and formic acid)
Acidification of Colon Enhances Diffusion of Ammonia from Blood into the Colon
Acidification of Colon Enhances Conversion of Ammonia (NH3) into Ammonium Ion (NH4+): as the ammonium ionis non-absorbable, this prevents colonic absorption of ammonium ion (and other amines)
Cathartic Effect of Lactulose with Increased Stool Volume and Decreased Time for Ammonia Absorption: caused by the osmotic effect of the organic acid metabolites of lactulose
Expulsion of ammonium ions and other nitrogenous substances from the colon
Increased fecal nitrogen excretion
Modification of Colonic Flora, Resulting in Displacement of Urease-Producing Bacteria with Non-Urease-Producing Bacteria
Increased Incorporation of Ammonia by Colonic Bacteria: for synthesis of nitrogenous compounds
Potential Drug Interactions
Neomycin (see Neomycin, [[Neomycin]]): although neomycin may theoretically deplete the intestinal bacteria that metabolize lactulose, this concern is probably not relevant (as lactulose + neomycin may be synergistic when used together in the treatment of hepatic encephalopathy)
Non-Absorbable Antacids: concomitant use of non-absorbable antacids (which raise colonic pH) may inhibit the activity of lactulose
Metabolism
Absorbed Lactulose: absorbed lactulose is excreted unchanged in the urine within 24 hrs
Administration
PO: 30 ml (20 g) q4-12hrs, titrated to 3-4 soft bowel movements per day
Enema: 300 ml (200 g) retained for 30-60 min with rectal balloon catheter, q4-6hrs
Dose Adjustment
Hepatic: not defined
Renal: not defined
Adverse Effects
Gastrointestinal Adverse Effects
Belching
Bloating/Flatulence
Cramping Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
Theoretical Risk of Explosion During Colonoscopic Electrocautery: no cases reported, mainly a theoretical concern (due lactulose-induced formation of large amounts of hydrogen gas)
Other Adverse Effects
Hypokalemia (see Hypokalemia, [[Hypokalemia]]): due to diarrhea
Hyponatremia (see Hyponatremia, [[Hyponatremia]]): observed mainly with lactulose use in infants
Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014 Aug;60(2):715-35. doi: 10.1002/hep.27210. Epub 2014 Jul 8 [MEDLINE]
