, Volume 4, Issue 1-2, pp 7-48

Lactulose: A Review of its Therapeutic and Pharmacological Properties with particular reference to ammonia metabolism and its mode of action in portal systemic encephalopathy

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Summary

Synopsis: Lactulose is a synthetic derivative of lactose which does not occurnaturally. It contains one molecule of galactose and one molecule of fructose and as a 50 % w/w syrup2 is advocated for the treatment of portal systemic encephalopathy and chronic constipation.

Following oral administration, lactulose reaches the colon virtually unchanged, where it is broken down by saccharolytic bacteria. There is no specific lactulase enzyme in the small intestine of man to hydrolyse the sugar. Little of the ingested dose is Key Words absorbed. It appears that its most likely mode of action in both portal systemic encephalopathy and in constipation is primarily due to acidification of the colonic contents, presumably by the organic acids (mainly lactic acid) formed following the bacterial hydrolysis of lactulose in the colon. In portal systemic encephalopathy it is tempting to believe that such an action might be associated with a decrease in the relative concentration of free ammonia, the major aetiological agent involved in the cerebral disturbance. Reversal of abnormal cerebral energy metabolism and improved ammonia tolerance has been demonstrated following lactulose administration in patients with portal systemic encephalopathy. An osmotic effect from the organic acid breakdown products of lactulose probably explains the laxative action in chronic constipation.

The majority of patients with chronic portal systemic encephalopathy respond to lactulose, on the basis of clinical and EEG evidence of improvement, and decrease in blood ammonia levels; provided it is given in an appropriate dosage and tolerated by the patient. A response has occurred in those with a portacaval shunt and in those who had been unsuccessfully managed on standard forms of therapy. Some patients however, may not respond to lactulose and others may respond better to neomycin. Failures of treatment appear to occur in preterminal patients or in those with mild symptoms of encephalopathy. Where successful, lactulose can be given on a long-term basis to prevent a recurrence of encephalopathy and can sometimes enable an increase in protein intake or intellectual activity. Although lactulose has been successful in chronic constipation, any practical superiority over conventional laxatives has yet to be established. Abdominal complaints and flatulence may occur during the early stages of treatment. In portal systemic encephalopathy, diarrhoea (and possibly hypokalaemia) is evidence of overdosage and should be avoided.

See subject index in each issue for further indexing terms.
‘Duphalac’ (Phflips-Duphar, Philips-Roxane).
Manuscript reviewed by: J. Bircher, Universität Bern, Institut für Klinische Pharmakologie, Bern, Switzerland; C.R.B. Blackburn, Department of Medicine, University of Sydney, NSW, Australia; J.P. Colombo, Inselspital Bern, Bern, Switzerland; B. Combes, Department of Internal Medicine, University of Texas, Medical School at Dallas, USA; H.O. Conn, Department of Medicine, Liver Disease Unit, Veterans Administration Hospital, West Haven, Connecticut, USA; U.P. Haemmerli, Medizinische Klinik, Stadtspital Triemli, Zürich, Switzerland; M. Ma, Department of Medicine, University of Sydney, NSW, Australia; F. Steigmann, Department of Gastroenterology, Cook County Hospital, Chicago, Illinois, USA; and R. Williams, Liver Unit, Department of Medicine, King’s College Hospital, London, England