Lactulose

Lactulose is a synthetic disaccharide used primarily as a laxative for chronic constipation and as an adjunct treatment for portal-systemic encephalopathy. For constipation, it is generally considered a secondary option after dietary and lifestyle modifications prove insufficient. While recognized globally as a safe and effective therapy, its exact efficacy in managing portal-systemic encephalopathy remains difficult to formally isolate in controlled clinical trials due to the ethical impossibility of withholding treatment from affected patients.

Lactulose is a disaccharide derivative of lactose used to treat constipation and portal systemic encephalopathy.

Lactulose is indicated for use as a laxative in the treatment of chronic constipation in adults and geriatric patients.

Additionally, lactulose is also employed as an adjunct to protein restriction and supportive therapy for the prevention and treatment of portal-systemic encephalopathy (PSE), including both the hepatic pre-coma and coma variations. In particular, lactulose solution has been effective at managing PSE resulting from surgical portacaval shunts or from chronic hepatic diseases like cirrhosis.

Moreover, there have also been studies demonstrating the capacity for lactulose to minimize the formation of gallstones and even some investigations regarding the experimental use of the agent in developing novel anticancer agents owing to its ability to bind galactin carbohydrates involved in various tumor progressions .

• Constipation
• Hepatic Encephalopathy (HE)

Lactulose formulations are most commonly administered via the oral route or the rectal route. Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut. In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.

Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose. Saccharolytic bacteria present in the large intestine subsequently break the substance down into organic acids like lactic acid and small amounts of formic and acetic acids. Such resultant volatile fatty acid metabolites, in combination with hydrogen and methane that is also generated consequently enhance intraluminal gas formation, peristaltic gut motility, and elicit an osmotic effect that facilitates an increase in the water content of stool as well as associated stool softening. All of these actions ultimately assist in facilitating and increasing the frequency of bowel movements in patients experiencing constipation, although it may take 24 to 48 hours after using the medication for this laxative effect to become evident.

At the same time, the formation of such acids via the metabolism of lactulose by colonic bacteria also acidifies the contents of the colon, thereby contributing to the treatment of portal-systemic encephalopathy (PSE). As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood. These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia. And finally, it is also believed that an acidic colonic environment results in the elimination of urease-producing bacteria that contribute to the formation of ammonia while surviving colonic bacteria use up any trapped ammonia in the colon as a source of nitrogen for protein synthesis.

After administration by the oral route, less than 3% of the given dose of lactulose solution is absorbed by the small intestine. The remaining unabsorbed lactulose reaches the large intestine where it is metabolized - but even then, negligible quantities of unchanged lactulose or its metabolites are absorbed across the colon.

Negligible amounts of lactulose - metabolized or non-metabolized - are absorbed into the body.. Most lactulose that is administered subsequently remains predominantly around the gastrointestinal tract area.

Negligible amounts of lactulose - metabolized or non-metabolized - are absorbed into the body.. Regardless, data regarding the protein binding of lactulose is not readily available or accessible.

The renal excretion of any lactulose that manages to be absorbed into the circulation has been determined to be 3% or less and is generally complete within 24 hours. Any unabsorbed lactulose is largely excreted with stool.

The data regarding the half-life of lactulose is not readily available or accessible.

Negligible amounts of lactulose - metabolized or non-metabolized - are absorbed into the body.. Regardless, data regarding the clearance of lactulose is not readily available or accessible.

It has been documented that the oral LD50 of lactulose is 48.8 mL/kg in mice and more than 30 mL/ kg in rats.

It is expected that overdosage with lactulose would result in abdominal cramps and diarrhea, both of which should be treated with fluid and electrolyte replacement as required.

Considering the use of lactulose during pregnancy in humans has not been formally investigated, the agent should only be used during pregnancy only when clearly needed. Similarly, it is unknown whether lactulose is distributed into human breastmilk. Use of the medication in nursing women should subsequently be undertaken with caution.

Reproduction studies in rats, mice, and rabbits have not revealed any evidence of impaired fertility as a result of administering lactulose.

Data regarding the safety and efficacy of using lactulose in children for the treatment of chronic constipation or portal-systemic encephalopathy (PSE) is either very limited or yet to be established.

Information regarding the long-term mutagenic potential of lactulose solution in animals or humans and about the long-term carcinogenic potential in humans are not available.

• Drink plenty of fluids. This drug may cause fluid loss.
• Take with or without food.

• Adults: Initially 3-6 tea-spoons daily, In long-term therapy 1½-6 tea-spoons daily
• Children up to 14 years: Initially 3 tea-spoons daily, In long-term therapy 1-2 tea-spoons daily
• Infants and toddlers: Initially 1-2 tea-spoons daily, In long-term therapy 1 tea-spoon daily

• Adults: 1-2 tea-spoons daily
• Children: 1 tea-spoon daily

• Hyper-ammoniemia in hepatopathy: a maximum of 18-30 tea-spoons daily.
• In portal systemic encephalopathy: hourly doses of 6-9 tea-spoons of Lactulose solution may be used to induce the rapid laxation. When the laxative effect has been achieved, the dose may then be reduced.