Lactulose

Lactulose

Systematic (IUPAC) name
4-O-β-D-Galactopyranosyl-β-D-fructofuranose OR (2S,3R,4S,5R,6R)-2-((2R,3S,4S,5R)-4,5-dihydroxy-2,5-bis(hydroxymethyl) tetrahydrofuran-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
Identifiers
CAS number	4618-18-2
ATC code	A06AD11
PubChem	11333
DrugBank	APRD01063
ChemSpider	10856
Chemical data
Formula	C12H22O11
Mol. mass	342.296 g/mol
Pharmacokinetic data
Bioavailability	Poorly absorbed
Metabolism	100% in colon by enteric bacteria
Half life	1.7-2 hours
Excretion	Fecal
Therapeutic considerations
Pregnancy cat.	B(US)
Legal status	P(UK)
Routes	Oral

Lactulose (IPA: ˈlæktjʊləʊz) is a synthetic sugar used in the treatment of constipation^[1] and hepatic encephalopathy, a complication of liver disease. It is a disaccharide (double-sugar) formed from one molecule each of the simple sugars (monosaccharides) fructose and galactose. The commercial syrup used for treatment of constipation is dyed yellow-orange. It is produced commercially by isomerization of lactose.

Constipation

In the treatment of chronic constipation^[2], the metabolites of lactulose draw water into the bowel, causing a cathartic effect through osmotic action. Unlike other laxatives that are recommended for temporary relief, lactulose can be taken daily for decades. [1] It is safe for people of all ages, except for those in a very small percentage of the population that are galactose intolerant. Dosage may have to be adjusted over time to produce the desired effect because the laxative effect can reduce somewhat with daily treatment [2].

In treating constipation lactulose works by increasing the water content and volume of the stools in the bowel, making them softer and easier to pass. Lactulose is made up of sugar molecules and is broken down by the bacteria that live in the lower part of the gut. This leads to the contents of the gut becoming more acidic, which reduces the absorption of a chemical called ammonia. The presence of ammonia in the gut causes water to be drawn into the lower bowel. This increases the amount of water in the stools, softening them and making them easier to pass. The added volume of gas and flatulence caused by fermentation of the lactulose adds to the volume of the fecal material, and makes it easier to expel. The slightly acidic condition of the colon caused by the presence of ammonia causes active peristalsis. The combined effect of all of these process relieves constipation in a very effective manner.

It is useful in treating people with chronic constipation due to forgetting or ignoring the need for defecation. The treatment is to start the dosage at a low amount and then gradually increase it over a period of weeks until the urgency is such that a daily bowel movement cannot possibly be ignored. After an efficacious dosage is determined, it is maintained indefinitely.

It is useful in treating people who abuse laxatives because lactulose has no toxic effect when taken at overdose levels, yet produces powerful results.

It is useful for negating the constipating effects of opiates and opioids.

It is useful for treatment of hemorrhoids because it produces a soft bowel movement without any straining.

It is helpful for treating children who withhold their bowel movements out of fear because when taken in sufficient quantity and then withheld, it produces a very insistent, irresistible and powerful urge to defecate.^[3]

It is considered a prebiotic because it enhances the beneficial bacterial flora of the intestine. [3]

Lactulose has an overly sweet taste that can be completely masked by mixing it with fruit juice or desserts. It can take 24 to 48 hours to work, but generally produces results within 4 hours if taken on a daily basis. It is best taken at breakfast along with a bowl of bran cereal.

Hepatic encephalopathy

In treating hepatic encephalopathy, lactulose helps "draw out" ammonia (NH₃) from the body. ^[4]

Lactulose is metabolized in the colon by bacterial flora to short chain fatty acids, acidifying the colonic contents. ^[5] This favors the formation of the nonabsorbable NH₄⁺ from NH₃, trapping NH₃ in the colon and effectively reducing plasma NH₃ concentrations.

The effectiveness of lactulose is somewhat controversial. ^{[6] [7]}

Lactulose Breath Test

This substance is used as a test of bacterial overgrowth in the small bowel (SIBO). Recently the reliability of lactulose for diagnosing SIBO has been seriously questioned. ^{[8] [9] [10]} A large amount of (non-resorbable) lactulose is given with subsequent testing of molecular hydrogen gas in the breath. The test is positive if an increase in exhaled hydrogen occurs before that which would be expected by colonocyte digestion. An earlier result would indicate digestion occurring within the small intestine.

Side effects

Common side effects are abdominal cramping, gas, borborygmus and flatulence. Less common side effects are nausea and vomiting. Excessively high dosage can cause explosive and uncontrollable diarrhea. In normal individuals, overdose is considered uncomfortable, but not life threatening.

In sensitive individuals, such as the elderly or people with reduced kidney function, excess dosage can result in dehydration and high sodium levels.

External links

• Medline Plus
• Actilax / Lactulose Virtual Cancer Centre

References