Haworth projection of lactulose (bottom)
|Trade names||Cholac, Generlac, Consulose, Duphalac, others|
|By mouth (oral solution)|
|ATC code||A06AD11 (WHO)|
|Metabolism||100% in colon by enteric bacteria|
|Onset of action||8 to 48 hours|
|Biological half-life||1.7–2 hours|
|Chemical and physical data|
|Molar mass||342.296 g/mol|
|3D model (Jmol)||Interactive image|
Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy. It is used by mouth for constipation and either by mouth or in the rectum for hepatic encephalopathy. It generally begins working after eight to twelve hours but may take up to two days to improve constipation.
Common side effects include abdominal bloating and cramps. There is the potential for electrolyte problems to occur as a result of diarrhea it produces. No evidence of harm to the baby has been found when used during pregnancy. It is generally regarded as safe during breastfeeding. It is classified as an osmotic laxative.
Lactulose was first made in 1929 and has been used medically since the 1950s. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic medication. The wholesale price in the developing world is about US$0.18 per dose. In the United States 30 doses of the liquid is about US$20. It is made from the milk sugar lactose and is composed of two simple sugars, galactose and fructose.
Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment. Lactulose is used for chronic idiopathic constipation, i.e. chronic constipation occurring without any identifiable cause. Lactulose may be used to counter the constipating effects of opioids, and in the symptomatic treatment of hemorrhoids as a stool softener.
The dosage of lactulose for chronic idiopathic constipation is adjusted depending on the constipation severity and desired effect, from a mild stool softener to causing diarrhea. Dosage is reduced in case of galactosemia as most preparations contain the monosaccharide galactose due to its synthesis process.
Lactulose is useful in treating hyperammonemia (high blood ammonia), which can lead to hepatic encephalopathy. Lactulose helps trap the ammonia (NH3) in the colon and bind to it. It does this by using gut flora to acidify the colon, transforming the freely diffusible ammonia into ammonium (NH+
4) which can no longer diffuse back into the blood. It is also useful for preventing hyperammonemia caused as a side effect of administration of valproic acid.
Lactulose for hepatic encephalopathy generally requires relatively large oral dosages three or four times a day with episodic diarrhea and constant flatulence almost a certain side effect. People who take lactulose at this level of dosage generally end up wearing an adult diaper and plastic pants for any activities away from home or at night (with a chux pad for the bed) because the diarrhea can occur swiftly and without much warning.
Small intestine bacterial overgrowth
Lactulose is used as a test of small intestine bacterial overgrowth (SIBO). Recently the reliability of it for diagnosing SIBO has been seriously questioned. A large amount of it 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 normal colonocyte digestion. An earlier result has been hypothesized to indicate digestion occurring within the small intestine. An alternate explanation for differences in results is the variance in small bowel transit time among tested subjects.
Common side effects of lactulose are abdominal cramping, borborygmus and flatulence. In normal individuals, overdose is considered uncomfortable, but not life-threatening. Uncommon side effects are nausea and vomiting. In sensitive individuals, such as the elderly or people with reduced kidney function, excess lactulose dosage can result in dehydration and electrolytic disturbances such as high sodium levels. Ingestion of lactulose does not cause a weight gain because it is a non-digestible, low calorie sugar that contains only about one calorie per millitre. Although lactulose has less potential to cause dental caries than sucrose, there is a minimal potential because it is a sugar. This should be taken into consideration when taken by people with a high susceptibility to this condition.
Mechanism of action
It is a disaccharide (double-sugar) formed from one molecule each of the simple sugars (monosaccharides) fructose and galactose. Lactulose is not normally present in raw milk but is a product of heat-processes: the greater the heat, the greater amount of this substance (from 3.5 mg/L in low temperature pasteurized milk to 744 mg/L in in-container sterilized milk). It is produced commercially by isomerization of lactose.
Lactulose is not absorbed in the small intestine nor broken down by human enzymes, thus stays in the digestive bolus through most of its course, causing retention of water through osmosis leading to softer, easier to pass stool. It has a secondary laxative effect in the colon, where it is fermented by the gut flora, producing metabolites which have osmotic powers and peristalsis-stimulating effects (such as acetate), but also methane associated with flatulence.
Lactulose is metabolized in the colon by bacterial flora to short chain fatty acids including lactic acid and acetic acid. These partially dissociate, acidifying the colonic contents (increasing the H+ concentration in the gut). This favors the formation of the nonabsorbable NH+
4 from NH3, trapping NH3 in the colon and effectively reducing plasma NH3 concentrations.
The effectiveness of lactulose in treating hepatic encephalopathy is somewhat controversial.[needs update] However, lactulose can effectively be used as secondary prophylaxis of hepatic encephalopathy in patients with cirrhosis. Moreover, recent studies showed improved cognitive functions of cirrhotic patients with minimal hepatic encephalopathy treated with lactulose.
Lactulose is not absorbed, does not affect the absorption of spironolactone, and may be used by diabetics. It is used in people with cirrhosis/hepatic encephalopathy to limit the proliferation of ammonia-forming gut organisms (although it's not an antibiotic, unlike rifaximin) and increase the clearance of protein load in the gut.
Society and culture
Lactulose is available without prescription in most countries. However, a prescription is required in the United States and Austria mainly over unfounded fears that it could be harmful to diabetics. Even though it is approved in most countries as a food additive, it is not allowed in the United States because it is viewed there as a pharmaceutical drug.
Lactulose is commonly used as a food additive to improve taste, promote intestinal health and promote intestinal transit time. Lactulose is known for its good acceptance, with limited side effects, similar to many other food products.
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