Lactulose /ˈlæktjʉloʊz/ is a synthetic, non-digestible sugar used in the treatment of chronic constipation[1] and hepatic encephalopathy, a complication of liver disease. It is a disaccharide (double-sugar) formed from one molecule each of thesimple sugars (monosaccharides) fructose and galactose. Lactulose is not normally present in raw milk, but is a product due to the heat-processes:[2] the more the heat, the more the presence of this substance (from 3.5 mg/l in low temperaturepasteurized milk to 744 mg/l in in-container sterilized milk).[3] It is produced commercially by isomerization of lactose.
It is broadly classified as an osmotic laxative. It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.
Medical uses[edit]
Constipation[edit]
Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment.[5] 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 a strong, irresistible bowel movement. Dosage is reduced in case of galactosemia as most preparations contain the monosaccharide galactose due to its synthesis process.
Hyperammonemia[edit]
Lactulose is useful in treating hyperammonemia (high blood ammonia), which can lead to hepatic encephalopathy. Lactulose helps trap the ammonia (NH3) in the colon.[6] It does this by using gut flora to acidify the colon, transforming the freely diffusible ammonia into ammonium (NH4+) which can no longer diffuse back into the blood.[7] It is also useful for preventing hyperammonemia caused as a side effect of administration of valproic acid.[8]
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[edit]
Lactulose is used as a test of small intestine bacterial overgrowth (SIBO). Recently the reliability of it for diagnosing SIBO has been seriously questioned.[9][10][11][12] 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 normalcolonocyte 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.[12]
Availability[edit]
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.[citation needed] 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.
Side effects[edit]
Food Additive[edit]
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.
Laxative[edit]
At higher dosage, in pharmaceutical usage, common side effects of lactulose are abdominal cramping, borborygmus, meteorism and pungent, noisy flatulence that some people find difficult to control in social situations. In normal individuals, overdose is considered uncomfortable, but not life-threatening.[13] Uncommon side effects are nausea andvomiting.
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 nondigestible, 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[edit]
Lactulose is a disaccharide that is not absorbed in the intestine nor broken down by human enzymes, and 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, producingmetabolites which have osmotic powers and peristalsis-stimulating effects (such as acetate), but also methane involved in flatulence.
Lactulose is metabolized in the colon by bacterial flora to short chain fatty acids including the production of the lactic acid and acetic acid. This partially dissociates, acidifying the colonic contents (increasing the H+ concentration in the gut).[7] 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 in treating hepatic encephalopathy is somewhat controversial.[14][15] However, lactulose can effectively be used as secondary prophylaxis of hepatic encephalopathy in patients with cirrhosis.[16] Moreover, recent studies showed improved cognitive functions of cirrhotic patients with minimal hepatic encephalopathy treated with lactulose.[17]
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 and increase the clearance of protein load in the gut.
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