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


Prescribers should remember that lactulose is a sugar, and although it has less potential to cause decay than sucrose, it is nonetheless a cause of dental decay, especially when prescribed to older people.
Prescribers should remember that lactulose is a sugar, and although it has less potential to cause dental decay than sucrose. It is nonetheless a cause of dental decay, especially when prescribed to older people who are generally more prone to dental deacy.


==References==
==References==

Revision as of 12:48, 5 July 2011

Lactulose
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityPoorly absorbed
Metabolism100% in colon by enteric bacteria
Elimination half-life1.7-2 hours
ExcretionFecal
Identifiers
  • 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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.022.752 Edit this at Wikidata
Chemical and physical data
FormulaC12H22O11
Molar mass342.296 g/mol g·mol−1
3D model (JSmol)
  • O[C@H]2[C@H](O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O)[C@H](O[C@]2(O)CO)CO
  • InChI=1S/C12H22O11/c13-1-4-6(16)7(17)8(18)11(21-4)22-9-5(2-14)23-12(20,3-15)10(9)19/h4-11,13-20H,1-3H2/t4-,5-,6+,7+,8-,9-,10+,11+,12-/m1/s1 checkY
  • Key:JCQLYHFGKNRPGE-FCVZTGTOSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Lactulose (Template:Pron-en) 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 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.[3] 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 decline with daily treatment.[citation needed]

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 partly 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 because there are carboxylic acids among its metabolites, which are not absorbed from the lower bowel. That in turn causes water to be retained in 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 acids causes active peristalsis. The combined effect of all of these processes 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 or increased as needed over time.

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, as in individuals who are on narcotic pain medication, are opioid dependent, or are receiving Opioid Replacement Therapy such as with methadone or buprenorphine for a previous opioid dependency. Although lactulose is one of the most effective and easily tolerated medicines for this indication, it has been shown that it is not as well tolerated or as effective, in most cases, as polyethylene glycol 3350Da, a powder for solution (Miralax or Dulcolax Balance), which has a virtually non-existent rate of side-effects. In fact, taking one of these two medications along with lactulose has proven to be more effective in cases of stubborn, chronic constipation.

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.[4]

It is considered a prebiotic because it enhances the beneficial bacterial flora of the intestine and is considered a digestive aid. [1]

It 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.

Some authorities do recommend twice a day dosage. If taken in the morning after breakfast and in the evening before bed, it is important to consider that lactulose, when taken on a regular basis, tends to work in about four hours. If given to small children who are in diapers, this is not a problem. However, for older children and adults, there is the ever present danger of voluminous defecation during sleep or being awake for hours on the toilet with a feeling of imminent expulsion. For evening dosage, a juvenile or adult diaper is recommended along with protective plastic pants. This is especially true if a sleeping pill is taken.

In common with other osmotic laxatives, lactulose can cause electrolytic imbalances in sensitive individuals (see side effects below). However, lactulose tends to do this less because it does not rely on mineral salts to draw fluid into the intestinal tract and also because it relies on nonosmotic modes of action: It stimulates peristalsis through acidification and gas and increases feeling of urgency through enlarging the volume of the bowel contents.

It is sold over the counter (without prescription) in most countries in the world. In the United States and Austria, it requires a prescription over fears that it could be dangerous to diabetics. However, lactulose is an indigestible sugar and has been proved to be safe even for them. [The Annals of Pharmacotherapy: Vol. 26, No. 10, pp. 1277–1282.]

For the very few people who are galactose intolerant, Kristalose, a powdered form of lactulose that can be mixed with fluids, is manufactured almost free of galactose.

Hepatic encephalopathy

In treating hepatic encephalopathy, lactulose helps "draw out" ammonia (NH3) from the body.[5]

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).[6] 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.[7][8]

Lactulose, also an osmotic laxative, is not absorbed, does not affect the absorption of spironolactone and may be used by diabetics. It is used in patients with cirrhosis/hepatic encephalopathy to limit the proliferation of ammonia forming gut organisms and increase the clearance of protein load in the gut.

Lactulose for hepatic encephalopathy generally requires oral dosage three or four times a day with diarrhea almost a certain side effect.

Lactulose Breath Test

This substance is used as a test of small intestine bacterial overgrowth syndrome (SIBO). Recently the reliability of lactulose for diagnosing SIBO has been seriously questioned.[9][10][11] 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, borborygmus, gas and pungent flatulence that some people find difficult to control in social situations. Excessively high dosage can cause explosive and uncontrollable diarrhea. In normal individuals, overdose is considered uncomfortable, but not life threatening. Uncommon normal side effects are nausea and vomiting.

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

Prescribers should remember that lactulose is a sugar, and although it has less potential to cause dental decay than sucrose. It is nonetheless a cause of dental decay, especially when prescribed to older people who are generally more prone to dental deacy.

References

  1. ^ Voskuijl W, de Lorijn F, Verwijs W; et al. (2004). "PEG 3350 (Transipeg) versus lactulose in the treatment of childhood functional constipation: a double blind, randomised, controlled, multicentre trial". Gut. 53 (11): 1590–4. doi:10.1136/gut.2004.043620. PMC 1774276. PMID 15479678. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Lactulose, MedlinePlus Drug Information
  3. ^ Duphalac product details
  4. ^ Lactulose at The Medical Dictionary
  5. ^ Paik YH, Lee KS, Han KH; et al. (2005). "Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study". Yonsei medical journal. 46 (3): 399–407. doi:10.3349/ymj.2005.46.3.399. PMC 2815818. PMID 15988813. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) [dead link]
  6. ^ Patil DH, Westaby D, Mahida YR; et al. (1987). "Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy". Gut. 28 (3): 255–9. doi:10.1136/gut.28.3.255. PMC 1432706. PMID 3570029. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  7. ^ Als-Nielsen B, Gluud LL, Gluud C (2004). "Nonabsorbable disaccharides for hepatic encephalopathy". Cochrane Database Syst Rev (2): CD003044. doi:10.1002/14651858.CD003044.pub2. PMID 15106187.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ Shawcross DL, Jalan R (2004). "Treatment of hepatic encephalopathy: it's not lactulose". BMJ (Clinical research ed.). 329 (7457): 112, author reply 112. doi:10.1136/bmj.329.7457.112. PMC 449830. PMID 15242927. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ Vanner, S (2008). "The lactulose breath test for diagnosing SIBO in IBS patients: another nail in the coffin". The American Journal of Gastroenterology. 103 (4): 964–965. doi:10.1111/j.1572-0241.2008.01798.x. PMID 18371132.
  10. ^ Barrett, J. S., Irving, P. M., Shepaerd, S. J., Muir, J. G., & Gibson, P. R. (2009). "Comparison of the prevalence of fructose and lactose malabsorption across chronic intestinal disorders". Alimentary Pharmacology & Therapeutics. 20 (2): 165–174. doi:10.1111/j.1365-2036.2009.04018.x. PMID 19392860.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Grover, M., Kanazawa, M., Palsson, O., Chitkara, D., Gangarosa, L., Drossman, D.; et al. (2008). "Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress". Neurogastroenterology Motility. 20 (9): 998–1008. doi:10.1111/j.1365-2982.2008.01142.x. PMID 18482250. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
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