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Lactulose

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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
Clinical data
Pronunciation
Trade names Cholac, Generlac, Consulose, and other
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability Poorly absorbed
Metabolism 100% in colon by enteric bacteria
Onset of action 8 to 48 hours[1][2]
Biological half-life 1.7-2 hours
Excretion Fecal
Identifiers
CAS Registry Number  Y
ATC code A06
PubChem CID:
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C12H22O11
Molecular mass 342.296 g/mol
 Y   

Lactulose is a non-absorbable health system.[9] It is available as a generic medication.[4] The wholesale price is about US$0.18 per dose.[10] In the United States 30 doses of the liquid is about US$20.[3] It is made from the milk sugar lactose.[11]

Contents

  • Medical uses 1
    • Constipation 1.1
    • Hyperammonemia 1.2
    • Small intestine bacterial overgrowth 1.3
    • Special populations 1.4
  • Side effects 2
  • Mechanism of action 3
  • Society and culture 4
    • Cost 4.1
    • Availability 4.2
    • Food additive 4.3
  • References 5
  • External links 6

Medical uses

Constipation

Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment.[12] 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

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.[13] 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.[14] It is also useful for preventing hyperammonemia caused as a side effect of administration of valproic acid.[15]

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.[16][17][18][19] 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.[19]

Special populations

No evidence of harm to the baby has been found when used during pregnancy.[3] It is generally regarded as safe during breastfeeding.[5]

Side effects

Common side effects of lactulose are abdominal cramping, borborygmus and flatulence. In normal individuals, overdose is considered uncomfortable, but not life-threatening.[20] 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 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

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 due to the heat-processes:[21] the more the heat, the more the presence of this substance (from 3.5 mg/l in low temperature pasteurized milk to 744 mg/l in in-container sterilized milk).[22] It is produced commercially by isomerization of lactose.

Lactulose is not absorbed in the small 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, producing metabolites 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).[14] 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.[23][24] However, lactulose can effectively be used as secondary prophylaxis of hepatic encephalopathy in patients with cirrhosis.[25] Moreover, recent studies showed improved cognitive functions of cirrhotic patients with minimal hepatic encephalopathy treated with lactulose.[26]

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.

Society and culture

Cost

It is available as a generic medication.[4] The wholesale price is about US$0.18 per dose.[10] In the United States 30 doses of the liquid is about US$20.[3]

Availability

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.

Food additive

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.

References

  1. ^ a b Goldman, edited by Ann; Hain, Richard; Liben, Stephen (2006). Oxford textbook of palliative care for children (2 ed.). Oxford: Oxford University Press. p. 352.  
  2. ^ a b Helms, Richard A. (2006). Textbook of therapeutics : drug and disease management (8 ed.). Philadelphia, Pa. [u.a.]: Lippincott Williams & Wilkins. p. 1310.  
  3. ^ a b c d e f "Lactulose". The American Society of Health-System Pharmacists. Retrieved Aug 11, 2015. 
  4. ^ a b c Hamilton, Richard J. (2013). Tarascon pocket pharmacopoeia : 2013 classic shirt-pocket edition (27 ed.). Burlington, Ma.: Jones & Bartlett Learning. p. 191.  
  5. ^ a b Jones, Wendy (2013). Breastfeeding and Medication. Routledge. p. 127.  
  6. ^ Whitlow, Charles (2009). Improved Outcomes in Colon and Rectal Surgery. New York: Informa Healthcare. p. 366.  
  7. ^ McSweeney, P.L.H.; Fox, P.F. (2009). Advanced dairy chemistry. (3rd ed.). New York: Springer-Verlag. p. 236.  
  8. ^ Schumann, C (November 2002). "Medical, nutritional and technological properties of lactulose. An update.". European journal of nutrition. 41 Suppl 1: I17–25.  
  9. ^ "WHO Model List of Essential Medicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  10. ^ a b "Lactulose". International Drug Price Indicator Guide. Retrieved 11 August 2015. 
  11. ^ Kuntz, Hans-Dieter (2008). Hepatology textbook and atlas : history, morphology, biochemistry, diagnostics, clinic, therapy (3 ed.). Heidelberg: Springer. p. 887.  
  12. ^ "Lactulose". nih.gov. Retrieved 25 August 2015. 
  13. ^ Shukla, S; Shukla, A; Mehboob, S; Guha, S (Mar 2011). "Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy.". Alimentary pharmacology & therapeutics 33 (6): 662–71.  
  14. ^ a b Patil DH, Westaby D, Mahida YR, Palmer KR, Rees R, Clark ML, Dawson AM, Silk DB (March 1987). "Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy". Gut 28 (3): 255–9.  
  15. ^ Gerstner, T; Buesing, D; Longin, E; Bendl, C; Wenzel, D; Scheid, B; Goetze, G; Macke, A; Lippert, G; Klostermann, W; Mayer, G; Augspach-Hofmann, R; Fitzek, S; Haensch, CA; Reuland, M; Koenig, SA (Sep 2006). "Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.". Seizure : the journal of the British Epilepsy Association 15 (6): 443–8.  
  16. ^ Vanner S (April 2008). "The lactulose breath test for diagnosing SIBO in IBS patients: another nail in the coffin". Am. J. Gastroenterol. 103 (4): 964–5.  
  17. ^ Barrett JS, Irving PM, Shepherd SJ, Muir JG, Gibson PR (July 2009). "Comparison of the prevalence of fructose and lactose malabsorption across chronic intestinal disorders". Aliment. Pharmacol. Ther. 30 (2): 165–74.  
  18. ^ Grover M, Kanazawa M, Palsson OS, Chitkara DK, Gangarosa LM, Drossman DA, Whitehead WE (September 2008). "Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress". Neurogastroenterol. Motil. 20 (9): 998–1008.  
  19. ^ a b Yu D, Cheeseman F, Vanner S (March 2011). "Combined oro-caecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro-caecal transit, not small intestinal bacterial overgrowth in patients with IBS". Gut 60 (3): 334–40.  
  20. ^ http://www.usp.org/pdf/EN/referenceStandards/msds/1356803.pdf
  21. ^ M. Luzzana, D. Agnellini, P. Cremonesi, G. Caramenti, S. De Vita (September–October 2003). "Milk lactose and lactulose determination by the differential pH technique" (PDF). Le Lait 83 (5): 409–16.  
  22. ^ E. Marconi, M. C. Messia, A. Amine, D. Moscone, F. Vernazza, F. Stocchi, G. Palleschi (2004). "Heat-treated milk differentiation by a sensitive lactulose assay" (PDF). Food Chemistry 84: 447–50.  
  23. ^ Als-Nielsen B, Gluud LL, Gluud C (2004). Als-Nielsen, Bodil, ed. "Nonabsorbable disaccharides for hepatic encephalopathy". Cochrane Database Syst Rev (2): CD003044.  
  24. ^ Shawcross DL, Jalan R (July 2004). "Treatment of hepatic encephalopathy: it's not lactulose". BMJ 329 (7457): 112; author reply 112.  
  25. ^ Sharma BC, Sharma P, Agrawal A, Sarin SK (September 2009). "Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo". Gastroenterology 137 (3): 885–91, 891.e1.  
  26. ^ Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R (March 2007). "Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy". Hepatology 45 (3): 549–59.  

External links

  • Medline Plus
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