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词条 Lactulose
释义

  1. Medical uses

     Constipation  Hyperammonemia  Small intestine bacterial overgrowth  Pregnancy 

  2. Side effects

  3. Mechanism of action

  4. Society and culture

     Name  Cost  Availability  Food additive 

  5. References

  6. External links

{{Drugbox
| Watchedfields = changed
| verifiedrevid = 458266592
| 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
| image = Lactulose structure.svg
| width = 225
| pronounce = {{IPAc-en|ˈ|l|æ|k|tj|ʊ|l|oʊ|z}}
| tradename = Cholac, Generlac, Consulose, Duphalac, others
| Drugs.com = {{drugs.com|monograph|lactulose}}
| MedlinePlus = a682338
| pregnancy_US = B
| legal_UK = GSL
| legal_US = OTC
| legal_status = OTC
| routes_of_administration = By mouth (oral solution)
| bioavailability = Poorly absorbed
| metabolism = 100% in colon by enteric bacteria
| onset = 8 to 48 hours[1][2]
| elimination_half-life = 1.7–2 hours
| excretion = Fecal
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 4618-18-2
| ATC_prefix = A06
| ATC_suffix = AD11
| PubChem = 11333
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00581
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10856
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9U7D5QH5AE
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00352
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6359
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 296306
| synonyms = 4-O-β-D-Galactosyl-D-fructose
| C=12 | H=22 | O=11
| smiles = 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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = JCQLYHFGKNRPGE-FCVZTGTOSA-N
}}Lactulose is a non-absorbable sugar used in the treatment of constipation and hepatic encephalopathy.[3][4] It is used by mouth for constipation and either by mouth or in the rectum for hepatic encephalopathy.[1] It generally begins working after 8-12 hours, but may take up to 2 days to improve constipation.[2][3]

Common side effects include abdominal bloating and cramps.[1] A potential exists for electrolyte problems as a result of the diarrhea it produces.[1] No evidence of harm to the baby has been found when used during pregnancy.[1] It is generally regarded as safe during breastfeeding.[4] It is classified as an osmotic laxative.[5]

Lactulose was first made in 1929, and has been used medically since the 1950s.[6][7] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[8] It is available as a generic and brand-name product.[9] In various countries it could be purchased for about {{USD}}0.16 per 15 ml of syrup (10 g of lactulose) in 2015.[10][11] In the United States, the cost of this amount is about US$0.63.[12] Lactulose is made from the milk sugar lactose, which is composed of two simple sugars, galactose and glucose.[13][1]

Medical uses

Constipation

Lactulose is used in the treatment of chronic constipation in patients of all ages as a long-term treatment.[14] 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 may be used to counter the constipating effects of opioids, and in the symptomatic treatment of hemorrhoids as a stool softener.

Hyperammonemia

Lactulose is useful in treating high blood ammonia, which can lead to hepatic encephalopathy. Lactulose helps trap the ammonia (NH3) in the colon and bind to it.[15] It does this by using gut flora to acidify the colon, transforming the freely diffusible ammonia into ammonium ions ({{chem|NH|4|+}}), which can no longer diffuse back into the blood.[16] It is also useful for preventing hyperammonemia caused as a side effect of administration of valproic acid.[17]

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 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.[18][19][20][21] 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.[21]

Pregnancy

No evidence of harm to the baby has been found when used during pregnancy.[1] It is generally regarded as safe during breastfeeding.[4]

Side effects

Common side effects of lactulose are abdominal cramping, borborygmus, and flatulence. In normal individuals, overdose is considered uncomfortable, but not life-threatening.[22] 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 electrolyte disturbances such as low magnesium levels. Ingestion of lactulose does not cause a weight gain because it is not digestible, with no nutritional value. Although lactulose is less likely to cause dental caries than sucrose, as a sugar, a potential for this exists. This should be taken into consideration when taken by people with a high susceptibility to this condition.

Mechanism of action

It is a disaccharide 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:[23] 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).[24] 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).[16] This favors the formation of the nonabsorbable {{chem|NH|4|+}} from NH3, trapping NH3 in the colon and effectively reducing plasma NH3 concentrations. Lactulose is therefore effective in treating hepatic encephalopathy.[25]{{Update inline|reason=Updated version https://www.ncbi.nlm.nih.gov/pubmed/27153247|date = February 2019}} Specifically, it is effective as secondary prevention of hepatic encephalopathy in people with cirrhosis.[26] Moreover, recent studies showed improved cognitive functions of in people with cirrhosis with minimal hepatic encephalopathy treated with lactulose.[27]

Society and culture

Name

Lactulose is its international nonproprietary name (INN).[28] It is sold under various brand names.

Cost

It is available as a generic medication.[9] The wholesale price is about US$0.18 per 15-ml dose.[29] In the United States, 30 doses of the liquid cost about $20.[12]

Availability

Lactulose is available without prescription in most countries, but a prescription is required in the United States, Nigeria, and Austria.

Food additive

In some countries, but not those mentioned above, lactulose is commonly used as a food additive to improve taste and promote intestinal transit.

References

1. ^1 2 3 4 5 6 {{cite web|title=Lactulose|url=https://www.drugs.com/monograph/lactulose.html|publisher=The American Society of Health-System Pharmacists|access-date=Aug 11, 2015|deadurl=no|archive-url=https://web.archive.org/web/20170908000000/http://www.drugs.com/monograph/lactulose.html|archive-date=2017-09-08|df=}}
2. ^1 {{cite book|last1=Goldman|first1=edited by Ann|last2=Hain|first2=Richard|last3=Liben|first3=Stephen | name-list-format = vanc |title=Oxford textbook of palliative care for children|date=2006|publisher=Oxford University Press|location=Oxford|isbn=9780198526537|page=352|edition=2|url=https://books.google.com/books?id=f1fTsoA4wDMC&pg=PA352|deadurl=no|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=f1fTsoA4wDMC&pg=PA352|archive-date=2017-09-08|df=}}
3. ^1 {{cite book|last1=Helms|first1=Richard A.|title=Textbook of therapeutics : drug and disease management|date=2006|publisher=Lippincott Williams & Wilkins|location=Philadelphia, Pa. [u.a.]|isbn=9780781757348|page=1310|edition=8|url=https://books.google.com/books?id=aVmRWrknaWgC&pg=PA1310|deadurl=no|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=aVmRWrknaWgC&pg=PA1310|archive-date=2017-09-08|df=}}
4. ^1 {{cite book|last1=Jones|first1=Wendy|title=Breastfeeding and Medication|date=2013|publisher=Routledge|isbn=9781136178153|page=127|url=https://books.google.com/books?id=0Y8lbCnF1mgC&pg=PA127|deadurl=no|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=0Y8lbCnF1mgC&pg=PA127|archive-date=2017-09-08|df=}}
5. ^{{cite book|last1=Whitlow|first1=Charles|title=Improved Outcomes in Colon and Rectal Surgery.|date=2009|publisher=Informa Healthcare|location=New York|isbn=9781420071535|page=366|url=https://books.google.com/books?id=9FfvBQAAQBAJ&pg=PT378|deadurl=no|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=9FfvBQAAQBAJ&pg=PT378|archive-date=2017-09-08|df=}}
6. ^{{cite book|url=https://books.google.com/books?id=hz9U9nzy-rQC&pg=PA236|title=Advanced dairy chemistry.|last=McSweeney|first=Paul L.H.|last2=Fox|first2=Patrick F.|date=2009|publisher=Springer-Verlag|isbn=9780387848655|edition=3rd|location=New York|page=236|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=hz9U9nzy-rQC&pg=PA236|archive-date=2017-09-08|deadurl=no|df=}}
7. ^{{cite journal | vauthors = Schumann C | title = Medical, nutritional and technological properties of lactulose. An update | journal = European Journal of Nutrition | volume = 41 Suppl 1 | pages = I17-25 | date = November 2002 | pmid = 12420112 | doi = 10.1007/s00394-002-1103-6 }}
8. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|access-date=8 December 2016|date=April 2015|deadurl=no|archive-url=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archive-date=13 December 2016|df=}}
9. ^1 2 {{cite book|last1=Hamilton|first1=Richard J.|title=Tarascon pocket pharmacopoeia : 2013 classic shirt-pocket edition|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, Ma.|isbn=9781449665869|page=111|edition=27|url=https://books.google.com/books?id=lwueJ4IAl4oC&pg=PA111|deadurl=no|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=lwueJ4IAl4oC&pg=PA111|archive-date=2017-09-08|df=}}
10. ^{{cite web|title=Lactulose|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=922&searchYear=2015|website=mshpriceguide.org|access-date=26 March 2017|deadurl=no|archive-url=https://web.archive.org/web/20170326230739/http://mshpriceguide.org/en/single-drug-information/?DMFId=922&searchYear=2015|archive-date=26 March 2017|df=}}
11. ^{{cite web|url=https://www.weldricks.co.uk/products/lactulose-solution-500ml|title=Lactulose Solution 500ml|website=Weldricks Pharmacy (UK)|date=|author=|access-date=31 March 2017|deadurl=no|archive-url=https://web.archive.org/web/20170331210608/https://www.weldricks.co.uk/products/lactulose-solution-500ml|archive-date=31 March 2017|df=}} A UK source of lactulose at £2.95 for 500 ml ($0.11/15 ml).
12. ^1 {{cite web |url=https://www.drugs.com/price-guide/lactulose |title=Lactulose Prices, Coupons & Patient Assistance Programs |website=Drugs.com |date= |author= |access-date=25 March 2017 |deadurl=no |archive-url=https://web.archive.org/web/20170326050722/https://www.drugs.com/price-guide/lactulose |archive-date=26 March 2017 |df= }} Source gives cost for 473 ml as about $20.
13. ^{{cite book|last1=Kuntz|first1=Hans-Dieter|title=Hepatology textbook and atlas : history, morphology, biochemistry, diagnostics, clinic, therapy|date=2008|publisher=Springer|location=Heidelberg|isbn=9783540768395|page=887|edition=3|url=https://books.google.com/books?id=oL6d9KuVqLQC&pg=PA887|deadurl=no|archive-url=https://web.archive.org/web/20170908140003/https://books.google.com/books?id=oL6d9KuVqLQC&pg=PA887|archive-date=2017-09-08|df=}}
14. ^{{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682338.html|title=Lactulose|work=nih.gov|access-date=25 August 2015|deadurl=no|archive-url=https://web.archive.org/web/20150905124827/https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682338.html|archive-date=5 September 2015|df=}}
15. ^{{cite journal | vauthors = Shukla S, Shukla A, Mehboob S, Guha S | title = Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy | journal = Alimentary Pharmacology & Therapeutics | volume = 33 | issue = 6 | pages = 662–71 | date = March 2011 | pmid = 21251030 | doi = 10.1111/j.1365-2036.2010.04574.x }}
16. ^1 {{cite journal | vauthors = Patil DH, Westaby D, Mahida YR, Palmer KR, Rees R, Clark ML, Dawson AM, Silk DB | title = Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy | journal = Gut | volume = 28 | issue = 3 | pages = 255–9 | date = March 1987 | pmid = 3570029 | pmc = 1432706 | doi = 10.1136/gut.28.3.255 }}
17. ^{{cite journal | vauthors = 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 | title = 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 | journal = Seizure | volume = 15 | issue = 6 | pages = 443–8 | date = September 2006 | pmid = 16787750 | doi = 10.1016/j.seizure.2006.05.007 }}
18. ^{{cite journal | vauthors = Vanner S | title = The lactulose breath test for diagnosing SIBO in IBS patients: another nail in the coffin | journal = The American Journal of Gastroenterology | volume = 103 | issue = 4 | pages = 964–5 | date = April 2008 | pmid = 18371132 | doi = 10.1111/j.1572-0241.2008.01798.x }}
19. ^{{cite journal | vauthors = Barrett JS, Irving PM, Shepherd SJ, Muir JG, Gibson PR | title = Comparison of the prevalence of fructose and lactose malabsorption across chronic intestinal disorders | journal = Alimentary Pharmacology & Therapeutics | volume = 30 | issue = 2 | pages = 165–74 | date = July 2009 | pmid = 19392860 | doi = 10.1111/j.1365-2036.2009.04018.x }}
20. ^{{cite journal | vauthors = Grover M, Kanazawa M, Palsson OS, Chitkara DK, Gangarosa LM, Drossman DA, Whitehead WE | title = Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress | journal = Neurogastroenterology and Motility | volume = 20 | issue = 9 | pages = 998–1008 | date = September 2008 | pmid = 18482250 | pmc = 3856223 | doi = 10.1111/j.1365-2982.2008.01142.x }}
21. ^1 {{cite journal | vauthors = Yu D, Cheeseman F, Vanner S | title = 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 | journal = Gut | volume = 60 | issue = 3 | pages = 334–40 | date = March 2011 | pmid = 21112950 | doi = 10.1136/gut.2009.205476 }}
22. ^{{cite web|title=Safety Data Sheet Lactulose|url=http://static.usp.org/pdf/EN/referenceStandards/msds/1356803.pdf|access-date=3 December 2016|date=2015}}
23. ^{{cite journal |author1=M. Luzzana |author2=D. Agnellini |author3=P. Cremonesi |author4=G. Caramenti |author5=S. De Vita |title=Milk lactose and lactulose determination by the differential pH technique |journal=Le Lait |volume=83 |issue=5 |pages=409–16 |date=September–October 2003 |url=http://lait.dairy-journal.org/articles/lait/pdf/2003/05/L3503.pdf |doi=10.1051/lait:2003022 |deadurl=no |archive-url=https://web.archive.org/web/20140512221309/http://lait.dairy-journal.org/articles/lait/pdf/2003/05/L3503.pdf |archive-date=2014-05-12 |df= }}
24. ^{{cite journal |author1=E. Marconi |author2=M. C. Messia |author3=A. Amine |author4=D. Moscone |author5=F. Vernazza |author6=F. Stocchi |author7=G. Palleschi |url=http://www.parmalat.it/documents/10157/29233/upload_00001438_Heat-treated%20milk%20differentiation%20by%20a%20sensitive.pdf |title=Heat-treated milk differentiation by a sensitive lactulose assay |journal=Food Chemistry |volume=84 |issue=3 |year=2004 |pages=447–50 |doi=10.1016/S0308-8146(03)00268-1 |deadurl=yes |archive-url=https://web.archive.org/web/20130616102238/http://www.parmalat.it/documents/10157/29233/upload_00001438_Heat-treated%20milk%20differentiation%20by%20a%20sensitive.pdf |archive-date=2013-06-16 |df= }}
25. ^{{cite journal | vauthors = Gluud LL, Vilstrup H, Morgan MY | title = Non-absorbable disaccharides versus placebo/no intervention and lactulose versus lactitol for the prevention and treatment of hepatic encephalopathy in people with cirrhosis | journal = The Cochrane Database of Systematic Reviews | volume = 4 | pages = CD003044 | date = April 2016 | pmid = 27089005 | doi = 10.1002/14651858.CD003044.pub3 }}
26. ^{{cite journal | vauthors = Sharma BC, Sharma P, Agrawal A, Sarin SK | title = Secondary prophylaxis of hepatic encephalopathy: an open-label randomized controlled trial of lactulose versus placebo | journal = Gastroenterology | volume = 137 | issue = 3 | pages = 885–91, 891.e1 | date = September 2009 | pmid = 19501587 | doi = 10.1053/j.gastro.2009.05.056 }}
27. ^{{cite journal | vauthors = Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R | title = Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy | journal = Hepatology | volume = 45 | issue = 3 | pages = 549–59 | date = March 2007 | pmid = 17326150 | doi = 10.1002/hep.21533 }}
28. ^{{cite web|title=International Nonproprietary Names for Pharmaceutical Preparations. Recommended International Non-Proprietary Names (Rec. I.N.N.): List 7|url=http://www.who.int/medicines/publications/druginformation/innlists/RL07.pdf|publisher=World Health Organization|access-date=9 November 2016|date=1967|page=8|deadurl=no|archive-url=https://web.archive.org/web/20160518192653/http://www.who.int/medicines/publications/druginformation/innlists/RL07.pdf|archive-date=18 May 2016|df=}}
29. ^{{cite web|title=Lactulose|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=922&searchYear=2014|archive-url=https://web.archive.org/web/20180122125109/http://mshpriceguide.org/en/single-drug-information/?DMFId=922&searchYear=2014|dead-url=yes|archive-date=22 January 2018|website=International Drug Price Indicator Guide|access-date=11 August 2015}}

External links

{{wikimedia|collapsible=true}}{{portal bar|Pharmacy and pharmacology|Medicine}}{{Carbohydrates}}{{Laxatives}}

6 : Carbohydrates|Disaccharides|Gastroenterology|Laxatives|RTT|World Health Organization essential medicines
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