Lilac

Lactulose.

Lilac syrup, which contains lactulose with other sugars eg, galactose and lactose, is used in the treatment of constipation and hepatic encephalopathy. Lactulose is a disaccharide, a sugar molecule composed of 2 smaller sugar molecules bonded together, in this case, fructose and galactose. Lactulose is a solid substance that is very soluble in water and has a sweet taste. It is sweeter than lactose but not as sweet as fructose. Chemically, lactulose is also known as 4-O-β-D-galactopyranosyl-D-fructofuranose. The molecular formula is C₁₂H₂₂O₁₁ with a molecular weight of 342.3 daltons.

Laxative.
Pharmacology: Mechanism of Action: Two mechanisms are believed to be involved in the laxative action of lactulose: First, metabolism of lactulose by bacteria results in reduced colonic pH which stimulates peristalsis and decreases stool transit time. In turn, decreased water reabsorption from the feces further facilitates the passage of soft well-formed stools. Second, increased osmotic pressure of fecal material secondary to an increase in colonic organic acids results in accumulation of fluid from surrounding tissues, helping to soften stool mass.
The therapeutic action of lactulose in ameliorating the symptoms of hepatic encephalopathy is considered to be a result of the following: Reduction of fecal pH leading to a reduced ammonia absorption via non-ionic diffusion and/or diffusion of ammonia from the blood into the gut. The trapped ammonia is then excreted in the stools; suppression of urase-producing organisms; induction of an osmotic type of diarrhea which diminishes fecal stasis with reduction of nitrogenous substances for ammonia production. Decreased absorption of ammonia from the gut also results from shortening intestinal transit time.
The actual mechanism may be a combination of these effects.
Pharmacokinetics: Absorption: Lactulose is poorly absorbed from the GIT and no enzyme capable of hydrolysis of this disaccharide is present in human GI tissue. As a result, oral doses of lactulose reach the colon virtually unchanged.
Less than 2% of lactulose is absorbed systematically. Absorption may be enhanced 4- to 6-fold by increasing the osmotic value of the intestinal contents.
Distribution: Lactulose given orally resulted in only small amounts reaching the blood.
Metabolism and Elimination: Following administration by mouth, lactulose passes essentially unchanged into the large intestine where it is metabolized by saccharolytic bacteria with the formation of simple organic acids, mainly lactic acid and small amounts of acetic and formic acids. The small amount of absorbed lactulose is subsequently excreted unchanged in the urine. Urinary excretion has been determined to be ≤3% and is essentially complete within 24 hrs.

Relief of constipation including chronic constipation. Portal systemic encephalopathy: Hepatic coma or precoma stages where hyperammonemia is present.

Constipation: Dosage can vary widely with the severity of the condition. A relatively large initial dose should be followed by a smaller maintenance dose after the first 3 days of treatment. Only 1 daily dose needs to be taken, preferably after breakfast.
Adults: Initially 15-30 mL as a single dose or in 2 divided doses. Children 5-10 years: 10 mL twice daily; ≤1-5 years: 5 mL twice daily.
Hepatic Encephalopathy: 30-50 mL 3 times a day, subsequently adjusted to produce 2 or 3 soft stools daily.

There have been no reports of accidental overdosage. In the event of an overdosage, it is expected that diarrhea and abdominal cramps would be the major symptoms. Medication should be terminated.

Patients who require a low lactose diet; with galactosemia or disaccharide deficiency; with intestinal obstruction.

A theoretical hazard may exist for patients treated with lactulose syrup who may be required to undergo electrocautery procedures during proctoscopy or colonoscopy if sugars reach the colon then bacterial breakdown causes hydrogen production. Accumulation of hydrogen gas in significant concentration in the presence of an electrical spark may result in an explosive reaction. Although this complication has not been reported with lactulose, patients on lactulose therapy undergoing such procedures should have a thorough bowel cleansing with nonfermentable solution.

General: As with all laxatives, extended use may cause dependence for bowel function. No laxative should be taken for >1 week without the advice of a physician. No laxative should be used in the presence of abdominal pain nausea, fever or vomiting, as such symptoms may signal appendicitis or an inflamed bowel.
Lactose Intolerance: Care should be taken in patients who are lactose-intolerant.
Diabetics: Lactulose syrup contains galactose and lactose and should be used with caution in diabetics as blood glucose levels may be elevated, usually after extended use.
Portal Systemic Encephalopathy: In the overall management of portal systemic encephalopathy, it should be recognized that there is a preexisting hepatic disease and efforts should be made to identify and treat the precipitating cause of hepatic coma. Other laxatives should not be used especially during the initial phase of therapy for portal systemic encephalopathy because the loose stools resulting from their use may falsely suggest that adequate dosing has been achieved.
Use in pregnancy: Lilac should be used during pregnancy only if clearly needed under the advice of a medical physician.
Use in lactation: It is not known whether lactulose is excreted in human milk but because most drugs are excreted in human milk, it should not be given to breastfeeding women unless the benefits to the mother outweigh the potential risks to the feeding infant.
Use in children: It is recommended that if lactulose syrup is given to infants or children for periods >1 month, this should be done under medical supervision.
Use in the elderly: Elderly, debilitated patients who receive lactulose for >6 months should have serum electrolytes (potassium, chloride, carbon dioxide) measured periodically.

Use in pregnancy: Lilac should be used during pregnancy only if clearly needed under the advice of a medical physician.
Use in lactation: It is not known whether lactulose is excreted in human milk but because most drugs are excreted in human milk, it should not be given to breastfeeding women unless the benefits to the mother outweigh the potential risks to the feeding infant.

Initial doses of lactulose may cause abdominal discomfort associated with flatulence and intestinal cramps. These symptoms normally disappear under continued therapy.
Nausea and vomiting have occasionally been reported following high doses.
Prolonged use or excessive dosage can lead to diarrhea with potential complications eg, loss of fluids, hypokalemia and hyponatremia.

No laxative should be taken within 2 hrs of another medication because the desired effect of the other medication may be reduced.
Antacids: Antacids given concurrently with lactulose may inhibit the desired lactulose-induced drop in colonic pH. Therefore, a possible lack of desired effect of treatment should be taken into consideration before such drugs are given concomitantly with lactulose.
Neomycin: In some situations, neomycin administered together with lactulose is more effective than either one alone.
Although, theoretically, the elimination of certain colonic bacteria by neomycin and possibly other anti-infective agents may interfere with the desired degradation of lactulose and thus prevent the acidification of colonic contents. There have been some reports that lactulose-fermenting bacteria are relatively resistant to neomycin, which may explain why a combination could work in some cases. The status of the lactulose-treated patients should be closely monitored in the event of concomitant oral antibiotic therapy.

Store at temperatures not exceeding 30°C. Protect from sunlight.
Under recommended storage conditions a normal darkening of color may occur. Such darkening is characteristic of sugar solutions and does not affect therapeutic efficacy.

Cholagogues, Cholelitholytics & Hepatic Protectors / Laxatives, Purgatives

A06AD11 - lactulose ; Belongs to the class of osmotically acting laxatives.

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