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Lactulose: Uses, MOA, Side effects, Dosage and Interactions

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Lactulose is a type of laxative used to treat constipation and hepatic encephalopathy. It is a semisynthetic disaccharide sugar that acts as an osmotic laxative.

Formulation

Lactulose is available as an aqueous solution of lactulose that contains more than 62% W/v of lactulose. It may contain lesser amounts of other sugars such as lactose, epilactose, galactose, and fructose. It also has antimicrobial preservatives

Category

Chemically it is a synthetic disaccharide sugar

Therapeutically it is classified as an ammonia reducer and a laxative

Lactulose is classified as category B in pregnancy.

Indications of lactulose

Lactulose is used in the treatment of constipation

It is also used in the treatment of hepatic encephalopathy.

It can also be used as an adjunct therapy in the management of partial seizures and treatment of generalized seizures of Lennox-Gastaut syndrome and primary generalized tonic-clonic seizures.

Mechanism of action and pharmacokinetics

On administration of lactulose orally, Lactulose gets to the colon (large intestine) in an unchanged in the colon. Lactulose is a disaccharide that is not a normal dietary constituent. Therefore humans do not possess a lactulase enzyme, so lactulose is neither digested nor absorbed but reaches the colon unchanged

In the colon, its metabolized by saccharolytic bacteria leading to the formation of simple organic acids lactic acid, formic and acetic acids which reduce the pH and acidify the fecal contents.

Lactulose then traps ammonia and other toxins within the intestinal lumen by this acidification, and in addition, they act as a cathartic and reduce ammonia absorption by reducing the colonic transit time;

This acidification leads to increased osmotic pressure in the colon (hyperosmolarity), which, in turn, pulls water into the colon increasing the stool water content and softening stool. This mechanism exerts a local osmotic effect in the colon resulting in increased fecal bulk and stimulation of peristalsis.

Lactulose produces a laxative effect after two to three days.

In the treatment of hepatic encephalopathy, lactulose makes intestinal contents more acidic than blood preventing ammonia from diffusing from the intestine into the blood, as occurs in hepatic encephalopathy.

This ammonia is then converted into ammonium ions and, by lactulose’s cathartic effect, is expelled in feces with other nitrogenous wastes thereby improving the encephalopathy associated with hyperammonemia. This improvement is because of a fall in blood ammonia concentration and improvement in mental function.

Small amounts of it are subsequently excreted unchanged in the urine.

It is well tolerated and very effective, but can be relatively expensive.

Lactulose is of particular value in the treatment of hepatic encephalopathy, because of its ability to discourage the proliferation of ammonia-producing organisms and the absorption of ammonia.

Side effects of lactulose

The use of lactulose can be associated with the following unwanted effects;

  • It may cause abdominal discomfort associated with flatulence or painful abdominal cramps
  • Nausea and vomiting have been reported following high doses
  • Prolonged use of lactulose may also result in diarrhea with excess loss of water and electrolytes i.e potassium
  • Some consider the taste to be unpleasant
  • Hypernatremia has also been reported on the use of lactulose
  • Hyperglycemia
  • Hypernatremia, hypokalemia, hypovolemia
  • Belching

Precautions when using this drug

It should not be given to patients with intestinal obstruction

It should not be used in patients on a low galactose diet and care should be taken in patients with lactose intolerance or in diabetic patients because of the presence of some free galactose and lactose sugars.

Severe lactic acidosis developed in a patient with adynamic ileus (paralytic ileus) who was being given lactulose of hepatic encephalopathy.

Administration

The medication is taken orally

It may take up to 48hours before an effect is obtained.

Lactulose is usually administered as a solution containing about 3.35g per 5mls together with other sugars such as galactose and lactose.

The usual dose is 15-30ml orally, once or twice a day up to 60mls per day. The doses are generally adjusted according to the patient’s needs.

In children who are between 5- 10 years old the initial dose is 10mls twice daily.

In children who are between 1-5 years old, the dosage is 2.5ml twice daily.

In patients with hepatic encephalopathy, a dose of 90-150 ml orally three times a day is used. The dose is subsequently adjusted to produce 2 to 3 soft stools each day.

Lactulose 300mls in 700ml of normal saline is used as a retention enema. The enema is retained for 30-60 minutes and repeated after every 4-6 hours until the patient is able to take oral medication.

Contraindications

The following contraindications are observed when using this drug. Take caution in patients;

  • Who are on a low galactose diet
  • With disaccharides deficiency
  • Who are on a lactose-free diet
  • With intestinal obstruction
  • With hypersensitivity to lactulose or its components,

Drug Interactions

Hyperosmolar laxatives don’t interact significantly with other drugs. However, oral drugs given 1 hour before administering polyethylene glycol PEG have significantly decreased absorption.

It can also show some interaction when used with antacids, antibiotics (especially oral neomycin), and other laxatives.

Moderate interactions of lactulose include:

  • calcium carbonate
  • deflazacort
  • dichlorphenamide
  • sodium bicarbonate
  • sodium citrate/citric acid

These medications decrease the effectiveness of lactulose

Diagnosis and testing

The sugar absorption test:

In healthy individuals, lactulose is largely unabsorbed from the gastrointestinal tract, but in coeliac disease, there is increased permeability to disaccharides such as lactulose and a paradoxical decrease in the absorption of monosaccharides.

This leads to the development of the differential sugar absorption test in which 2 sugars are given simultaneously by mouth and the urinary recovery of each is determined. Mannitol is commonly used as the monosaccharide components and lactose as the disaccharide component.

Alternatives include mannitol plus cellobiose and rhamnose plus lactulose.

This absorption is useful in the investigation of intestinal disease.

The lactulose breath test:

When taken it is converted by bacteria in the large bowel to short-chain fatty acids with the production of small quantities of hydrogen gas. The hydrogen is then rapidly absorbed and is exhaled in the breath and measurement of its production is used to measure orofaecal transit time and carbohydrate malabsorption.

However small doses of lactulose shorten transit time, which may limit the value of this test.

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Post References

  • NCBI, Harpers textbook of basic and clinical pharmacology

  • Revised on: 2021-07-10 02:56:07