Background
Unlike lactose (milk sugar), lactulose does not occur naturally, except in very small amounts in heated milk, as a product of isomerization from lactose. The production of lactulose from lactose was first described in 1930. The sugar attracted interest in 1956 when Petuely demonstrated an increase in the number of lactobacilli in the stool when lactulose was administered to adults and infants. He concluded that administration could have a beneficial effect against the side effects of treatment with broad-spectrum antibiotics. He also showed that lactulose could be used in the treatment of constipation due to its laxative effect. Later, it was discovered that lactulose could also be used to treat hepatic encephalopathy.
Products
Lactulose is commercially available as syrup, powder, and granules (Gatinar, Duphalac, Rudolac + galactose + lactose). It has been approved in many countries since 1969.
Structure and properties
Lactulose (C12H22O11, Mr = 342.3 g/mol) is a semisynthetic disaccharide of galactose and fructose linked by a β-1,4-glycosidic bond. It is an isomeration product of lactose, which serves as the starting substance for its production. Lactulose is a white to almost white crystalline powder that is readily soluble in water.
Effect
Lactulose (ATC A06AD11) has a laxative and prebiotic effect on intestinal microflora. It lowers the concentration of ammonia in the blood.
Mechanism of action
Lactuolse enters the colon undigested because lactulose-splitting glycosidases are not present at the mucosa of the small intestine. There it is fermented by intestinal bacteria to form acids, such as lactic acid and other short-chain fatty acids, which stimulate peristalsis. Osmotic water retention increases intestinal contents and stimulates intestinal peristalsis. Various mechanisms of action are discussed for the ammonia-lowering effect of lactulose:
- The pH reduction induced by the breakdown of lactulose leads to protonation of the toxic, readily absorbable ammonia. The positively charged ammonium ion is no longer absorbed.
- By lowering the pH, the proteolytic intestinal flora is pushed back in favor of the saccharolytic, which produces less ammonia. This prevents the growth of certain pathogenic germs, such as salmonella, which prefer a neutral to slightly alkaline environment.
- The excess carbohydrate creates a relative deficit of nitrogen for the bacteria, which can be compensated by the microbial consumption of ammonia.
Indication
Lactulose is used to treat constipation and hepatic encephalopathy (hyperammonemia). Lactulose is also used as a prebiotic, but is not approved as a drug for this purpose.
Dosage
According to package insert. Lactulose is given as a single dose or divided throughout the day. It may be taken undiluted or dissolved in a drink or yogurt. Normal bowel movements may not be achieved for 24 to 48 hours.
Contraindications
- Hypersensitivity
- Intolerance
- Galactose or lactose intolerance
- Intestinal obstruction
- Icterus
- Acute inflammatory gastrointestinal diseases
- Bleeding of unknown cause in the digestive tract
- Severe disturbances of water and electrolyte balance.
Full precautions can be found in the drug label.
Interactions
Lactulose may increase potassium loss at high doses.
Adverse effects
Flatulence (leakage of intestinal gas) may occur as an adverse effect at the beginning of therapy. Electrolyte disturbances may occur when high doses are administered, as in encephalopathy treatment.
