TULAC Oral Solution

Indications

• Chronic constipation
• Portal-systemic encephalopathy

Dosage

Children: Child 1-11 months: 2.5 mL twice daily, adjusted according to response. Child 1-4 years: 5 mL twice daily, adjusted according to response. Child 5-10 years: 10 mL twice daily, adjusted according to response. Child 5-17 years: 5-20 mL twice daily, adjusted according

Adults: Initially 15 mL twice daily, adjusted according to response. For hepatic encephalopathy, doses can be 30-50 mL three times a day, adjusted to produce 2-3 soft stools per day.

Mechanism of action

Lactulose is broken down by saccharolytic bacteria in the large intestine into organic acids, such as lactic acid, which increases intraluminal gas formation and enhances peristaltic gut motility. This osmotic effect increases water content in stool, facilitating bowel movements. Additionally, it acidifies the colonic contents, helping to treat portal-systemic encephalopathy by promoting the conversion of ammonia to ammonium ions, which are less absorbable.

Pharmacodynamics

Lactulose has minimal systemic absorption, exerting its effects predominantly within the gastrointestinal tract. It enhances stool volume and softens stool, which may lead to increased bowel sounds, feelings of bloating, belching, flatus, and diarrhea. These effects contribute to its laxative properties and its role in treating hepatic encephalopathy.

Pharmacokinetics

Lactulose is poorly absorbed from the gastrointestinal tract and exerts its action locally. It typically takes 24 to 48 hours to manifest its laxative effect. The substance is not metabolized before reaching the colon, where it is fermented by gut bacteria, resulting in the production of short-chain fatty acids and gases.

Contra-indications

• Galactosaemia
• Gastrointestinal obstruction
• Gastrointestinal perforation
• Risk of gastrointestinal perforation
• Lactose intolerance

Adverse effects

• Diarrhoea
• Gastrointestinal discomfort
• Nausea
• Abdominal pain
• Flatulence
• Vomiting
• Electrolyte imbalance

Precautions

• Caution in patients with a history of gastrointestinal disorders
• Monitor for electrolyte imbalance in prolonged use

Pregnancy

Not known to be harmful, but manufacturer advises to avoid.

Breast-feeding

Manufacturer advises to avoid.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Lactulose 10g/15ml oral solution
• Lactulose 680 mg per 1 ml
• Lactulose granules

Mechanism of action

Lactulose is a synthetic disaccharide derivative of lactose that consists of one molecule of galactose and one molecule of fructose. Saccharolytic bacteria present in the large intestine subsequently break the substance down into organic acids like lactic acid and small amounts of formic and acetic acids. Such resultant volatile fatty acid metabolites, in combination with hydrogen and methane that is also generated consequently enhance intraluminal gas formation, peristaltic gut motility, and elicit an osmotic effect that facilitates an increase in the water content of stool as well as associated stool softening. All of these actions ultimately assist in facilitating and increasing the frequency of bowel movements in patients experiencing constipation, although it may take 24 to 48 hours after using the medication for this laxative effect to become evident. At the same time, the formation of such acids via the metabolism of lactulose by colonic bacteria also acidifies the contents of the colon, thereby contributing to the treatment of portal-systemic encephalopathy (PSE). As one of the principal features of PSE involves the accumulation of nitrogenous waste products like ammonia in the systemic circulation, a state in which the colonic contents become more acidic than blood allows ammonia in the circulation to diffuse into the colon.. Furthermore, ammonia that diffuses into the acidic colon is ionized to ammonium ions that are incapable of being absorbed back into the blood. These effects, combined with the laxative action of lactulose facilitates the excretion of excess ammonia. And finally, it is also believed that an acidic colonic environment results in the elimination of urease-producing bacteria that contribute to the formation of ammonia while surviving colonic bacteria use up any trapped ammonia in the colon as a source of nitrogen for protein synthesis.

Pharmacodynamics

Lactulose formulations are most commonly administered via the oral route or the rectal route. Consequently, because the substance experiences minimal absorption by the gut it typically remains localized in the gastrointestinal tract environment and ultimately demonstrates almost all of its pharmacologic effects within the gut. In particular, as lactulose elicits its laxative effects in enhancing stool amounts and softening stool, such biochemical and physiologic activities can cause increased bowel sounds (borborygmi), a feeling of bloatedness, belching, frequent flatus, and diarrhea.