DUPHALAC 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

Indications

• Insecticide for agricultural use
• Research tool in toxicology

Dosage

Children: Refer to the BNF for Children for specific dosing and administration guidelines.

Adults: Refer to the BNF for specific dosing and administration guidelines.

Mechanism of action

Methyl parathion acts primarily by inhibiting the enzyme acetylcholinesterase, which is essential for the breakdown of the neurotransmitter acetylcholine. Its active metabolite, methyl paraoxon, is a potent inhibitor of both acetylcholinesterase and butyrylcholinesterase. The inhibition of these enzymes results in the accumulation of acetylcholine at synapses, leading to overstimulation of cholinergic receptors and resultant toxic effects.

Pharmacodynamics

The pharmacodynamics of methyl parathion involve its action as a noncompetitive inhibitor of acetylcholinesterase, causing prolonged effects of acetylcholine due to its inability to be hydrolyzed. The resultant cholinergic toxicity can lead to symptoms such as muscle twitching, respiratory distress, and potentially fatal outcomes if not treated promptly. The extent of inhibition is dose-dependent, with significant toxicity occurring after substantial enzyme inhibition.

Pharmacokinetics

Methyl parathion is absorbed through the gastrointestinal tract and can also be absorbed through the skin and respiratory tract. It is metabolized in the liver to form methyl paraoxon, which is responsible for the majority of its toxic effects. The distribution of methyl parathion in body tissues is influenced by its lipophilicity, and it is primarily excreted as metabolites in the urine. The elimination half-life and specific pharmacokinetic parameters can vary based on individual metabolism and exposure levels.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether this drug is excreted in human milk. Caution is advised when administering to nursing women.

Storage

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

Formulations

• Liquid formulation

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.

Mechanism of action

Acute poisoning ... is related to ... inhibiting action on enzyme acetylcholinesterase. Toxic manifestations generally occur only after more than 50% of plasma cholinesterase is inhibited. ... Methyl parathion ... depend on oxidative activation by replacement of thiono-sulfur with oxygen for ... toxicity. Methyl parathion has only a slight inhibitory action on acetylcholinesterase and butyrylcholinesterase, but its active metabolite, methyl paraoxon, is a potent inhibitor of both these enzymes. A study was conducted examining the inhibition of (Ca2+ and Mg2+)-ATPase by parathion (56382) and methyl parathion. Enzyme activity was assessed spectrophotometrically in pig erythrocyte membranes containing calcium2+ (Ca2+) and magnesium2+ and in solubilized membrane preparations incubated with the test agents. The enzyme response to ATP was biphasic. Equations expressing the kinetics of the substrate curves described two classes of the ATP binding active site, one with high affinity and low maximum rate and one with low affinity and high maximum rate. High affinity active sites were stimulated by low ATP concentrations (20 uM), whereas low affinity active sites were stimulated by high ATP levels (2 mM). Parathion and methylparathion dose dependently inhibited enzyme activity; parathion had a greater inhibitory effect than methylparathion. Lineweaver-Burke and Dixon plots indicated noncompetitive inhibition. Parathion and methylparathion induced enzyme inhibition occurred over a range of free calcium ion concentrations (0.5 to 5 mM); the inhibition was significantly greater at lower Ca2+ concentrations (1 to 100 uM) than at higher concentrations. The authors conclude that parathion and methylparathion inhibit ATPase activity by binding to a site on the enzyme rather than through an interaction with associated lipids. For more Mechanism of Action (Complete) data for METHYL PARATHION (6 total), please visit the HSDB record page.