BROOKLAX CHOCOLATE 250MG TABLET

Indications

• Constipation
• Bowel preparation prior to surgical procedures
• Occasional use for laxative effect

Dosage

Children: Refer to BNF for Children for specific pediatric dosing guidelines.

Adults: Refer to BNF for specific dosing information. Typical adult dosing for constipation may involve a single oral dose of 10 to 15 mg, taken as needed.

Mechanism of action

Phenolphthalein alters fluid and electrolyte absorption in the intestines, producing net intestinal fluid accumulation and laxative effects. It increases concentrations of cyclic 3'-5'-adenosine monophosphate (cAMP) in colonic mucosal cells, affecting cell permeability and promoting fluid accumulation. Additionally, phenolphthalein stimulates intestinal activity, particularly in the colon, approximately 6 hours after ingestion. It also inhibits water absorption in both the large and small intestines, contributing to its laxative effects.

Pharmacodynamics

Phenolphthalein acts primarily by stimulating the secretion of intestinal fluids and enhancing motility in the gastrointestinal tract. Its laxative effects are mediated by increased intestinal fluid volume and reduced water absorption. The compound may also influence prostaglandin E biosynthesis in the colon, further enhancing its action. However, the identification of hydroxyphenolphthalein (a metabolite) raises concerns about its potential toxicity and genotoxicity.

Pharmacokinetics

Phenolphthalein is absorbed after oral administration and is metabolized in the liver. Its onset of action occurs around 6 hours post-ingestion, with peak effects typically noted thereafter. The compound is primarily excreted in urine, and its pharmacokinetic profile may be influenced by individual metabolic rates and gastrointestinal transit times.

Adverse effects

• Abdominal cramps
• Diarrhea
• Nausea
• Vomiting
• Electrolyte imbalance
• Dehydration
• Potential carcinogenic effects with prolonged use

Precautions

• Use with caution in patients with renal impairment
• May cause dependence or overuse leading to chronic laxative use
• Monitor electrolyte levels during prolonged use

Pregnancy

Phenolphthalein should be avoided during pregnancy due to potential risks to the fetus, including possible carcinogenic effects.

Breast-feeding

It is not recommended to use phenolphthalein while breastfeeding due to potential risks to the infant.

Storage

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

Formulations

• Oral tablets
• Liquid formulations

Mechanism of action

Stimulant drugs alter fluid and electrolyte absorption, producing net intestinal fluid accumulation and laxation. Increased concentrations of cyclic 3'-5'-adenosine monophosphate (CAMP) occurring in clonic mucosal cells may alter the permeability of these cells leading to net fluid accumulation and laxative action. Phenolphthalein also acts directly or reflexly to increase the the activity of the small intestine. Phenolphthalein acts mainly on the colon about 6 hours after ingestion. When taken orally, it is thought to be dissolved by intestinal juices and bile and to stimulate intestinal musculature, chiefly that of colon. Phenolphthalein increased intestinal fluid volume in rat colon in situ, apparently via stimulation of prostaglandin E biosynthesis in colon. Water absorption from intestines of 6 pt with ileostomies and from rats was measured after administration of phenolphthalein. Results indicate that some laxative effects result from inhibition of water absorption in large and small intestines. .... A catechol metabolite of PT, hydroxyphenolphthalein (PT-CAT), was recently identified and may be the molecular species responsible for at least part of the toxicity/carcinogenicity of PT. We hypothesize that PT-CAT inhibits the enzyme catechol-O-methyltransferase (COMT) and therefore potentiates genotoxicity by either PT-CAT itself or the endogenous catechol estrogens (CEs) in susceptible tissues. The present studies were conducted to determine the effects of PT treatment and PT-CAT itself on the COMT-mediated metabolism of 4- and 2-hydroxyestradiol both in vitro and in vivo. Female mice were treated with PT (50 mg/kg/d) for 21 days and then euthanized. PT-CAT concentration in urine reached plateau levels by 7 days of exposure. An O-methylated metabolite of PT-CAT was detected in feces. In vitro experiments demonstrated that PT treatment resulted in an increase in free CEs, which are normally cleared by COMT and a concurrent decrease in the capacity of hepatic catechol clearance by COMT. In vitro, PT-CAT was a substrate of COMT, with kinetic properties within the range measured with endogenous substrates. PT-CAT was an extremely potent mixed-type inhibitor of the O-methylation of the catechol estrogens, with 90-300 nM IC50s.