Laxatives

Clinical presentation and etiology of constipation

A defecation frequency of at least 3 times a week is considered physiologically normal. If bowel movements occur less frequently, constipation is diagnosed. The development of this condition can be triggered by multiple factors:

• Alimentary: dietary fiber deficiency in the diet.
• Iatrogenic: adverse effects of various medications.
• Endocrine and somatic: motility disorders secondary to systemic diseases.
• Age-related: natural changes in gastrointestinal function in elderly patients.

Basic mechanisms and complications of therapy

General pharmacology identifies three key principles of action for drugs affecting defecation:

1. Osmotic (hydrophilic): fluid retention directly within the intestinal lumen.
2. Transport: blockade of fluid absorption by the mucous membrane.
3. Prokinetic: direct stimulation of motility and propulsive activity.

Prolonged and uncontrolled laxative therapy is unsafe. Typical complications include drug-induced diarrhea, allergic reactions, malabsorption syndrome (impaired nutrient absorption), and secondary intestinal atonia, in which smooth muscle tone is critically reduced.

Agents causing mechanical irritation

This group increases the volume of intestinal contents, leading to the irritation of mechanoreceptors and stimulation of peristalsis.

• Saline laxatives: sodium sulfate (Glauber's salt), magnesium sulfate, and Carlsbad salt (a mixture of sodium and potassium sulfates, sodium bicarbonate, and sodium chloride). They are poorly absorbed, increase osmotic pressure, and act throughout the entire intestine. The effect occurs in 4–6 hours. Administered orally at 15–20 g, primarily in acute poisonings for the rapid removal of toxins. Not used for chronic constipation.
• Disaccharides: lactulose. This is a synthetic combination of galactose and fructose. The drug is not digested in the upper gastrointestinal tract, but in the colon it is hydrolyzed by microflora into monosaccharides, increasing osmotic pressure. Prescribed for chronic constipation.
• Bulking agents: kelp (Laminaria) and methylcellulose. They act predominantly in the large intestine and are indicated for chronic atonic constipation.

Chemoreceptor-stimulating agents

• Synthetic drugs (diphenylmethane derivatives): phenolphthalein, oxyphenisatin, bisacodyl, sodium picosulfate. They possess a resorptive type of action: they are absorbed in the small intestine, secreted into the lumen of the colon, and irritate its mucosa. They act only in the colon; their effect is weaker than that of saline laxatives and appears in 6–8 hours. Bisacodyl is hydrolyzed in an alkaline medium (when taken orally, it works in 5–7 hours; rectally, within an hour). Oxyphenisatin acts via its metabolite dihydroxyphenylisatin.
• Herbal anthraglycosides: senna preparations (Senade), rhubarb root, buckthorn bark. The sugar moiety is cleaved off in the colon, forming anthracene derivatives (emodin, chrysophanic acid) that accelerate bowel emptying within 8–12 hours. Rhubarb root contains many resinous substances that provide additional irritation.
• Oils: castor oil. In the small intestine, under the action of the enzyme lipase, it is converted into ricinoleic acid. It acts throughout the entire intestine.

Additional drug groups

For combination therapy, agents with other sites of action are used:

• Lubricants (softeners): liquid paraffin and almond oil. Not absorbed when taken orally, they mechanically lubricate the mucosa and soften fecal masses, providing a mild laxative effect.
• Prokinetics: tegaserod, which is a partial $5\text{-HT}_4$ receptor agonist (serotonergic action).
• Carminatives (antifoaming agents): simethicone, dill fruit, and fennel fruit. They relieve flatulence.
• Peripheral opioid receptor antagonists: methylnaltrexone. Its main feature is the inability to cross the blood-brain barrier.

Class and exam questions

What else to study on this topic

• Pharmacokinetics of synthetic diphenylmethane derivatives (features of the resorptive type of action).
• Biochemical process of activation of herbal anthraglycosides in the colon.
• The role of the enzyme lipase in the metabolism of castor oil and the formation of ricinoleic acid.
• Differential selection of laxatives in acute poisonings and chronic atonic constipation.
• Mechanism of action of serotonergic prokinetics using tegaserod as an example.

Other topics in the section «Drugs Affecting Digestive System Functions»

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.