Clinical presentation and etiology of constipation
A defecation frequency of at least 3 times per week is considered a physiological norm. If bowel movements occur less frequently, constipation is diagnosed. The development of this condition can be triggered by multiple factors:
- 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 GI function in elderly patients.
Main mechanisms and therapy complications
General pharmacology distinguishes three key principles of drug action affecting defecation:
- Osmotic (hydrophilic): fluid retention directly within the intestinal lumen.
- Transport-based: blockade of fluid absorption by the mucosa.
- 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 (15–20 g), primarily in acute poisonings for the rapid elimination of toxins. They are not used for chronic constipation.
- Disaccharides: lactulose. This is a synthetic combination of galactose and fructose. The drug is not hydrolyzed in the upper GI tract; in the colon, it is broken down by microflora into monosaccharides, increasing osmotic pressure. Indicated for chronic constipation.
- Bulk-forming agents: kelp (Laminaria) and methylcellulose. They act predominantly in the large intestine and are indicated for chronic atonic constipation.
Agents irritating chemoreceptors
- Synthetic drugs (diphenylmethane derivatives): phenolphthalein, oxyphenisatin, bisacodyl, sodium picosulfate. They possess a resorptive type of action: absorbed in the small intestine, secreted into the lumen of the colon, and irritate its mucosa. They act exclusively in the large intestine; 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.
- Plant anthraglycosides: senna preparations (Senade), rhubarb root (Rheum palmatum), and buckthorn bark. In the colon, the sugar moiety is cleaved off, forming anthracene derivatives (emodin, chrysophanic acid) that accelerate bowel evacuation in 8–12 hours. Rhubarb root contains numerous resinous substances providing additional irritation.
- Oils: castor oil. In the small intestine, the enzyme lipase converts it into ricinoleic acid. It acts throughout the entire gastrointestinal tract.
Additional drug groups
For combination therapy, agents with alternative sites of action are used:
- Lubricants (emollients): mineral oil and almond oil. They are not absorbed when taken orally, mechanically lubricate the mucosa, and soften stool, providing a mild laxative effect.
- Prokinetics: tegaserod, a partial $5 ext{-HT}_4$ receptor agonist (serotonergic action).
- Carminatives (antifoaming agents): simethicone, dill fruit (Anethum graveolens), and fennel fruit (Foeniculum vulgare). They eliminate flatulence.
- Peripheral opioid receptor antagonists: methylnaltrexone. Its key feature is its inability to cross the blood-brain barrier.