Classification and Mechanism of Action
In the pharmacological classification of the gastrointestinal tract, misoprostol belongs to gastro-cytoprotective agents. These drugs increase the resistance of the gastric and duodenal mucosa to the aggressive action of gastric juice.
Based on their mechanism of action, gastroprotectors are divided into two subclasses. The first consists of agents that form a mechanical protective film (e.g., sucralfate or bismuth compounds). The second subclass includes agents that enhance mucus secretion, represented by synthetic prostaglandin analogs (misoprostol, enprostil) as well as licorice derivatives (carbenoxolone).
At the cellular level, misoprostol binds to prostaglandin receptors, which leads to the inhibition of cAMP synthesis and the suppression of hydrochloric acid secretion. Concurrently, powerful protective mechanisms are activated:
- Stimulation of thick mucus and bicarbonate production.
- Activation of surfactant-like phospholipid synthesis.
- Significant improvement in microcirculation and blood flow within the gastric wall.
Prevention and Treatment of NSAID-Induced Gastropathy
The primary clinical indication for prescribing misoprostol is the prevention and treatment of erosive and ulcerative lesions of the mucosa caused by ulcerogenic drugs (primarily nonsteroidal anti-inflammatory drugs and glucocorticoids).
Pathogenesis of mucosal damage during NSAID use:
- The drugs cause non-reactive inhibition of the cyclooxygenase-1 (COX-1) enzyme.
- This leads to a sharp decline in the synthesis of protective endogenous prostaglandins ($PGE_2$, $PGI_2$) in the gastric wall.
- A critical imbalance between aggressive and protective factors develops: hydrochloric acid (HCl) secretion increases while the production of protective mucus and bicarbonates drops.
- Consequently, mucosal ulceration occurs.
- The situation is exacerbated by a high risk of gastrointestinal bleeding, as NSAIDs simultaneously inhibit platelet aggregation.
Effective pharmacoprophylaxis for these conditions involves either synthetic prostaglandin analogs (misoprostol) or proton pump inhibitors (e.g., omeprazole). An alternative protective strategy is replacing the offending drug with selective COX-2 inhibitors (celecoxib), which have less impact on gastric prostaglandins. Meanwhile, the folk remedy of drinking milk to coat the stomach is largely ineffective; milk provides only a temporary buffering effect but does not prevent direct mucosal contact damage or the systemic drop in prostaglandin levels. Furthermore, calcium ions from milk can secondarily stimulate acid secretion.
Adverse Effects and Obstetric Applications
The main gastrointestinal adverse effects of misoprostol include dyspeptic symptoms such as nausea and diarrhea. Patients also frequently report headaches. A related drug, enprostil (a prostaglandin $E_2$ analog), has a similar pharmacological profile but is characterized by better tolerability and a lower incidence of adverse events.
A strict contraindication to the use of misoprostol in gastroenterology is pregnancy. This is because prostaglandins strongly affect uterine tone by stimulating contractile activity.
However, this exact property has found widespread use in obstetric practice for medical termination of pregnancy in the first trimester. The procedure is performed strictly by specialist physicians and consists of two stages:
- First stage: A single oral dose of mifepristone—an antigestagenic drug that competes with progesterone for receptors, depriving the gestational sac of hormonal support.
- Second stage (48 hours later): Oral administration of misoprostol. It induces strong myometrial contractions, leading to the expulsion of the gestational sac.