Capeserod

Cisapride is a gastroprokinetic agent that acts as a serotonin 5-HT4 agonist. It was primarily used to treat gastrointestinal disorders such as gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and gastroparesis. Cisapride works by enhancing the release of acetylcholine at the myenteric plexus, which in turn stimulates gastrointestinal motility and accelerates gastric emptying. Despite its effectiveness in improving GI motility, the use of cisapride has been significantly restricted due to its association with serious cardiac side effects, including QT interval prolongation and rare cases of torsades de pointes, which can lead to sudden cardiac death.

Mechanism of Action

Cisapride acts as a serotonin (5-HT4) receptor agonist. By stimulating these receptors, cisapride enhances the release of acetylcholine from the enteric neurons. This action increases gastrointestinal motility, enhances lower esophageal sphincter tone, and accelerates gastric emptying. The drug does not have significant action on gastric acid secretion.

Indications

Initially, cisapride was indicated for the treatment of nocturnal heartburn due to gastroesophageal reflux disease (GERD), for the relief of symptoms of non-ulcer dyspepsia, and for the management of gastroparesis in diabetic patients. Its use was based on its ability to improve GI motility.

Side Effects and Safety Concerns

The most common side effects of cisapride include abdominal pain, diarrhea, and headache. However, its safety profile changed significantly after reports emerged linking cisapride to serious cardiac arrhythmias, particularly QT interval prolongation and torsades de pointes. These side effects are believed to be due to cisapride's ability to block potassium channels in the heart, leading to changes in cardiac electrical activity.

As a result of these safety concerns, cisapride was withdrawn from many markets worldwide and its use has been severely restricted in others. It is now available only under special access programs where patients are closely monitored for cardiac side effects.

Regulatory Status

Following reports of cardiac arrhythmias and deaths, regulatory agencies in several countries, including the United States Food and Drug Administration (FDA), took action to limit the use of cisapride. In the United States, cisapride was removed from the market in 2000, but it can still be obtained through a special FDA-regulated program designed to ensure that patients who might benefit from the drug can do so with minimal risk.

Conclusion

While cisapride was once a widely used medication for improving gastrointestinal motility, its association with serious cardiac side effects has led to its withdrawal from the market in many countries and strict restrictions on its use in others. Patients who may benefit from cisapride must be carefully selected and monitored to minimize the risk of cardiac complications.