Which of the following prokinetic drugs has been implicated in causing serious ventricular arrhythmias, paicularly in patietns concurrently receiving erythromycin or ketoconazole?
**Core Concept**
Cisapride, a prokinetic agent, was used to enhance gastrointestinal motility by increasing acetylcholine release in the enteric nervous system. However, its use was associated with serious cardiac side effects due to its effect on cardiac potassium channels.
**Why the Correct Answer is Right**
Cisapride works by inhibiting the serotonin 5-HT4 receptor, which leads to an increase in acetylcholine release. This results in increased gastrointestinal motility. However, cisapride also blocks the potassium channels in the heart, which can lead to prolongation of the QT interval and an increased risk of serious ventricular arrhythmias. This risk is further increased when cisapride is concurrently administered with erythromycin or ketoconazole, which can also block cardiac potassium channels, thereby potentiating the cardiac effects of cisapride.
**Why Each Wrong Option is Incorrect**
**Option A:** Metoclopramide is another prokinetic agent, but it does not have the same cardiac side effects as cisapride. Metoclopramide works by blocking dopamine receptors in the chemoreceptor trigger zone, which leads to an increase in acetylcholine release and gastrointestinal motility.
**Option B:** Domperidone is a dopamine antagonist that is also used as a prokinetic agent. Unlike cisapride, domperidone does not cross the blood-brain barrier and therefore does not have the same risk of causing serious cardiac side effects.
**Option C:** Erythromycin is an antibiotic that can also have prokinetic effects, but it is not the correct answer because the question asks for a prokinetic drug that causes serious ventricular arrhythmias.
**Option D:** Ketoconazole is an antifungal agent that can also block cardiac potassium channels, but it is not a prokinetic drug.
**Clinical Pearl / High-Yield Fact**
Cisapride was withdrawn from the market in many countries due to its association with serious cardiac side effects. This highlights the importance of monitoring cardiac function in patients taking prokinetic agents, particularly those with a history of cardiac disease.
**Correct Answer: C. Cisapride.**