What is acid reflux?

Prokinetic Drugs
Until recently, three prokinetic drugs were available for the treatment of GERD: bethanechol, a cholinergic agonist; metoclopramide, a dopamine antagonist; and cisapride, a serotonin (5-HT 4) receptor agonist, which increases acetylcholine release in the myenteric plexus. These drugs improve reflux symptoms by increasing LES pressure, acid clearance, or gastric emptying. However, none alter the frequency of transient LESRs, and their physiological activity decreases as the disease severity worsens. Therefore, all the current prokinetics provide modest benefit in controlling heartburn, but they have little efficacy in healing esophagitis unless they are combined with an acid inhibiting drug. The use of prokinetic drugs is limited by their side effect profiles. Bethanechol commonly causes flushing, blurred vision, headaches, abdominal cramps, and urinary frequency. Metoclopramide, which crosses the blood-brain barrier, has a 20% to 50% incidence of fatigue, lethargy, anxiety, and restlessness and rarely causes tremor, parkinsonism, or tardive dyskinesia. It is possible to decrease the frequency of these side effects by dose reduction, by increasing the dosing regimen to twice a day, by taking a larger single dose before dinner or at bedtime, or by using a sustained-release tablet. Domperidone, another dopamine antagonist and one that does not cross the blood-brain barrier, has fewer side effects, but it is not available in the United States. Although the best prokinetic drug for treating GERD with an excellent safety profile, cisapride was withdrawn from the United States market because of increased reports of serious cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation) with associated cardiac arrest and deaths related to possible drug interactions. These drugs included common antibiotics (clarithromycin, erythromycin), antifungals (fluconazole, itraconazole, ketoconazole), and some antiviral agents. When taken with cisapride, these drugs inhibited the cytochrome P450 3A4 enzyme that metabolizes cisapride, thereby increasing cisapride blood levels to potentially dangerous values.