What is acid reflux?

Proton Pump Inhibitors
This class of drugs markedly diminishes gastric acid secretion by inhibiting the final common pathway of acid secretion, the H +, K +-ATPase pump. PPIs inhibit daytime, nocturnal, and meal-stimulated acid secretion to a significantly greater degree than H 2RAs, but they rarely make patients achlorhydric. Unlike H 2RAs, the degree of acid inhibition with PPIs does not correlate with plasma concentration, but it is related to the concentration and duration. After oral ingestion, acid inhibition is delayed because PPIs need to accumulate in the secretory canaliculus of the parietal cell to bind irreversibly to actively secreting proton pumps. Therefore, the slower a PPI is cleared from the plasma, the more of it is available for delivery to the proton pumps. PPIs are best taken before the first meal of the day, when most proton pumps are active. Because not all pumps are active at any given time, a single PPI dose does not inhibit all pumps. A second dose, if needed, can be taken before the evening meal. The five available PPIs are omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole, the S-isomer of the racemic omeprazole. Their superior efficacy compared with H 2RAs is based on their ability to maintain an intragastric pH high than 4 between 15 to 21 hours daily compared with approximately 8 hours daily with the H 2RAs. Multiple studies show that the PPIs are superior to H 2RAs in completely relieving heartburn symptoms in most patients with severe GERD, usually within 1 to 2 weeks. Symptom relief is slightly better in patients with erosive as compared with nonerosive disease. Controlled studies and a large metaanalysis report complete healing of even severe ulcerative esophagitis after 8 weeks in more than 80% of patients taking PPIs compared with 51% of patients taking H 2RAs and 28% receiving placebo. In those patients not healing initially, prolonged therapy with the same dose or an increased dose usually resulted in 100% healing. Studies with PPIs consistently show that they are superior to both regular and high-dose H 2RA therapy, but therapeutic efficacy among PPIs is similar. However, a large study found that the newest PPI, esomeprazole, at a dose of 40 mg, was superior to the parent compound (omeprazole, 20 mg) for complete healing of esophagitis at 4 and 8 weeks. This superiority over omeprazole is related to higher systemic bioavailability and less interpatient variability with esomeprazole. One PPI, pantoprazole, is available in the United States for intravenous use. All the PPIs, are well tolerated with headaches and diarrhea described as the most common side effects in clinical trials. Although increased gastrin levels are reported with all the PPIs, the elevations generally do not exceed the normal range for gastrin and return to normal values within 1 week of stopping the drug. Omeprazole may decrease the clearance of diazepam and warfarin because of competition for the cytochrome P450 isoenzyme P2C19. The four newer PPIs have minimal or no important drug-drug interactions.