Gastroesophageal reflux disease is a chronic disorder. It is important to educate the patients to modify their lifestyle and habits that may promote Gastroesophageal reflux and encourage them to adopt new habits that will bring long-term beneficial results.
- Dietary and lifestyle changes recommended include the following:
- Elevation of the head of the bed (15.2 cm [6 in.]) may be achieved by the placement of 15.2 cm (6-in.) blocks under the head of the bed or a 15.2 cm (6-in.) foam-rubber wedge in place of or under the pillow.
- Fatty and fried foods.
- Tomato products.
- Citrus juices and fruits.
- Coffee, tea, and carbonated beverages.
- Carminatives (spearmint, peppermint).
- Large meals that would distend the stomach.
- Three small-to-moderate-sized nutritionally balanced meals a day.
- High-protein, low-fat diet.
- No eating 3 to 4 hours prior to reclining or going to sleep.
- Weight loss, if overweight.
- Avoid using tight belts or girdles that increase intraabdominal pressure.
- Avoid drugs that promote Gastroesophageal reflux (reduce lower esophageal sphincter pressure, esophageal clearing)
- Progesterone or progesterone-containing birth control pills.
- Beta-adrenergic agonists.
- Calcium channel blockers.
Frequent use of antacids and lozenges (e.g., every 2 hours) is recommended. The most effective and commonly used antacids are those that contain a combination of magnesium and aluminum hydroxides.
For patients with renal failure, only aluminum hydroxide- containing antacids are recommended, since magnesium may accumulate in the blood. Low-sodium preparations (e.g., Riopan) are available for patients on severe sodium restriction.
Drugs that decrease gastric acid output.
Those most commonly used drugs are histamine-2 (H2) blockers. For patients with intermittent, infrequent or mild symptoms of Gastroesophageal reflux, H2 blockers may be prescribed. These drugs are usually effective in controlling symptoms of mild to moderate Gastroesophageal reflux, but have not been shown to effectively heal erosive esophagitis. H2-blockers do not suppress gastric secretions completely. They decrease gastric acid secretion by binding to the histamine receptor on the parietal cell in a competitive fashion.
When their concentration decreases around the parietal cell histamine binds to the parietal cell receptor and acid secretion is resumed. Thus, regular and frequent dosing is essential. H2 blockers also have very limited acid suppressive ability at times of eating and the gastric pH rarely rises above 2 to 3. Because Gastroesophageal reflux occurs most commonly during and after eating, acid and pepsin activity is not eliminated with H2 blockers and their effectiveness is thus limited.
- Cimetidine (Tagamet), 300 mg q.i.d. or 400 to 800 mg q12h a.c. and h.s.
- Ranitidine (Zantac), 150 to 300 mg q12h.
- Famotidine (Pepcid), 20 to 40 mg at h.s.
- Nizatidine, 150 to 300 mg q12h.
- Tagamet, Zantac, and Pepcid are also available at lower doses as over-the-counter medications.
The final step of gastric acid secretion by the parietal cell involves the extrusion of a proton or a hydrogen ion (H+) into the gastric lumen in exchange of a potassium ion (K+), which enters the parietal cell via the H+ K+-ATPase or the «proton pump.» proton-pump inhibitors are a group of drugs designed to inhibit acid secretion by forming a covalent bond within the proton pump and, thus, inhibiting the exchange of (H+) and (K+) ions permanently by that proton pump.
These drugs are extremely effective in inhibition of gastric acid secretion for 19 to 24 hours and allow the gastric pH to rise above 4 or 5, thus, also eliminating the pepsin activity. Proton-pump inhibitors have been shown to effectively heal erosive esophagitis, diminish the formation of esophageal strictures, and control most symptoms and signs of Gastroesophageal reflux disease. Proton-pump inhibitors when used continuously prevent recurrence of erosive esophagitis. As a group of drugs, they are safe and have minimal side effects. In most instances, they are used as first line therapy for Gastroesophageal reflux disease.
Currently, there are five commercially available proton-pump inhibitors approved by the U.S. Food and Drug Administration (FDA) for healing erosive Gastroesophageal reflux disease. These are Omeprazole (Prilosec), 20 to 40 mg p.o. (q.d. or b.i.d.; lansoprazole (Prevacid), 15 to 30 mg p.o. (q.d. or b.i.d.); rabeprazole sodium (Aciphex), 20 mg p.o. (q.d.); pantoprazole (Protonix), 40 mg p.o. (q.d.); and esomeprazole magnesium (Nexium), 20 to 40 mg p.o. (q.d.).
All proton-pump inhibitors are most effective if taken 15 to 30 minutes before breakfast. Omeprazole, lansoprazole, pantoprazole, and esomeprazole magnesium are excreted in the urine. Rabeprazole sodium is mostly excreted in bile. No dose adjustments are necessary in renal or hepatic insufficiency. Omeprazole, esomeprazole magnesium, lansoprazole, and rabeprazole sodium are metabolized by the p450 system in the liver and may have minor drug-drug interactions with some drugs; however, these have not been shown to be clinically significant.
Pantoprazole has no known drug-drug interactions. Clinical experience with pantoprazole 40 mg p.o. q.d. and esomeprazole magnesium 40 mg p.o. q.d. have shown better nighttime acid control and less Gastroesophageal reflux symptoms. Pantoprazole is also available in intravenous formulation and has been FDA-approved for use at 40 mg intravenous per day in patients with Gastroesophageal reflux disease who are unable to receive medications by the oral route.
Side effects of proton-pump inhibitors are rare and include minor headaches, diarrhea, and nausea. A new formulation of esomeprazole magnesium (Nexium), which only contains the levo- or S-isomer, is has recently been approved by the FDA. Esomeprazole magnesium is metabolized slower by the liver than the R-isomer, thus, has a longer duration of action than the racemic formulation. At 40 mg orally per day, it has been shown to be significantly more effective than the racemic mixture (Prilosec, 20 mg per day) in healing erosive esophagitis.
Proton-pump inhibitors have revolutionized the treatment of Gastroesophageal reflux disease and most of its complications. These drugs have been noted to be safe and free of long-term complications. Initial concerns about gastric bacterial overgrowth, Vitamin B12 and iron malabsorption, and causation of gastric carcinoid tumors have not been clinically observed.
Drugs that increase lower esophageal sphincter pressure and esophageal clearance.
- Metoclopramide hydrochloride, a dopamine antagonist, has been shown to increase lower esophageal sphincter pressure and to improve esophageal and gastric emptying. It counteracts the receptive relaxation of the gastric fundus and increases duodenal and small- bowel motility. It is also a centrally active antiemetic. This drug is especially helpful in patients with Gastroesophageal reflux disease and abnormalities of gastric emptying. Since metoclopramide crosses the blood-brain barrier, 10% of patients seem to experience psychotropic side effects (e.g., somnolence, lassitude, restlessness, anxiety, insomnia, and, rarely, extrapyramidal reactions). These side effects are reversible with cessation of the drug. Elevated prolactin levels may occur and cause galactorrhea. The usual dosage is 10 to 20 mg q.i.d., 15 to 30 minutes a.c. and h.s.
- Other prokinetic drugs such as domperidone and cisapride do not cross the blood-brain barrier and have only the peripheral effects of metoclopramide. These drugs have excellent promotility qualities and have been used successfully in the treatment of Gastroesophageal reflux disease. However, cisapride due to its drug-drug interactions with those drugs that prolong the Q-T interval (on electrocardiogram) and the possibility of precipitating cardiac arrhythmias has been removed from the market in the United States by the manufacturer. Cisapride and domperidone are available in Canada and other countries.
- Drugs that enhance mucosal resistance. As the importance of mucosal resistance is appreciated, drugs that potentiate cytoprotection and mucosal resistance are being added to the medical armamentarium of acid-peptic disease.
- Sucralfate (Carafate), an aluminum sucrose polysulfate shown to be effective in healing duodenal ulcers due to its cytoprotective action, has not been shown to be highly effective in patients with esophagitis.
- Prostaglandin analogs (e.g., misoprostol) have also been shown to be cytoprotective and effective in the treatment of peptic ulcer disease, but has not been found highly effective in the treatment of Gastroesophageal reflux disease.
The results of maintenance therapy with H2-receptor antagonists are disappointing. Neither twice-daily nor single-dose-bedtime regimens of cimetidine or ranitidine are significantly more effective than placebo in preventing symptomatic or endoscopic evidence of relapse. However, maintenance therapy with 20 mg of omeprazole daily sustains endoscopic healing in most patients with severe, recalcitrant esophagitis. In some patients, the dosage needs to be increased to 40 mg.
Significant and persistent elevations in fasting serum gastrin concentrations may occur in a minority of patients. It is important to note that up to 90% of patients who healed with omeprazole treatment had recurrence of their esophagitis within 6 months of stopping treatment, indicating that some form of chronic treatment is needed. Similar excellent results have also been achieved with the other proton-pump inhibitors (lansoprazole, rabeprazole sodium, pantoprazole, and esomeprazole magnesium) at the same doses used to heal erosive esophagitis.