Controlling nocturnal GERD with rabeprazole
Proof that it decreases heartburn, regurgitation, and leads to better sleep
For millions of people the world over, the sensations are all too familiar: a vague burning feeling inside the chest, the uneasy regurgitation of sour material in the mouth, and the occasional salivary hypersecretion after meals. Still, gastroesophageal-reflux disease (GERD) represents a far more dangerous clinical spectrum than these chronic, disruptive symptoms. Untreated, the disorder may lead to reflux esophagitis (varying in severity from mild, invisible inflammatory changes, to friable mucOSAl LESions that bleed and cause fibrosis) and-in some cases-to Barrett's esophagus and subsequent esophageal adenocarcinoma.
In a symposium organized by HI-Eisai Pharmaceutical during the PhiliPPIne Society of Gastroenterology midyear convention in November, Dr. Jose Sollano, chief of the University of Santo Tomas Hospital (USTH) section of gastroenterology, and Dr. Jimmy Bautista, consultant at the USTH, discussed nighttime gastroesophageal reflux and breakthroughs in its treatment.
Acid reflux
GERD involves a pathophysiologic failure of the normal safeguards against reflux of the stomach's contents: the lower esophageal sphincter (LES), the diaphragmatic crura, and the anatomic location of the gastroesophageal junction--all maintaining the lower-esophageal pressure that prevents the backflow of gastric contents. Certain processes that disrupt any of these defenses--congenital incompetence of the diaphragmatic crural muscle, pregnancy, smooth-muscle relaxants that compromise the myogenic tone of the LES--result in GERD. Often, however, the decrease in LES pressure results from muscular weakness of no apparent cause.
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Reflux alone does not constitute the disease. "[The] reflux should achieve a certain degree of acidity or toxicity to cause both symptom and…esophagitis," stressed Sollano. The amount of acid secreted, however, is not as important as the milieu surrounding the esophageal mucOSA. "It is really acid in the wrong place in a mucOSA that is not customized to withstand acid."
Studies show that up to 15 percent of individuals experience GERD symptoms at least once a week, and nearly seven percent every day, affecting sleep and work productivity.
Obstructive sleep apnea (OSA), has also been associated with nighttime reflux. Both diseases have overlaPPIng risk factors, both present with daytime somnolence and inattentiveness due to the sleep disturbances, and both seem to aggravate the other.
Pump not the protons
Bautista and his colleagues (2003) postulated that antireflux treatment has a positive effect on sleep quality in patients with nocturnal GERD. In a randomized,placebo-controlled trial, patients who received a proton-pump inhibitor (PPI) experienced improvements: decrease in the number of daytime naps, in snoring, in the number of arousals, and in the frequency and severity of heartburn and regurgitation. They slept longer and better.
Among the latest generation of PPIs is sodium rabeprazole which, unlike other PPIs, achieves plasma concentrations on the first day, which are then maintained on subsequent days of daily dosing. Evidence on the clinical benefits of sodium rabeprazole has been steadily accumulating. Fitzgerald et al. (2001) and Robinson et al. (2002) showed that rabeprazole is effective in GERD patients resistant to prior treatments with omeprazole and lansoprazole. Holtmann (2002) demonstrated a faster reduction of severe heartburn with rabeprazole compared with omeprazole. A study by Ke Mei-Yun concluded that rabeprazole "showed high relief rate of reflux symptoms in the first week, and more significant relief two weeks later, with [a] high rate of healed reflux esophagitis."
In uncomplicated GERD that warrants the initiation of a PPI, studies recommend to start with a single dose of sodium rabeprazole just before breakfast. Explained Sollano: "It is during early morning when parietal cells are most active. Most PPIs act on parietal cells."
"At nighttime sodium rabeprazole gives you a little bit of [a] numerical advantage," he added, citing a study by Katz et al. (2002). Pehlivanov et al. (2003) showed that sodium rabeprazole 20 mg significantly reduced nocturnal gastroesophageal-reflux episodes.
Several researchers have sought to determine the best combinations for the reduction of nocturnal acid breakthroughs and nighttime GERD. Ours et al. (2003) reported a significantly higher percentage of patients without acid breakthroughs when treated with twice-daily PPI and an H2 receptor antagonist (H2RA). Katz et al. (2002) listed down various combinations--twice-daily PPI with H2RA at bedtime, twice-daily PPI, PPI in the morning and H2RA in the evening, PPI once daily, and a high dose H2RA--to have the highest antisecretory efficacies. Shimatani et al. (2004) showed rabeprazole 10 mg twice daily to be superior to 20 mg once daily rabeprazole in the suppression of nighttime gastric acid.
"The way to go, perhaps, is to give PPI on a BID dose or a PPI with an H2 blocker suppression," suggested Sollano.
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