Don’t Ask, Don’t Tell with Helicobacter pylori
February 15, 2001 3 minutes read
Don’t Ask, Don’t Tell with Helicobacter pylori
Abstract & commentary
Synopsis: H. pylori has a number of special properties that allow it to survive in the hostile gastric environment; "don’t ask, don’t tell" may be appropriate for patients with heartburn as a presenting symptom (i.e., discovery of H. pylori and its eradication may worsen GERD); PPIs do not completely eliminate acid and their pharmacology makes achievement of achlorhydria impossible.
Source: Sachs G, et al. Aliment Pharmacol Ther 2000;14:1383-1401.
This review comprehensively addresses many issues in the molecular physiology of gastric secretion, presents an overview of acid-peptic disease, and tries to provide some insight into the biology of Helicobacter pylori. For example, it is pointed out that proton pump inhibitors (PPIs) accumulate in the acid space (pH < 4) of parietal cells: 1000-fold for omeprazole, lansoprazole, and pantoprazole, and 10,000-fold for rabeprazole. Once PPIs are converted to sulphenamides, they become permanent cations that no longer can easily traverse cannalicular membranes (thus trapping them where formed). PPIs must be administered with food so as to assure active proton pumps are inhibited. All PPI formulations must protect the acid-labile prodrugs with some sort of enteric coating. The morning meal appears to activate 75% of proton pumps, and this accounts for the recommended administration of PPIs with breakfast. Twenty-five percent of proton pumps are replaced daily (half-life of pumps about 50 hours) and maximal PPI effects thus do not occur until the third day of PPI dosing. Due to new pump synthesis, maximum acid inhibition by a daily PPI dose is about 66%, and even bid dosing only can maximally inhibit 80% of acid production.
PPIs are less effective in inhibiting acid after H. pylori eradication. Reflux symptoms and complication may worsen after H. pylori is eradicated due to loss of the "antacid" ammonia that is produced by H. pylori for its own protection against otherwise "fatal" gastric acidity. This ammonia production may be particularly significant as a source of acid neutralization at times of relatively low acid secretion without meal-related buffering (e.g., at night).
Although H. pylori is associated with gastric and duodenal ulcer and a four-fold increase in the risk of adenocarcinoma, more than 80% of H. pylori-infected individuals never have the slightest symptomatology or damage. Furthermore, both ulcers due to H. pylori and cancer of the stomach appear to be vanishing in this country. At least in the United States, treatment of H. pylori provides no benefit vs. placebo for dyspepsia.
COMMENT BY MALCOLM ROBINSON, MD, FACP, FACG
Many gastroenterologists are abandoning the "test and treat" strategy for patients with dyspepsia. A growing body of evidence exists to support the notion that H. pylori is mostly a harmless commensal or even may be protective against such "epidemic" maladies as GERD, Barrett’s esophagus, and adenocarcinoma of the esophagus. There is no benefit to finding or eradicating H. pylori in patients with heartburn as their presenting symptom, and the elimination of such infection may worsen symptoms in such patients and could lead to increased PPI resistance.
"Don’t ask, don’t tell" should probably be the watchword for H. pylori except in definite ulcer disease, mucosa-associated lymphoid tissue lymphoma, and perhaps in individuals with ethnic predilection or strong family history of gastric adenocarcinoma. Understanding PPI pharmacology should lead to more appropriate use of these valuable therapeutic agents.
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