Omeprazole: Long-Term Safety

Abstract

Based on the experience from more than 10,000 individuals omeprazole has been found to be safe and is well tolerated. Side effects are few and do not differ from those observed during H₂-blocker treatment. Effects on endocrine cells observed in animals during toxicological studies include increase of antral G cells, decrease of antral D cells and increase of fundic ECL cells. The increase of G cells and the decrease of D cells is the consequence of achlorhydria achieved by very high omeprazole dosages and results in hypergastrinaemia. Hypergastrinaemia is responsible for ECL cell hyperplasia. Lifelong hypergastrinaemia in rats has been found to induce carcinoid tumours. This gastrin-carcinoid sequence is unlikely to occur in man with an omeprazole dosage recommended for treatment of peptic diseases. Therapeutic doses in man do not produce complete achlorhydria. Therefore, serum gastrin levels increase in man during omeprazole treatment only moderately and are similar in magnitude as after selective proximal vagotomy. Available results on gastric endocrine cells in patients treated with omeprazole for up to 2 years could not demonstrate significant changes in G, D and ECL cell densities. It is concluded that omeprazole is, in man, as safe as H₂ blockers if administered in doses recommended for treatment of peptic diseases.

Chronic Use of Proton Pump Inhibitors and the Quantity of G, D, and Ecl Cells in the Stomach

“…However, changes in this magnitude have not been observed in humans 16 . As with our study, Arnold and Koop 2 did not find differences in G cell or D cell counts, nor in ECL cell density, in patients with severe reflux esophagitis treated with 40 mg/day of omeprazole for up to nine months; they did not indicate the HP infection status of their patients. Patients infected with strains of HP that express CagA, a cytotoxin encoded by the A gene that acts as a virulence factor strongly associated with severe gastritis have been found to have a reduced D-cell density in the antrum with no changes in the number of G cells 15 .…”

“…PPI therapy can lead to an increase in serum levels of gastrin 2,7,16 . Hypergastrinemia occurs through a negative feedback mechanism between the intragastric pH and antral G cell activity 16 .…”

“…According to Arnold and Koop 2 , although serum gastrin increases over the short- and long-term with PPI treatment, it is rare that gastrin levels exceed those observed after a proximal selective vagotomy and occurs when the inhibition of the stimulus to acid secretion exceeds 80%. These authors point out that in studies of patients receiving omeprazole at doses of 40-60 mg/day for a period of 1-2 years, moderate gastrin increases are observed with inter-individual variation.…”

“…Using antibodies for gastrin, somatostatin, and chromogranin, they found higher proportions of ECL cells in the gastric body than elsewhere in the stomach. Arnold and Koop 2 noted that ECL cells are almost exclusively restricted to the fundic mucosa and account for 40-60% of the endocrine cells in this part of the stomach. The number of ECL cells found in the gastric body in our study using anti-HDC IHC was lower than the numbers of D cells found in the control group and in the PPI group, with or without HP infection.…”

<i>Saitohin</i> and <i>APOE</i> Polymorphisms Influence Cognition and Function in Persons with Advanced Alzheimer Disease

“…The Cohen-Mansfield Agitation Inventory (CMAI)-Long Version provided a detailed assessment of agitated behavior [25]. The CMAI-Long Version uses 29 items to measure 3 types of behaviors: verbal agitation, physical agitation and physical aggression.…”