Pharmacological Approach to Gastric Acid Suppression: Past, Present, and Future.

Less than 2 centuries have elapsed since the identification of hydrochloric acid in the stomach. The clarification of the molecular mechanisms allowed the effective therapeutic suppression of gastric acid secretion. The spectacular advances in the treatment of acid-related disorders represent a synthesis of the contributions of several brilliant pharmacologists, basic scientists, and clinical physicians. Effective gastric acid suppressive therapy has dramatically improved the therapy and outcome of acid-related disorders. The introduction of proton pump inhibitors (PPIs) in clinical practice has significantly changed the medical management of upper gastrointestinal disorders. PPIs represent the "gold-standard" therapy in acid-related disorders. However, some challenges persist in the therapy of acid related diseases, including management of patients who respond inadequately to PPI therapy, more effective gastroprotection, or more powerful antisecretory treatment for the eradication of Helicobacter pylori infection. New antisecretory drugs are currently being developed and investigated to further provide a more effective and profound gastric acid secretion inhibition. The major advance has been the development of acid pump -antagonists, the potassium channel acid blocking drugs (-P-CABs). Long-term studies comparing P-CABs with PPIs will help to define the exact place and safety profile of this class of drug in the management of acid-related disorders.

Association of Incidence of Acid-related Upper Gastrointestinal Disorders With Glycated Hemoglobin Level.

CONTEXT: Previous cross-sectional studies show diabetes and higher levels of plasma hemoglobin A1c (HbA1c) are associated with a higher prevalence of gastrointestinal (GI) complications. However, whether the glycemic status is associated with incident acid-related upper GI disorders remains unclear. OBJECTIVE: We aimed to determine the effect of hyperglycemia per se, in terms of HbA1c, on the incidence of acid-related disorders. METHODS: We analyzed consecutive subjects who had undergone repeated upper endoscopies as part of the health examinations at the National Taiwan University Hospital from 2005 to 2011. Acid-related endoscopic abnormalities were defined as erosive esophagitis (EE), Barrett's esophagus (BE), and peptic ulcer disease (PUD), which included gastric ulcers (GUs) and duodenal ulcers (DUs). All subjects were categorized by 3 tertiles of HbA1c levels. We analyzed the occurrence of respective acid-related disorders during the follow-up period. RESULTS: A total of 11 391 participants (mean HbA1c level 5.6 ±â€…0.7%) were enrolled in this longitudinal study. During the 38 426.3 person-years of follow-up (mean duration 3.37 ±â€…1.59 years), the incidence of EE, BE, GU, DU, PUD, and any acid-related disorders were 22.1%, 0.5%, 4.5%, 8.6%, 12.3%, and 30.3%, respectively. The higher HbA1c level was associated with higher risk of disease incidents, except BE, during the follow-up (all log-rank P < .001). In the Cox regression analyses with confounding factors fully adjusted, the hazard ratios for EE, GU, DU, PUD, and acid-related disorders were 1.174, 1.339, 1.24, 1.24, and 1.186, respectively, for the third tertile of HbA1c (all P < .05). CONCLUSION: Higher HbA1c level was associated with a higher risk of acid-related upper GI endoscopic abnormalities. Efforts toward better glycemic control may help to prevent the development of late GI complications.

Gastro-esophageal reflux and antisecretory drugs use among patients with chronic autoimmune atrophic gastritis: a study with pH-impedance monitoring.

BACKGROUND: Patients with chronic autoimmune atrophic gastritis (CAAG) often refer digestive symptoms and are prescribed antisecretory medications. Aims were to investigate: (i) gastro-esophageal reflux (GER), (ii) psychopathological profile, (iii) frequency of use and clinical benefit of antisecretory drugs. METHODS: Prospective observational study on 41 CAAG patients who underwent: 24 h multichannel intra-luminal impedance-pH (MII-pH) monitoring off-therapy, standardized medical interview and psychological questionnaire (i.e., SCL-90R). The medical interview was repeated at least 1 month after MII-pH in patients who were using antisecretory drugs. Statistical analysis was performed calculating median (10th-90th percentiles) and risk ratios (RR) with 95% confidence interval. KEY RESULTS: Median intra-gastric pH was 6.2 (4.6-7.0). One patient had acid reflux (AC) associated with symptoms, five had increased total reflux number and four had symptoms associated to non-acid reflux (NA) (patients referred as 'GER positive'). Using patients 'GER negative' with normal SCL-90R as reference, the RR of being symptomatic in patients GER positive was 2.1 (1.1-4.1) if SCL-90R was normal and 0.9 (0.5-1.7) if it was altered (difference in RR significant being p = 0.04). Seventeen/28 (61%) symptomatic patients were on antisecretory drugs, which were stopped in 16 of them according to results of MII-pH and clinical evaluation after 574 days (48-796) showed that symptoms were unchanged. CONCLUSIONS & INFERENCES: In patients with CAAG (i) AC reflux rarely occurred whereas increased NA reflux was not infrequent both being related to symptoms in some patients, (ii) psychopathological profile has a role in symptoms' occurrence, (iii) antisecretory drugs were generally inappropriately used and clinically ineffective.