Long-term Administration Of Proton Pump Inhibitors Research Articles

Effects of the Long-term Treatment of Proton Pump Inhibitors on the Function of Kidney and Liver in Laboratory Female Rats.

Proton pump inhibitors (PPIs) are a group of medications effectively used to inhibit gastric acid secretion and to treat many acid-related disorders, including gastroesophageal reflux disease and other gastric disorders. Recent studies recommended that they may be associated with the risk ofchronic kidney diseaseand liver disease. Therefore, the current study aimed to investigate the effect of long-term treatment with PPIs on kidney and liver function in laboratory rats. Fifteen female albino white rats (Rattusnorvigicus) were randomly assigned to three groups of five animals. The control group was fed regular pellet, group PPI-2 received standard pellet diet and was given esomeprazole (10 mg/kg b.w.) via daily oral gavage in mornings for two weeks, and group PPI-3 was fed standard pellet diet and was given esomeprazole (10 mg/kg b.w.) via daily oral gavage in mornings for three months. Blood samples were taken after 2 weeks and 3 months by cardiac puncture for measuring serum creatinine, urea, total bilirubin, alanine aminotransferase(ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). In addition, kidney and liver tissues were histopathologically evaluated. Serum creatinine, urea, ALT, total bilirubin, and ALP significantly increased in group PPI-3, compared to other groups. Histopathological study of the kidneys and liver revealed normal histology structure in the control group and the rats of the PPI-2 group, while some histological changes were observed in the liver and kidney of the animals in the PPI-3 group. The histological changes included the widening of Bowman's space and shrunken glomeruli, whereas the renal tubules had congested tubular cells. Furthermore, congestion in the blood vessels and hepatic cells degradation were observed in the liver. These data indicate that the long-term administration of PPIs has adverse effects on the structure and function of the kidney and liver.

Long-term use of proton pump inhibitors does not affect ectopic and metachronous recurrence of gastric cancer after endoscopic treatment

Objective: Long-term administration of proton pump inhibitors (PPIs) after eradication of Helicobacter pylori infection has been reported to increase the risk for development of gastric cancer (GC). We investigated whether long-term administration of PPI affects ectopic and metachronous recurrence of GC after endoscopic treatment.Methods: Participants were 687 patients who underwent endoscopic treatment for GC from January 2005 to March 2018. Questionnaire surveys and medical record reviews of medications, including PPIs, H2 receptor antagonists and low-dose aspirin (LDA) were conducted for all patients. The influence of PPI in ectopic and metachronous recurrence of GC was evaluated with Cox’s proportional hazard analysis.Results: Patients who did not respond to the questionnaire and those who underwent additional treatment after endoscopic treatment were excluded from analyses; 418 patients were included. During an average observation period of 1608 days (range, 375–4993 days), 136 patients (32.5%) took PPIs for more than 1 year and 94 took PPIs for more than 3 years; of those, 40 had ectopic and metachronous recurrences. Cox’s proportional hazards analysis revealed that long-term use of PPIs (for both 1 year and 3 years) was not a risk factor for recurrence. In addition, age, severity of gastric atrophy, long-term use of LDA, current infection with H. pylori, and cure achieved with the first endoscopic treatment were also not risk factors for recurrence.Conclusions: Long-term use of PPIs does not affect ectopic and metachronous recurrence of GC after endoscopic treatment.

Effect of proton pump inhibitors on sympathetic hyperinnervation in infarcted rats: Role of magnesium.

The long-term use of proton pump inhibitors (PPIs) has been shown to increase the risk of cardiovascular mortality, however the molecular mechanisms are unknown. Superoxide has been implicated in the regulation of nerve growth factor (NGF), a mediator of sympathetic innervation. The purpose of this study was to determine whether PPIs increase ventricular arrhythmias through magnesium-mediated superoxide production in infarcted rats. Male Wistar rats were randomly assigned to receive vehicle, omeprazole, omeprazole + magnesium sulfate, or famotidine treatment for 4 weeks starting 24 hours after the induction of myocardial infarction by ligating the coronary artery. Increased myocardial superoxide and nitrotyrosine levels were noted post-infarction, in addition to a significant upregulation of NGF expression on mRNA and protein levels. Sympathetic hyperinnervation after infarction was confirmed by measuring myocardial norepinephrine and immunofluorescent analysis. Compared with the vehicle, omeprazole-treated infarcted rats had significantly reduced myocardial magnesium content, increased oxidant production, and increased sympathetic innervation, which in turn increased ventricular arrhythmias. These effects were prevented by the coadministration of magnesium sulfate. In an in vivo study, an omeprazole-induced increase in NGF was associated with a superoxide pathway, which was further confirmed by an ex vivo study showing the attenuation of NGF levels after coadministration of the superoxide scavenger Tiron. Magnesium sulfate did not further attenuate NGF levels compared with omeprazole + Tiron. Our results indicate that the long-term administration of PPIs was associated with reduced tissue magnesium content and increased myocardial superoxide production, which exacerbated ventricular arrhythmias after infarction. Magnesium may be a potential target for PPI-related arrhythmias after infarction.

Hemorrhagic polyps formed like fundic gland polyps during long-term proton pump inhibitor administration

We report a rare case of hemorrhagic gastric polyps resulting in anemia during long-term proton pump inhibitor (PPI) administration that endoscopically looked like a fundic gland polyp (FGP). A 44-year-old man presented complaining of anemia and tarry stools. Esophagogastroduodenoscopy (EGD) demonstrated multiple white edematous polyps in the corpus and antrum, which were considered to be FGPs. We attempted endoscopic hemostasis but hemorrhaging increased because of hemorrhagic polyps and vulnerable gastric mucosa. Re-bleeding occurred several times. Polyp resection was performed at 24 polyp sites. We also ceased the administration of PPI. Microscopically, polyps showed characteristics of hyperplasia in the foveolar epithelium, extensions of fundic glands, and edema of the stroma. The proliferation of parietal and chief cells was also observed. Immunohistochemically, aquaporin-4 (AQP4) and KCNQ1-positive parietal cells and dilated mucous glands were found from the basal side to the apical side of the mucosa. These findings were compatible with the development of lesions associated with the long-term administration of PPI. EGD revealed an improvement in the vulnerability of gastric mucosa and the development of polyps, with no further gastric polyps observed 1 year after discharge. Bleeding from polyps resembling FGPs is generally rare, with indications that long-term PPI administration may induce such bleeding.

Sa1624 Effect of Long-Term PPI Administration on NSAID-Induced Small Intestinal Lesions and Therapeutic Effect of Irsogladine, a Gastroprotective Drug, for Such Lesions in Healthy Volunteers

Proton-pump inhibitors (PPIs) such as omeprazole are a standard treatment to prevent non-steroidal anti-inflammatory drugs (NSAIDs)-induced upper gastrointestinal mucosal injuries. However, it is unclear how small intestinal injuries are affected by long-term administration of PPIs and NSAIDs. Therefore, we investigated small intestinal lesions induced by 10 weeks' concomitant use of PPIs and NSAIDs in healthy volunteers. Moreover, we also examined the therapeutic efficacy of irsogladine for such lesions.

Long-term administration of PPI reduces treatment failures after esophageal variceal band ligation: a randomized, controlled trial

Elective esophageal variceal ligation (EVL) is performed to decrease the risk of variceal hemorrhage. EVL is associated with adverse effects, including post-ligated bleeding, chest pain, and dysphagia. Proton pump inhibitors (PPIs) are the most potent pharmacological agents for inhibition of gastric acid secretion. However, the long-term effect of PPIs after EVL remains unclear. The aim of this study was to assess the efficacy of rabeprazole, a PPI, after variceal eradication by EVL. We performed a randomized, controlled trial in Kitasato University East Hospital. The primary endpoint was treatment failure, defined as variceal hemorrhage or severe medical complications. Between July 2007 and September 2010, 43 patients were randomized into this study and followed up until September 2010. Twenty-one patients in the rabeprazole arm received 10 mg rabeprazole daily after EVL, and 22 patients in the control received no antisecretory treatment from the same stage. Baseline characteristics did not differ between the groups (median Child-Pugh score, 6; median age, 62 years; median follow-up, 18.7 months). The trial was stopped early after an interim analysis showed that the risk of bleeding and failure of rabeprazole treatment was lower than that of no antisecretory treatment with the log-rank test showing a significant difference between the groups (P = 0.007) and a hazard ratio of 0.098 [95% confidence interval, 0.012-0.79 (P = 0.029)]. Long-term administration of PPIs reduced the risk of treatment failure after EVL. Acid suppression therapy should also be considered as a treatment option after EVL.

Long-term proton pump inhibitor administration worsens atrophic corpus gastritis and promotes adenocarcinoma development in Mongolian gerbils infected with Helicobacter pylori

BackgroundWe investigated whether corpus atrophic gastritis worsens in Mongolian gerbils (MGs) after long-term administration of proton pump inhibitor (PPI). MGs are an excellent model for studying Helicobacter pylori-related gastritis and...

Two Cases of Refractory Post-Bulbar Duodenal Ulcer

Two young man patients with refractory post-bulbar duodenal ulcer (post-bulbar ulcer) were encountered. They had a single punched-out ulcer in the absence of an underlying disease. Patient 1 was Helicobacter pylori (Hp)-positive, and did not respond to Hp eradication therapy. The ulcer scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after a reduction in the dose. Patient 2 was Hp-negative. His ulcer did not scar even after long-term PPI administration, but it formed a fistula into the gallbladder, and the fistula was surgically closed. In both patients, laboratory and imaging studies excluded Zollinger-Ellison syndrome, but suggested a hyperacidic tendency. Unlike duodenal bulb ulcer (bulbar ulcer), the post-bulbar ulcer in Patient 1 did not heal with Hp eradication therapy, suggesting that post-bulbar ulcer differs etiologically from bulbar ulcer. We speculate that the possible causes of the refractoriness to treatment in both patients were ulcer penetration, callosity formation, and insufficient inhibition of gastric acid secretion due to the impaired passage of PPI into the deep portion of the duodenum as a result of luminal narrowing.

Role of Anti-Parietal Cell Antibody in Helicobacter pylori -associated Atrophic Gastritis: Evaluation in a Country of High Prevalence of Atrophic Gastritis

Background: Helicobacter pylori plays an important part in the progression of atrophic gastritis; however, markers for predicting the progression of atrophic gastritis remain unidentified. We investigated the relation between the degree of atrophic gastritis and the amount of anti-parietal cell antibodies (APCAs) present. Methods: In 219 Japanese patients, APCA was investigated by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. The grade of corpus atrophy was estimated by histology and serum pepsinogen levels. Serum levels of pepsinogen were evaluated by radio-immunoassay. Results: Helicobacter pylori infection did not affect the APCA levels determined by ELISA. Long-term administration of proton-pump inhibitors and H. pylori eradication did not influence the levels of APCAs. However, in H. pylori -positive patients, the levels of APCA determined by ELISA were statistically higher in patients with severe atrophy than in those with mild atrophy as determined histologically (0.67 ± 0.48 versus 0.45 ± 0.40; A492, mean ± s , P = 0.01) and serologically by pepsinogen levels (0.66 ± 0.51 versus 0.44 ± 0.40, P = 0.002). The levels of pepsinogen I/II ratio were correlated with APCA levels only in the H. pylori -positive group. Western blotting showed that major antigen was identical with the β -subunit of H + ,K + -ATPase. Conclusion: APCA plays an important part in the progression of corpus atrophy after H. pylori infection.