Balancing the Risks and Benefits of Proton Pump Inhibitors

Gill, James M.; Player, Marty S.; Metz, David C.

doi:10.1370/afm.1269

Cited by 12 publications

(12 citation statements)

References 18 publications

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“…[2][3][4] We also confirmed that the increase in gastric bleeding was significantly prevented by antisecretory drugs such as omeprazole or famotidine, which supports clinical findings that inhibiting gastric acid secretion is effective in the treatment of gastric bleeding. [5][6][7][8] Furthermore, the present study showed that the bleeding and hemorrhagic lesions caused by the luminal perfusion with ASA plus clopidogrel pretreatment under acid stimulation were also dosedependently and significantly mitigated by mucosal protective drugs such rebamipide, irsogladine, or teprenone.…”

Section: Discussionsupporting

confidence: 54%

“…[2][3][4] Antisecretory drugs such as proton pump inhibitors (PPIs) or histamine H2 receptor antagonists are effective in preventing the upper GI bleeding induced by the concomitant use of antiplatelet drugs with NSAIDs and low-dose ASA. [5][6][7][8] The antiplatelet drug clopidogrel is a prodrug, the actions of which may be related to adenosine diphosphate (ADP) receptors on platelet cell membranes. 9 This drug specifically and irreversibly inhibits the P2Y12 subtype of the ADP receptor, which is important for the aggregation of platelets and cross-linking by the protein fibrin.…”

Section: Introductionmentioning

confidence: 99%

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Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats

Takeuchi

Takayama

Hashimoto

et al. 2014

J of Gastro and Hepatol

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Background and Aim: We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats. Methods: Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3-30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion. Results: Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose-dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs. Conclusions: These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs.

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Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats

Takeuchi

Takayama

Hashimoto

et al. 2014

J of Gastro and Hepatol

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“…Erythropoiesis influencing substances were associated with HTS formation and comprised proton pump inhibitors, folic acid antagonists, erythropoietin and micronutrients involved in erythropoiesis. Proton pump inhibitors were included, because they can interfere with erythropoiesis by causing vitamin B12 and ferritin deficiencies …”

Section: Discussionmentioning

confidence: 99%

Going into surgery: Risk factors for hypertrophic scarring

Butzelaar

Soykan

Garre³

et al. 2015

Wound Repair Regeneration

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The aim of this study was to examine the association between possible risk factors for excessive scarring and the formation of hypertrophic scars (HTS). Hypertrophic skin scarring remains a difficult problem in medicine and can cause considerable morbidity. Nevertheless, few extensive prospective studies have been conducted which assess risk factors in relation to HTS formation. Therefore, a prospective observational study was performed. Patients who had elective cardiothoracic surgery were followed for the duration of 1 year and information was collected about a variety of possible risk factors in these patients. The associations between the risk factors and the development of HTSs were investigated. Body mass index, ethnic background, and scar related factors are positively associated with HTS formation. Antihypertensive therapeutics and factors influencing erythropoiesis are negatively associated with HTS formation.

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“…1 PPIs exhibit a well-established safety profile and reduce gastric acid more effectively than histamine-2 receptor antagonists or antacids. 2 As a result, several PPIs are available over the counter. However, observational studies suggest that longterm PPI therapy is associated with osteoporotic fractures, hypomagnesemia, and vitamin B 12 deficiency.…”

mentioning

confidence: 99%

“…However, observational studies suggest that longterm PPI therapy is associated with osteoporotic fractures, hypomagnesemia, and vitamin B 12 deficiency. 2,3 A large body of epidemiological data has detected an association between PPI use and fracture risk. 4,5 The clinical importance of this association is unclear because odds ratios are low, there is no consistent dose-response relationship, and confounding factors exist in many studies.…”

mentioning

confidence: 99%

Dexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women

et al. 2019

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BACKGROUND & AIMS: Epidemiological studies have associated proton pump inhibitor (PPI) therapy with osteoporotic fractures, but it is not clear if PPIs directly cause osteoporosis. We evaluated the effect of dexlansoprazole and esomeprazole on bone turnover, bone mineral density (BMD), true fractional calcium absorption (TFCA), serum and urine levels of minerals, and levels of parathyroid hormone (PTH) in healthy postmenopausal women. METHODS: We performed a prospective, multicenter, double-blind study of 115 healthy, postmenopausal women (45 to 75 years of age) from November 4, 2010, through August 7, 2014. Women were randomly assigned to groups given dexlansoprazole (60 mg), esomeprazole (40 mg), or placebo daily for 26 weeks. We measured plasma levels of procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX) at 0 (baseline), 13, and 26 weeks. Primary outcomes were percent change in P1NP and CTX between weeks 0 and 26. We also measured changes in serum and urine levels of mineral, BMD, PTH (all subjects), and TFCA (n ¼ 30). RESULTS: Between baseline and week 26, there were no significant within-group differences in markers of bone turnover; there was a nonsignificant increase in CTX levels in the dexlansoprazole group (0.12 ng/mL). The esomeprazole and dexlansoprazole groups had significantly increased levels of P1NP (18.2% and 19.2%, respectively) and CTX (22.0% and 27.4%, respectively) at week 26 compared with the placebo group, although these values remained within normal ranges. There were no statistically significant differences between groups in serum or urine levels of minerals, BMD, or PTH at week 26. PPI therapy did not reduce TFCA. CONCLUSIONS: In a prospective study of postmenopausal women, we found significant increases in markers of bone turnover in women given PPI therapy compared with women given placebo, but levels remained within the normal reference range. We found no significant differences among groups in changes in BMD, PTH, serum or urine levels of minerals, or TFCA. Our findings indicate that 26 weeks of treatment with a PPI has no clinically meaningful effects on bone homeostasis. Clinicaltrials.gov no: NCT01216293

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Balancing the Risks and Benefits of Proton Pump Inhibitors

Cited by 12 publications

References 18 publications

Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats

Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats

Going into surgery: Risk factors for hypertrophic scarring

Dexlansoprazole and Esomeprazole Do Not Affect Bone Homeostasis in Healthy Postmenopausal Women

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