Gastric acid inhibition in the treatment of peptic ulcer hemorrhage

Abstract

Upper gastrointestinal bleeding from peptic ulcer disease is a common clinical event, resulting in considerable patient morbidity and significant health care costs. Inhibiting gastric acid secretion is a key component in improving clinical outcomes, including reducing rebleeding, transfusion requirements, and surgery. Raising intragastric pH promotes clot stability and reduces the influences of gastric acid and pepsin. Patients with high-risk stigmata for ulcer bleeding (arterial bleeding, nonbleeding visible vessels, and adherent clots) benefit significantly from and should receive high-dose intravenous proton pump inhibitors (PPIs) after successful endoscopic hemostasis. For patients with low-risk stigmata (flat spots or clean ulcer base), oral PPI therapy alone is sufficient. For oozing bleeding (an intermediate risk finding), successful endoscopic hemostasis and oral PPI are recommended. Using intravenous PPIs before endoscopy appears to reduce the frequency of finding high-risk stigmata on later endoscopy, but has not been shown to improve clinical outcomes. High-dose oral PPIs may be as effective as intravenous infusion in achieving positive clinical outcomes, but this has not been documented by randomized studies and its cost-effectiveness is unclear.

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

“…[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.…”

“…1 Although ASA is most commonly used for the secondary prevention of vascular events, most clinical trials have suggested the superiority of combined antiplatelet treatment over ASA alone in preventing thrombotic outcomes. 5 However, the risk of GI bleeding was shown to be increased due to the concomitant use of antiplatelet drugs with NSAIDs or low-dose ASA. [2][3][4] We previously confirmed that clopidogrel aggravated the severity of NSAID-generated antral ulcers in rats, converting nonhemorrhagic lesions into hemorrhagic ones.…”

“…These results confirmed the importance of luminal acid in the pathogenesis of ASA-induced gastric damage 21 and the increased risk of gastric bleeding due to the concomitant use of ASA and clopidogrel. 5 Three factors have been proposed to be essential for the generation of gastric lesions: (i) epithelial barrier disruption, (ii) luminal acid, and (iii) mucosal ischemia. 22 Many studies have demonstrated that ASA disrupts the gastric mucosal barrier and damages the stomach in the presence of acid.…”

“…22 Many studies have demonstrated that ASA disrupts the gastric mucosal barrier and damages the stomach in the presence of acid. 5,21,23 Gastric mucosal blood flow was shown to be increased in response to barrier disruption, mediated by endogenous prostaglandins (PGs) derived from cyclooxygenase (COX)-1, which prevents local acidosis due to acid back-diffusion. 24 However, ASA attenuates this hyperemic response by suppressing PG production through the nonselective inhibition of COX activity.…”

“…[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.…”