The Effect of H₂Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy

Abstract

The first histamine H2 receptor antagonists (H2RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H2RAs block the production of acid by H + , K + -ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H2RAs are highly selective, and they do not affect H1 receptors. Moreover, they are not anticholinergic agents. Sequential development of H2RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H2RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H2RAs at night. The effectiveness of nighttime dose of H2RA suggests a major role of histamine in nocturnal acid secretion. H2RAs reduce secretion of gastric acid, and each H2RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H2RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders. (Korean J Gastroenterol 2017;70:4-12)

The Role of Histamine and Histamine Receptors in Mast Cell-Mediated Allergy and Inflammation: The Hunt for New Therapeutic Targets

“…H 1 -antihistamines, such as azatadine, cetirizine, and mizolastine are used for the treatment mast cell activated diseases ( 106 ). Cimetidine, ranitidine, famotidine, and nizatidine are H2R selective antihistamines that reduce gastric acid secretion ( 107 ). H3R antihistamines include thioperamide, clobenpropit, BF2.…”

Enigmatic Histamine Receptor H4 for Potential Treatment of Multiple Inflammatory, Autoimmune, and Related Diseases

“…A plethora of studies have related the heterogenic and complex pharmacology of histamine receptors to various diseases: H 1 R to the allergic inflammation, anaphylaxis, and motion sickness [28,29], H 2 R to the stimulation of gastric acid secretion leading to peptic ulcer, GERD and aspiration pneumonitis [30,31], H 3 R to the neurotransmission controlling sleep, cognitive processes, schizophrenia, epilepsy, and pain [32][33][34][35][36][37], and H 4 R to the immune responses (cancers, myocarditis) and inflammation [38][39][40][41][42] (Figure 2). The H 3 and H 4 receptors have relatively high affinity for histamine (5-10 nM) compared to the low affinity of H 1 R and H 2 R which is in the µM range [6,43].…”

Gastroprotective Effects of Paeonia Extract Mixture HT074 against Experimental Gastric Ulcers in Rats

“…However, because gastric acid is only one of the many ulcerogenic factors, new treatments need to also focus on other protective factors [10]. For this reason, mucosal protective agents with relatively low side effect can be a good alternative [11]. Medicinal herbs have been used as an alternative therapeutic source for the treatment of gastric ulcers [12].…”