Genomes and Genes
histamine h2 antagonists
Summary: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.
- Taha A, McCloskey C, Prasad R, Bezlyak V. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial. Lancet. 2009;374:119-25 pubmed publisher..These findings widen the therapeutic options for the prevention of gastrointestinal damage in patients needing vascular protection. Merck Laboratories and Astellas Pharma. ..
- Goel S, Bommireddipalli S, Depuey E. Effect of proton pump inhibitors and H2 antagonists on the stomach wall in 99mTc-sestamibi cardiac imaging. J Nucl Med Technol. 2009;37:240-3 pubmed publisher..Therefore, it is important to elicit a history of prolonged PPI use to better anticipate the possibility of increased stomach wall activity, which can confound the image quality and interpretation. ..
- Lin P, Chang C, Hsu P, Tseng P, Huang Y. The efficacy and safety of proton pump inhibitors vs histamine-2 receptor antagonists for stress ulcer bleeding prophylaxis among critical care patients: a meta-analysis. Crit Care Med. 2010;38:1197-205 pubmed publisher..Because of limited trial data, future well-designed and powerful randomized, clinical trials are warranted. ..
- Howell M, Novack V, Grgurich P, Soulliard D, Novack L, Pencina M, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170:784-90 pubmed publisher..This evidence of a dose-response effect provides further support for the potentially causal nature of iatrogenic acid suppression in the development of nosocomial C difficile infection. ..
- Dublin S, Walker R, Jackson M, Nelson J, Weiss N, Jackson L. Use of proton pump inhibitors and H2 blockers and risk of pneumonia in older adults: a population-based case-control study. Pharmacoepidemiol Drug Saf. 2010;19:792-802 pubmed publisher..32, 95% CI 1.17-1.49, for current PPI use versus nonuse). Use of PPIs and H2 blockers is not associated with increased pneumonia risk in older adults. The increased risk observed in some prior studies may reflect confounding. ..
- Pasina L, Nobili A, Tettamanti M, Riva E, Lucca U, Piccinelli R, et al. Co-prescription of gastroprotective agents in patients taking non-selective NSAIDs or COX-2 selective inhibitors: analysis of prescriptions. Int J Clin Pharmacol Ther. 2010;48:735-43 pubmed..COXIBs seem to be used in patients at high risk of GI toxicity. However, the fear of GI adverse reactions and the uncertain safety profile of COXIBs leads many physicians to boost the gastroprotection by prescribing a PPI. ..
- Eom C, Jeon C, Lim J, Cho E, Park S, Lee K. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310-9 pubmed publisher..Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk. ..
- McCoole M, Baer K, Christie A. Histaminergic signaling in the central nervous system of Daphnia and a role for it in the control of phototactic behavior. J Exp Biol. 2011;214:1773-82 pubmed publisher..Taken collectively, our results show that an extensive histaminergic system is present in Daphnia species, including the visual system, and that this amine is involved in the control of phototaxis in these animals. ..
- Barkun A, Bardou M, Pham C, Martel M. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol. 2012;107:507-20; quiz 521 pubmed publisher..The objective of this study was to evaluate the efficacy of PPIs vs. H2RAs in the prophylaxis of SRMB in critically ill adults with risk factors for bleeding...
- Kwok C, Arthur A, Anibueze C, Singh S, Cavallazzi R, Loke Y. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107:1011-9 pubmed publisher..This risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful. ..
- Beltrame F, Yamauti C, Caneguim B, Cerri P, Miraglia S, Sasso Cerri E. Cimetidine-induced vascular cell apoptosis impairs testicular microvasculature in adult rats. Histol Histopathol. 2012;27:1343-51 pubmed publisher..A possible antagonist effect of cimetidine on the H? receptors and/or androgen receptors in the vascular cells may be responsible for the impairment of the testicular microvasculature. ..
- Herzig S, Howell M, Ngo L, Marcantonio E. Acid-suppressive medication use and the risk for hospital-acquired pneumonia. JAMA. 2009;301:2120-8 pubmed publisher..In subset analyses, statistically significant risk was demonstrated only for proton-pump inhibitor use. ..
- Van Marrewijk C, Mujakovic S, Fransen G, Numans M, de Wit N, Muris J, et al. Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial. Lancet. 2009;373:215-25 pubmed publisher..Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care. ..
- Zarrindast M, Moghadam A, Rostami P, Roohbakhsh A. The effects of histaminergic agents in the central amygdala of rats in the elevated plus-maze test of anxiety. Behav Pharmacol. 2005;16:643-9 pubmed..5 microl bilateral. The results suggest that histamine may modulate anxiety via H1 but not H2 receptors in the rat central amygdala. ..
- Okayama M, Tsubouchi R, Kato S, Takeuchi K. Protective effect of lafutidine, a novel histamine H2-receptor antagonist, on dextran sulfate sodium-induced colonic inflammation through capsaicin-sensitive afferent neurons in rats. Dig Dis Sci. 2004;49:1696-704 pubmed..This action might be attributable at least partly to the enhancement of colonic mucus secretion. ..
- Wang J, Su B, Ding Z, Du X, Wang B. Cimetidine enhances immune response of HBV DNA vaccination via impairment of the regulatory function of regulatory T cells. Biochem Biophys Res Commun. 2008;372:491-6 pubmed publisher..Collectively these findings suggest that CIM enhances the immune responses of HBV DNA vaccine through the stimulation of pro-inflammatory and inhibition of anti-inflammatory cytokine expression patterns. ..
- Yu E, Blackwell T, Ensrud K, Hillier T, Lane N, Orwoll E, et al. Acid-suppressive medications and risk of bone loss and fracture in older adults. Calcif Tissue Int. 2008;83:251-9 pubmed publisher..The use of PPIs in older women, and perhaps older men with low calcium intake, may be associated with a modestly increased risk of nonspine fracture. ..
- Kantorova I, Svoboda P, Scheer P, Doubek J, Rehorkova D, Bosakova H, et al. Stress ulcer prophylaxis in critically ill patients: a randomized controlled trial. Hepatogastroenterology. 2004;51:757-61 pubmed..Furthermore, our data suggested that especially gastric pH increasing medication could increase the risk for nosocomial pneumonia. Routine prophylaxis for stress-related bleeding even in high-risk patients seems not to be justified. ..
- Fukuda M, Kusama K, Sakashita H. Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression. BMC Cancer. 2008;8:376 pubmed publisher..These findings suggest that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine via induction of apoptosis and in which NCAM plays a role. ..
- Yang Y, Lewis J, Epstein S, Metz D. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-53 pubmed..41 [95% CI, 1.28-1.56]; 3 years, 1.54 [95% CI, 1.37-1.73]; and 4 years, 1.59 [95% CI, 1.39-1.80]; P<.001 for all comparisons). Long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture. ..
- Garcia Rodriguez L, Lagergren J, Lindblad M. Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK. Gut. 2006;55:1538-44 pubmed..However, these associations are most likely explained by the underlying treatment indication being a risk factor for the cancer rather than an independent harmful effect of these agents per se. ..
- Shimatani T, Inoue M, Kuroiwa T, Xu J, Nakamura M, Tazuma S, et al. Lafutidine, a newly developed antiulcer drug, elevates postprandial intragastric pH and increases plasma calcitonin gene-related peptide and somatostatin concentrations in humans: comparisons with famotidine. Dig Dis Sci. 2006;51:114-20 pubmed..We concluded that lafutidine increases plasma concentrations of CGRP and somatostatin in humans, which may result in inhibition of postprandial acid secretion and gastroprotective activity. ..
- Rascon Aguilar I, Pamer M, Wludyka P, Cury J, Coultas D, Lambiase L, et al. Role of gastroesophageal reflux symptoms in exacerbations of COPD. Chest. 2006;130:1096-101 pubmed..2/yr vs 1.6/yr, p = 0.02). The presence of GER symptoms appears to be associated with increased exacerbations of COPD. ..
- Untersmayr E, Bakos N, Schöll I, Kundi M, Roth Walter F, Szalai K, et al. Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients. FASEB J. 2005;19:656-8 pubmed..In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients. ..
- Kumar K, Krishna D, Palit G. Histaminergic H1 receptors mediate L-histidine-induced anxiety in elevated plus-maze test in mice. Behav Pharmacol. 2007;18:213-7 pubmed..Our results indicate that anxiogenic effects of central histaminergic system appear to be mediated prominently by activation of H1 receptors. ..
- Leonard J, Marshall J, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102:2047-56; quiz 2057 pubmed..05-3.92). There is an association between acid suppression and an increased risk of enteric infection. Further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal. ..
- Dial S, Alrasadi K, Manoukian C, Huang A, Menzies D. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171:33-8 pubmed..6, 95% CI 1.4-5.2) and use of proton pump inhibitors (adjusted OR 2.7, 95% CI 1.4-5.2). Patients in hospital who received proton pump inhibitors were at increased risk of C. difficile diarrhea. ..
- Jayatilaka S, Shakov R, Eddi R, Bakaj G, Baddoura W, DeBari V. Clostridium difficile infection in an urban medical center: five-year analysis of infection rates among adult admissions and association with the use of proton pump inhibitors. Ann Clin Lab Sci. 2007;37:241-7 pubmed..73, 95%CI: 0.26 to 2.06; p = 0.5520). These data suggest that the widespread prescription of PPI for stress ulcer prophylaxis in acute care facilities may contribute to the increased incidence of CDAD. ..
- Sarkar M, Hennessy S, Yang Y. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008;149:391-8 pubmed..No radiographic evidence was available to corroborate a diagnosis of CAP. Proton-pump inhibitor therapy started within the past 30 days was associated with an increased risk for CAP, whereas longer-term current use was not. ..
- Ichikawa T, Ota H, Sugiyama A, Maruta F, Ikezawa T, Hotta K, et al. Effects of a novel histamine H2-receptor antagonist, lafutidine, on the mucus barrier of human gastric mucosa. J Gastroenterol Hepatol. 2007;22:1800-5 pubmed..There was no difference between the two groups in the mucin content of the deep mucosa. Lafutidine, given at clinical dosages, not only inhibits acid secretion but also strengthens the mucus barrier of the human gastric mucosa. ..
- Valuck R, Ruscin J. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004;57:422-8 pubmed..These findings support an association between chronic use of H2RA/PPI by older adults and development of vitamin B(12) deficiency. Additional studies are needed to confirm these findings. ..
- Chey W, Inadomi J, Booher A, Sharma V, Fendrick A, Howden C. Primary-care physicians' perceptions and practices on the management of GERD: results of a national survey. Am J Gastroenterol. 2005;100:1237-42 pubmed..Our survey has identified a number of areas of controversy and confusion related to the management of GERD. We hope that our findings can assist in the development of educational materials on GERD for PCPs. ..
- Maeyama S, Yoshihara H, Kamada T, Kubota S, Kobayashi I, Tsuji S, et al. [Effect of maintenance therapy by H2RA on the recurrence of gastric and duodenal ulcer and on the occurrence of reflux esophagitis, gastric erosions, and duodenal erosions after H. pylori eradication]. Nihon Rinsho. 2005;63 Suppl 11:512-5 pubmed
- Dial S, Delaney J, Barkun A, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989-95 pubmed..The unexpected increase in risk with nonsteroidal anti-inflammatory drug use should be investigated further. ..
- da Silva W, Bonini J, Bevilaqua L, Izquierdo I, Cammarota M. Histamine enhances inhibitory avoidance memory consolidation through a H2 receptor-dependent mechanism. Neurobiol Learn Mem. 2006;86:100-6 pubmed
- Fukushima K, Aoi Y, Kato S, Takeuchi K. Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins. World J Gastroenterol. 2006;12:3031-7 pubmed..It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1. ..
- Robertson D, Larsson H, Friis S, Pedersen L, Baron J, Sørensen H. Proton pump inhibitor use and risk of colorectal cancer: a population-based, case-control study. Gastroenterology. 2007;133:755-60 pubmed..07; 95% CI, 0.86-1.34) or long-term users (>7 years; adjusted OR = 1.09; 95% CI, 0.58-2.06). The use of PPIs in clinical practice does not measurably increase the risk of CRC. ..
- Moayyedi P, Talley N. Gastro-oesophageal reflux disease. Lancet. 2006;367:2086-100 pubmed..The role of endoscopic therapy is uncertain. Anti-reflux surgery is probably as effective as PPI therapy although there is a low operative mortality and morbidity. ..
- Harada N, Okajima K. Inhibition of neutrophil activation by lafutidine, an H2-receptor antagonist, through enhancement of sensory neuron activation contributes to the reduction of stress-induced gastric mucosal injury in rats. Dig Dis Sci. 2007;52:469-77 pubmed..These observations suggest that lafutidine might reduce WIR-induced gastric mucosal injury not only by inhibiting acid secretion but also by inhibiting neutrophil activation through enhancement of sensory neuron activation. ..
- Cofiel L, Mattioli R. Involvement of histamine receptors in the acquisition of inhibitory avoidance in Carassius auratus. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1246-50 pubmed..Thus, it can be suggested that both receptors, H(1) and H(2), are involved in the acquisition of a new task in this species. ..
- Lefranc F, Yeaton P, Brotchi J, Kiss R. Cimetidine, an unexpected anti-tumor agent, and its potential for the treatment of glioblastoma (review). Int J Oncol. 2006;28:1021-30 pubmed
- Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2 receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue Int. 2006;79:76-83 pubmed..In all cases, the changes in risk estimates were small and the clinical significance was limited. ..
- Laheij R, Sturkenboom M, Hassing R, Dieleman J, Stricker B, Jansen J. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292:1955-60 pubmed..For H2-receptor antagonist users, the variation in dose was restricted. Current use of gastric acid-suppressive therapy was associated with an increased risk of community-acquired pneumonia. ..
- Brett S. Science review: The use of proton pump inhibitors for gastric acid suppression in critical illness. Crit Care. 2005;9:45-50 pubmed..This review seeks to present the pharmacological evidence that may inform decision-making about the prescription of drugs for prophylaxis of SRMD. ..
- Clark K, Lam L, Currow D. Reducing gastric secretions--a role for histamine 2 antagonists or proton pump inhibitors in malignant bowel obstruction?. Support Care Cancer. 2009;17:1463-8 pubmed publisher..This forms a sound basis from which to develop further research aimed at improving the care of people with malignant bowel obstructions. ..
- Manzoni P, De Luca D, Stronati M, Jacqz Aigrain E, Ruffinazzi G, Luparia M, et al. Prevention of nosocomial infections in neonatal intensive care units. Am J Perinatol. 2013;30:81-8 pubmed publisher..Additional measures may include the use of lactoferrin, fluconazole, and nystatin and specific measures to prevent ventilator associated pneumonia. ..
- Wedi B, Wieczorek D, Raap U, Kapp A. [Urticaria … and treatment fails]. Hautarzt. 2013;64:656-63 pubmed publisher..Further controlled studies are vitally needed to achieve the goal of complete symptom relief in urticaria. ..
- Gisbert J, Calvet X, Ferrandiz J, Mascort J, Alonso Coello P, Marzo M. [Clinical practice guideline on the management of patients with dyspepsia. Update 2012]. Gastroenterol Hepatol. 2012;35:725.e1-38 pubmed publisher..To classify the scientific evidence and strengthen the recommendations, the GRADE (Grading of Recommendations Assessment, Development and Evaluation Working Group) system has been used (http://www.gradeworkinggroup.org/). ..
- Fernando S, Broadfoot A. Chronic urticaria--assessment and treatment. Aust Fam Physician. 2010;39:135-8 pubmed..Second generation antihistamines are the mainstay of treatment and usually twice daily regimens are required for adequate control. H2 antagonists, doxepin and immunomodulation may be necessary in some patients. ..
- Jee S, Jung H, Min B, Choi K, Rhee P, Kang Y, et al. [Guidelines for the treatment of functional dyspepsia]. Korean J Gastroenterol. 2011;57:67-81 pubmed..Psychotherapy is effective for those who have severe symptoms and refractoriness. Further studies are strongly needed to develop better treatment strategies for Korean patients with FD. ..
- Dasher D, Burkhart C, Morrell D. Immunotherapy for childhood warts. Pediatr Ann. 2009;38:373-9 pubmed..Although none of the immunologically-based treatments listed above (see Table, page 377) is FDA-approved for warts, they provide the treating physician with options for patients with warts that are resistant to standard treatments. ..
- Dutta U, Armstrong D. Novel pharmaceutical approaches to reflux disease. Gastroenterol Clin North Am. 2013;42:93-117 pubmed publisher..Advances will come, not from a 'one size fits all' approach but rather from novel pharmaceuticals allied to novel investigations to permit targeted, personalized reflux therapy. ..
- Szukiewicz D, Szewczyk G, Mittal T, Rongies W, Maslinski S. Involvement of histamine and histamine H2 receptors in nicotinamide-induced differentiation of human amniotic epithelial cells into insulin-producing cells. Inflamm Res. 2010;59 Suppl 2:S209-11 pubmed publisher..4%, respectively. H(1) receptor antagonist did not affect MCPP. Nicotinamide-induced pancreatic differentiation of HAEC into beta-like cells may be augmented, probably at its earlier stage, by histamine acting via H(2) receptors. ..
- Kinoshita Y, Chiba T. Therapeutic effects of famotidine on chronic symptomatic gastritis: subgroup analysis from FUTURE study. J Gastroenterol. 2012;47:377-86 pubmed publisher..Famotidine is effective to relieve abdominal symptoms and improve QOL, not only in patients with Rome III-defined FD, but also in those with chronic symptomatic gastritis. ..
- El Serag H, Fitzgerald S, Richardson P. The extent and determinants of prescribing and adherence with acid-reducing medications: a national claims database study. Am J Gastroenterol. 2009;104:2161-7 pubmed publisher..The use of prescription PPIs or H2RAs, as well as adherence and persistence with these medications, is lower than expected. The absence of BE and more recent diagnosis are associated with even lower prescription rates. ..
- Ogawa Y, Ichinokawa Y, Hiruma M, Machida Y, Funakushi N, Sadamasa H, et al. Retrospective cohort study on combination therapy with the histamine H2-receptor antagonist lafutidine for antihistamine-resistant chronic urticaria. J Dermatolog Treat. 2013;24:463-5 pubmed publisher..Lafutidine appears to be a promising addition to histamine H1-receptor antagonist therapy for the treatment of chronic urticaria resistant to treatment with H1-receptor antagonists alone. ..