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Previous studies found that histamine H2 receptor antagonists (H2RAs) had blood pressure lowering and cardioprotective effects, but the impact of H2RAs on the survival outcomes of critically ill patients with essential hypertension is still unclear. The aim of this study was to investigate the association of H2RAs exposure with all-cause mortality in patients with essential hypertension based on Medical Information Mart for Intensive Care III database. A total of 17,739 patients were included, involving 8482 H2RAs users and 9257 non-H2RAs users. Propensity score matching (PSM) was performed to improve balance between 2 groups that were exposed to H2RAs or not. Kaplan-Meier survival curves were used to compare the cumulative survival rates and multivariable Cox regression models were performed to evaluate the association between H2RAs exposure and all-cause mortality. After 1:1 PSM, 4416 pairs of patients were enrolled. The results revealed potentially significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortalities in multivariate analyses (HR = 0.783, 95% CI: 0.696-0.882 for 30-day; HR = 0.860, 95% CI: 0.778-0.950 for 90-day; and HR = 0.883, 95% CI: 0.811-0.961 for 1-year mortality, respectively). Covariate effect analyses showed that the use of H2RAs was more beneficial in essential hypertension patients with age ≥ 60, BMI ≥ 25 kg/m2, coronary arteriosclerosis, stroke, and acute kidney failure, respectively. In conclusion, H2RAs exposure was related to lower mortalities in critically ill patients with essential hypertension, which provided novel potential strategy for the use of H2RAs in essential hypertension patients.
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Enfermedad Crítica , Hipertensión Esencial , Antagonistas de los Receptores H2 de la Histamina , Humanos , Masculino , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Hipertensión Esencial/tratamiento farmacológico , Hipertensión Esencial/mortalidad , Anciano , Enfermedad Crítica/mortalidadRESUMEN
Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.
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Histamina , Neoplasias , Humanos , Histamina/metabolismo , Estudios Retrospectivos , Calidad de Vida , Antagonistas de los Receptores H2 de la Histamina , Antagonistas de los Receptores Histamínicos/farmacología , Antagonistas de los Receptores Histamínicos/uso terapéutico , Receptores Histamínicos H2/genética , Receptores Histamínicos H2/metabolismo , Neoplasias/tratamiento farmacológico , Microambiente TumoralRESUMEN
Proton pump inhibitor (PPI) use may be associated with renal dysfunction. Renal dysfunction in PPI users requires evaluation of development and progression risks simultaneously, using estimated glomerular filtration rate (eGFR) slope, which indicates changes in eGFR per year. To the best of our knowledge, no studies have evaluated eGFR slope in PPI users. This study investigated the association between PPI use and renal dysfunction using eGFR slope. A single-center cohort study was conducted using the health records data at Hamamatsu University Hospital in Japan. Participants were defined as first users of acid-suppressing drugs (PPIs or Histamine H2 receptor antagonists (H2RAs)) from 2010 to 2021 and continuously prescribed for ≥ 90 days. The H2RA group was used for the propensity-score matching (PSM) to the PPI group to minimize the effects of confounders. The eGFR slope was estimated using a linear mixed effects model. Participants were stratified by baseline eGFR and age, respectively, as subgroup analyses. A total of 4,649 acid-suppressing drug users met the inclusion criteria, including 950 taking H2RAs and 3,699 PPIs. After PSM, 911 patients were assigned to each group. The eGFR slopes of the PPI and H2RA users were -4.75 (95% CI: -6.29, -3.20) and -3.40 (-4.38, -2.42), respectively. The difference between the groups was not significant. Significant declines in eGFR were observed with PPIs with baseline eGFR ≥ 90 and age < 65. PPI use for ≥ 90 days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.
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Tasa de Filtración Glomerular , Antagonistas de los Receptores H2 de la Histamina , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Estudios de Cohortes , Japón , Anciano de 80 o más Años , AdultoRESUMEN
Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as ß-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and ß-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and ß-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III). Methods: Study population was divided into 4 groups: ß-blockers + H2RAs group, ß-blockers group, H2RAs group, and Non-ß-blockers + Non-H2RAs group. Kaplan-Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups. Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in ß-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in ß-blockers + H2RAs group were significantly lower than those of patients in ß-blockers group, respectively (HR: 0.64, 95%CI: 0.50-0.82 for 30-day; HR: 0.80, 95%CI: 0.69-0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74-0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76-0.94 for 10-year mortality, respectively). Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as ß-blockers; and, furthermore, H2RAs and ß-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF.
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Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual meta-analyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.
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Enterocolitis Necrotizante , Neumonía , Humanos , Recién Nacido , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversosAsunto(s)
COVID-19 , Famotidina , Humanos , Famotidina/uso terapéutico , Resultado del Tratamiento , SARS-CoV-2RESUMEN
AIMS: Previous studies reported that histamine H2 receptor antagonists (H2RAs) had cardioprotective effects. However, the effect of H2RAs on mortality of critical ill patients with heart failure (HF) remains unclear. The aim of this study was to clarify the association between H2RAs and all-cause mortality of critical ill patients with HF based on Medical Information Mart for Intensive Care III database (MIMIC-III). METHODS AND RESULTS: Propensity score matching (PSM) was applied to account for the baseline differences between two groups that were exposed to H2RAs or not. The study primary outcome was all-cause mortality. Kaplan-Meier curves and multivariable Cox regression models were employed to estimate the effects of H2RAs on mortality of critical ill patients with HF. A total of 10 387 patients were included, involving 4440 H2RAs users and 5947 non-H2RAs users. After matching, 3130 pairs of patients were matched between H2RAs users and non-H2RAs users. The results showed significant association between H2RAs exposure and decreased 30-day, 90-day, and 1-year mortality in both univariate analyses and multivariate analyses [hazard ratio (HR) = 0.73, 95% confidence interval (CI): 0.65-0.83 for 30-day; HR = 0.80, 95%CI: 0.72-0.89 for 90-day; and HR = 0.83, 95%CI: 0.76-0.90 for 1-year mortality, respectively] by Cox regression after PSM. Furthermore, stratified analyses revealed that the 30-day, 90-day, and 1-year mortality of ranitidine users were significantly lower than those of famotidine users, respectively. CONCLUSION: Histamine H2 receptor antagonists exposure was associated with lower mortality in critical ill patients with HF. Furthermore, ranitidine might be superior to famotidine in reducing mortality of critical ill patients with HF.
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Insuficiencia Cardíaca , Antagonistas de los Receptores H2 de la Histamina , Humanos , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Ranitidina , Famotidina , Estudios de Cohortes , Enfermedad Crítica , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
Since the discovery of the histamine H2 receptor (H2R), radioligands were among the most powerful tools to investigate its role and function. Initially, radiolabeling was used to investigate human and rodent tissues regarding their receptor expression. Later, radioligands gained increasing significance as pharmacological tools in in vitro assays. Although tritium-labeling was mainly used for this purpose, labeling with carbon-14 is preferred for metabolic studies of drug candidates. After the more-or-less successful application of numerous labeled H2R antagonists, the recent development of the G protein-biased radioligand [3H]UR-KAT479 represents another step forward to elucidate the widely unknown role of the H2R in the central nervous system through future studies.
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Receptores Histamínicos H2/metabolismo , Tritio/farmacología , Animales , Descubrimiento de Drogas , Humanos , Ligandos , Tritio/química , Tritio/metabolismoRESUMEN
Peroxymonosulfate (PMS) is an appealing oxidant for organic contaminant destruction relying on radical generation after activation. Herein, we report PMS-promoted rapid degradation of histamine H2-receptor antagonists (HRAs) through non-radical process for the first time. Five commonly used HRAs, i.e., ranitidine (RNTD), cimetidine (CMTD), famotidine (FMTD), nizatidine (NZTD) and roxatidine (RXTD), were examined their reactivity towards PMS. Results show that HRAs (except RXTD) exhibit high reactivity towards PMS, with apparent second-order rate constants from 403 to 872 M-1s-1 at pH 7.0. Radical scavenging experiments excluded the contribution of radicals to PMS-promoted degradation of HRAs, and this non-radical process was unaffected by the real water matrices. Structure-activity assessment and theoretical calculation indicated that the thioether sulfur in HRAs (except RXTD) was the main reactive site for PMS oxidation. Transformation product analysis further elucidated oxidation of the thioether sulfur to sulfoxide product through an oxygen atom transfer process. Moreover, the thioether sulfur on the straight chain was more susceptible to oxygen transfer with PMS than that on the thiazole ring of HRAs. Toxicity evaluation indicated the ecotoxicity of HRAs could be remarkably reduced after PMS oxidation. Hence, this work provides a promising strategy to rapidly remove HRAs and significantly reduce their toxicity in water treatment.
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Contaminantes Químicos del Agua , Agua , Histamina , Cinética , Oxidación-Reducción , PeróxidosRESUMEN
Proton pump inhibitors (PPIs), long thought to be safe, are associated with a number of nonkidney adverse health outcomes and several untoward kidney outcomes, including hypomagnesemia, acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, kidney failure, and increased risk for all-cause mortality and mortality due to chronic kidney disease. PPIs are abundantly prescribed, rarely deprescribed, and frequently purchased over the counter. They are frequently used without medical indication, and when medically indicated, they are often used for much longer than needed. In this In Practice review, we summarize evidence linking PPI use with adverse events in general and adverse kidney outcomes in particular. We review the literature on the association of PPI use and risk for hypomagnesemia, acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, end-stage kidney disease, and death. We provide an assessment of how this evidence should inform clinical practice. We review the impact of this evidence on patients' perception of risk, synthesize PPI deprescription literature, and provide our recommendations on how to approach PPI use and deprescription.
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Deprescripciones , Medicina Basada en la Evidencia/métodos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Inhibidores de la Bomba de Protones/efectos adversos , Prescripciones de Medicamentos/normas , Medicina Basada en la Evidencia/normas , Humanos , Enfermedades Renales/diagnóstico , Factores de RiesgoRESUMEN
PURPOSE: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. METHODS: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. RESULTS: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. CONCLUSION: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.
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Antiulcerosos/administración & dosificación , Utilización de Medicamentos/estadística & datos numéricos , Dispepsia/tratamiento farmacológico , Ácido Gástrico/metabolismo , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Inhibidores de la Bomba de Protones/administración & dosificación , Antiulcerosos/economía , Antiulcerosos/uso terapéutico , Australia , Utilización de Medicamentos/economía , Dispepsia/metabolismo , Gastos en Salud , Antagonistas de los Receptores H2 de la Histamina/economía , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Programas Nacionales de Salud , Pautas de la Práctica en Medicina/estadística & datos numéricos , Inhibidores de la Bomba de Protones/economía , Inhibidores de la Bomba de Protones/uso terapéutico , República de CoreaRESUMEN
There is a need to find/discover novel leads to treat complex and/or multi-factorial disease(s). Curcumin (CUR) is one of the promising lead molecules which need its further evaluation against NSAID-induced gastroenteropathy. Hence, the aim of the present study was to explore the pharmaco-mechanistic efficacy of CUR against NSAID-induced gastroenteropathy. Rats were treated twice daily with CUR (25, 50 and 100 mg kg-1 peroral) or vehicle for 10 days. In some experiments, diclofenac sodium (DIC; 9 mg kg-1) was administered orally twice daily for the final 5 days of CUR/vehicle administration. After the last dose on 9th day, rats were fasted. 12 h after the last dose on 10th day, rats were euthanized and their GI tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and GI luminal pH alterations along with haemato-biochemical estimations. The macroscopic, biochemical, haematological and histological evidences suggested that co-administration of CUR resulted in dose dependent attenuation of the NSAID-induced gastroenteropathic damage and the mechanisms may be related to its ability to prevent the NSAID-induced alterations in the GI luminal pH, lipid peroxidation/oxidative stress, GI blood loss and intestinal permeability alteration. Based on these pharmaco-mechanistic results we propose it as a promising lead to treat NSAID-gastroenteropahty.
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Curcuma/química , Curcumina/farmacología , Diclofenaco/toxicidad , Hemorragia Gastrointestinal/inducido químicamente , Úlcera Gástrica/inducido químicamente , Animales , Antiinflamatorios no Esteroideos/toxicidad , Curcumina/química , Hemorragia Gastrointestinal/prevención & control , Masculino , Ratas , Ratas Wistar , Úlcera Gástrica/prevención & controlRESUMEN
BACKGROUND: It has been recently reported that histamine H2 receptor antagonists (H2RAs) are associated with impairment of ventricular remodeling and incident heart failure. In addition, favorable pleiotropic effects and adverse effects of proton pump inhibitors (PPIs) on cardiovascular disease have also been reported. We examined the associations of acid suppressive therapy using H2RAs or PPIs with cardiac mortality in patients with heart failure. METHODS AND RESULTS: In total, 1191 consecutive heart failure patients were divided into 3 groups: a non-acid suppressive therapy group (n=363), an H2RA group (n=164), and a PPI group (n=664). In the follow-up period (mean 995 days), 169 cardiac deaths occurred. In the Kaplan-Meier analysis, cardiac mortality was significantly lower in the PPI group than in the H2RA and non-acid suppressive therapy groups (11.0% versus 21.3% and 16.8%, respectively; log-rank P=0.004). In the multivariable Cox proportional hazards analysis, use of PPIs, but not H2RAs, was found to be an independent predictor of cardiac mortality (PPIs: hazard ratio 0.488, P=0.002; H2RAs: hazard ratio 0.855, P=0.579). The propensity-matched 1:1 cohort was assessed based on propensity score (H2RAs, n=164; PPIs, n=164). Cardiac mortality was significantly lower in the PPI group than in the H2RA group in the postmatched cohort (log-rank P=0.025). In the Cox proportional hazards analysis, the use of PPIs was a predictor of cardiac mortality in the postmatched cohort (hazard ratio 0.528, P=0.028). CONCLUSIONS: PPIs may be associated with better outcome in patients with heart failure.
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Enfermedades Gastrointestinales/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Anciano , Anciano de 80 o más Años , Fármacos Cardiovasculares/uso terapéutico , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/mortalidad , Enfermedades Gastrointestinales/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polifarmacia , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Factores Protectores , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: Hyperphosphatemia is one of the common complications in patients undergoing hemodialysis. Although calcium carbonate (CaC) is often used to control serum inorganic phosphorus level in dialysis patients, co-administration of gastric acid reducers (ARs) may interfere with the phosphate binding effect of CaC. We performed a retrospective medical chart review to study whether ARs attenuate the hypophosphatemic effect of CaC in patients undergoing hemodialysis. METHODS: One hundred and eight chronic hemodialysis patients receiving either CaC alone or CaC concomitant with one of the ARs (proton pump inhibitors and histamine H2-receptor antagonists) were retrieved from the medical charts in Juntendo University Nerima Hospital. The patients were subdivided according to the interval between hemodialysis sessions (interdialysis interval of 48 or 72 h). A multivariate analysis was performed to identify clinical covariates associated with the variability of serum inorganic phosphorus levels. The study protocol was approved by the Institutional Review Board before the study was begun. RESULTS: Among patients on hemodialysis with a 72-h interdialysis interval, the magnitude of increase in serum inorganic phosphorus concentration in patients receiving CaC and AR was significantly greater than in those receiving CaC alone. While a similar trend was observed among patients with a 48-h interdialysis interval, the difference did not reach a significant level. A multivariate regression analysis revealed that concomitant administration of ARs with CaC and a longer interdialysis interval (72 h) were significantly and independently associated with the magnitude of increase in serum phosphorus concentration between dialysis sessions. No significant differences in albumin-corrected serum calcium concentrations and incidence of pathological fractures were observed between patients receiving CaC alone and those receiving CaC with ARs. CONCLUSIONS: Concomitant use of ARs with CaC may attenuate the hypophosphatemic effect of CaC in patients undergoing chronic hemodialysis. When hemodialysis patients require prescription of ARs for the prevention of upper gastrointestinal mucosal diseases (such as peptic ulcer), it may be prudent to choose a phosphate binder other than CaC.
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BACKGROUND: Refractory gastroesophageal reflux-induced chronic cough (GERC) is difficult to manage. The purpose of the study is to evaluate the efficacy of a novel stepwise protocol for treating this condition. METHODS: A total of 103 consecutive patients with suspected refractory reflux-induced chronic cough failing to a standard anti-reflux therapy were treated with a stepwise therapy. Treatment commences with high-dose omeprazole and, if necessary, is escalated to subsequent sequential treatment with ranitidine and finally baclofen. The primary end-point was overall cough resolution, and the secondary end-point was cough resolution after each treatment step. RESULTS: High-dose omeprazole eliminated or improved cough in 28.1% of patients (n=29). Further stepwise of treatment with the addition of ranitide yielded a favorable response in an additional 12.6% (n=13) of patients, and subsequent escalation to baclofen provoked response in another 36.9% (n=38) of patients. Overall, this stepwise protocol was successful in 77.6% (n=80) of patients. The diurnal cough symptom score fell from 3 [1] to 1 [0] (Z=6.316, P=0.000), and the nocturnal cough symptom score decreased from 1 [1] to 0 [1] (Z=-4.511, P=0.000), with a corresponding reduction in the Gastroesophageal Reflux Diagnostic Questionnaire score from 8.6±1.7 to 6.8±0.7 (t=3.612, P=0.000). Conversely, the cough threshold C2 to capsaicin was increased from 0.49 (0.49) µmol/L to 1.95 (2.92) µmol/L (Z=-5.892, P=0.000), and the cough threshold C5 was increased from 1.95 (2.92) µmol/L to 7.8 (5.85) µmol/L (Z=-5.171, P=0.000). CONCLUSIONS: Sequential stepwise anti-reflux therapy is a useful therapeutic strategy for refractory reflux-induced chronic cough.
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BACKGROUND: Histamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine-induced anaphylaxis occurred in Korea from 2007 to 2014. OBJECTIVE: The purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine-induced anaphylaxis. METHODS: Ranitidine-related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected, and clinical manifestations, outcomes, and drug-related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single centre. Twenty-three patients participated in in vivo and in vitro studies. Skin tests, oral provocation tests, and laboratory tests were performed, including tests using other kinds of histamine H2 receptor antagonists. RESULTS: Over 7 years, 584 patients suffered adverse reactions to ranitidine. The most common manifestation was cutaneous symptoms. Among them, 99 patients (17.0%) experienced anaphylaxis. In a single-centre study, skin prick tests were positive in 91.7% of ranitidine-induced anaphylaxis patients (11/12); the optimal concentration was 20 mg/mL. Detection of ranitidine-specific immunoglobulin E failed. Cimetidine and proton pump inhibitors showed no cross-reactivity with ranitidine based on the skin prick test, oral provocation test, or clinical determination. Surprisingly, 82.6% of patients reintroduced ranitidine and re-experienced the same adverse reactions because ranitidine was not considered the culprit drug. CONCLUSIONS AND CLINICAL RELEVANCE: Although ranitidine is known as a safe drug, it can also cause diverse adverse reactions, including anaphylaxis. This study demonstrates the need to pay attention to adverse reactions to ranitidine and consider ranitidine as a cause of anaphylaxis.
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Anafilaxia/diagnóstico , Anafilaxia/etiología , Hipersensibilidad a las Drogas/diagnóstico , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Ranitidina/efectos adversos , Adulto , Anafilaxia/epidemiología , Reacciones Cruzadas/inmunología , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Incidencia , Masculino , Persona de Mediana Edad , Fenotipo , Vigilancia de la Población , Inhibidores de la Bomba de Protones/efectos adversos , República de Corea/epidemiología , Pruebas CutáneasRESUMEN
Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed's own filter of: 'child: birth-18 years'. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H2 receptor antagonists (H2 RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H2 RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Reflujo Gastroesofágico/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Adolescente , Niño , Preescolar , Bases de Datos Factuales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Antagonistas de los Receptores H2 de la Histamina/administración & dosificación , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Humanos , Lactante , Recién Nacido , Inhibidores de la Bomba de Protones/administración & dosificación , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
PURPOSE: This study aimed to compare use of histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), 2001-2005, in the elderly and social security beneficiaries in Australia (AUS) and Nova Scotia, Canada (NS). METHODS: Prescription dispensing data were collected for all subsidised H2RAs and PPIs. In AUS, dispensing data for concession beneficiaries were obtained from the Pharmaceutical Benefits Scheme database. In NS, data were sourced from the Pharmacare database. Relevant population data were used to convert to World Health Organisation Anatomic Therapeutic Chemical defined daily doses (2005) per 1000 beneficiaries per day (DDD/1000/day). RESULTS: Overall use of gastroprotective agents was similar and rising in NS and AUS (100-160 DDD/1000/day) over this 5-year time window. However, the proportion of this use accounted for by PPIs was far higher in AUS (over 85% by 2005) than in NS (23% rising to 35% over the 5 years). In AUS, PPI use rose from 50 to about 140 DDD/1000/day over the 5 years, whereas PPI use in NS rose slowly to less than 60 DDD/1000/day by 2005. H2RA use in NS was always high (over 100 DDD/1000/day), whereas in AUS, H2RA use fell from 54 to around 24 DDD/1000/day over this period. CONCLUSIONS: AUS had much higher use of PPIs than NS over 2001-2005. The proportion of PPIs in all gastroprotective agents rose in AUS to be nearly 90%. The differences in utilisation during this time window could lead to differences in health outcomes from either lower gastro-intestinal bleeding risk or higher long-term adverse effects of PPIs.
Asunto(s)
Antiulcerosos/uso terapéutico , Revisión de la Utilización de Medicamentos/tendencias , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Pautas de la Práctica en Medicina/tendencias , Inhibidores de la Bomba de Protones/uso terapéutico , Factores de Edad , Australia , Distribución de Chi-Cuadrado , Minería de Datos , Bases de Datos Factuales/estadística & datos numéricos , Prescripciones de Medicamentos/estadística & datos numéricos , Humanos , Nueva Escocia , Farmacoepidemiología , Farmacovigilancia , Seguridad Social , Factores de TiempoRESUMEN
H(2)-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H(2)-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H(2)-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H(2)-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H(2)-receptor antagonist hypersensitivity.
RESUMEN
H2-receptor antagonists, such as cimetidine, ranitidine and famotidine, are some of the most commonly prescribed medications for gastric acid-related disorders. These compounds are generally well-tolerated and anaphylactic reactions to them are rare. Here, we report two cases of H2-receptor antagonist-induced anaphylactic reactions: the first presented with sudden dyspnea, sneezing, urticaria, and swelling of the eyelids after ranitidine intake. The second presented with sudden severe urticaria, facial swelling, chest discomfort, dizziness, and hypotension. Possible cross-reactivity with other H2-receptor antagonists was assessed by oral challenge and skin tests. To date, only a few reports addressing cross-reactivity among H2-receptor antagonists have been published. We review the literature and summarize the data available on drug cross-reactivity in H2-receptor antagonist hypersensitivity.