Histamine Receptor Antagonists Research Articles

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinemia. a cross-sectional study in outpatient gastroenterology clinics

Objective: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. Method: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. And comprised patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for >3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. Results: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinemia and 70(42%) with hypreprolactinemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Pateints having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinemia. Conclusion: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management. Key Words: Proton pump inhibitors, Long-term therapy, Hyperprolactinemia, Omeprazole, Prolactin.

Treatment of Heartburn: A Survey of Ontario and Québec Community Pharmacists.

The shift of proton pump inhibitors (PPIs) from prescription to nonprescription (nonRx) status in Canada has altered pharmacist treatment options for heartburn. This report examines pharmacist approaches to therapy based on case severity; pharmacist confidence and consult duration were also explored. A 2022 online survey gathered data from Ontario and Québec pharmacists regarding their therapeutic approaches for two hypothetical heartburn cases. A total of 715 pharmacists participated, with most having 1-10 years of experience. In Ontario, common choices for the milder case included a solo histamine-2 receptor antagonist (H2RA) (21.2%), combination H2RA + antacid (29.4%), and nonRx PPI (22.3%). For the more severe case, common choices for Québec were switches to nonRx H2RA (22.1%), combination H2RA + antacid (13.4%), a nonRx PPI (24.9%), or prescription PPI (22.5%). Pharmacists often recommended switching medications or referring patients with recurring symptoms after seven days. The approaches varied significantly between cases and provinces. The Ontario pharmacists favoured a combination H2RA + antacid for the milder case, while the Québec pharmacists preferred a solo H2RA. For the more severe case, both groups often chose nonRx H2RA followed by nonRx PPI. Despite the differences, the pharmacists demonstrated confidence in managing these situations. These findings highlight potential debates regarding optimal therapeutic approaches and the impact of drug scheduling on patient care.

PREPARATION AND EVALUATION OF LAFUTIDINE NANOEMULSION AS ORAL DELIVERY SYSTEM

Objective: Lafutidine is a histamine (H2) receptor antagonist utilized for the treatment of gastric ulcer. Its oral bioavailability is low due to poor water solubility and an extensive first-pass hepatic. So, the present work aims to formulate and characterize of an oil in water (o/w) nanoemulsion of lafutidine as oral liquid dosage form and this could enhance drug solubility and improve its bioavailability. Methods: The pseudo-ternary phase diagrams were constructed via titration method. The diagram plots derived from oil, various ratios of surfactant and co-surfactant (S mix), and double distilled water. The selected optimized lafutidine nanoemulsions formula was determined via a variety of investigational studies like particle size, polydispersity index (PDI), zeta potential, pH, drug content and an in vitro drug release. Results: Characterization studies revealed that the optimum formula of nanoemulsions was (NE5), which consist of 0.2% of lafutidine, 30 % of surfactant and co-surfactant (S mix) (3:1), which mean (22.5%of tween 20:7.5% of polyethylene glycol 200 (PEG 200), 10% of peppermint oil and 59.4% of double distilled water. The optimized formula exhibited droplets size (62.56-96.2 nm), PDI (0.11), good pH value (7.1), zeta potential (-32.2 mV), high drug content (99.2%), in vitro release of lafutidine was significantly higher (P<0.05) for NE5. Scanning probe microscopy (SPM) revealed that the droplets size of NE5 was in nano-scale. Conclusion: It is possible to conclude that the optimized formula (NE5) was promised formula of nanoemulsion for increasing the orally delivered lafutidine bioavailability.

Liposomal Nanocarriers of Preassembled Glycocalyx Restore Venular Permeability in Sepsis: Assessed Quantitatively with a Novel Microchamber System

Background: The endothelial glycocalyx (EG), covering the luminal side of endothelial cells, regulates vascular permeability and senses wall shear stress. In sepsis, EG undergoes degradation leading to increased permeability and edema formation. We hypothesized that restoring EG integrity using liposomal nanocarriers of preassembled glycocalyx (LNPG) will restore normal venular permeability in a lipopolysaccharide (LPS)-induced sepsis model of mice. Methods: To test this hypothesis, we designed a unique perfusion microchamber in which the vascular permeability of isolated and cannulated mice mesenteric venules could be assessed by measuring the concentration of Evans blue dye (EBD) by fluorescent spectroscopy in microliter-samples of extravascular solution (ES). Results: Histamine-induced time- and dose-dependent increases in EBD in the ES could be measured, confirming the sensitivity of the microchamber system. Notably, the histamine-induced increase in permeability was significantly attenuated by histamine receptor (H1) antagonist, triprolidine hydrochloride. Subsequently, mice were treated with LPS, or LPS + LNPG. Compared to control mice, venules from LPS-treated mice showed a significant increased permeability, which was significantly reduced by LNPG administration. Moreover, in the presence of wall shear stress, intraluminal administration of LNPG significantly reduced the permeability in isolated venules from LPS-treated mice. Conclusion: Our newly developed microchamber system can quantitatively measure the permeability of isolated venules. LPS-induced sepsis increases permeability of venules that is attenuated by in vivo LNPG administration, which is also reestablished endothelial vasomotor responses to shear stress. Thus, LNPG presents a promising therapeutic potential for restoring EG function and thereby mitigating the increased permeability in sepsis. Support: National Institute of Health [grant number: HL144528, Dong Sun] and the Uehara Memorial Foundation [grant number: 202241049, Shinya Ishiko) and Hungarian Academy of Sciences Post-Covid 2021-34 (AK) and MIT of Hungary, National Research, Development, and Innovation Fund, OTKA K 132596 (AK). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of Antacids on the Survival of Patients With Metastatic Urothelial Carcinoma Treated With Pembrolizumab

IntroductionConcomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. Patients and MethodsThis retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan–Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. ResultsOverall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan–Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. ConclusionPPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

Prenatal exposure to acid suppressor medications and development of ductus arteriosus in term newborn.

The ductus arteriosus normally closes after birth. Histamine2 Receptor Antagonist (H2RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids - Proton Pump Inhibitors (PPI) and H2RA. Population-based matched case-control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001-2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the post-delivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H2RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC) Results. PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H2RA (OR4.18) and PPIs (OR3.50) (all p<0.001). PDA association with exposure window was similar in each trimester (1.5-2%) for both H2RA and PPI. PDA Incidence in term infants in our population was greater than previously reported. PPI and H2RA are both anti-acids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

A Comprehensive Review on Peptic Ulcer

Abstract: Up to 10% people in the world are affected by a chronic condition known as peptic ulcer. Peptic ulcer development is influenced by the pH of gastric juice and a decline in mucosal defenses. Protonpump inhibitors, histamine (H2) receptor antagonists, prostaglandin analogues and sucralfate have all been used to treat peptic ulcer disease. There has been a continuing search for an appropriate, palliative, and curative agent for the treatment of peptic ulcer disease using natural materials of plant and animal origin due to the complexity, cost, and toxicity of these medications. The goal of this review was to examine medicinal plants, phytochemicals, pathways, and research models that have been applied to the treatment of PUD in order to assess the potential contribution of natural substances to the development of herbal treatments for PUD. A literature search was used to find information utilising electronic databases such as Web of Science, Google Scholar, PubMed, Sci Finder, Reaxys, and Cochrane.

Novel Carbon Nanotubes/Gold Nanoparticles Modified Carbon Paste Electrochemical Sensor for Antazoline Determination in Aqueous Humor

Antazoline (ANT) is a H1 histamine receptor antagonist having anticholinergic properties used to decrease nasal congestion. It is found in eye drops usually in combination with either tetryzoline (TET) or xylometazoline (XLO). In this work, a novel electrochemical sensor based on carbon paste electrode (CPE) is developed for simple, rapid, sensitive, and selective determination of antazoline in pure form, different pharmaceutical formulations and in presence of aqueous humor. CPE is modified with nanoparticles multiwalled carbon nanotube (MWCNT) composite and further decorated with gold nanoparticles using amperometric electrodeposition technique to attain Au-NP@MWCNT/CPE for enhancing sensor sensitivity. Linearity is divided into two linear segments and found to be 2 × 10–7 − 2 × 10−6 (1st Linear segment) and 2 × 10–6 − 2 × 10−5 (2nd Linear segment) with limit of detection and quantification of 1.77 × 10−7 and 5.37 × 10−7, respectively. High sensitivity, selectivity, and reproducibility of the modified electrode towards determination of antazoline have promoted its applicability in different dosage forms and in rabbit aqueous humor. This method has noticeable potential applications in quality control, pharmacokinetic studies, and routine determination of antazoline drug in binary pharmaceutical formulations.

Associations between Proton-Pump Inhibitor Usage, Allergy, and Asthma: An Analysis of NHANES 2005–2006

Introduction: Acid suppression medications, such as proton-pump inhibitors (PPIs) and histamine-2 receptor antagonists, are commonly prescribed for the treatment of gastroesophageal reflux disease and other gastrointestinal disorders. However, concerns regarding potential long-term side effects are brought up by the overuse of PPIs. This study aimed to investigate the relationship between PPI usage, allergy, and asthma in the general US population. Methods: Data of individuals aged ≥20 years who had information on PPI use and questionnaires on allergy and asthma in the US National Health and Nutrition Examination Survey (NHANES) 2005–2006 were analyzed. Univariate and multivariable logistic regression analyses were performed to determine the associations between PPI use, prevalent allergy, and asthma. Results: A total of 4,481 participants (representing 198,543,007 US individuals after weighting) were included in the analyses. PPI use was not significantly associated with the presence of allergy or asthma in the general study population after adjustment. However, in females without steroid exposure, PPI use was significantly associated with increased odds of allergy (adjusted odds ratio [aOR] = 1.69, 95% confidence interval [CI]: 1.002–2.86), among which esomeprazole use was significantly associated with increased odds of allergy (aOR = 2.68, 95% CI: 1.30–5.54) and lansoprazole with increased odds of asthma (aOR = 3.44, 95% CI: 1.50–7.87) as compared to no PPI use. Duration of PPI use was not significantly associated with allergy or asthma. Conclusions: In US women without steroid exposure, PPI use is associated with increased likelihood of prevalent allergy and asthma.

Appropriateness and Cost of Prophylaxis Stress Ulcer for Inpatient in the Internal Medicine Department in a Government Hospital: A Cross-Sectional Study

Guidelines from the American Society of Health-System Pharmacists (ASHP) 1999 prohibit acid-suppressing therapy for stress ulcer prophylaxis (SUP) in patients who are not critically ill. Stress ulcer prophylaxis is not recommended in non-ICU patients with &lt;2 risk factors. Inappropriate use of SUP can increase costs for patients. This study aims to evaluate the use and the cost of SUP. This research was a non-experimental observational study with a cross-sectional approach. Data was collected retrospectively using the consecutive sampling method with a random sampling technique on the medical records of inpatients in the internal medicine ward of Sleman Regional Public Hospital from January to December 2020, totaling 340 samples. The results showed that proton pump inhibitors were the most widely used acid-suppressing drugs, with 45.8%. Furthermore, the histamine-2 receptor antagonist was 42.6%, the sucralfate group was 7.4%, and the antacid group was 4.2%. Of 340 patients, 57 (16.8%) were in the proper indication based on the guidelines, and 283 (83.2%) were under the wrong indication for SUP. They were using SUP with the proper indication so that the therapy could save treatment costs by Rp. 19,933,582. There was a high prevalence of inappropriate SUP prescriptions among inpatients in the internal medicine department; if these drugs were given with the appropriate indications, they could save more on the prophylaxis cost. Clinician pharmacists should develop an effective intervention strategy to reduce inappropriate SUP drugs.

Connecting the Dots: Heart Failure and Insomnia

Introduction and aim. This study investigates the relationship between heart failure (HF) and insomnia, focusing on this two-way association’s clinical significance, epidemiology, and management.&#x0D; Material and methods. Literature available in November 2023 was searched using Pubmed, Medline, Google Scholar, and Europe PMC with keywords associated with Heart Failure, Insomnia, and related pharmaceuticals. 69 articles were included.&#x0D; Analysis of the literature. Insomnia is associated with higher mortality and a potential risk of sudden cardiac death, particularly in individuals with HF. Treatment is challenging and side effects can worsen the symptoms of HF. The use of benzodiazepines in HF patients raises concerns about cardiovascular risks, prompting the exploration of other medications like nonbenzodiazepines, antidepressants with sedative effects, and histamine receptor antagonists. On the other hand, HF is also a condition that affects sleep quality. Drugs including ACE-I, beta-blockers, MRA, and SGLT2i are essential for its treatment. Some of them may have an impact on the intensity of insomnia.&#x0D; Conclusion. Considering the impact of insomnia medications on heart failure outcomes and vice versa is necessary. It is important to consider all aspects when treating these two conditions simultaneously.

Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand.

Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

The combined use of anti-peptic agents is associated with an increased risk of osteoporotic fracture: a nationwide case-control study.

Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of "PPI and H2RA" (HR, 1.58; p = 0.010) as well as "PPI, H2RA, and MPA" (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, "MPA and PPI or H2RA" was not associated with an increased risk of osteoporotic fracture. This study found that the combined use of "PPI and H2RA" was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Combination of H1 and H2 Histamine Receptor Antagonists: Current Knowledge and Perspectives of a Classic Treatment Strategy.

Histamine receptor antagonists, which can bind to specific histamine receptors on target cells, exhibit substantial therapeutic efficacy in managing a variety of histamine-mediated disorders. Notably, histamine H1 and H2 receptor antagonists have been extensively investigated and universally acknowledged as recommended treatment agents for numerous allergic diseases and acid-related disorders, respectively. Historically, the combination of H1 and H2 receptor antagonists has been considered a classic treatment strategy, demonstrating relatively superior efficacy compared with single-drug therapies in the treatment of diverse histamine-mediated diseases. The latest emerging studies have additionally suggested the underlying roles of histamine and H1R and H2R in the development of anxiety disorders, arthritic diseases, and postexercise hypotension. Nevertheless, there is still a lack of systematic reviews on the clinical efficacy of combination therapy, greatly limiting our understanding of its clinical application. Here, we present a comprehensive overview of the current knowledge and perspectives regarding the combination of H1 and H2 histamine receptor antagonists in various histamine-mediated disorders. Furthermore, we critically analyze the adverse effects and limitations associated with combination therapy while suggesting potential solutions. Our review can offer a systematic summary and promising insights into the in-depth and effective application of the combination of H1 and H2 receptor antagonists.

Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.

Effects of H2-Receptor Antagonists on the Exposure of Dacomitinib.

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small-cell lung cancer (NSCLC) and EGFR-activating mutations. Proton-pump inhibitors decreased dacomitinib exposure. This analysis summarizes the effect of Histamine-2 receptor antagonists (H2RAs) on dacomitinib exposure. A within-patient comparison of the steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RAs was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption physiologically based pharmacokinetic (PBPK) model was constructed and verified using clinical pharmacokinetic (PK) data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib's PKs. The adjusted geometric mean of the dacomitinib Ctrough,ss of the dacomitinib parent, metabolite and active moiety following co-administration with an H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without an H2RA (p > 0.05). The PBPK modeling showed negligible change in dacomitinib maximum concentration (Cmax) and area under the drug concentration-time curve (AUC) over 0-24 h after H2RA administration when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.

Association between proton pump inhibitors use and risk of asthma in Korea: A prevalent new-user cohort study.

There have been conflicting mechanisms that proton pump inhibitors (PPIs) may promote or prevent asthma development. However, the evidence on the association of PPI use with the risk of asthma and its exposure-response relationship has been limited. We aim to identify the association between the use of PPIs and the incidence of asthma, compared with use of histamine 2 receptor antagonists (H2RAs). A nationwide, prevalent new-user cohort study was conducted using Korea's National Sample Cohort database. Patients were defined as PPI or H2RA users between 2003 and 2019. PPI users matched to H2RA users based on time-conditional propensity score. Cox proportional hazards model was used to estimate adjusted hazard ratios with 95% confidence intervals of incident asthma associated with PPI use by duration of use, cumulative dose, and average dose per duration. Among the 250,041 pairs, PPI users (51.3% male; mean [SD] age, 42.6 [16.5]; mean follow-up, 6.7 years) showed a higher incidence rate of asthma (7.94 events per 1000 person-year) compared to H2RA users (3.70 events per 1000 person-year) with adjusted hazard ratio of 2.15 (95% confidence interval = 2.08-2.21). The risk of asthma was significantly increased across all observed groups of duration of use, cumulative dose, and average dose per duration. This study suggested that PPI use is associated with an increased risk of developing asthma compared to H2RA use.

Proton Pump Inhibitors Use in Kidney Transplant Recipients: A Population-Based Study.

Kidney transplant recipients are commonly prescribed proton-pump inhibitors (PPIs), but due to concern for polypharmacy, chronic use should be limited. The objective was to describe PPI use in kidney transplant recipients beyond their first year of transplant to better inform and support deprescribing initiatives. We conducted a retrospective, population-based cohort study using linked health care databases. This study was conducted in Alberta, Canada. We included all prevalent adult, kidney-only transplant recipients between April 2008 and December 2017 who received their transplant between May 2002 and December 2017. The primary outcome was ongoing or new PPI use and patterns of use, including frequency and duration of therapy, and assessment of indication for PPI use. We ascertained baseline characteristics, covariate information, and outcome data from the Alberta Kidney Disease Network (AKDN). We compared recipients with evidence of a PPI prescription in the 3 months prior to study entry to those with a histamine-2-receptor antagonist (H2Ra) fill and those with neither. We identified 1823 kidney transplant recipients, of whom 868 (48%) were on a PPI, 215 (12%) were on an H2Ra, and 740 (41%) were on neither at baseline. Over a median follow-up of 5.4 years (interquartile range [IQR] = 2.6-9.3), there were almost 45 000 unique PPI prescriptions dispensed, the majority (80%) of which were filled by initial PPI users. Recipients who were on a PPI at baseline would spend 91% (IQR = 70-98) of their graft survival time on a PPI in follow-up, and nephrologists were the main prescribers. We identified an indication for ongoing PPI use in 54% of recipients with the most common indication being concurrent antiplatelet use (26%). Our kidney transplant recipients have access to universal health care coverage which may limit generalizability. We identified common gastrointestinal indications for PPI use but did not include rare conditions due to concerns about the validity of diagnostic codes. In addition, symptoms suggestive of reflux may not be well coded as the focus of follow-up visits is more likely to focus on kidney transplant. Many kidney transplant recipients are prescribed a PPI at, or beyond, the 1-year post-transplant date and are likely to stay on a PPI in follow-up. Almost half of the recipients in our study did not have an identifiable indication for ongoing PPI use. Nephrologists frequently prescribe PPIs to kidney transplant recipients and should be involved in deprescribing initiatives to reduce polypharmacy.

Psychotropic Drug-Related Weight Gain and Its Treatment.

Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.