H2-receptor Antagonists Research Articles

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

Effectiveness of promethazine on preoperative and intraoperative sequelae in cleft palate surgeries.

Anxiety and nosocomial infection are the most common reported problems in children undergoing cleft surgeries. Research shows that there is an enigma in the use of antihistamine therapy in children for the management of upper respiratory tract infection. 'Promethazine' is a first-generation H1 receptor antagonist, and antihistamine also has strong sedative effects. Our study aims at evaluating the Effectiveness of Promethazine (Phenergan) in preoperative and intra operative sequelae in cleft surgeries. This is a single-centre, parallel, randomized, double-blinded randomized control clinical trial, which was conducted among 128 children between 2 and 4 years of age undergoing cleft palate surgery under general anaesthesia. After randomization, the case group was subjected to promethazine syrup 1 mg/kg body weight twice a day, orally for 3 days. The primary outcomes were preoperative anxiety levels which were recorded by children fear scale. The secondary outcomes include preoperative sleep quality and cough rate of children which are recorded by using sleep and cough objective scale respectively. The intraoperative heart rate is monitored with an ECG connected to a monitor. Promethazine causes a reduction in the anxiety level by 70%, 64% reduction in cold and cough, improvement in sleep score by 70% and the heart rate was found to be stable throughout the surgery when compared to the control group. As the benefits of promethazine in cleft palate surgery rule over its adverse effects, promethazine is considered safe to be used as premedication for children undergoing cleft palate surgeries.

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.

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.

Retracted: Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier K+-Channel Currents in Murine Thymocytes.

[This retracts the article DOI: 10.1155/2019/6261951.].

Role of Histamine H3 Receptor Antagonist Pitolisant in Early Neural Differentiation of Mouse Embryonic Stem Cells.

The histamine H3 receptor, prominently expressed in neurons with a minor presence in glial cells, acts as both an autoreceptor and an alloreceptor, controlling the release of histamine and other neurotransmitters. The receptor impacts various essential physiological processes. Our team's initial investigations had demonstrated that the histamine H3 receptor antagonists could facilitate nerve regeneration by promoting the histamine H1 receptors on primary neural stem cells (NSCs) in the traumatic brain injury mouse, which suggested the potential of histamine H3 receptor as a promising target for treating neurological disorders and promoting nerve regeneration. Pitolisant (PITO) is the only histamine H3 receptor antagonist approved by the Food and Drug Administration (FDA) for treating narcolepsy. However, there is no report on Pitolisant in neural development or regeneration, and it is urgent to be further studied in strong biological activity models in vitro. The embryonic stem (ES) cells were differentiated into neural cells in vitro, which replicated the neurodevelopmental processes that occur in vivo. It also provided an alternative model for studying neurodevelopmental processes and testing drugs for neurological conditions. Therefore, we aimed to elucidate the regulatory role of Pitolisant in the early differentiation of ES cells into neural cells. Our results demonstrated that Pitolisant could promote the differentiation of ES cells toward NSCs and stimulated the formation of growth cones. Furthermore, Pitolisant was capable of inducing the polarization of NSCs through the cAMP-LKB1-SAD/MARK2 pathway, but had no significant effect on later neuronal maturation. Pitolisant altered mitochondrial morphology and upregulated the levels of mitochondrion-related proteins TOM20, Drp1, and p-Drp1, and reversed the inhibitory effect of Mdivi-1 on mitochondrial fission during the early neural differentiation of ES cells. In addition, Pitolisant induced the increase in cytosolic Ca2+. Our study provided an experimental foundation for the potential application of histamine H3 receptor-targeted modulators in the field of neuroregeneration.

Preliminary studies of 1,5-benzoxazepine derivatives as potential histamine H3 receptor antagonists.

Aims: Our research aimed to evaluate how the rigidification of the characteristic 3-aminopropyloxy linker by incorporating it into 1,5-benzoxazepinesaffects the potency of histamine H3 receptor (H3R) antagonists/inverse agonists. This research constitutes a starting point for the full characterization of the pharmacological properties of this group of compounds. Materials & methods: Several 1,5-benzoxazepine derivatives were synthesized and pharmacologically tested as potential H3R antagonist/inverse agonists. In a addition, the effect of the derivatives on acetylcholinesterase andbutyrylcholinesterase inhibition and cytotoxicity were tested. Results: The studies indicated 1,5-benzoxazepine containing three carbon side chainsas a compound for further modification. Conclusion: Further optimization of the lead structure is necessary, which will favorably affect biological targets.

Is pitolisant safe for clinical use? A retrospective pharmacovigilance study focus on the post-marketing safety.

Pitolisant, a novel histamine H3-receptor antagonist, holds significant promise for treating narcolepsy. However, a petition, which highlighted that pitolisant was associated with deaths during clinical trials, has propelled it into the spotlight of widespread societal attention on April 3, 2023. Till now, the clinical safety of pitolisant remains a heatedly debated topic. This study aimed to offer a comprehensive assessment of the safety profile of pitolisant in real-world clinical settings. Adverse event reports where pitolisant was the primary suspect drug were extracted from the FDA Adverse Event Reporting System database. The clinical characteristics and concomitant drugs of the pitolisant-associated adverse events were analyzed. The potential adverse event signals of pitolisant were explored using four disproportionality analysis methods. Furthermore, the difference in pitolisant-associated adverse event signals was investigated concerning sex, age, weight, and dose. A total of 526 reports and 1695 adverse events with pitolisant as the primary suspected drug were identified. The most significant adverse event signals were generally mild and of short duration. The concomitant drugs of pitolisant were highly intricate, mainly included drugs for treating narcolepsy as well as antidepressants. Seven new significant adverse event signals emerged. The safety profile of pitolisant exhibited no significant differences across age and dose groups, although slight variations were observed in relation to sex and weight. The findings from reports of death and life-threatening outcomes underscore the importance of enhanced monitoring for cardiac and respiratory adverse reactions when utilizing pitolisant. This study provided a broader understanding of the safety profile of pitolisant.

Changes in estimated glomerular filtration rate in patients administered proton pump inhibitors: a single-center cohort study.

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 ≥ 90days. 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 ≥ 90days may hasten eGFR decline compared to H2RA use, especially in patients with eGFR ≥ 90 or age < 65.

Improved gastric residence time of famotidine by raft-forming drug delivery system using DOE.

This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by enhancing gastric residence time (GRT) and preventing gastro-esophageal reflux disease (GERD). Various combinations of raft-forming agents, such as Tragacanth gum (TG), guar gum (GG), and xanthan gum (XG), were evaluated alongside sodium alginate (SA) to develop an effective raft. Preformulation studies and preliminary screening were conducted to identify the most suitable raft-forming agent, and GG was chosen due to its mucilaginous properties. The formulation was optimized using a 32 full factorial design, with the quantities of GG and SA as independent factors and apparent viscosity and in-vitro drug release (%) as dependent factors. The in vivo floating behavior study was performed for optimized and stabilized formulation. Among the tested batches, F6 was selected as the optimized formulation. It exhibited desirable characteristics such as adequate raft weight for extended floating in gastric fluid, improved apparent viscosity, and a significant percentage of drug release at 12h. A mathematical model was applied to the in-vitro data to gain insights into the drug release mechanism of the formulation. The stability of the suspension was assessed under accelerated conditions, and it demonstrated satisfactory stability. The formulation remains floating in the Rabbit stomach for more than 12h. It concludes that the developed formulation has enhanced bioavailability in the combination of GG and SA. The floating layer of the raft prevents acid reflux, and the famotidine is retained for an extended period of time in the gastric region, preventing excess acid secretion. The developed formulations are effective for stomach ulcers and GERD, with the effect of reducing acid secretion by H2 receptor antagonists.

Determination of 145 pharmaceuticals and personal care products in eleven categories in water by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry

Pharmaceuticals and personal care products (PPCPs) are emerging contaminants frequently detected in aquatic environments at trace levels. These chemicals have diverse structures and physicochemical properties and includes pharmaceuticals like antibiotics, antihypertensive drugs, antiviral drugs, and psychotropic drugs that are widely used in large quantities worldwide. Considering the large number of pharmaceuticals currently in usage, it is crucial to establish a priority list of PPCPs that should be monitored and/or treated first. An accurate understanding of the occurrence and levels of PPCPs in aquatic environments is essential for providing objective materials for monitoring these emerging contaminants. Therefore, accurate, efficient, sensitive, and high-throughput screening techniques need to be established for determining and quantifying PPCPs. This study developed a method for the determination of 145 PPCPs (grouped into eleven categories: antibiotics, antihypertensive drugs, antidiabetic drugs, antiviral drugs, β-receptor agonists, nitroimidazoles, H2 receptor antagonists, psychotropic drugs, hypolipidemic drugs, non-steroidal anti-inflammatory drugs, and others) in water. The method was based on large volume direct injection without sample enrichment and cleanup and used ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-MS/MS). Water samples were collected and filtered through a 0.22-μm regenerated cellulose (RC) filter membrane. Subsequently, Na2EDTA was added to the samples to adjust their pH to 6.0-8.0. Internal standards were mixed with the solutions, and because of the addition of Na2EDTA, the interference of metal ions could be eliminated in the determination of compounds, especially for tetracycline and quinolone antibiotics. Among the six filter membranes tested in this study (PES, PFTE-Q, PFTE, MCE, GHP, and RC), RC filter membranes were screened for water sample filtration. The UHPLC-MS/MS parameters were optimized by comparing the results of various mobile phases, as well as by establishing the best instrumental conditions. The 145 PPCPs were separated using an Phenomenex Kinetex C18 column (50 mm×3 mm, 2.6 μm) via gradient elution. The mobile phases were 0.1% (v/v) formic acid aqueous solution containing 5 mmol/L ammonium formate and acetonitrile for positive ion modes, 5 mmol/L aqueous solutions of ammonium formate and acetonitrile for negative ion modes. The samples were quantified using the scheduled multiple reaction monitoring (scheduled-MRM) mode with electrospray ionization in positive and negative ion modes. A standard internal calibration procedure was used to calculate contents of sample. The established method was systematically verified, and it demonstrated a good linear relationship. The average recoveries of the 145 PPCPs at the three spiked levels were in the range of 80.4%-128% with relative standard deviations (RSDs, n=6) of 0.6%-15.6%. The method detection limits (MDLs) ranged from 0.015 to 5.515 ng/L. Finally, the optimization method was applied to analyze the 145 PPCPs in 11 surface water samples and 6 drinking water samples. Overall, 93 (64%) out of the 145 analytes were detected. The total contents of the PPCPs in surface water samples ranged from 276.9 to 2705.7 ng/L. The detection frequencies of antidiabetic, antiviral, and psychotropic drugs were 100%. The total contents of the PPCPs in drinking water samples ranged from 140.5 to 211.5 ng/L, and antibiotics, antidiabetic drugs, and antiviral drugs comprised the largest proportion of analytes (by mass concentration) in drinking water samples. Our method exhibited high analytical speed and high sensitivity. It is thus suitable for the trace analysis and determination of the 145 PPCPs in environmental water and showed improved detection efficiency for PPCPs in water, indicating that it has a high potential for practical applications. This study can extend technical support for further pollution-level analysis of PPCPs in water and provide an objective basis for environmental management.

The story of clobenpropit and CXCR4: can be an effective drug in cancer and autoimmune diseases?

Clobenpropit is a histamine H3 receptor antagonist and has developed as a potential therapeutic drug due to its ability to inhibit CXCR4, a chemokine receptor involved in autoimmune diseases and cancer pathogenesis. The CXCL12/CXCR4 axis involves several biological phenomena, including cell proliferation, migration, angiogenesis, inflammation, and metastasis. Accordingly, inhibiting CXCR4 can have promising clinical outcomes in patients with malignancy or autoimmune disorders. Based on available knowledge, Clobenpropit can effectively regulate the release of monocyte-derived inflammatory cytokine in autoimmune diseases such as juvenile idiopathic arthritis (JIA), presenting a potential targeted target with possible advantages over current therapeutic approaches. This review summarizes the intricate interplay between Clobenpropit and CXCR4 and the molecular mechanisms underlying their interactions, comprehensively analyzing their impact on immune regulation. Furthermore, we discuss preclinical and clinical investigations highlighting the probable efficacy of Clobenpropit for managing autoimmune diseases and cancer. Through this study, we aim to clarify the immunomodulatory role of Clobenpropit and its advantages and disadvantages as a novel therapeutic opportunity.

Non-indicated initiation of proton pump inhibitor and risk of adverse outcomes in patients with underlying chronic kidney disease: a nationwide, retrospective, cohort study

ObjectiveEvidence related to the risk of kidney damage by proton pump inhibitor (PPI) initiation in patients with ‘underlying’ chronic kidney disease (CKD) remains scarce, although PPI use is generally associated...

The Structural Basis of DL0410, a Novel Multi-Target Candidate Drug for the Treatment of Alzheimer’s Disease

Alzheimer’s disease (AD) is a complicated disease for which there are still no ideal one-target drugs, while multi-target drugs are closer to ideal drugs and will provide new solutions for the clinical treatment of AD. DL0410 is a promising multi-target drug candidate for AD treatment that is not only a significant inhibitor against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) but also an antagonist of histamine H3 receptor (H3R), and its therapeutic efficacy in treating cognitive dysfunction has been validated in a series of AD-related animal models, including scopolamine-induced mice, D-galactose-induced and Aβ-induced mice, and APP/PS1 and SAMP8 mice. Although the structure of DL0410 has been analyzed using various detection techniques, such as MS and NMR, its three-dimensional crystal structure still requires further confirmation. In this study, the crystal of DL0410 was grown in aqueous solution, and its structure was detected using the X-ray diffraction method. The crystal data, atomic coordinates, bond lengths, angles, and hydrogen bonds of DL0410 were obtained. Its stability was proven by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Based on this study, the molecular docking of DL0410 with AChE, BuChE, and H3R was performed to uncover their interaction mechanisms and explain their bioactivities. This study provides important information for new multi-target drug design and the research and development of new drugs for AD treatment.

Formulation and Evaluation of Sublingual Tablets of Meclizine Hydrochloride

The aim of the present research is to formulate sublingual tablet of Meclizine Hydrochloride using direct compression method. Moreover the purpose of developing this dosage form is to provide rapid onset of action beneficial in managing conditions of nausea, vomiting and vertigo, and also overcome the problems of solubility of drug by inclusion complexes. The disease like nausea and vomiting required fast onset of action which is necessary for the fast pharmacological action. So, the sublingual route of administration were better way of medication and overcome the problems like dysphagia. The Meclizine hydrochloride is histamine H1 receptor antagonist with antiemetic and antivertigo properties. The oral bioavailability is low (25%), with low solubility (BCS class 2 drug), and metabolized by Hepatic CYP2D6 enzyme by the process of hepatic hydroxylation. Sublingual tablet of antiemetic drug meclizine hydrochloride will be prepared by direct compression method. The Solubility of sublingual tablets will be enhanced by Inclusion complexes. These are prepared by weighed amount of drug mixed with β-cyclodextrin in different dose ratios [1:1,1:2] was wetted with small drops of water to form kneaded like paste and triturated in mortar pestle for several hours resulting in evaporation of solvent. The inclusion complexes was collected and dried for 48 hours and pulverized using mortar and pestle and then sieved through mesh #60. Then properly mixed with other excipients in polybag for 1 hour. The powder like complex was used for further evaluation studies and to form sublingual tablets by direct compression method.

COMORBID DISORDERS OF THE SLEEP CYCLE – AWAKENESS IN KINDLING RATS UNDER THE CONDITIONS OF USING THE H₃ RECEPTOR ANTAGONIST PITOLISANT

Studies of the neuropathophysiological mechanisms of chronic epileptic activity, whicharise with the participation of the endogenous histaminergic system of the brain, allowus to justify effective complex means of controlling both convulsive manifestations andcomorbid states, which include sleep and wakefulness disorders.Aim of the work – to study the characteristics of the sleep-wake cycle in rats with PTZinduced kindling under the condition of using the H3 receptor antagonist pitolisant.Methods. The kindling syndrome was induced in Wistar rats by daily administration ofpentylenetetrazole (PTZ) (35.0 mg/kg, i. p.) for three weeks. In rats in the course of kindlingdevelopment, pitolisant (5,0 mg/kg, i. p.) was used for 30 min before epileptogen administration.Research results. In rats with developed kindling, the paradoxical sleep phase wasreduced to 7,1% of the total observation period (4 hours) and its fragmentation increased39,7% and the latent period of paradoxical sleep was 24,0% less compared to the controlgroup (P&lt;0,05). Pitolizant treatment was accompanied by an increase in the durationof the awake phase, which was 29% of the total observation time (P&gt;0,05). At the sametime, the duration of paradoxical sleep was 11,6% (P&gt;0,05), and the slow-wave sleepphase was 71,0% (P&gt;0,05). The number of sleep-wake cycles unreliably exceeded theindicator in the control group 17,2% (P&gt;0,05). Latent periods of falling asleep exceededthe indicator in the control group 44,1% (P&lt;0,05) and at the same time was higher thanin kindling rats 60,2% (P&lt;0,05). The latency period of paradoxical sleep was 34.2%higher than kindling rats (P&lt;0.05). &#x0D; Conclusions. The formation of PTZ-kindling is accompanied by a reduction in the latent period of emergence and the total duration of the paradoxical phase of sleep, as well as an increase in its fragmentation. Blocking of H3 histamine receptors by pitolisan during the formation of kindling by administration of pentylenetetrazol prevents the occurrence of wake-sleep cycle disorders.

Acid-suppressive drugs: A systematic review and network meta-analysis of their nocturnal acid-inhibitory effect.

Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs). To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA). Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB. This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.

Functional Dyspepsia (FD) and the Use of Sulpiride (Atypical Antipsychotic) in Family Practice– A Case Report

Functional dyspepsia (FD), a commonly prevalent multifactorial disorder of gut-brain interaction (DGBI), is encountered and managed in family practice and gastroenterology clinics. The diagnosis is solely clinical based on Rome-IV criteria, excluding the organic, systemic, or metabolic causes. Management is often challenging ranging from lifestyle modifications, H-pylori eradication, H2-receptor antagonists, proton pump inhibitors, and prokinetics (1st-line) to antidepressants, and antipsychotics (2nd line) of therapy, once the patient shows no response to 1st line. In severe cases, refractory to 1st &amp; the 2nd line of treatment needs a team approach and gut-brain behavioral therapy. Herein, we present a young female patient diagnosed with FD, managed well with 2nd-line treatment (Sulpiride), an atypical antipsychotic medication, as the patient's symptoms showed no improvement with first-line treatment.

An Overview of Antihistamines and their Properties used for Treatment of Different Diseases.

By comparing the histamine impact to the instant response to an injected foreign protein in previously sensitized animals, one might hypothesize that histamine may be involved in this reaction. Through all four of the recognized types of histamine receptors, histamine is also essential for the control of immunological function and acute and chronic allergic inflammation. Recent evidence points to anti-IgE antibodies and specific antibodies to cytokines like IL-4 or IL-5 that are associated with allergic inflammation as probable causes of Allergic Rhinitis. The therapeutic advantage of antihistamines is a decrease in allergy symptoms and any other allergy-related symptoms. We research the many diseases and dose forms in which antihistamines are used. Pediatric age groups have never been thoroughly studied for firstgeneration antihistamines. Oral antihistamines are suggested as the first line of therapy for people with mild to severe intermittent Allergic Rhinitis symptoms. Currently, approximately 100 different antihistamine-containing medicines and around 20 different H1-receptor antagonists are available for therapeutic use. Antihistamines of the second generation are more efficient and secure than those of the first generation. We conducted a research on the sedative and non-sedative effects of antihistamines used to treat various diseases. The present investigation highlights the use of antihistamines in various diseases at different ages, their sedative and non-sedative effect, and their utility in treating insomnia based on their safety and current use among the patient population, as well as our observation.

Development and Evaluation of Ranitidine Floating Tablet for Ulcer Healing and Soothing

In this current work floating tablets of ranitidine and aloe vera was prepared. The objective behind the work was to develop a formulation of H2 antagonist in collaboration with aloe vera to produce an ulcer soothing and ulcer protective effect. Ranitidine is a histamine H2-receptor antagonist. It is widely prescribed in active duodenal ulcers, gastric ulcers, Zollinger-Ellison syndrome, gastroesophageal reflux disease, and erosive esophagitis. The effective treatment of erosive esophagitis requires administration of 150 mg of Ranitidine, four times a day. A conventional dose of 150 mg can inhibit gastric acid whereas aloe vera will produce ulcer soothing affect and laxative effect too. In- vitro buoyancy studies were performed for all the ten formulations as per the method described by Rosa et al. The randomly selected tablets from each formulation were kept in a 100ml beaker containing simulated gastric fluid, pH 1.2 as per USP. The time taken for the tablet to rise to the surface and float was taken as floating lag time (FLT).