Histamine H2 Blockers Research Articles

Population pharmacokinetics and exposure-response relationships of maribavir in transplant recipients with cytomegalovirus infection.

Maribavir is approved for management of post-transplant cytomegalovirus (CMV) infections refractory and/or resistant to CMV therapies at a dose of 400mg twice daily (BID). Population pharmacokinetic (PopPK) and exposure-response analyses were conducted to support the appropriateness of 400mg BID dosing. A PopPK model was developed using non-linear mixed-effects modeling with pooled maribavir plasma concentration-time data from phase 1 and 2 studies (from 100mg up to 1200mg as single or repeated doses) and the phase 3 SOLSTICE study (400mg BID). Exposure-response analyses were performed for efficacy, safety, and viral resistance based on data collected in the SOLSTICE study. Maribavir PK after oral administration was adequately described by a two-compartment model with first-order elimination, first-order absorption, and an absorption lag-time. There was no evidence that maribavir PK was affected by age, sex, race, diarrhea, vomiting, disease characteristics, or concomitant use of histamine H2 blockers, or proton pump inhibitors. In the SOLSTICE study, higher maribavir exposure was not associated with increased probability of achieving CMV DNA viremia clearance, nor with reduced probability of treatment-emergent maribavir-resistant CMV mutations. A statistically significant association with maribavir exposure was identified for taste disturbance, fatigue, and treatment-emergent serious adverse events, while transplant type, enrollment region, CMV DNA level at baseline, and/or CMV resistance at baseline were identified as additional risk factors for these safety outcomes. In conclusion, the findings of these PopPK and exposure-response analyses provide further support for the recommended maribavir dose of 400mg BID.

2446. Effect of the Implementation of a Fluconazole Prophylaxis Protocol on the Incidence of Invasive Fungal Infection in High-Risk Neonates

Abstract Background Invasive fungal infection (IFI) is one of the most important causes of morbidity and mortality in the neonatal intensive care unit. International societies have supported the use of fluconazole prophylaxis for neonates weighing < 1000 grams, but administration to other high-risk patients remains controversial. An institutional fluconazole prophylaxis guideline was implemented in December 2020 to include two other groups of neonates. Methods One hundred thirty infants who were admitted at the NICU from January 2020 to January 2022 and fulfilled one of the following criteria: weight of < 1000 grams (Group A), weight of ≤1500 grams and on broad-spectrum antibiotics (Group B), or weight of >1500 grams and on prolonged nil per os (NPO) (Group C) were included in the study. They were divided into two groups: those who were born prior to the implementation of the protocol (January to December 2020) and not given fluconazole prophylaxis, and those born after (January 2021 to January 2022) and given prophylaxis. The primary outcome was the development of IFI. Results A total of 130 infants were included in this study with 21 (5 control, 16 prophylaxis), 69 (28 control, 41 prophylaxis), and 40 (16 control, 24 prophylaxis) patients in Groups A, B, and C, respectively. There were no significant differences in the development of IFI among the groups (Group A: control - 40%, prophylaxis - 62%; Group B: control - 21.4%, prophylaxis - 22%; Group C: control - 29.2%, prophylaxis 31.5%) with a p-value of > 0.05. The presence of a central vascular access line, endotracheal tube, placement on NPO, histamine H2-blockers, and necrotizing enterocolitis were associated with the development of IFI. Candida parapsilosis comprised 60% of isolates. All isolates had 100% susceptibility to fluconazole. Jaundice developed in 3.7% of patients given fluconazole, with elevations in AST, ALT, and TB. Incidence of fungal infection in high-risk neonates There were no significant differences in the development of IFI among the three high-risk groups, with p-value of > 0.05. Conclusion Invasive fungal infection remains a heavy burden to high-risk neonates. The protocol at present does not significantly prevent the occurrence of IFI. There is a need to revise the protocol to include the presence of a combination of multiple risk factors (central line, endotracheal tube, prolonged NPO, H2-blockers, and necrotizing enterocolitis) before initiating fluconazole prophylaxis. Disclosures All Authors: No reported disclosures

Prevalence of polypharmacy in heart failure patients: A retrospective cross-sectional study in a tertiary hospital in Saudi Arabia

BackgroundCardiovascular disease is the leading cause of death and disability worldwide. It is a general term used to describe a group of disorders that affect the heart or blood vessels. This study aimed to evaluate the prevalence and predictors of polypharmacy in patients with heart failure. MethodsWe conducted a cross-sectional study in a tertiary hospital in Saudi Arabia. Data was extracted from an electronic database between January 2019, and December 2022. The study included all adult patients with heart failure who visited outpatient clinics; individuals with cancer were excluded. The outcome variable in our study was “polypharmacy” which was defined as the use of eight or more medications. Descriptive analysis was performed using frequencies and percentages for categorical variables. In addition, Multivariate logistic regression was used to assess the covariates associated with polypharmacy. ResultsA total of 331 patients with heart failure were included in this study. The prevalence of polypharmacy among our HF population was 39.88 %. Most participants were male (60.73 %), and 60 years or older (68 %). The most frequently used medications were beta-blockers (67.98 %) and diuretics (58.31 %), whereas the least frequently used medications were hydralazine and histamine H2 blockers (5.74, and 3.02 %, respectively). Polypharmacy was likely to be a non-significantly higher in individuals aged between 60 and 69 years (adjusted odds ratio (AOR) = 1.52; 95 % confidence interval (CI) 0.78–2.98) and suffering from hypertension (AOR = 1.48; 95 % CI 0.83–2.64). However, patients with heart failure and diabetes mellitus had a significant six-fold higher of polypharmacy than those without diabetes mellitus (AOR = 6.55; 95 % CI 3.71–11.56). ConclusionPatients with heart failure often use multiple medications. Patients with heart failure together with diabetes have a higher risk of polypharmacy. Therefore, healthcare professionals should manage polypharmacy to improve the outcomes in patients with heart failure.

Detection of potential drug-drug interactions for risk of acute kidney injury: a population-based case-control study using interpretable machine-learning models.

Background: Acute kidney injury (AKI), with an increase in serum creatinine, is a common adverse drug event. Although various clinical studies have investigated whether a combination of two nephrotoxic drugs has an increased risk of AKI using traditional statistical models such as multivariable logistic regression (MLR), the evaluation metrics have not been evaluated despite the fact that traditional statistical models may over-fit the data. The aim of the present study was to detect drug-drug interactions with an increased risk of AKI by interpreting machine-learning models to avoid overfitting. Methods: We developed six machine-learning models trained using electronic medical records: MLR, logistic least absolute shrinkage and selection operator regression (LLR), random forest, extreme gradient boosting (XGB) tree, and two support vector machine models (kernel = linear function and radial basis function). In order to detect drug-drug interactions, the XGB and LLR models that showed good predictive performance were interpreted by SHapley Additive exPlanations (SHAP) and relative excess risk due to interaction (RERI), respectively. Results: Among approximately 2.5 million patients, 65,667 patients were extracted from the electronic medical records, and assigned to case (N = 5,319) and control (N = 60,348) groups. In the XGB model, a combination of loop diuretic and histamine H2 blocker [mean (|SHAP|) = 0.011] was identified as a relatively important risk factor for AKI. The combination of loop diuretic and H2 blocker showed a significant synergistic interaction on an additive scale (RERI 1.289, 95% confidence interval 0.226-5.591) also in the LLR model. Conclusion: The present population-based case-control study using interpretable machine-learning models suggested that although the relative importance of the individual and combined effects of loop diuretics and H2 blockers is lower than that of well-known risk factors such as older age and sex, concomitant use of a loop diuretic and histamine H2 blocker is associated with increased risk of AKI.

Using anti-acid therapy in era of COVID-19 pandemic: Potential pros and cons

This review articles shows evidence that while PPI treatment may be associated with an increased risk of SARS-CoV-2 infection, recent findings have shown no effect of current PPI treatment on COVID-19 outcome, suggesting that previous inconsistent results were likely due to differences in study design and population. Attempts to transfer patients with COVID-19 infection to H2 histamine blockers are not entirely justified, since despite some positive aspects in the effect on the virus, standard therapeutic doses of drugs for the treatment of gastroesophageal reflux disease and other acid-associated diseases are insufficient to achieve a clinical effect at this category of patients.

Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer.

BackgroundIn early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose‐dense (DD) doxorubicin‐cyclophosphamide (AC)–paclitaxel regimen.Patients, Materials, and MethodsIn this prospective, single‐arm study, patients who completed four cycles of DD‐AC for stage I–III breast cancer received paclitaxel 175 mg/m2 every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3–4 HSRs.ResultsAmong 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%–20.0%) patients had any‐grade HSRs, for a total of 22 (4.5%; 3.1%–6.4%) HSRs over 486 paclitaxel cycles. Any‐grade HSRs occurred in 1.6% (0.3%–5.0%), 6.5% (3.3%–11.3%), 7.4% (3.9%–12.5%), and 2.6% (0.7%–6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%–2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any‐grade HSRs occurred in 2.7% (3/111; 0.7%–6.8%) and 0.9% (1/109; 0.05%–4.3%) of patients in cycle 3 and 4, respectively.ConclusionCorticosteroid premedication can be safely omitted in cycles 3 and 4 of dose‐dense paclitaxel if HSRs are not observed during cycles 1 and 2.Implications for PracticeBecause of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care.

Нестероидные противовоспалительные средства: современное представление о механизмах повреждения пищеварительного тракта, минусы препаратов патогенетического лечения и перспективы биологической терапии НПВС-индуцированной эзофагогастроэнтероколонопатии

Актуальность. Нестероидные противовоспалительные средства (НПВС) ежедневно применяют более чем 30 млн человек, а их арсенал насчитывает свыше 80 препаратов и около 1000 созданных на их основе лекарственных форм. Они широко используются во многих сферах медицины и являются одной из наиболее клинически значимых групп лекарственных средств. Однако при использовании НПВС достаточно часто могут возникать побочные реакции, наиболее распространенными из них являются повреждения желудочно-кишечного тракта. Цель: охарактеризовать со­временное представление о механизмах повреждения пищеварительного тракта НПВС, оценить недостатки существующих препаратов патогенетического лечения и перспективы биологической терапии НПВС-индуцированной эзофагогастроэнтероколонопатии криоконсервированным экстрактом плаценты человека. Материалы и методы. Проведен анализ работ, опубликованных в 2010–2020 гг., в которых освещались сведения об эпидемиологии, патогенезе, диагностике и тактике лечения поражений пищевода и желудочно-кишечного тракта, индуцированных НПВС, а также биологические свойства криоконсервированного экстракта плаценты человека как средства биологической терапии. Результаты. Лечение НПВС-индуцированной эзофагогастроэнтероколонопатии классически направлено на кислотосупрессивную терапию (ингибиторы протонной помпы, Н2-гистаминоблокаторы и др.), применение гастроцитопротекторов (де-нол, сукральфат и др.) и препаратов, восстанавливающих содержание простагландинов в слизистой оболочке (мизопростол, ребамипид и др.). Однако все указанные группы лекарственных средств недостаточно удовлетворяют клиницистов, поскольку направлены преимущественно на лечение НПВС-гастропатии и имеют побочные эффекты. Новым перспективным направлением повышения безопасности НПВС на сегодняшний день является применение средств биологической терапии, источниками которых выступают микроорганизмы, органы и ткани растительного или животного происхождения, клетки или жидкости (в том числе кровь и плазма) человеческого или животного происхождения и биотехнологические клеточные конструкции. Выводы. Использование НПВС значительно ограничивается присущими им побочными эффектами, наи­более распространенными являются нарушения со стороны желудочно-кишечного тракта. Криоконсервированный экстракт плаценты человека является перспективным средством биологической терапии ульцерогенных повреждений желудочно-кишечного тракта, индуцированных НПВС.

Theoretical evaluation of electroanalitical determination of diazoline (mebhydrolin) on a polymer electrode

Mebhydrolin, the active substance of diazoline, is a histamine H1-blocker that possesses the anti-allergic, anti-pruritic, antioxidative properties as well as weak sedative effect. It is used to treat diseases and pathological conditions. Its long-term and excessive use leads to different side effects and complications such as granulocytopenia, neutropenia, dyscrasia, and granulocytosis. That is why the development of effective methods for determining the concentration of this drug is vital. There are no reports to date available on the electrochemical determination of diazoline (mebhydrolin). Based on the structural characteristics of the molecule it can be concluded that it is an electroactive compound. Its oxidation can effectively occur on the conductive polymer layer. Moreover, the electrochemical behavior of the drug promises to be very interesting, as it is developed by a complicated mechanism. In this work, the electrochemical determination of a mebhydrolin concentration on the leading polymer was studied from a theoretical point of view. The polymerization and the reactions sequences was describe by a mathematical model, which was derived and analyzed using linear stability theory and bifurcation analysis. From the model analysis we concluded that: a). The polymer electrode promotes an electrooxidation of mebhydrolin and the system is electroanalytically effective. The relationship between the electrochemical parameter (the current) and the concentration of nitrite is described and it is linear in nature. Therefore, the analytical signal can be easily interpreted. b). The electroanalytical process occurs in the diffusion mode at low concentrations of the analyte and in the adsorption mode at high concentration. c). The oscillatory behavior of this system is possible. It is caused by the effects of the electrochemical stage on PES as well as also by surface instabilities.

Potential synergistic effects of novel hematopoietic prostaglandin D synthase inhibitor TAS-205 and different types of anti-allergic medicine on nasal obstruction in a Guinea pig model of experimental allergic rhinitis

Nasal obstruction is one of the most bothersome symptoms of allergic rhinitis (AR) affecting sleep-related quality of life in AR patients. Although several treatments were tested to control nasal obstruction, some patients with moderate to severe AR do not respond to current treatments, including the combined administration of different types of anti-allergic medicine. Thus, new options for AR treatment are needed. This study aimed to evaluate the effects of combined treatment with a novel inhibitor of hematopoietic prostaglandin D synthase (HPGDS), TAS-205, and different types of anti-allergic medicine on nasal obstruction in AR. Firstly, we demonstrated that TAS-205 selectively inhibited prostaglandin D2 (PGD2) synthesis in an enzymatic assay in a cell-based assay and in vivo models of AR. Moreover, treatment with TAS-205 alone suppressed eosinophil infiltration into the nasal cavity and late phase nasal obstruction. The combined administration of TAS-205 with montelukast, a cysteinyl leukotriene receptor 1 antagonist, showed significant additive inhibitory effects on eosinophil infiltration and late phase nasal obstruction compared to treatment with each agent alone. In contrast, concomitant treatment with TAS-205 and fexofenadine, a histamine H1 blocker, showed inhibitory effects on late phase and early phase nasal obstruction, although the magnitude of the inhibitory effects upon combined administration was comparable to that of each single treatment. These results suggest that combined treatment with an HPGDS inhibitor and different types of anti-allergic medicine may be a promising strategy to control nasal obstruction in AR patients.

HYBID (alias KIAA1199/CEMIP) and hyaluronan synthase coordinately regulate hyaluronan metabolism in histamine-stimulated skin fibroblasts

The immune-regulatory compound histamine is involved in the metabolism of the essential skin component hyaluronan (HA). We previously reported that histamine up-regulates the expression of HYBID (hyaluronan-binding protein involved in hyaluronan depolymerization, also called CEMIP or KIAA1199), which plays a key role in HA degradation. However, no information is available about histamine's effects on HA synthase (HAS) expression, the molecular sizes of HA species produced, and histamine receptors and their signaling pathways in skin fibroblasts. Moreover, histamine's effects on photoaged skin remain elusive. Here, we show that histamine increases HA degradation by up-regulating HYBID and down-regulating HAS2 in human skin fibroblasts in a dose- and time-dependent manner and thereby decreases the total amounts and sizes of newly produced HA. Histamine H1 blocker abrogated the histamine effects on HYBID up-regulation, HAS2 suppression, and HA degradation. Histamine H1 agonist exhibited effects on HA levels, composition, and breakdown similar to those of histamine. Of note, blockade of protein kinase Cδ or PI3K-Akt signaling abolished histamine-mediated HYBID stimulation and HAS2 suppression, respectively. Immunohistochemical experiments revealed a significant ∼2-fold increase in tryptase-positive mast cells in photoaged skin, where HYBID and HAS2 expression levels were increased and decreased, respectively, compared with photoprotected skin. These results indicate that histamine controls HA metabolism by up-regulating HYBID and down-regulating HAS2 via distinct signaling pathways downstream of histamine receptor H1. They further suggest that histamine may contribute to photoaged skin damage by skewing HA metabolism toward degradation.

Acid-neutralising capacity and pharmacoeconomic studies of commercially available antacids in the Qassim Region of Saudi Arabia

Background: Antacids are common over-the-counter medications for relief in common dyspeptic symptoms. However, antacid use has decreased with the availability powerful acid suppressant medications such as histamine H2 blockers, proton-pump inhibitors and prostaglandin analogues. Of late, a resurgence in the usage of antacids has been noted because of the improved profiles of newer antacid formulations, for example, the addition of pain-relieving component, oxetacaine (a local anaesthetic), anti-flatulent (alginate base compounds), in some antacid preparations. Aims and Objectives: The study investigated the efficacy (in terms of acid-neutralising capacity [ANC]) and cost-effectiveness of commercially available antacid formulations (both liquid and solid formulations). Materials and Methods: ANC was carried out using simple titrimetric methods and cost-effectiveness of antacid preparations was based on cost (in Saudi riyal) per milliequivalents of the acid neutralised. Results: ANC/gram was highest for antacid A1 (Moxal Plus solid) and lowest for antacid A3 (Fawar effervescent powder). The ANC/gram varied greatly among different antacid products and it ranged from 3.48 to 13.18. In general, solid antacids showed a high ANC/gram compared to the liquid antacids. Furthermore, solid antacids were also found to be cost-effective compared to liquid dosage forms. In terms of efficacy, the newer antacid containing simethicone (A1) was found to be more cost-effective followed an antacid containing calcium carbonate (A2) and magnesium carbonate. Conclusion: In conclusion, mentioning ANC on antacid formulation labels may help to guide the choice of appropriate antacid, while cost-effectiveness study would govern the prescribing pattern of an antacid.

Инфекция, вызванная Clostridioides (Clostridium) difficile. Обзор актуальных клинических рекомендаций

Clostridioides difficile (CDI) infection is a disease associated with a disruption of the gut microbiome with over-colonization of C. difficile, the toxins of which cause inflammation and damage to the colon. A dynamic assessment of the CDI prevalence indicates a significant increase in laboratory-confirmed cases of infection and a high mortality associated with it. C. difficile is recognized as the main causative agent of nosocomial infections in Europe, USA, Canada and Australia, which develops 48 hours after hospitalization in a medical facility and within 12 weeks after discharge. The severity of CDI is determined by the severity of infectious-toxic, diarrheal and abdominal syndromes. Severe CDI is characterized by manifestations of colitis, accompanied by severe leukocytosis, a decrease in albumin levels and an increase in serum creatinine levels. Development of fulminant forms, pseudomembranous colitis, toxic megacolon, intestinal perforation, sepsis is possible. The risk factors include in-hospital stay; recent use of antibiotics (within the previous 12 weeks, especially the use of fluoroquinolones, cephalosporins of III–IV generations, carbapenems and clindamycin), PPI and H2-histamine blockers; presence of inflammatory bowel diseases (ulcerative colitis, Crohn’s disease), immunodeficiency states, including iatrogenic; recent endoscopic examinations, surgical interventions on the gastrointestinal tract, tube feeding, enemas; possible contact with a family member who recently had a C..difficile infection. The «gold standard» for confirming the CDI diagnosis is the identification of the causative agent and/or toxins of C. difficile in the stool using specific laboratory research methods. Vancomycin or metronidazole are recommended as first-line therapy.

Clinical pharmacology of antisecretory drugs. Focus on H2-histamine receptor blockers

The purpose of the review is to illuminate the physiology of hydrochloric acid secretion and the clinical pharmacology of H2-histamine receptor blockers, also known as H2-histamine receptor antagonists, H2-histamine blockers, and H2-blockers.The main provisions. Antagonists of H2-histamine receptors (cimetidine, ranitidine, famotidine, nizatidine, lafutidin) selectively block the histamine receptors of parietal cells, preventing the activation of acid secretion by histamine secreted by enterochromaffin-like cells of the stomach. When using the means of this pharmacological group, both the total amount of gastric juice and its acidity decrease. H2-histamine blockers are rapidly absorbed after oral administration and for a long time inhibit the basal and stimulated acidity of the gastric mucosa. This class of drugs is approved by the FDA for short-term use in the treatment of uncomplicated gastroesophageal reflux disease, peptic ulcer or duodenal ulcer, hypersecretion of the stomach and mild infrequent heartburn. Off-label H2-histamine receptor blockers can also be used to prevent stress ulcers, esophagitis, gastritis, and gastrointestinal bleeding. Sometimes H2-histamine blockers are included in the Helicobacter pylori eradication regimen. Due to their safety, H2-histamine blockers are sold over the counter. However, they are gradually replaced by even more effective drugs - inhibitors of H+,K+-ATPase (PPI).Conclusion. H2-histamine receptor antagonists inhibit basal, nocturnal and stimulated secretion. Despite the presence of powerful antisecretory drugs in the doctor’s arsenal, such as proton pump inhibitors, H2-histamine blockers have not lost their importance in clinical practice. The knowledge of the clinical pharmacology of H2-histamine receptor blockers allows a competent approach to the choice of a treatment strategy and monitoring the safety and effectiveness of treatment of patients with acid-dependent diseases.

Marine Bacterial Compounds Evaluated by In Silico Studies as Antipsychotic Drugs Against Schizophrenia.

Schizophrenia (SCZ) is one of the brain disorders which affects the thinking and behavioral skills of patients. This disorder comes along with an overproduction of kynurenic acid in the cerebrospinal fluid and the prefrontal cortex of SCZ patients. In this study, marine bacterial compounds were screened for their suitability as antagonists against human kynurenine aminotransferase (hKAT-1) which causes the synthesis of kynurenic acid downstream which ultimately causes the SCZ disorder according to the kynurenic hypothesis of SCZ. The marine actinobacterial compound bonactin shows more promising results than other tested marine compounds such as the histamine H2 blocker famotidine and indole-3-acetic acid (IAC) from docking and in silico toxicological studies carried out here. The obtained results of the Grid-based Ligand Docking with Energetics (Glide) scores of extra-precision (XP) Glide against the target protein hKAT-1 on IAC, famotidine, and bonactin were - 6.581, - 6.500 and - 7.730kcal/mol where Glide energies were - 29.84, - 28.391, and - 47.565kcal/mol, respectively. Bonactin is known as an antibacterial and antifungal compound being extracted from a marine Streptomyces sp. Comparing tested compounds against the drug target hKAT-1, bonactin alone showed the best Glide score and Glide energy on the target protein hKAT-1.

Preventive and therapeutic strategies of pharmaco-correction gastropathy induced by nonsteroidal anti-inflammatory drugs

Today the problem of prevention and treatment of gastropathy associated with nonsteroidal anti-inflammatory drugs has not lost its relevance. In order to reduce the ulcerogenicity of non-steroidal anti-inflammatory drugs, it is classically accepted to supplement the therapy scheme with preparations of other pharmacological groups - antacids, alginates, M-cholinoblockers, gastrin receptor antagonists, H2-histamine blockers, proton pump inhibitors, synthetic analogues of prostaglandins or stimulators of their synthesis, reparants, gastroprotectors. Nowadays, it was suggested I was suggested the use of drugs which have pharmacological properties polyvector (vinboron, thiotriazoline et al.). Also, the scientists started of combined preparations “NSAIDs + drugs other pharmacological groups” - indotril (indomethacin + thiotriazoline) diklokor (diclofenac + quercetin) Artrotek (diclofenac sodium + misoprostol) dueksis (ibuprofen + famotidine) vimovo (naproxen + esomeprazole) aksorid (ketoprofen + omeprazole) tioaspekard (thiotriazoline + ACK) aspifat (ACK + sucralfate), Alka-Zelttser® (ACK + sodium bicarbonate), and others. The second direction is preventing and improving NSAID gastrotoxicity protrudes improving existing non-steroidal drugs - modification of gaseous molecules (NO, H2S, CO), amino acid derivatives, modulators “effector function” of afferent terminals n. vagus (amtolmetina guatsil) то pairing with nanoparticles biometals (Zn-ibuprofen, Zn-naproxen, Zn-indomethacin). (For citation: Hladkykh FV. Preventive and therapeutic strategies of pharmaco-correction gastropathy induced by nonsteroidal anti-inflammatory drugs. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):14-23. doi: 10.17816/RCF15414-23).

Histamine H2-Blocker and Proton Pump Inhibitor Use and the Risk of Pneumonia in Acute Stroke: A Retrospective Analysis on Susceptible Patients.

BackgroundAlthough histamine H2-blockers (H2B) and proton pump inhibitors (PPI) are used commonly to prevent gastrointestinal bleeding in acute stroke, they are implicated in the increased risk of pneumonia in other disease populations. In acute stroke, the presence of distinctive risk factors of pneumonia, including dysphagia and impaired consciousness, makes inclusive analysis vulnerable to confounding. Our aim was to assess whether acid-suppressive drugs increase pneumonia in acute stroke in a population controlled for confounding.MethodsWe analyzed acute stroke patients admitted to a tertiary care hospital. To minimize confounding, we only included subjects who could not feed orally during 14 days of hospitalization. Exposure was defined as H2B or PPI, given in days; the outcome was development of pneumonia within this period. The incidence was calculated from the total number of pneumonias divided by the sum of person-days at risk. We additionally performed multivariate Poisson regression and propensity score analyses, although the restriction largely eliminated the need for multivariate adjustment.ResultsA total of 132 pneumonias occurred in 3582 person-days. The incidence was 3.69%/person-day (95% confidence interval (CI); 3.03–4.37%/day). All subjects had dysphagia. Stroke severity and consciousness disturbances were well-balanced between the groups exposed to H2B, PPI, or none. The relative risk (RR) compared with the unexposed was 1.22 in H2B (95%CI; 0.83–1.81) and 2.07 in PPI (95% CI; 1.13–3.62). The RR of PPI compared with H2B was 1.69 (95%CI; 0.95–2.89). In multivariate regression analysis, the RRs of H2B and PPI were 1.24 (95% CI; 0.85–1.81) and 2.00 (95% CI; 1.12–3.57), respectively; in propensity score analyses they were 1.17 (95% CI; 0.89–1.54) and 2.13 (95% CI; 1.60–2.84).ConclusionsThe results of this study suggested that prophylactic acid-suppressive therapy with PPI may have to be avoided in acute stroke patients susceptible to pneumonia.

Safety of histamine H2 blocker concomitant administration in patients treated with high dose methotrexate regimen.

e21643Background: Despite its effectiveness proven in a wide range of oncologic malignancies, use of high dose methotrexate (MTX) regimen is limited by potentially lethal non-hematologic toxicities...

Biosensor cell assay for measuring real-time aldosterone-induced release of histamine from mesenteric arteries.

The aims were to develop a method for real-time detection of histamine release and to test whether incubation with aldosterone induces histamine release from isolated, perfused mice mesenteric arteries. Fura-2-loaded HEK-293 cells transfected with the histamine H1 receptor was used as a sensitive biosensor assay for histamine release from isolated mouse mesenteric arteries. Activation of the H1 receptor by histamine was measured as an increased number of intracellular Ca2+ transient peaks using fluorescence imaging. The developed biosensor was sensitive to histamine in physiological relevant concentrations and responded to substances released by the artery preparation. Aldosterone treatment of mesenteric arteries from wild-type mice for 50min resulted in an increased number of intracellular Ca2+ transient peaks in the biosensor cells, which was significantly inhibited by the histamine H1 blocker pyrilamine. Mesenteric arteries from mast cell-deficient SASH mice induced similar pyrilamine-sensitive Ca2+ transient response in the biosensor cells. Mesenteric arteries from wild-type and SASH mice expressed histamine decarboxylase mRNA, indicating that mast cells are not the only source of histamine release. The developed biosensor assay can measure release of substances from vascular preparations. Histamine is released from the vessel preparation in response to aldosterone treatment independently of mast cells. The assay enables us to study a new signaling mechanism for vascular responses induced by aldosterone.

Drug utilization pattern of NSAIDs assessed with the anatomical therapeutic chemical classification/defined daily dose system in an orthopedic department

To study the drug utilization pattern of NSAIDs using the Anatomical Therapeutic Chemical classification/Defined Daily Dose (ATC/DDD) system in patients admitted to the orthopedic department of a tertiary-care teaching hospital. A cross-sectional prospective observational study was carried out in 200 patients from March to August 2014. Demographic information, disease related details, drug history and adverse drug reactions (ADRs) were recorded by personal interview and from case files daily for drug utilization analysis. The majority of patients were aged 18–30 years (30 %), most were male (80 %) and the most common orthopaedic condition causing hospitalization was fracture/dislocation (77 %). The most commonly prescribed drug group was analgesics, with NSAIDs being the most commonly prescribed type of analgesic (97 %). The majority of prescribed drugs were from the World Health Organization (WHO) Essential Medicine List (92 %) and Indian national essential drug list (100 %). Polypharmacy and high polypharmacy was reported in 71 and 14.5 % of patients respectively. No fixed-dose combinations of analgesics were used. Oral tablet diclofenac (M01AB05) 50 mg was the most frequently prescribed analgesic (97 % of patients; 840.5 DDD), followed by intravenous injection tramadol (N02AX02) in 56 % (189.3 DDD), intramuscular injection diclofenac (M01AB05) 75 mg in 55 % (87 DDD) and oral tablet paracetamol (N02BE01) 500 mg in 38.5 % (58.3 DDD) of patients. ADRs (mainly gastritis despite concomitant use of histamine H2 blockers) were reported in 4 % of patients; all ADRs were of ‘possible’ category according to the WHO–Uppsala Monitoring Centre causality assessment method. Fracture-dislocation and arthritis were the most common causes for hospitalization in the orthopedic department. Selection of analgesics and their dosage regimen complied with the WHO guidelines of pain management.

Improvement of Sleepiness in Connective Tissue Disorders Following H1/H2 Blockade

Improvement of Sleepiness in Connective Tissue Disorders Following H1/H2 Blockade This report describes two patients with connective tissue disorders, Ehlers-Danlos syndrome and systemic lupus erythematosus (SLE), presenting with excessive daytime sleepiness. It has been suggested that these conditions involve activation of mast cells, which in turn is at least partially responsible for the symptoms of sleepiness. The two patients described were treated with H1 and H2 histamine blockers, and had experienced profound improvement in their subjective symptoms. These cases will hopefully inspire further research and discussion in this area.