Disulfiram-like reactions occur when alcohol is consumed concurrently with certain drugs and can sometimes be fatal. Some cephalosporins such as cefoperazone could cause disulfiram-like reaction, known as cephalosporin-induced disulfiram-like reactions (CIDLRs). We describe a case of cefmetazole (CMZ)-treated CIDLR triggered by alcohol consumption. A 72-year-old Japanese man, treated with CMZ for perforated appendicitis and subsequent paralytic ileus, presented with skin flushing and chest discomfort, developing 30 min after consuming usual meals and alcohol. CIDLR was diagnosed due to recent use of CMZ and the symptoms alleviated without any medication. This is the first case report of a CMZ-induced disulfiram-like reaction.

In addition to sensitivity, selectivity, and portability, chemical sensing systems must generate reliable signals and offer modular configurability to address various small molecule targets, particularly in environmental applications. We present a versatile, modular strategy utilizing ratiometric molecularly imprinted particle probes based on BODIPY indicators and dyes for recognition and internal referencing. Our approach employs polystyrene core particles doped with a red fluorescent BODIPY as an internal standard, providing built-in reference for environmental influences. A molecularly imprinted polymer (MIP) recognition shell, incorporating a green-fluorescent BODIPY indicator monomer with a thiourea binding site for carboxylate-containing analytes, is grafted from the core particles in the presence of the analyte as the template. The dual-fluorescent MIP probe detects fexofenadine as the model analyte with a change in green emission signal referenced against a stable red signal, achieving a detection limit of 0.13 μM and a broad dynamic range from 0.16 μM to 1.2 mM, with good discrimination against other antibiotics in acetonitrile. By selecting a versatile dye scaffold and recognition element, this approach can be extended to other carboxylate-containing analytes and/or wavelength combinations, potentially serving as a robust multiplexing platform.

UNASSIGNED: Chronic spontaneous urticaria (CSU) is characterized by urticaria persisting for more than 6 weeks and leading to significant morbidity. Antihistamines, especially sgAH (second generation antihistamines) are the first line of treatment for CSU.
UNASSIGNED: This consensus aimed to review the existing translational research on the receptor occupancy of antihistamines, including levocetirizine, and establish its role in the treatment of CSU. The consensus was led by the Antihistamine Receptor Occupancy Group (AROG) from India, an expert panel of twelve dermatologists from various regions with a mix of institutional and practitioner backgrounds. This consensus analyzed the existing translational research on the receptor occupancy of levocetirizine to establish its clinical efficacy and safety of levocetirizine in the treatment of CSU using the grading of recommendations assessment, development, and evaluation (GRADE) method as compared to the varied SGAH.
UNASSIGNED: Second-generation antihistamines constitute the first step in the therapeutic ladder for managing CSU. Levocetirizine has high bioavailability, a high affinity for and occupancy of the H1 receptor, a rapid onset of action, limited distribution, and minimal hepatic metabolism. It exhibits significant anti-inflammatory effects at clinically relevant concentrations. The marked receptor occupancy translates to better efficacy as compared to similarly dosed SGAH and the lower cost of the molecule makes it an appropriate drug for chronic use. Receptor occupancy should serve as the basis of intra-class head-to-head trials for CSU.

In a double-blind, randomized controlled trial, we investigated the effectiveness of adding antiplatelet drugs to up-dosing antihistamines for the treatment of chronic spontaneous urticaria (CSU) in patients with elevated D-dimer levels who had an inadequate response to conventional antihistamine doses. Twenty patients with Urticaria Activity Score over 7 days (UAS7) ≥16 and D-dimer >500 ng/mL were randomized to receive either antiplatelet therapy (cilostazol 150 mg/day + dipyridamole 50 mg/day) with antihistamine (desloratadine 20 mg/day) or antihistamine alone for 4 weeks. The antiplatelet group demonstrated a greater decrease in UAS7 compared to the control group (28.10 to 8.90 vs. 22.90 to 16.40, p < 0.001 vs. p = 0.054). Both groups experienced improved quality of life (DLQI), but the improvement was greater in the antiplatelet group (p = 0.046). D-dimer levels decreased only in the antiplatelet group (1133.67 ng/mL to 581.89 ng/mL, p = 0.013) with no significant change observed in the control group. This suggests that combining dipyridamole and cilostazol with up-dosing antihistamines may be more effective for CSU patients with high D-dimer levels compared to up-dosing antihistamines alone. This could be due to a reduction in platelet activation, as evidenced by the decrease in D-dimer levels observed in the antiplatelet group.

Allergic rhinitis (AR) can significantly reduce the quality of life of patients leading to increased fatigue, mood changes, cognitive impairment, and depression. In clinical practice, insufficient effectiveness of initial AR monotherapy is often noted, and a significant proportion of patients referring for medical care have moderate-severe AR. In this regard, the issues of optimization of combined pharmacological treatment of AR are becoming more and more urgent. This paper provides analysis of the opportunities of combined pharmacotherapy within the framework of current management strategy of AR. Based on the results of some studies and known pharmacological properties of medications it is being discussed the advantages of combined use of intranasal corticosteroids and leukotriene receptor antagonists, in particular mometasone furoate and montelukast, in the therapy of AR, including such comorbidities as bronchial asthma, chronic polyposis rhinosinusitis and pharyngeal tonsil hyperplasia. Some aspects of combination therapy with montelukast and second-generation systemic antihistamines as an alternative approach in case of inability to take intranasal corticosteroids, including the reasonability of using a fixed combination of montelukast and levocetirizine, are analyzed from the perspective of rational pharmacotherapy. The problem of interchangeability of brand-name and generic drugs for the treatment of AR is discussed, considering the almost complete absence of studies of their therapeutic equivalence.
Аллергический ринит (АР) может существенно снижать качество жизни пациентов, приводя к повышенной утомляемости, изменениям настроения, нарушениям когнитивной функции, депрессии. При этом в клинической практике часто отмечается недостаточная эффективность начальной монотерапии АР, а значительное число больных, обращающихся за медицинской помощью, имеют среднетяжелое и тяжелое течение заболевания. В связи с этим все более актуальными становятся вопросы оптимизации комбинированного медикаментозного лечения АР. В статье представлен анализ возможностей комбинированной фармакотерапии в рамках современной стратегии ведения пациентов с АР. На основе результатов ряда исследований и известных фармакологических свойств препаратов обсуждены преимущества совместного применения интраназальных глюкокортикостероидов и антагонистов лейкотриеновых рецепторов, в частности мометазона фуроата и монтелукаста, в терапии АР, в том числе при сочетании с бронхиальной астмой, хроническим полипозным риносинуситом и гиперплазией глоточной миндалины. Проанализированы некоторые аспекты комбинированной терапии монтелукастом и системными антигистаминными препаратами последнего поколения в качестве альтернативного подхода в случае невозможности приема интраназальных кортикостероидов, включая целесообразность применения фиксированной комбинации монтелукаста и левоцетиризина, с позиций рациональной фармакотерапии. Обсуждена проблема взаимозаменяемости оригинальных и воспроизведенных препаратов для лечения АР с учетом практически полного отсутствия исследований их терапевтической эквивалентности.

There is insufficient evidence regarding the comparative efficacy and safety of pharmacological treatments of allergic rhinitis (AR). In the context of informing the 2024 revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, we plan to perform three systematic reviews of randomized controlled trials (RCTs) comparing the desirable and undesirable effects (i) between intranasal and oral medications for AR; (ii) between combinations of intranasal and oral medications versus nasal or oral medications alone; and (iii) among different intranasal specific medications. We will search four electronic bibliographic databases and three clinical trials databases for RCTs examining patients ≥ 12 years old with seasonal or perennial AR. Assessed outcomes will include the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. If appropriate, we will perform a pairwise random-effects meta-analysis for each pair of assessed medication classes and outcomes, as well as a network meta-analysis to assess the comparative efficacy of intranasal medications among each other. Heterogeneity will be explored by sensitivity and subgroup analyses. This set of systematic reviews will allow for a comprehensive assessment of the effectiveness and safety of pharmacological interventions for AR and inform recommendations in the context of the ARIA guidelines.

UNASSIGNED: Comprehensive long-term follow-up data regarding chronic spontaneous urticaria (CSU) among general populations, especially from the Indian subcontinent is scanty.
UNASSIGNED: The aim of the study were to analyze the clinico-epidemiological profile, comorbidities of CSU patients, and factors affecting patient response to various doses of levocetirizine.
UNASSIGNED: In this retrospective cohort study, complete history regarding demographic profile, clinical examination, investigations, treatment given, and follow-up details of all CSU patients attending urticaria clinic between 2010 and 2019 were analyzed. These were considered variables to determine the factors playing a role in response to various doses of levocetirizine.
UNASSIGNED: Totally, 1104 files of CSU were analyzed. The male-to-female ratio was 1:1.5 with a mean age of 33.03 ± 14.33 years. Thyroid dysfunction and atopy were seen in 142 (12.8%) and 184 (16.7%) patients, respectively. Vitamin D deficiency and high serum immunoglobulin E (IgE) levels were seen in 461 (41.7%) and 340 (30.7%) patients, respectively. Immunosuppressives were required at some point in 196 (17.7%) patients. Patients with higher levels of serum IgE and D-dimer (P < 0.05) were found to require frequent updosing of levocetirizine, while age, sex, duration of illness, presence of angioedema, co-morbidities, identifiable precipitating factors, presence of diurnal variation, family history, and vitamin D deficiency were found to not have an effect on levocetirizine dosing.
UNASSIGNED: Ours is a large single-center study exemplifying the biomarkers including baseline serum IgE and D-dimer levels, which could identify a CSU patient who could warrant a higher dose of antihistamine/antihistamine refractory urticaria.

The incidence of allergic rhinitis (AR) in Asia and the world is steadily rising. Patients experience incomplete symptom relief despite existing treatment options, which warrants the need for new therapeutic regimes. Azelastine hydrochloride/fluticasone propionate (MP-AzeFlu), a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate has been indicated in the treatment of AR. The current review discusses the effects of MP-AzeFlu versus conventional therapies in achieving superior clinical improvement with a very rapid onset of action (5 minutes). The superiority of MP-AzeFlu in offering complete symptom control with sustained relief in patients with AR compared to the existing therapeutic options is also discussed. MP-AzeFlu has been shown to improve the quality of life for patients with AR, thereby enhancing patient adherence to therapy and establishing its preference for the treatment of AR. Currently, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines recommend the use of a combination of intranasal corticosteroids and intranasal antihistamines as first-line treatment in patients with persistent AR with visual analog scores ≥5 or when prior treatment with single agents has been ineffective. Widely published data on the efficacy and safety of its prolonged use in adults and children have validated that effective treatment of AR can be achieved with MP-AzeFlu.

UNASSIGNED: Fexofenadine is a second-generation inverse agonist of H1-receptor of histamine which is highly selective with proven efficacy in relieving symptoms associated with allergic conditions. It has an additional benefit of not penetrating the blood-brain barrier and therefore do not induce sedation and not impair the cognitive function/psychomotor performance. This review aimed at providing evidence based on available controlled studies to reinforce the non-sedative property of fexofenadine for treating patients with allergic rhinitis and urticaria.
UNASSIGNED: We performed an electronic literature search using keywords such as fexofenadine, drowsiness, somnolence, sedation, fatigue, cognitive, impairment, psychomotor, driving performances, sleep, rapid eye movement, alertness, clinical study, in vitro study, in vivo study, and pharmacodynamics in the Embase search engine. The review included randomized controlled trials, review articles, systematic reviews, and meta-analyses, together with post-marketing analysis conducted in healthy subjects and patients with allergy and were focused on comparing the antihistaminic potential or safety of fexofenadine with other antihistamines or placebo.
UNASSIGNED: Positron emission tomography (PET) and proportional impairment ratio (PIR) data along with other objective tests from various studies confirmed the non-sedative property of fexofenadine. Results of brain H1-receptor occupancy (H1RO) obtained from PET showed no H1RO by fexofenadine, the receptor which is known to cause sedation of H1 antihistamines. Most studies calculating PIR value as 0 showed fexofenadine to be a non-impairing oral antihistamine regardless of dose. Clinical trials in adults and children showed fexofenadine to be well tolerated without sedative effect or impairment of cognitive/psychomotor function even at higher than recommended doses.
UNASSIGNED: Published literature based on various parameters and clinical trials conducted for evaluating the effect of fexofenadine on sedation and central nervous system shows fexofenadine is both clinically effective and non-sedating.

Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.