Doxepin cream is not effective in reducing itch in burn scar patients: A multicenter triple-blind randomized clinical crossover trial

ObjectiveTo evaluate the effect of doxepin hydrochloride 5% cream on reducing pruritus in burn scar patients compared to a placebo cream.MethodWe conducted a multicenter triple-blind randomized clinical placebo-controlled crossover trial in which burn patients ≥18 years with an itch intensity ≥3 on a Visual Analogue Scale (VAS) were randomized between a doxepin-placebo or placebo-doxepin treatment protocol. Patients used each cream during two weeks with a wash-out period of one week in between. Primary outcome was change in itch intensity in two weeks’ time using the VAS. Secondary outcome included the impact of itch (Burn Itch Questionnaire). Other parameters were the use of hydrating cream, silicon treatment, pressure garments, and other antipruritic medication.ResultsTwenty-seven patients were included. The change in itch intensity (VAS) was not different during the doxepin and placebo period (p = 0.994); neither the doxepin cream nor placebo cream reduced itch intensity. However, based on the Burn Itch Questionnaire, we observed a statistically significant decrease in itch intensity and improvement in impact scores in both treatment groups, but no difference in the degree of reduction between the groups.ConclusionDoxepin cream was not effective in reducing pruritus in our burn patient study population.     

The Use of Antihistamines in Safety-critical Jobs: A Meeting Report

Summary

The use of sedating agents by aircrew and those with safety-critical occupations has raised serious concern and has been extensively debated for several years. This meeting report summarizes the findings of an international panel of experts in aerospace medicine and L allergic rhinitis who were brought together to discuss issues related to the use of antihistamines, in particular the selective, H1-receptor antagonist fexofenadine, in pilots. The presentations covered a wide range of topics including methods for accurately assessing sedation and impairment, and the validity of laboratory testing versus simulator assessments. The panel also examined data on sedation and impairment levels with currently available antihistamines and assessed the impact of these data on their use by pilots and aircrew. It was the consensus of the meeting that fexofenadine can be safely recommended for use in individuals involved in skilled activities, such as pilots, without the concern of sedation above recommended therapeutic doses.     

抗组胺药在变应性鼻炎中的作用机制及应用进展

变应性鼻炎（AR）是一种鼻黏膜的慢性非感染性炎症,主要是由机体接触致敏变应原后诱发的由特异性免疫球蛋白E（IgE）介导的、多种炎性细胞（如肥大细胞、嗜碱性粒细胞等）参与的鼻黏膜的高敏反应。组胺在AR发病中发挥重要作用,是引起鼻痒、喷嚏、流涕等临床症状的核心介质。抗组胺药物通常通过拮抗组胺相关受体来阻断组胺与受体结合,从而影响变态反应发生的过程。因此,抗组胺药在AR治疗中的应用也越来越重要而广泛。本文主要就抗组胺药在AR中的作用机制及治疗进展作一综述,探讨其在AR的应用价值。     

A comparison of zopiclone and propiomazine as hypnotics in outpatients: A multicentre,double-blind,randomized, parallel-group comparison of zopiclone and propiomazine in insomniacs

Summary

In a double-blind, parallel-group study of 135 patients with a mean age of 60 years, zopiclone 5?mg was compared with propiomazine 25?mg. The patients rated their sleep in a diary. There were statistically significant differences in favour of zopiclone for nine out of 13 variables measuring subjective sleep quality and quantity. Concerning side-effects, bad taste was reported more frequently in the zopiclone group and restless legs in the propiomazine group.     

变应性鼻炎的药物治疗策略

变应性鼻炎(allergic rhinitis,AR)是耳鼻咽喉科常见的疾病,也是重要的变态反应性疾病之一.全球AR患者超过5亿,我国大陆地区AR的患病率为4％～38％[1].AR在给患者生活质量造成严重影响的同时,亦给社会带来沉重的经济负担[2].     

Differential thermodynamic driving force of first- and second-generation antihistamines to determine their binding affinity for human H1 receptors

Differential binding sites for first- and second-generation antihistamines were indicated on the basis of the crystal structure of human histamine H₁ receptors. In this study, we evaluated differences between the thermodynamic driving forces of first- and second-generation antihistamines for human H₁ receptors and their structural determinants. The binding enthalpy and entropy of 20 antihistamines were estimated with the van’t Hoff equation using their dissociation constants obtained from their displacement curves against the binding of [³H]mepyramine to membrane preparations of Chinese hamster ovary cells expressing human H₁ receptors at various temperatures from 4 °C to 37 °C. Structural determinants of antihistamines for their thermodynamic binding properties were assessed by quantitative structure–activity relationship (QSAR) analyses. We found that entropy-dependent binding was more evident in second- than first-generation antihistamines, resulting in enthalpy–entropy compensation between the binding forces of first- and second-generation antihistamines. QSAR analyses indicated that enthalpy–entropy compensation was determined by the sum of degrees, maximal electrostatic potentials, water-accessible surface area and hydrogen binding acceptor count of antihistamines to regulate their affinity for receptors. In conclusion, it was revealed that entropy-dependent hydrophobic interaction was more important in the binding of second-generation antihistamines, even though the hydrophilicity of second-generation antihistamines is generally increased. Furthermore, their structural determinants responsible for enthalpy–entropy compensation were explored by QSAR analyses. These findings may contribute to understanding the fundamental mechanisms of how the affinity of ligands for their receptors is regulated.     

Burns pruritus—A study of current practices in the UK

Pruritus is a universal symptom associated with burns healing. Little research has been conducted to assess physicians’ attitudes and management principles in specialist units. A survey of UK burn units has identified a variety of opinions on the importance of various factors affecting the incidence of pruritus and a lack of a systematic approach in the assessment and treatment of this distressing symptom. A clear pattern emerged favouring the use of antihistaminergic agents for burns pruritus management with a low uptake of agents acting on the central nervous system as well as non-pharmacological adjuncts. The cumulative responses from the cohort of respondents are presented and issues pertinent to further research and clinical management are discussed.     

抗组胺药联合物理疗法治疗玫瑰糠疹疗效观察

目的探讨抗组胺药联合窄谱中波紫外线（NB-UVB）治疗玫瑰糠疹（PR）的疗效。方法将96例诊断明确的PR患者,随机分治疗组（50例）和对照组（46例）,两组患者性别、年龄、病情之间无明显差别,具有可比性。治疗组在抗组胺药物治疗同时接受NB-UVB治疗仪治疗,对照组仅予抗组胺药物治疗。治疗3周后同时评价疗效。结果治疗组平均治愈时间（9.21d）明显短于对照组（21.32d）,P〈0.01。3周后对照组痊愈20例,显效10例;治疗组痊愈47例,显效2例。治疗组治愈率显著高于对照组（P〈0.01）。结论抗组胺药联合NB-UVB治疗PR疗效好、安全、方便,值得推广应用。     

Antihistamine effects on experimental middle ear inflammatory model

Allergy is thought to be one of the etiologic factors in otitis media. The purpose of this study was to determine the histopathologic effects of H1 histamine receptor antagonists in an experimental histamine-induced middle ear inflammation model. In group A (20 rabbits), histamine challenge followed a 3-day intramuscular pretreatment with a single dose of 0.1 ml hydroxyzine hydrochloride (50 mg/ml) per day. In group B (20 rabbits), histamine challenge followed a 3-day pretreatment with a single dose 1.2 mg desloratadine per day orally. In group C (20 rabbits), histamine challenge followed a 3-day pretreatment with a single dose 1.2 mg levocetirizine per day orally. On the fourth day after baseline otomicroscopy 0.5 ml histamine 20 mg/ml was injected transtympanically on the right. Middle ear mucosa was removed and the following parameters were assessed: edema, vascular dilatation and congestion, inflammation, acute inflammatory component, presence of eosinophils, activity of the inflammation and fibrosis. A semi-quantitative grading system of 0-3 was used for grading of all parameters and statistical analysis performed by using the Mann-Whitney non-parametric test. Group A mucosae showed lower grades of all the parameters evaluated compared with those of group B. Histopathology of the mucosae of group C showed lower grade of inflammation compared with group B with significant statistical difference for the seven parameters tested. Our data validate the use of antihistamines in the treatment of refractory OME of allergic origin. Oldest H1 antagonists can be replaced by the newest agents who counteract successfully histamine effects, without any interactions or adverse effects from central nervous system.     

Effects of antihistamines on isolation-induced fighting in mice

A series of antihistamines representing many structural types and pharmacological spectra antagonized isolation-induced fighting in mice. Antagonism of fighting by these compounds was correlated with anti-cholinergic potency as measured by prevention of physostigmine-induced lethality but did not correlate with antihistaminic or anti-tetrabenazine potency. Antagomism of fighting was not related to effects of these drugs on spontaneous motor activity.