组胺和抗组胺药的研究进展

组胺与H1受体结合可增强抗原提呈细胞的能力,促进肥大细胞和嗜碱性粒细胞中组胺和其他介质的释放,在荨麻疹等过敏性疾病的发病中起着作用。第一代川抗组胺药由于相对分子质量小,嗜脂性,易通过血脑屏障,临床应用可产生较多不良反应,尤其是对警觉性、认知等的影响。第二代H1抗组胺药相对分子质量大,受体专一性强、亲和力高,抗组胺活性更强,安全性更好,国外指南均推荐作为荨麻疹的一线治疗药物,治疗剂量可增至标准剂量的4倍以提高疗效,仍具有很好的安全性。H3、H4抗组胺药也已进入临床试验,有望治疗过敏性疾病及瘙痒症。     

非组胺1受体的组胺受体配体在皮肤科的应用

组胺通过4种受体在多种皮肤病中发挥作用,其中,H2受体、H3受体、H4受体的生物学效应各有其特点,其配体在皮肤病的应用中发挥不同的作用.H2受体拮抗剂主要与H1受体拮抗剂联合治疗慢性荨麻疹等,尚可用于治疗皮肤疣,带状疱疹,单纯疱疹,雄激素源性脱发及痤疮等;H3受体配体可能存在镇痛止痒抗变态反应的作用;H4受体拮抗剂在多种变态反应炎性疾病模型中显示出抗炎止痒的疗效.     

组胺、组胺受体与变态反应

近年来,随着分子生物学和免疫学技术的发展,对组胺、特别是组胺受体在变态反应形成中的作用研究起到重要的推动作用。相继已经发现H1、H2、H3和H4等4种类型的受体,其中H4受体是新近发现的与变态反应密切相关的重要受体之一。本文就有关问题简述如下。     

H1抗组胺药物研究进展

人体内组胺受体主要有H1、H2、H3和H4四种受体类型,组胺主要通过受体发挥生物学作用。目前H1抗组胺药物主要用于治疗荨麻疹及其他过敏性疾病,中枢神经系统疾病和前庭疾病。第一代H1抗组胺药物用于治疗过敏性疾病并无规范的研究,多数临床试验不符合当前随机双盲对照试验的标准。与之相比,第二代H1抗组胺药物均有大量充分的试验支持。临床上大部分H1抗组胺药物安全有效,但其中枢神经系统及心脏的不良反应不容忽视。     

抗组胺药在皮肤科应用的进展

１９１０年Ｄａｌｅ与Ｌａｉｄｌａｗ发现组胺与变态反应有着密切的关系，组胺（ｈｉｓｔａｍｉｎｅ）广泛存在于组织细胞中，尤以肥大细胞和嗜碱粒细胞含量最高。组胺的效应细胞上有两类组胺受体，即Ｈ１和Ｈ２受体，前者与组胺结合后导致外周血管扩张、通透性增加，平滑...     

磺胺药过敏患者对三种抗组胺药过敏1例

患者男 ,50岁 ,因“右下肢湿疹两年加重半月” ,于1 998年 5月来我院就诊。给予口服赛庚啶 ,外搽蒽肤霜治疗。口服赛庚啶 1次 4ｍｇ约 8小时后患者突感面、颈部灼热、瘙痒 ,胸、腹、背部出现针尖大小红色丘疹伴剧痒。考虑药疹 (麻疹样发疹型 )。对其静脉推注葡萄糖酸钙 1ｇ,口服强的松 1 0ｍｇ,一日三次。两天后皮疹基本消退 ,痒感消失。因原湿疹未愈 ,予停服赛庚啶 ,改服扑尔敏。患者服用 1片4ｍｇ后约 1小时 ,突然感觉胸闷、气急 ,面、颈部出现片状风团块 ,胸、腹、背、腰、四肢近端出现弥漫性红色丘疹 ,同时伴有腹部隐痛 ,皮疹处灼热剧痒…     

关注抗组胺药治疗慢性荨麻疹应用的策略

抗组胺药通过拮抗H1受体来阻断组胺与受体的结合,从而影响变态反应发生的过程,是治疗慢性荨麻疹的基本药物。最新研究表明,抗组胺药还可通过其他机制发挥更广泛的药理作用。本文就目前临床抗组胺药物选择及使用的策略进行探讨。     

3种抗组胺药抗组胺及抗花生四烯酸作用的比较研究

目的:比较咪唑斯汀、氯雷他定、西替利嗪3种抗组胺药的抗组胺及抗花生四烯酸的作用。方法:给大鼠左、右爪分别皮下注射花生四烯酸(1.0g/L,0.1mL)和组胺(10g/L,0.1mL)构建鼠爪水肿炎性模型。在注射花生四烯酸和组胺2h前分别给予咪唑斯汀、氯雷他定、西替利嗪(0.6mg/kg)灌胃,注射后应用体积测量仪分别测定给药后鼠爪体积在不同时间点的变化。结果:咪唑斯汀可抑制花生四烯酸所致的鼠爪水肿(P<0.05),西替利嗪、氯雷他定对其无明显抑制作用;咪唑斯汀对组胺所致的鼠爪水肿有抑制作用(P<0.05),抑制作用强于氯雷他定组,但与西替利嗪组比较无统计学差异(P>0.05)。结论:咪唑斯汀具有抗组胺和抗花生四烯酸的作用,且其抗组胺作用强于氯雷他定;与氯雷他定、西替利嗪相比,咪唑斯汀表现出其独特的抗花生四烯酸的作用。     

Effective treatment of pruritus in atopic dermatitis using H1 antihistamines (second-generation antihistamines): changes in blood histamine and tryptase levels

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory and allergic skin disease that almost always begins in childhood and follows a course of remittance and flare-up. AD is characterized by intense pruritus and itchiness that can be triggered by an interplay of genetic, immunologic and environmental factors. Of the mediators, histamine is one of the most potent inducers of pruritus. Serum tryptase, which is also a mediator, may be used to examine allergic disease as well. The development of minimal sedation H1 antihistamines (second-generation antihistamines) has revolutionized treatment of allergic diseases. OBJECTIVE: The present study examines the efficacy of second-generation antihistamines in relieving pruritus due to AD. In addition, the relationship between AD pruritus and antihistamine therapy was analyzed by measuring the blood histamine and tryptase levels. METHODS: Thirty-two AD patients were recruited and underwent second-generation antihistamine therapy for 2 weeks. Seventeen received combined topical corticosteroid treatment (Group 1) and the other 15 did not receive steroid treatment (Group 2). The Severity Index and Pruritus Score were assessed as an AD clinical activity index and compared with baseline data. RESULTS: Both the Severity Index and Pruritus Score improved significantly in Group 1 (P<0.001, P<0.05). Group 2 demonstrated a significant improvement in Pruritus Score (P<0.05), but not in the Severity Index. Plasma histamine levels were significantly higher in AD at baseline compared with healthy controls. CONCLUSION: Following antihistamine therapy, these levels decreased significantly in both AD groups (P<0.05). There was a significant correlation between baseline blood histamine and typtase levels. However, this correlation was not evident following treatment. This may reflect insufficient detection capabilities of the measuring assay. The present results suggest that second-generation antihistamine therapy provides an effective clinical treatment for AD, with a notable improvement in pruritus. Furthermore, antihistamine therapy reduced plasma histamine levels in AD patients. These findings further suggest that high blood histamine and tryptase levels in AD patients contribute to the pathogenesis of this disorder, including the onset of pruritus.     

第二代抗组胺药及其新成员咪唑斯汀

概述了自上世纪80年代后问世的各种第二代非中枢镇静作用H1拮抗剂的药代动力学,药效学,不良反应及适应证等,对其优缺点作了比较;并着重介绍了最近推出的抗组胺药咪唑斯汀,它具有选择性拮抗H1受体和抗5-脂氧合酶的双重活性,是较理想的抗组胺药,用于治疗急,慢性荨麻疹及寒冷性荨麻疹等过敏性疾病。     

Evaluation of the efficacy of antihistamines using human monocyte-derived dendritic cells stimulated with histamine

BACKGROUND: It has been reported that histamine induces CD86 expression and chemokine production in human immature monocyte-derived dendritic cells (MoDCs), which can be blocked by both H(1)- and H(2)-receptor antagonists. OBJECTIVE: We sought to examine whether the efficacy of H(1)-type antihistamines can be assessed by using MoDCs. METHODS: We examined the suppressive effects of 1 H(2)-type antihistamine (cimetidine) and 5 different H(1)-type antihistamines (cetirizine, diphenhydramine, ketotifen, olopatadine, and emedastine) on the induction of CD86 and IL-8 production by MoDCs from 23 healthy individuals stimulated with histamine. We also examined the responses of MoDCs from 13 patients with chronic urticaria to these antihistamines, and compared the in vitro efficacy with the actual clinical response to antihistamines evaluated by patient and physician assessments. RESULTS: All the antihistamines we examined suppressed the increase of CD86(+) cells after histamine stimulation in a dose-dependent fashion, and all H(1)-type antihistamines were more efficacious than cimetidine. IL-8 production stimulated with histamine was also suppressed by cetirizine, ketotifen, and olopatadine. Unexpectedly, the suppressive effect of these antihistamines on the CD86 augmentation was highly variable among different healthy control participants. Interestingly, in 10 of 13 cases of chronic urticaria, this in vitro analysis of antihistamines correlated with the clinical response to antihistamines. CONCLUSION: This study suggests that the evaluation of antihistamines using MoDCs can be a useful method for the screening of effective antihistamines, for the comparison of the efficacy of antihistamines, and for predicting the efficacy of antihistamines on an individual basis.     

当代大学生婚恋观的调查与思考

目的：了解当代大学生的婚恋态度,为学校健康教育提供依据。方法：采用问卷调查的方法,对泰安市256名大学生进行婚恋态度的调查。结果：赞成大学期间恋爱者占绝大多数（82.6%）,而且多数（77.7%）认为恋爱目的是为了选择人生伴侣,但仅有12.8%的被调查者认为大学期间的恋人会最终成为夫妻;同时部分被调查者对婚前性行为持宽容和认同态度。在选择配偶时考虑的前4位条件是,诚实可靠、富有感情、受过良好教育、身体健康,但男女生存在差异。结论：当代大学生具有理性的婚恋观,虽然传统观念对大学生还有一定影响,但是现代科学教育对他们的影响更深。     

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Background:Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines.Objectives:To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test.Methods:A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine.Results:All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p >0.03)..Study limitations:A single-center study evaluating only aspects related to histamine.Conclusions:Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.     

Dyes and preservatives in oral antihistamines

Antihistamines are commonly used in the treatment of urticaria. Some antihistamines contain dyes and preservatives which have themselves been shown to produce or exacerbate urticaria; the presence of these substances is not indicated in the usual formularies and a list of commonly prescribed antihistamines is presented, detailing the azo dyes, other dyes and preservatives contained therein.