从抗组胺药的作用机制谈其治疗慢性荨麻疹的应用策略

抗组胺药物通常通过拮抗H1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.近年来研究发现,抗组胺药可以通过H1受体依赖和非依赖途径起更广泛的抗炎作用,并可以成为反激动剂在组胺缺乏的情况下实施对组胺受体活性的抑制.这些机制促进抗组胺药临床治疗慢性荨麻疹产生新的理念.     

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。     

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。     

荨麻疹

20121602关注抗组胺药治疗慢性荨麻疹应用的策略/郝飞(三军大西南医院皮肤科),钟华,宋志强∥实用皮肤病学杂志.-2012,5(1).-2～4①抗组胺药作用机制研究是临床用药策略变化的依据,竞争性与H1受体结合从而阻断变态反应;抗炎作用通过非H1受体依赖性和H1受体依赖性两个方面;反激动剂在组胺缺乏的情况下实施对组胺受体的抑制;镇静类抗组胺药、非镇静抗组胺药,既无中枢镇静作用又有明确抗炎作用。②抗组胺药物应用策略需     

对组胺受体和抗组胺药的新认识

人体内组胺受体主要有H1、H2、H3、H4 4种类型,属于G蛋白偶联受体(GPCRs).最新的研究发现,GPCRs以结构活性方式存在,抗组胺药具有负性内在活性,能够阻断组胺受体的自发活性.绝大多数抗组胺药是受体的反向激动剂,在临床上具有广泛的应用前景.     

第二代抗组胺药非索非那定中枢安全性研究进展

抗组胺药(H1受体拮抗剂)是对症治疗荨麻疹、变应性鼻炎、哮喘以及瘙痒等变态反应性疾病的主要药物.第一代抗组胺药因其镇静和抗胆碱能等副作用,已被相对无镇静作用的第二代抗组胺药所替代.非索非那定是第二代H1抗组胺药,无镇静、抗胆碱能作用,不能透过血脑屏障,因此该药能够在外周组织有效阻断H1受体,但无损害中枢神经系统(CNS)功能的作用.本文就非索非那定中枢安全性的研究进展进行综述.     

应用新一代抗组胺药物的体会和评价

抗组胺药物是皮肤科和耳鼻喉科常用的主要药物之一。目前临床医生公认的新一代抗组胺药物有：息斯敏、氯雷他定、仙特敏、皿治林等，它们共同的特点是：对H1受体的选择性强，亲和力高，药物的分子较大，有一个长的侧链，脂溶性差或呈水溶性，故对血脑屏障穿透性低，所以镇静作用极小，与H1受体的结合作用时间长，有些药物的活性代谢产物可继续发挥作用，延     

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。     

抗组胺药联合转移因子治疗慢性荨麻疹疗效观察

目的　观察抗组胺药联合转移因子治疗慢性荨麻疹的疗效。方法　分别采用组胺H1和H2 受体拮抗剂、转移因子及三者联合治疗。结果　抗组胺药组与转移因子组疗效相近 (P >0 .0 5 ) ,联合治疗组疗效与其它两组相比 ,疗效有极其显著性差异 (P <0 .0 1)。结论　联合治疗组治疗慢性荨麻疹疗效显著。     

咪唑斯汀的双重作用及临床应用

说明了咪唑斯汀抗组胺H1-受体 ,抑制组胺释放的作用 ,同时阐明了咪唑斯汀具有抑制 5 脂氧合酶从而抑制炎症反应的作用机制 ,并进一步综述其在荨麻疹、过敏性鼻炎、特应性皮炎及支气管哮喘等方面的临床应用     

Antihistamines and their role as antipruritics

Antihistamines that bind to the histamine 1 receptor (H1) serve as important therapeutic agents to counter the effects of histamine in the skin. Two generations of antihistamines exist; however, second-generation agents are more advantageous because they cause less sedation, have a longer half life and are more selective for the H1 receptor. While H1 antihistamines have proven to be effective at reversing the pruritus and cutaneous lesions of chronic urticaria, their ability to treat pruritus associated with other cutaneous and systemic diseases is unproven.     

抗组胺药在特殊人群中的应用

抗组胺药物是皮肤科治疗过敏性疾病最常见的药物之一,在大部分人群中有着较好的疗效及耐受性。由于其适用范围广泛,安全性显得尤为重要。对于儿童、孕妇、哺乳期妇女、老年人以及肝、肾功能不全的过敏性疾病患者,应用抗组胺药时应充分考虑每一种药物的药效学、代谢特点以及药物之间的相互作用,权衡用药收益和可能带来的不良反应,选择相应的安全性高的抗组胺药物,或者通过减少常规用药剂量、延长用药间隔时间等方法使安全性达到最大。     

Contact allergy to antihistamines is not common

Topical antihistamines are available as creams, lotions, eyedrops, nasal preparations, aerosols, and suppositories. Antihistamines (or H₁-receptor antagonists) have antipruritic properties, a mild local anesthetic effect and may also diminish capillary permeability. They can be classified into 6 groups by their chemical structure (1): alkylamines, ethanolamines, ethylenediamines, phenothiazines, piperazines, and other H1-receptor antagonists. Application to the skin is generally considered to carry an unacceptably high risk of sensitization (1, 2). Recently, several cases have been reported of allergic contact dermatitis from topically-applied doxepin hydrochloride, a tricyclic antidepressant that has very potent antihistaminic activity (3–5).     

Desloratidine for the treatment of chronic urticaria

Chronic urticaria is a common dermatologic condition that is idiopathic in most cases. Antihistamines are the mainstays of treatment for this condition. The newer, second and third generation antihistamines are the preferred agents because of their improved safety profile and comparable efficacy to the first generation antihistamines. Desloratadine is a new non-sedating H1-receptor agonist. Based on clinical studies, desloratadine is a valuable new addition to the available treatment options and should be considered as a first-line therapy for patients with chronic urticaria.     

Use of antipsychotic drugs in dermatology

Antipsychotic drugs can be beneficial in dermatology because of their both central nervous system and peripheral effects. All antipsychotic drugs have a central postsynaptic dopamine D2 receptor blocking effect, which underlies their antipsychotic action. The antipsychotic drugs have varying degrees of histamine H1-receptor, cholinergic muscarinic receptor, and α1-adrenergic receptor blocking effects, which can affect cutaneous perception and the autonomic reactivity of the skin and can be potentially beneficial in the management of certain histamine or sympathetically mediated dermatologic manifestations (eg, urticaria, pruritus, hyperhidrosis). In addition to their antipsychotic effect, antipsychotic drugs also have a general anxiolytic effect related in part to their α1-adrenergic receptor blocking action, which can be of benefit in many dermatologic conditions, including pruritus. The antipsychotic drugs are most commonly used in dermatology for the management of a delusional disorder, somatic type, manifesting as delusional infestation, and as monotherapy or as augmentation therapy of selective serotonin reuptake inhibitor (SSRI) antidepressants, and for management of trichotillomania and skin-picking or excoriation disorder. There is earlier literature (1) on the possible beneficial effect of the phenothiazine antipsychotics in a wide range of pruritic dermatoses, and (2) the efficacy of pimozide as adjunctive therapy for metastatic melanoma, which both warrant further investigation.     

生物制剂治疗慢性荨麻疹的进展

慢性荨麻疹是皮肤科常见的一种反复发作的过敏性疾病,抗组胺药是一线治疗药物,但近一半患者疗效欠佳.慢性荨麻疹病因复杂,包括Th1/Th2细胞亚群失衡、炎症介质异常、IgE及抗IgE高亲和力受体的抗体异常等,可能是慢性荨麻疹难以治愈的重要原因之一.生物制剂对免疫异常具有选择性调节或阻滞作用,成为慢性荨麻疹及其他荨麻疹疾病的治疗新手段或方法.这些生物制剂主要有:卡介苗多糖核酸、丙种球蛋白、肿瘤坏死因子α抑制剂、白细胞介素1阻滞剂、利妥昔单抗、奥马珠单抗等,在慢性荨麻疹治疗中具有重要地位,其中奥马珠单抗是抗lgE单克隆抗体,具有良好的疗效/风险比,耐受性好,是治疗慢性荨麻疹较理想的生物制剂之一.     

Regulatory effects of antihistamines on the responses to staphylococcal enterotoxin B of human monocyte-derived dendritic cells and CD4+ T cells

BACKGROUND: Antihistamines are widely used for the treatment of allergic diseases, such as urticaria and allergic rhinitis. They are also effective for the treatment of diseases in which T cells are mainly involved in the pathogenesis, such as atopic dermatitis (AD) and contact dermatitis. Dendritic cells (DCs) drive polarization of naive T cells into Th1 or Th2 subsets, and are also likely to be involved in AD pathogenesis. OBJECTIVES: The aim of this study was to determine the effects of antihistamines on DCs and CD4(+) T cells. METHODS: Human monocyte-derived DCs (MoDCs) and autologous CD4(+) T cells were obtained from healthy subjects, and cultured together or independently in the presence of antihistamines. As a stimulant, we used staphylococcal enterotoxin B or the combination of anti-CD3 monoclonal antibody (mAb) and anti-CD28 mAb. The concentrations of cytokines and chemokines in culture supernatants were measured by ELISA. The expression of surface molecules on MoDCs was measured by flow cytometry. Cell proliferation in the cocultures of MoDCs and CD4(+) T cells (DC-T cocultures) was measured by a [(3)H] thymidine incorporation assay. RESULTS: Antihistamines inhibited the production of IFN-gamma, and enhanced the production of IL-4 in DC-T cocultures. Antihistamines inhibited the production of TNF-alpha, TARC, MDC, IP-10, and Mig from MoDCs. Epinastine, one of antihistamines, suppressed the expression of ICAM-1 (CD54) on MoDCs. Epinastine also inhibited the proliferation of CD4(+) T cells cocultured with MoDCs. CONCLUSIONS: Our findings show that antihistamines regulate immune responses by affecting the interaction between DCs and CD4(+) T cells, and further DCs and CD4(+) T cells independently, which may partially contribute to the control of allergic diseases such as AD and contact dermatitis.     

中国黑素瘤研究进展与新治疗策略

【摘要】 尽管黑素瘤发病率正快速增长,但其在中国所占比例低,肿瘤科医生关注少。黑素瘤患者首诊科室主要是皮肤科,皮肤科医生能综合分析临床诊断、病理诊断、外科治疗和药物治疗,对黑素瘤的诊治具有独特优势。中国学者近年在黑素瘤的细胞死亡调控、表观遗传学修饰、靶向药物耐药、肿瘤微环境和肿瘤免疫调控等方面已获得很大进展。中国独有的一类新药干扰素α-1b不仅可用于Ⅱ、Ⅲ期高危黑素瘤的辅助治疗,对Ⅳ期黑素瘤也有很好的疗效,不良反应远低于干扰素α-2b。与白色人种不同,亚洲人皮肤黑素瘤以肢端型及黏膜型为主。以干扰素α-1b为基础制定联合治疗策略,探索其与程序性死亡受体-配体1抑制剂、靶向药物或血管生成抑制剂等的联合治疗方案,正在为挽救Ⅳ期黑素瘤患者带来希望。     

The emerging role of physician assistants in the delivery of dermatologic health care

The NAMCS provides a wealth of information on use of PAs in all practices, including dermatology. Two important points regarding the NAMCS and SDPA data are addressed here: the number of visits to PAs for dermatologic symptoms and the expected growth of PA use in dermatologists' offices. Dermatologic symptoms were evaluated frequently by PAs, accounting for 14% of PA visits. These statistics do not address the number of referrals those PAs made to dermatologists. Perhaps PAs as a group should be targeted for increased dermatologic education, particularly stressing the need for appropriate referral to a dermatologist. PAs could increase the number of dermatology referrals from primary care offices with improved understanding of the importance of the dermatologist in the management of patients' overall skin health. At projected growth rates, the number of PAs employed by dermatologists should exceed 500 by the end of 2000. Most of this growth has been in private practices and rarely in HMOs or in large multispecialty clinics. There are a number of reasons for this growth, as follows: A PA may help reduce the patient load on the dermatologist, especially with sameday appointments and drop-ins. Some dermatologists are moving away from clinical dermatology into cosmetics, which not only leaves a vacuum in clinical dermatology, but also creates job opportunities for PAs in cosmetic dermatology. Regarding managed care growth, PAs can have a positive impact on the problem of having to see more patients for less money. PAs are cost-effective. In the 1998 SDPA survey, the ratio of billings generated (production) to gross income for the average dermatology PA ranged from 3:1 to 6:1. Even with inexperienced PAs new to dermatology, this ratio was usually at least 2:1 at the end of the first year. PAs can cover satellite offices, allowing for practice expansion. Effective with the new Medicare laws of January 1, 1998, PAs can now see new Medicare patients or Medicare patients with new conditions without the physician being on site, opening up the possibility for satellite offices in remote areas. Just as dermatologists may move toward specialization in surgery, cosmetics, or medical dermatology, PAs may do the same, filling a niche in a particular practice. As in other specialties, patient acceptance of seeing dermatology PAs has not been a significant problem. Continued access to the dermatologist remains unfettered, but, over time, many patients become willing to see either. Are PAs likely to become future competitors of dermatologists? Genuinely concerned dermatologists worry that a dermatology-trained PA will become part of a gatekeeper system that impedes patient access to dermatologists. This is not happening and is not at all likely to become a trend, for a number of reasons. First, primary care cannot compete with dermatology practices in remuneration for PAs. Just as financial benefits in high-production specialty practices entice physicians, the same benefits entice PAs as well. Second, according to member surveys of the SDPA, virtually 100% of fellow members work with dermatologists. Although PAs can work in any type of practice and evaluate dermatologic symptoms just as a general practitioner would, PAs who specialize in dermatology primarily practice with dermatologists, a collegial association most PAs seek out. PAs have steadfastly maintained their dependent, noncompetitive relationship with physicians and would not have it any other way. Although PAs see a good number of patients (2.8 million) with dermatologic symptoms, the NAMCS data indicate that most (72%) of these patients are also seen by a physician. Third, physicians are ultimately responsible for the actions of their PA employee. A general practitioner not trained to perform excisions or manage certain dermatologic conditions should not allow a PA to perform such duties. Similar to much of medicine, the PA profession continues to evolve, with many members moving awa     

Andrology

Andrology is part of dermatology in Germany, as it arose from dermatology as a subspecialty. Accordingly training in andrology is part of the curriculum for specialty certification in dermatology. All dermatologists are required to “have experience in the diagnosis of andrologic disorders and their subsequent treatment”. The specialty of andrology deals with male infertility problems including questions regarding fertility prophylaxis, contraception, erectile dysfunction, disturbance in libido, ejaculation and copulation, and primary and secondary hypogonadism, as well as male aging and diseases of the male breast. Evaluation and treatment of the partner may also be necessary. Ejaculate analysis is the most important laboratory tool and each dermatologist must be qualified in its performance.