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。     

抗组胺药物在皮炎湿疹类疾病中的应用

组胺参与荨麻疹和特应性皮炎等常见疾病的发病机制,故抗组胺药物是皮肤科最常用的系统用药之一.已发现的四种组胺G蛋白耦联受体中,人皮肤主要表达H1和H2亚型.抗组胺药物也称为组胺受体反向激动剂,除了抗组胺作用外,同时具有不依赖于H1受体的抗炎效应.虽然抗组胺药物在临床被广泛用于治疗皮炎湿疹类疾病,但其具体机制仍不明确,证据尚有待探讨.     

第二代H1抗组胺药治疗皮肤病的进展

第二代Ｈ１抗组胺药较第一代常规抗组胺药有许多优点，它们很少通过血脑屏障或对脑Ｈ１受体的亲和力低于与周围经Ｈ１受体的亲和力，因此这些药物具有持久的抗组胺作用并产生较小的镇静作用。由于显著减少了它们的副作用，因而将更广泛地用于过敏性疾病的治疗，并将逐渐取代常规抗组胺药。     

卢帕他定——新型的组胺H1受体和血小板活化因子受体双重拮抗剂

卢帕他定是一种具有组胺H1受体和血小板活化因子受体双重拮抗作用的新型抗过敏药,能够作用于过敏反应发生的不同环节进而抑制炎症反应.药效学研究表明卢帕他定具有与二代抗组胺药相似或更强的抗组胺活性.该药对中枢神经系统影响较小,安全剂量范围较广.临床研究表明,卢帕他定低剂量口服能有效地控制季节性和常年过敏性鼻炎的症状.卢帕他定对部分过敏性皮肤疾病的临床研究也在进行之中.     

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.     

抗组胺药物及其新药研究进展

组胺与组胺受体结合后引发以组胺为主的炎性介质释放,导致变态反应性疾病的发生.H1受体拮抗剂是抗组胺药物之一,可阻断组胺与Hl受体结合,从而抑制组胺发挥其生物学效应.Hl受体拮抗剂主要用于治疗由组胺释放诱发的变态反应性疾病.第一代抗组胺药作用时间短,有明显的镇静作用.第二代抗组胺药药效与第一代相近或强于第一代,作用时间长,无明显的中枢镇静作用,但有心脏毒性,故新药的研究成为热点.     

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。     

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。     

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.     

第二代抗组胺药临床应用中的若干问题

第二代抗组胺药安全有效，已成为临床上治疗过敏性皮肤病的主要药物之一，但仍存在一些有争议的问题。本文从药理作用来探讨临床用药几个值得注意的问题，包括药物在体内的相互作用、药物致心脏毒性的机制及相关因素、正确评价对中枢神经系统的镇静作用以及如何看待抗组胺药更广泛的药理作用等。     

Second-Generation H1-Antihistamines in Chronic Urticaria

The effects of urticaria are predominantly mediated by histamine release; therefore, H1-antihistamines are the mainstay of treatment. Second-generation H1-antihistamines, compared with their first-generation counterparts, have demonstrated improved peripheral H1-receptor selectivity and decreased lipophilicity (which minimizes CNS adverse effects), and antiallergic properties in addition to being histamine inverse agonists. Evidence of clinical efficacy and tolerability of second-generation H1-antihistamines available in the US for the treatment of chronic urticaria (CU) was analyzed using the GRADE system to develop the strength of recommendations for particular therapies. The evidence for the safety and efficacy of the majority of second-generation H1-antihistamines available in the US is of high quality and leads to a strong recommendation for their use in CU. There is a limited amount of data of variable quality comparing the efficacy between various second-generation H1-antihistamines in CU leading to weak recommendations for using cetirizine over fexofenadine and levocetirizine over desloratadine. Limited data of variable quality exist for the efficacy of higher doses of second-generation H1-antihistamines in CU patients not responsive to standard doses. These limited data lead to a strong recommendation that higher than recommended doses of fexofenadine do not offer greater efficacy in control of CU and a weak recommendation that higher doses of levocetirizine and desloratadine are more effective in CU unresponsive to standard doses. More studies of higher quality are required to make any firm recommendations regarding second-generation H1-antihistamines in the treatment of physical urticarias. All second-generation H1-antihistamines appear to be very well tolerated in CU patients, with rare reports of adverse effects. Due to the relatively large gaps in the quantity and quality of evidence, particularly for choice of H1-antihistamines, use of higher doses, and use in physical urticarias, greater emphasis in management decisions should be based on the risk/benefit ratio and the patient's personal values and preferences (including cost) in clinical decision making.     

Pharmakoprophylaxe und Begleitmedikation bei spezifischer Immuntherapie

Drugs that are used in relation to allergen-specific immunotherapy (SIT) can be separated into pharmacoprophylaxis to avoid or decrease local and systemic adverse effects of SIT and in co-medications to treat other diseases. Regarding pharmacoprophylaxis, H1-antihistamines are able to reduce local and mild systemic, but not severe systemic side effects of SIT. H1-antihistamines do not attenuate the efficacy of SIT. Severe systemic side effects have been blocked in some cases with omalizumab; currently this agent can be used off-label during venom SIT. With regard to co-medication, the concomitant use of immunomodulating drugs during SIT must be individualized, if the effective profile and side effects of the immunomodulating drug are well-known and a negative effect on SIT is not likely. Recently approved immunosuppressive drugs and biologics are perceived critically due to their unpredictable immunologic effects. For forensic reasons cardioselective beta blockers should be discontinued although no data are available demonstrating adverse effects. If discontinuation is not justified and venom SIT is indicated, SIT can be performed while taking beta blockers. In contrast, ACE-inhibitors should always be stopped in patients with insect venom allergy.     

Cutaneous drug eruption with two antihistaminic drugs of a same chemical family: cetirizine and hydroxyzine

BACKGROUND: H1-antihistamines are widely used to relieve symptoms of allergic disorders. A few skins reactions to H1-antihistamines have been described in the literature. We report the first case of cutaneous drug eruption as fixed drug eruption with 2 antihistamines of the same chemical family: cetirizine and hydroxyzine. CASE REPORT: A 73 year-old man was admitted because of a third cutaneous eruption with the same morphologic features of the same sites as before. The first and second eruption appeared after 4 hours of cetirizine intake, the third eruption appeared after 4 hours of hydroxyzine intake. Healing was obtained after stopping the medication. Histology showed induced drug reaction. Patch tests with cetirizine and hydroxyzine were negative, except false positivity with dimethylsulfoxide vehicles. DISCUSSION: The diagnosis of cutaneous drug eruption as non pigmenting fixed drug eruption related to cetirizine and hydroxyzine was retained. Allergy to both H1 antihistamines can be explained by the fact that they've got the same chemical node that is piperazine, and by the fact that cetirizine is the main metabolite of hydroxyzine. Oral test provocation was omitted because the patient had already reexposed himself to the drugs. To identify the drug responsible for fixed drug eruption, peroral provocation tests are the most valuable method, but carry the risk of a strong reaction. Some authors use patch tests, but their positivity is inconstant. Their interest in fixed drug eruption is undergoing assessment.     

Atopic dermatitis and allergic rhinitis--do co-effects in therapy exist?

Atopic dermatitis and allergic rhinitis frequently appear together in the same patients. The pathogenesis of both disorders is complex and still incompletely understood. Nevertheless, pathophysiological overlaps suggest the existence of potential therapeutic co-effects. While data pointing towards a positive effect of allergen elimination for both diseases is still limited, there is now increasing evidence showing beneficial effects of specific immunotherapy in patients suffering from atopic dermatitis and additional type I allergies. H(1)-antihistamines were also found to exert moderate positive effects on the symptoms of atopic dermatitis in single studies. In summary, a limited therapeutic co-effect of the above mentioned treatment options can be expected in case of the parallel existence of atopic dermatitis and allergic rhinitis in the same patient. More studies on this issue during the next years are desirable. In addition, a better understanding of the pathophysiology should have a positive impact on the treatment of atopic manifestations such as atopic dermatitis and allergic rhinitis.     

EAACI/GA2LEN/EDF/WAO荨麻疹指南:治疗

本指南经2008年第三次国际荨麻疹共识会议讨论达成,由EAACI、GA2LEN、EDF和WAO联合倡议。荨麻疹的一线治疗建议使用非镇静的H1受体拮抗剂。如果标准治疗剂量不起效,建议可将剂量增加到标准治疗剂量的四倍。如果仍无效果,建议采用二线治疗。选择二线治疗时,应权衡利弊和综合考虑治疗的费用。由于糖皮质激素具有不可避免的不良反应,故不推荐长期使用。     

Psychopharmakatherapie bei Pruritus

Pruritus represents one of the most bothersome symptoms of skin and internal diseases, and can also occur without an underlying detectable cause. It is well known that chronic pruritus seriously affects the quality of life in patients. The management of pruritus is challenging, especially if the underlying cause is not identifiable. Besides therapy with increased dosage of non-sedating H1-antihistamines, which is often not successful in severe pruritus, tri- or tetracyclic antidepressants and selective serotonin-reuptake inhibitors are recommended for therapy, as discussed in this review.     

Urticaria a frígore. Respuesta al tratamiento con montelukast

—Physical urticarias represent a group of diseases of indeterminate cause, whose treatment is at times difficult. Cold urticaria is brought on by the exposure of the skin to low temperatures, and patients who suffer from it must be studied to rule out cryopathy, especially the presence of cryoglobulins in the blood. Treatment of cold urticaria may be disappointing, and it is usually based on a combination of H1-antihistamines. According to published studies, leukotrienes are important mediators in cold urticaria, and its successful treatment using leukotriene antagonist drugs has been reported, alone or combined with antihistamines.We describe a case of cold urticaria that was controlled through the combined administration of cetirizine and montelukast.     

Side-effects of drugs on the male sexual function

There are many drugs that may influence libido, erection, or ejaculation. In most cases, the sexual function is impaired, whereas enhancement is rarely seen. Such effects most likely occur in the course of treatment with drugs: interfering with the regulation of sexual hormones; exerting effects on central nervous mechanisms; influencing the autonomic nervous system; or causing changes of the peripheral blood flow.     

Centrally acting drugs for erectile dysfunction: Do they have a future?

Initial placebo-controlled trials with sublingual apomorphine showed promising results for the drug as an option in the pharmacologic management of erectile dysfunction (ED). More recent studies propose poor erectile effects by apomorphine sublingual in patients with diabetes and fewer benefits than sildenafil in patients with ED. In June this year, the European Medicines Agency declared that due to commercial reasons, the marketing authorization for Uprima (Abbott Laboratories, Abbott Park, IL) was not renewed, and the drug is no longer available in the European Union. This does not mean that receptor functions in the central nervous system are uninteresting pharmacologic targets for ED. Experiences with apomorphine sublingual in humans should be acknowledged for a more careful preclinical and clinical characterization of agents with a central nervous system site of action. This article focuses on information obtained from human trials of central acting drugs for ED.     

Urticaria: current opinions about etiology, diagnosis and therapy

In the last few decades an increasing understanding of the pathomechanisms involved in urticaria has highlighted the heterogeneity of different subtypes. According to the new European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum (EAACI/GA(2)LEN/ EDF) guidelines, urticaria subtypes can be grouped into spontaneous urticaria, which includes acute urticaria and chronic urticaria, the physical urticarias, and other urticaria disorders, including, for example, contact urticaria. Clarity of nomenclature is required not only to choose the correct measures in diagnosis and management, but also to compare data from different studies. Urticaria has a profound impact on quality of life and performance. Effective treatment is thus required in all cases where avoidance of eliciting factors is not feasible. For symptomatic relief, non-sedating H1-antihistamines are the first choice in most subtypes of urticaria; however, double-blind controlled studies have shown that the dosages required may exceed those recommended for other diseases, e.g. allergic rhinitis. The current guidelines therefore suggest increasing the dosage up to four-fold, whereas alternative treatments should be reserved as add-on therapy for unresponsive patients.