Pharmacology of Antihistamines

H_1-antihistamines, the mainstay of treatment for urticaria, were developed from anticholinergic drugs more than 70 years ago. They act as inverse agonists rather than antagonists of histamine H₁-receptors which are members of the G-protein family. The older first generation H_1-antihistamines penetrate readily into the brain to cause sedation, drowsiness, fatigue and impaired concentration and memory causing detrimental effects on learning and examination performance in children and on impairment of the ability of adults to work and drive. Their use should be discouraged. The newer second-generation H₁-antihistamines are safer, cause less sedation and are more efficacious. Three drugs widely used for symptomatic relief in urticaria, desloratadine, levocetirizine and fexofenadine are highlighted in this review. Of these levocetirizine and fexofenadine are the most potent in humans in vivo. However, levocetirizine may cause somnolence in susceptible individuals, whereas fexofenadine has a relatively short duration of action and may be required to be given twice daily for all round daily protection. Although desloratadine is less potent, it has the advantages of rarely causing somnolence and having a long duration of action.     

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.     

Antihistamines and alternatives in physical urticaria

ABSTRACT: The mainstay of management of physical urticaria is symptomatic therapy with H₁-type antihistamines, with preference being given to the nonsedating drugs. Patients vary in their responsiveness, in dependence of the type of physical urticaria. If even higher doses of H₁ blockers fail, dapsone, sulfazalazine, chloroquine, and danazol may be tried as alternatives. Corticosteroids, though highly effective, are contraindicated because of long-term adverse effects. Patients should also be advised to avoid eliciting stimuli or to use exposure only to induce the so-called hardening, under medical supervision. Physicians should exclude sustaining diseases or drug intake. In cold urticaria, a trial with antibiotics is worthwhile. If all these possibilities are utilized to the advantage of the individual patient, physical urticaria is a generally well-managed disease.     

Antihistamines in the Treatment of Atopic Dermatitis

Background: Atopic dermatitis (AD) is an inflammatory skin disorder that is exceedingly challenging to treat. A prominent feature of AD is chronic pruritus. Early evidence suggested that pruritus in AD was partially due to mast cell release of histamine. Conversely, recent studies do not validate the role of histamine in the pathogenesis of pruritus. Conventional management continues to include the wide use of antihistamines to treat the persistent itch, however, there is an urgent need for therapy which will reduce the severity of pruritus for these patients. Objective: To review the evidence in the literature for the use of antihistamines in the treatment of atopic dermatitis. Methods: A MEDLINE search (1966–2002) was performed to obtain studies examining the use of antihistamines in the treatment of atopic dermatitis. Search terms included: atopic dermatitis; eczema; antihistamines; azatadine; brompheniramine; cetirizine; chlorpheniramine; clemastine; cyclizine; cyproheptadine; desloratadine; diphenhydramine; fexofenadine; hydroxyzine; loratadine; meclizine; promethazine; trimeprazine. Further references were gathered from these publications. Results: Historically, antihistamines have been used in the treatment of AD. However, this review shows that the evidence for its use is inconclusive. At present, several antihistamines continue to provide relief of pruritus by central sedation, and they can also be used therapeutically for concomitant allergic conditions associated with AD. More clinical trials examining the therapeutic efficacy of antihistamines, especially with the newer nonsedating antihistamines, are necessary to elucidate their role in the treatment of AD. Conclusion: Dermatologists require additional evidence regarding the efficacy of antihistamines and their mechanism of action in the treatment of AD to enhance patient care.

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Antécédents: La dermatite atopique (DA) est un trouble inflammatoire de la peau qui est excessivement difficile à guérire. Elle se caractérise principalement par la présence de prurit. De premières études ont montré que la présence de prurit est en partie attribuable à la libération de lhistamine par les mastocytes. Or, des études plus récentes nont pas validé le rôle de lhistamine dans la pathogenèse du prurit. Les traitements conventionnels des démangeaisons continuent de faire appel aux antihistaminiques; toutefois, il existe un besoin pressant pour une thérapie qui réduirait la gravité du prurit chez ces patients. Objectif: Passer en revue lusage des médicaments antihistaminiques dans le traitement de la dermatite atopique, rapporté dans les publications spécialisées. Méthodes: Une recherche dans MEDLINE (1966–2002) a été effectuée en vue de regrouper les études menées sur lusage des antihistaminiques dans le traitement de la dermatite atopique. Les termes clés comprenaient: atopic dematitis; eczema; antihistamines; azatadine; brompheniramine; cetirizine; chlorpheniramine; clemastine; cyclizine; cyproheptadine; desloratadine; diphénhydramine; fexofenadine; hydroxyzine; loratadine; meclizine; promethazine; trimeprazine. Des références supplémentaires ont été également obtenues de ces publications. Résultats: Depuis toujours, les antihistaminiques ont été utilisés dans le traitement de la DA. Néanmoins, cette revue montre que leur efficacité na pas été établie. Actuellement, plusieurs médicaments antihistaminiques soulagent les démangeaisons par effet sédatif. On peut également y avoir recours contre les allergies associées à la DA. Des essais cliniques évaluant lefficacité des antihistaminiques, surtout les nouveaux produits ne comportant pas de calmants, sont nécessaires afin dévaluer leur rôle dans le traitement de la DA. Conclusion: Afin daméliorer les soins offerts aux patients, les dermatologues ont besoin davantage de preuves en ce qui a trait à lefficacité des antihistaminiques et à leur mécanisme daction dans le traitement de la DA.

     

Excipients in Oral Antihistamines Can Perpetuate Allergic Contact Dermatitis

Propylene glycol is a well‐documented causative agent of allergic contact dermatitis (ACD). It is also reported to cause systemic dermatitis after ingestion of foods or medicines containing it and after intravenous injection of a medicine with propylene glycol in its base. We describe two adolescents with sensitivity to propylene glycol confirmed by patch testing whose dermatitis improved dramatically after cessation of oral antihistamines containing propylene glycol. We report these cases to alert providers to the potential for worsening of ACD due to systemic exposure to propylene glycol in patients with a cutaneous sensitivity to the allergen.     

The Effect of Antihistamines on Ultraviolet-Light–Induced Erythema

Because of the possible role of histamine as an early mediator of ultraviolet light induced erythema, we studied a group of volunteers treated with both H1 and H2 blockers, alone and in combination, before and at various time intervals after, UVL irradiation. No difference was found in the degree of erythema produced by any of the antihistamines used, whether alone or in combination, when compared with the saline control.     

雷公藤多苷联合抗组胺药治疗慢性荨麻疹临床疗效及生活质量的观察

目的 临床观察雷公藤多苷联合不同的第二代抗组胺药治疗慢性荨麻疹的临床疗效及对患者生活质量的影响.方法 360例慢性荨麻疹患者,随机分为六组.治疗组为雷公藤多苷联合不同的抗组胺药(氯雷他定、西替利嗪、咪唑斯汀)各一组,以及仅使用不同抗组胺药(氯雷他定、西替利嗪、咪唑斯汀)各一组作为对照组的治疗方案.六组于治疗前后记录荨麻疹症状评分以及皮肤病生活质量评分表.结果 治疗4周后,雷公藤多苷和抗组胺药联合应用的治疗组的症状评分均低于仅使用抗组胺药物的对照组(P＜0.001),有效率治疗组也高于对照组(P＜0.05).在生活质量方面,治疗组的DLQI评分在用药2周与4周后均显著低于对照组(P＜0.05,P＜0.001)结论 使用雷公藤多苷联合抗组胺药(尤其是咪唑斯汀)能够更快的减轻患者症状,提高患者的生活质量.     

Autologous Serum Therapy in Chronic Urticaria: A Promising Complement to Antihistamines

Background:

Chronic urticaria (CU) is a vexing problem and patients of CU suffer from the morbidity that arise from irritable itch and weals and are also subjected to a huge antihistamine pill burden. The symptoms are more in autoreactive urticaria (AU) where auto-antibodies in blood flares-up the condition. Search for newer effective modalities which can reduce pill burden is a felt need.

Aims:

This study evaluates the effectiveness of autologous serum therapy (AST) in CU and also determines its usefulness in AU.

Materials and Methods:

Double blind, parallel group, randomized, controlled study. Fifty four patients were given AST and 57 patients were given injection normal saline (placebo), along with cetirizine in an on-demand basis in both groups. AST/Placebo was given weekly for nine weeks and followed-up for a total period of 24 weeks. AU was diagnosed by autologous serum skin test. Urticaria total severity score (TSS), Urticaria activity score (UAS), Dermatologic life quality index (DLQI) was used as primary effectiveness variables. Safety parameters assessed were the spontaneously reported adverse events and laboratory parameters.

Results:

TSS showed significant improvement from baseline, 7^th week and 8^th week onwards in AST group and placebo group respectively. Group comparison showed significant improvement 4^th week onwards. UAS showed similar results. DLQI showed significant improvement in AST group compared to placebo at the end of study. Both AU and non-AU patients showed comparable improvement of TSS.

Conclusion:

AST shows promise in treatment of urticaria regardless of the autoreactive nature.     

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。     

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.