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ABSTRACT: When compared to older first‐generation antihistamines, second‐generation antihistamines are characterized by improved selectivity for histamine receptors, absence of sedation, and, possibly, antiallergic properties distinct from their antihistaminic activity. Such a pharmacologic profile, arising from specific pharmacodynamic and pharmacokinetic properties, bears an obvious clinical advantage for the therapy of allergic diseases; thus second‐generation antihistamines have become the treatment of choice for chronic urticaria and allergic rhinitis. Despite such a therapeutic advantage, adverse cardiovascular effects associated with the use of some congeners belonging to the class of second‐generation antihistamines (particularly terfenadine and astemizole) have been reported, and a major concern about the therapeutic selection of antihistamines now is represented by their potentially severe arrhythmogenic properties. This article reviews the recent advances in the understanding of the pathogenesis and etiology of the cardiotoxic actions of some second‐generation antihistamines, underlining their molecular actions at the level of K+ channels controlling the cardiac action potential. In particular, emphasis is given to the interaction of second‐generation antihistamines with the K+ channels encoded by the human ether‐a‐gogo‐related gene (HERG), which is crucially involved in the repolarization process of the cardiac action potential. This review will also focus on the recent concerns over the potential cardiac adverse effects of first‐generation H1 receptor blockers. The present exploration of the molecular basis of the adverse cardiac effects of antihistamines shows how important contributions in deciphering such complex phenomenon have emerged from disciplines and techniques not traditionally related to immunology, such as molecular genetics and cellular electrophysiology; it seems possible to anticipate that the exchange of results from such different disciplines in the future will provide patients and physicians with medications with improved therapeutic efficacy and safety for the clinical management of allergic diseases. 相似文献
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Maurer M Weller K Bindslev-Jensen C Giménez-Arnau A Bousquet PJ Bousquet J Canonica GW Church MK Godse KV Grattan CE Greaves MW Hide M Kalogeromitros D Kaplan AP Saini SS Zhu XJ Zuberbier T 《Allergy》2011,66(3):317-330
Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought. At any time, 0.5-1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age. The duration of the disease is generally 1-5 years but is likely to be longer in more severe cases, cases with concurrent angioedema, in combination with physical urticaria or with a positive autologous serum skin test (autoreactivity). Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life. In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult. Nonsedating H?-antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in < 50% of patients. Although guideline-recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients have only little benefit from H? -antihistamines. Consequently, there is a great need for new therapeutic strategies. 相似文献
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《Expert opinion on drug safety》2013,12(12):1667-1698
Introduction: Approximately 10 – 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists.Areas covered: This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post hoc because of several previously published meta-analyses and commentaries on this medication.Expert opinion: The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: i) selection of appropriate study population; ii) ascertainment of antihistamine exposures; and iii) ascertainment of birth defect outcomes. Selected antihistamines have been very well studied (e.g., loratadine); others, especially H2-receptor antagonists, require additional study before an assessment of safety with respect to birth defect risk could be made. 相似文献
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Twelve healthy volunteers were randomly allocated to receiving in a double-blind cross-over fashion levocabastine eye drops (0.5 mg/ml solution) and placebo. They were advised to instill 2 drops per eye, four times daily. Each treatment was administered for a period of 1 week. Before and after each treatment period psychomotor function was assessed using Critical Flicker Fusion Test and the Choice Reaction Time Test. At the same time intervals a subjective evaluation of sedation was given using a Visual Analogue of Sedation. Both objective and subjective measurements showed that no significant treatment effects could be detected. It is concluded that repeated instillations of levocabastine eye drops are devoid of any sedative side effects. 相似文献
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Background Previous studies have shown that antihistamities provide little or no protection against the recruitment of leucocytes in allergic inflammation. Objective We wanted to examine if threshold doses of histamine can potentiate chemoattractant-induced leukocyte adhesion and if complete inhibition of histamine-induced microvascular effects is necessary to reduce allergic leucocyte recruitment. Methods The role of histamine in allergic leucocyte recruitment was examined by use of intravital microscopy of the hamster cheek pouch microcirculation. Results We found that topical administration of histamine caused a concentration-dependent increase in microvascular permeability in the cheek pouch; i.e. 0.3 μM histamine caused no detectable plasma leakage, while 1 μM and 10 μM histamine resulted in 29 ± 9.3 and 356 ± 47 leakage sites/cm2 cheek pouch area, respectively. The percentage of postcapillary venules with more than five adherent leucocytes (an index of early leucocyte recruitment) was 1.1 ± 0.51% in the control situation, and did not increase significantly after stimulation with histamine alone (0.3–10μM) or with 1 nM ieukotriene B4 (LTB4). On the other hand, coapplication of 10μM histamine and 1 nM LTB4 increased leucocyte adhesion 24-fold. In fact, the 10 times lower dose of histamine (1 μM) together with 1 nM LTB4 increased leucocyte adhesion to a similar extent (20 fold). The increase in vascular permeabihty evoked by exogenous 10μM histamine (with or without LTB4), or by histamine released from activated mast cells (antigen challenge), was completely reversed by local pretreatment with the H1-receptor antagonist mepyramine. This mepyramine treatment also abohshed the enhanced leucocyte adhesion in response to coapplication of histamine and LTB4. Moreover, mepyramine, which had no effect on leucocyte recruitment evoked by 3 nM LTB4per se, reduced antigen-induced recruitment of leucocytes to the extravascular tissue by 79.5 ± 14.8%. Conclusion We conclude that threshold concentrations of histamine can strikingly potentiate chemoattractant-induced leucocyte responses, and that in order to reduce allergic leucocyte recruitment it may be necessary to use antihistamines in doses high enough to abolish the microvascular actions of histamine. 相似文献
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This article covers an interesting topic. Paraneoplastic pruritus is rare but can be severe. It can sometimes be resistant to usual treatments. In our case, it was resistant to antihistamines but was relieved by inhibitors of serotonin scrapping. 相似文献