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The aim of this study was to compare the effect of antileukotriene (anti-LT), antihistamine, and a combination of anti-LT and antihistamine on the symptoms and nasal resistance in allergic rhinitis patients.
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Substantial evidence implicates mast cells and their main constituent histamine in the pathogenesis of visceral hypersensitivity. We explored the specific contribution of histamine H4 (H4R) and H1 (H1R) receptors to visceral hypersensitivity in a postinflammatory rat model.
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From 2001 to 2011, the FDA approved 9 single-enantiomer products: dexlansoprazole, levoleucovorin, levocetirizine, armodafinil, arformoterol, eszopiclone, escitalopram, dexmethylphenidate, and esomeprazole. Of those 9 drugs, 3 had at least 1 pre-approval randomized trial that included the racemic precursor as a direct comparator, but there was no evidence of superiority of the single enantiomer over the racemic at comparable doses. Between 2001 and 2011, US Medicaid programs spent approximately $6.3 billion on these 9 single-enantiomer drugs.
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The antigen-induced expression of eotaxin by endothelial cells and the adherence and subsequent migration of eosinophils from the microvasculature to the tissues are rapid events partially under the control of histamine released from degranulating mast cells.
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Brain histamine is involved in a wide range of physiological functions such as regulation of the sleep-wake cycle, arousal, cognition, and memory mainly through interactions with histamine H1 receptors (H1Rs). Neurons producing histamine, histaminergic neurons, are exclusively located in the posterior hypothalamus and transmit histamine to almost all regions of the brain. Histamine H1 antagonists, or antihistamines, often prescribed for treatment of allergic disorders, sometimes induce sleepiness and cognitive deficits. It is understood that the mechanism of such CNS side effects is that antihistamine blocks H1Rs in the brain. The purpose of the present study was to compare the CNS side effects of different antihistamines. Subjective sleepiness was measured using the Stanford Sleepiness Scale (SSS) and psychomotor performance was examined by a tachistoscope testing system in healthy, young, Japanese volunteers (16 males, 20-28 yrs.) before and after oral administration of antihistamines such as fexofenadine (FEX) and cetirizine (CET). Additionally, H1R occupancy by antihistamines was examined by PET with 11C-doxepin in 8 volunteers. The results of SSS and psychomotor tests demonstrated that FEX tended to be less sedative than CET though the difference was not statistically significant. PET measurements revealed that no H1Rs in the cerebral cortex were occupied by FEX while about 30% of H1Rs were occupied by CET. In summary, it was confirmed that histamine and H1Rs are involved in maintaining arousal and cognition in humans, and that the severity of clinical symptoms is correlated to the amount of antihistamine that penetrated into the brain.
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Second-generation histamine H(1) receptor antagonists are recognized as being highly effective treatments for allergic-based disease and are among the most frequently prescribed drugs in the world. The newer antihistamines represent a heterogeneous group of compounds with markedly different chemical structures, a spectrum of antihistaminic properties, adverse effects, half-life, tissue distribution, metabolism and varying degrees of anti-inflammatory effects. Histamine is an important mast cell- and basophil-derived mediator that has been implicated in the pathogenesis of asthma, resulting in smooth muscle contraction, mucus hypersecretion, and increased vascular permeability leading to mucosal edema. Antihistamines should never be used as monotherapy for asthma but there is evidence that these drugs give a measure of protection in histamine-induced bronchoconstriction. Furthermore, several studies have demonstrated that the use of second-generation antihistamines, as adjunct therapy, may benefit those patients whose allergic asthma co-exists with allergic rhinitis. Indeed, many patients present with both allergic rhinitis and asthma. The link between the upper and lower respiratory airways is now well established and there is increasing evidence that allergic rhinitis is a risk factor for the development of asthma. More recently, a number of novel antihistamines have been developed which are either metabolites of active drugs or enantiomers and there is emerging evidence that at least one of these drugs, desloratadine, may give significant symptomatic benefit in some types of asthma. It is of interest to note that cetirizine provides a primary pharmacological intervention strategy to prevent the development of asthma in specifically-sensitized high risk groups of infants. Moreover, the documented anti-inflammatory activities of antihistamines may provide a novel mechanism of action for the therapeutic control of virus-induced asthma exacerbations by inhibiting the expression of intercellular adhesion molecule-1 (ICAM-1) by airway epithelial cells. Finally, several well-conducted studies suggest that combination therapy with antihistamines and antileukotrienes may be as effective as corticosteroid use in patients with allergic asthma and seasonal allergic rhinitis.
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Cetirizine but not prednisolone inhibited the early-phase response (37%, P = 0.004). In contrast prednisolone, but not cetirizine, significantly inhibited the size of the late-phase reaction at 24 h (70%, P = 0.021). This was associated with significant decreases in total (MBP+) and activated (EG2+) eosinophils (P = 0.019 and 0.014, respectively), as compared with placebo. There were also clear but non-significant reductions in interleukin-3, interleukin-4, interleukin-5 and granulocyte/macrophage-colony stimulating factor mRNA+ cells.
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In chronic intractable diarrhea, colonic or duodenal biopsy specimens may appear unremarkable on routine hematoxylin-eosin staining, but increased mast cells may be demonstrated by immunohistochemistry for mast cell tryptase, with the novel term mastocytic enterocolitis describing this condition. Similar increases in mast cells are not apparent in control populations or in patients with other specific diseases that cause chronic diarrhea. The cause of the increased mast cells remains to be elucidated.
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Sixty-one cases of chronic urticaria were randomly divided into an observation group (n = 31) and a control group (n = 30). They were treated respectively with Bo's abdominal acupuncture and cetirizine. Their therapeutic effects were compared.
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Histamine receptors mediate nociceptive pathways, especially in the central nervous system. Some studies have demonstrated the analgesic effects of histamine receptor antagonists in the peripheral nervous system. It is not clear whether the local analgesic effect is class-specific or drug-specific.
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The pharmacologic activity and potency of the two enantiomers of cetirizine in the management of allergic skin conditions were investigated by studying the effect of treatment with 5.0 mg cetirizine; 2.5 mg levocetirizine, the (R)-enantiomer; and 2.5 mg ucb 28557, the (S)-enantiomer, on histamine-induced wheal and flare response in 18 healthy volunteers. Each treatment was administered as a single oral dose in randomized, double-blind, and crossover manner, and the efficacy of treatment was assessed over a period of 32 h, as per cent inhibition of the histamine-induced wheal and flare areas before treatment. Blood and urine samples were collected in a time-dependent manner and analyzed for the total amounts of each study drug, to elucidate their pharmacokinetic profiles.
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This study was a 12-week, double-blind, randomized, placebo-controlled trial. Sixty children with AR aged 6-13 years with nasal total symptoms score (NTSS) ≥5 who fulfilled the inclusion criteria were enrolled. Patients were randomized into two groups with 28 participants receiving levocetirizine plus placebo and 32 participants receiving regular levocetirizine plus LP (HF.A00232) for the first 8 weeks, with a shift to levocetirizine as rescue treatment during the following 4 weeks. Parameters evaluated, including nasal, throat, and eye TSS (NTSS, TTSS, and ETSS, respectively), TSS and levocetirizine use, were recorded daily. Physical examinations and Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQs) were administered at each visit. In addition, blood samples were obtained for evaluation of cytokines including interleukin-4, interferon-γ, interleukin-10, and transforming growth factor-β at baseline, Week 8, and Week 12.
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The suppressive activity of LCT on OPN functions on nasal epithelial cells may be responsible for the attenuating effect of the agent on allergic diseases.
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Our results suggest a protective effect of cetirizine against high-fat diet-induced beta-cell dysfunction, but not against autoimmune beta-cell destruction.
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Chronic urticaria is a problem for both physician and patient. In an effort to avoid the risks associated with corticosteroid treatment, many first-generation H1-receptor antagonists have been tried and found to induce undesirable levels of sedation when given in amounts sufficient to control urticaria. Cetirizine, a pharmacologically active oxidized metabolite of hydroxyzine, was developed to provide selective H1-receptor inhibition without depression of the central nervous system. In a 4-week, multicenter, double-blind, placebo-controlled safety and efficacy study, cetirizine, in a once-a-day dose (5 to 20 mg), was equivalent in efficacy to hydroxyzine in divided doses (25 to 75 mg/day). The incidence of somnolence in the cetirizine group was not significantly different from that of the placebo group. However, in the hydroxyzine group, the incidence of somnolence was significantly higher than that in the placebo group (p = 0.001). The results of this study demonstrate that cetirizine has a greater safety margin over the older parent drug hydroxyzine.
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To determine the effectiveness of 2 second-generation antihistamines in modulating motion sickness induced by Coriolis vestibular cross-coupling stimulation.
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Cetirizine does not prevent the incidence or affect the severity of nevirapine-associated rash.
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A previous study showed the inhibitory effects of loratadine on histamine-induced wheal, flare and itch in human skin to be very variable between individuals. It was hypothesised that this variability may have been due to differences in the rates of metabolism of loratadine to its active form, desloratadine. This double blind, crossover study examined the effects of desloratadine in 12 healthy volunteers. Levocetirizine was used as a comparator.
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The histamine-induced wheal and flare response was used to compare quantitatively the antihistaminic potency of levocetirizine and desloratadine.
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A group of ten normal volunteers were studied, each subject visiting the laboratory on three occasions with intervals of at least 2 weeks between visits.
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We describe the case of a 30-year-old woman who reported several episodes of anaphylaxis with angioedema and relapsing urticaria. Some events were related to nonsteroidal anti-inflammatory drug intake and one episode followed alcohol ingestion, but in most cases no triggers could be identified. Specific immunoglobulin E determination was negative for food and drug allergens, C3 and C4 were in the normal range, C1 inhibitor was slightly reduced and serum tryptase was undetectable. In vivo autologous serum skin test and in vitro basophil histamine release assay were positive indicating the presence of circulating histamine-releasing factors. When oral tolerance tests were performed, only doxycycline was tolerated whereas levofloxacin, clarithromycin, nimesulide and tramadol caused mild urticaria. Premedication with cetirizine allowed the patient to tolerate levofloxacin, clarithromycin and nimesulide. The demonstration of circulating histamine-releasing factors in a patient with idiopathic anaphylaxis and multiple drug allergy syndrome provides a new mechanistic insight and might open the way to new therapeutic approaches.
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P-glycoprotein (P-gp) is a drug efflux pump expressed, amongst others, on the luminal surface of the cerebral endothelial cells forming the blood-brain barrier. Studies in rodents have demonstrated that antihistamines that are substrates of the P-gp transporter display no or minor central nervous system (CNS) effects as compared to antihistamines that are not P-gp transporter substrates.
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We investigated the suitability of cetirizine HCl (cetirizine) for the initial treatment of chronic urticaria. A secondary aim was to identify the optimal alternative treatments when switching from this drug to other drugs in patients who are dissatisfied with cetirizine. We started cetirizine at a once-daily dose of 10 mg for 2 weeks and then, depending on the course of symptoms in individual patients, it was either continued, titrated to a higher dose, or switched to other drugs (antihistamines including H2 blockers) for a further 2 weeks. Degrees of patient satisfaction and ratings by physicians were analyzed, as were adverse events. At 2 weeks after the start of treatment, among 74 patients included in the final evaluation 55 (74.3%) expressed satisfaction with cetirizine therapy. Those not satisfied included five (6.7%) who felt drowsy after taking the drug and 14 (18.9%) in whom the drug had not demonstrated adequate efficacy. After optimizing the treatment on a per-patient basis, including switching from cetirizine to other drugs, the percentage satisfied with treatment at 4 weeks was 83.7% (62/74). In the group of patients who were satisfied with the therapy at 2 weeks, attending physicians confirmed that wheals and scratches were significantly alleviated at 2 and 4 weeks, respectively. Adverse effects were mild and uncommon. Cetirizine as an initial treatment for chronic urticaria appears effective and safe. For patients in whom cetirizine fails to satisfactorily alleviate symptoms as well as those who complain of drowsiness, switching to other antihistamine drugs may be an effective strategy.