Second-Generation Antihistamines

Abstract

Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice. In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated. Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer. For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.

Sensitive Determination of Cetirizine Using CdS Quantum dots as Oxidase Mimic-mediated Chemiluminescence of Sulfite

“…Marked affinity of cetirizine for peripheral histamine H1 receptors results in anti-allergic properties, but has the advantage that it lacks the CNS depressant effects often encountered in anti-histamines. Cetirizine is a potent and well tolerated nonsedating antihistamine drug for the treatment of seasonal and prennial allergic rhinitis and chronic urticarial (Slater et al, 1999).…”

The Effect of Histamine H1 Receptor Antagonists on the Morphine-Induced Antinociception in the Acute Trigeminal Model of Nociception in Rats

“…Tissue distribution studies in rats revealed that fexofenadine does not cross the blood-brain barrier [24,25]. We used fexofenadine in this study because it is very selective for H 1 receptor and only occupied peripheral histamine H 1 receptors, whereas chlorpheniramine as a firstgeneration of antihistamines have been attributed to poor H 1 -receptor specificity and also easily crossing the blood-brain barrier (BBB) and acts on the both peripheral and central receptors [26]. Cetirizine is a second-generation antihistamine with reduced brainpenetrating activity and more H 1 binding selectivity in comparison with the first-generation of antihistamine [26].…”

“…We used fexofenadine in this study because it is very selective for H 1 receptor and only occupied peripheral histamine H 1 receptors, whereas chlorpheniramine as a firstgeneration of antihistamines have been attributed to poor H 1 -receptor specificity and also easily crossing the blood-brain barrier (BBB) and acts on the both peripheral and central receptors [26]. Cetirizine is a second-generation antihistamine with reduced brainpenetrating activity and more H 1 binding selectivity in comparison with the first-generation of antihistamine [26]. Tashiro et al (2002) reported that the administration of cetirizine 20 mg/kg in the human subjects could cause occupation of 30% of histamine H 1 receptors in the cerebral cortex [25].…”

Management of Allergic Rhinitis

“…H 1 receptors are found on nerve endings, and distributed in the brain, smooth muscle and glandular cells, endothelial cells, the adrenal medulla and heart. 25 Since their inception, first generation antihistamines remain one of the most widely used classes of drugs in the world. Diphenhydramine, chlorpheniramine, hydroxyzine, brompheniramine, and doxylamine are included in this class.…”

“…Other mechanisms that differ from the first generation antihistamines are thought to include inhibition of calcium ion influx across the mast cells thus preventing mediator release. 25 In terms of tolerability, the nonsedating antihistamines have been shown to have similar side effect profiles as placebo and are less impairing with respect to sleep, EEG, cognitive performance and anticholinergic side effects. 33 Furthermore, since newer agents are efficacious, cetirizine, fexofenadine, and loratadine are logical choices for treating allergic rhinitis in pediatric patients < 12 years of age.…”