Second-generation antihistamines - A comparative review

Second-generation histamine H-1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adve rse effects that occur with older H-1 receptor antagonists. This article ev aluates second-generation antihistamines, including acrivastine, astemizole , azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mi zolastine and terfenadine, for significant features that affect choice. In addition to their primary mechanism of antagonising histamine at the H-1 receptor, these agents may act on other mediators of the allergic reaction . However, the clinical significance of activity beyond that mediated by hi stamine H-1 receptor antagonism has yet to be demonstrated. Most of the agents reviewed are metabolised by the liver to active metaboli tes that play a significant role in their effect. Conditions that result in accumulation of astemizole. ebastine and terfenadine may prolong the QT in terval and result in torsade de pointer;. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis. all agents are effective and the choice should be ba sed on other factors. For urticaria, cetirizine rind mizolastine demonstrat e superior suppression of wheal and flare at the dosages recommended by the manufacturer. For atopic dermatitis, as adjunctive therapy to reduce pruri tus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although cu rrent evidence does not suggest a primary role fur these agents in the mana gement of asthma, it does support their use for asthmatic patients when the re is coexisting allergic rhinitis, dermatitis or urticaria.