Advances in the pharmacotherapy of allergic rhinitis: second-generation H1-receptor antagonists

Allergic rhinitis, whether seasonal or perennial, potentially affects up to 30% of the population. Pharmacotherapy for allergic rhinitis that is directed at symptomatic relief traditionally includes antihistamines as one of the first lines of therapy. All antihistamines are H1-receptor antagonists, or H1 blockers; they are reversible, competitive inhibitors of the actions of histamine, a critical mediator in the pathophysiology of the allergic response. Nearly all antihistamines (with the exception of the second-generation antihistamine cetirizine) are metabolized by the hepatic cytochrome P-450 system. Potentially fatal adverse effects of antihistamines may include heart arrhythmias from overdosage. Hepatic or cardiac dysfunction also predisposes to heart arrhythmias in patients who take antihistamines. Concomitant administration of macrolide antibiotics or antifungal agents with antihistamines may also predispose patients to potentially fatal heart arrhythmias. First-generation H1 blockers (e.g., the ethanolamines, ethylenediamines, alkylamines, piperazines, and phenothiazines) offer rapid relief of symptoms (usually within 15 or 30 minutes) but have the potential for significant sedation and for adverse reactions and drug interactions, as previously described. In contrast, however, the second-generation H1-antagonists (e.g., clemastine, terfenadine, astemizole, acrivastine, loratadine, and cetirizine) offer equal or superior relief but have markedly decreased sedation potential. This article compares first- and second-generation H1 blockers to provide clinicians with a better understanding of each agent's actions, potential side effects, and efficacy as antihistamine therapy.