ANTIHISTAMINES - TOPICAL VS ORAL-ADMINISTRATION

The pathogenesis of allergic rhinitis is complex, involving not only h istamine and mast cell-derived tryptase, but also eosinophil- and neut rophil-derived mediators, cytokines, and intercellular cell adhesion m olecules (ICAM-1). It is surprising that antihistamines, which block o nly one component of the process, have proved so effective in the mana gement of allergic rhinitis. Research has therefore focused on whether antihistamines have additional pharmacological activities. In vitro s tudies have shown that high concentrations of second generation antihi stamines can block inflammatory mediator release from basophils and ma st cells, and reduce ICAM-1 expression in epithelial cell lines. In vi vo studies have also shown an effect on the allergen-induced inflammat ory reaction; both oral and intranasal antihistamines cause a reductio n in nasal symptoms and inflammatory cell influx. Oral terfenadine and cetirizine and intranasal levocabastine and azelastine have also demo nstrated a lowering of ICAM-1 expression on epithelial cells. With reg ard to clinical efficacy, topical levocabastine (0.5 mg/mL eye drop so lution and 0.5 mg/mL nasal spray) was shown to be more effective than oral terfenadine (60 mg twice daily) in relieving ocular itch (P = 0.0 2) and reducing nasal symptoms in allergic rhinoconjunctivitis. In a f urther study, levocabastine eye drops were as effective and well toler ated as sodium cromoglycate in seasonal allergic rhinitis. Intranasal azelastine (0.28 mg twice daily) showed a trend for superior relief of rhinorrhoea and nasal obstruction compared with oral terfenadine (60 mg twice daily). In addition, intranasal azelastine (0.28 mg twice dai ly) resulted in significant reductions in sneezing, nasal obstruction, rhinorrhoea and itching in perennial rhinitis, compared with the lowe r efficacy of beclomethasone dipropionate (0.1 mg twice daily). As wel l as benefits in efficacy, topical administration is associated with i mproved safety. Some antihistamines, particularly those metabolized in the liver, are associated with occasional reports of severe side-effe cts. It is therefore logical to administer antihistamines directly to the target organ.