ABSTRACT
First-generation histamine-1-receptor (H1-receptor) antagonists such as diphenhydramine, triprolidine, hydroxyzine, and chlorpheniramine (chlorphenamine), frequently cause somnolence, performance impairment, and other adverse central nervous system (CNS) effects. Various subjective and objective methods have been utilized to detect these adverse effects. Because the CNS changes induced by H1-antagonists are complex and cannot be reflected in one measurement, a variety of assessments are required. Dosing strategies have been proposed to circumvent these unwanted effects (pm dosing, relying on tolerance to CNS effects to develop) but their effectiveness is at best uncertain. Second-generation H1-antagonists such as loratadine, cetirizine, fexofenadine, ebastine, and mizolastine represent a true advance in therapeutics. At manufacturers’ recommended dosages, they result in little or no sedation in contrast to their predecessors, and do not exacerbate the adverse CNS effects of alcohol or other CNS-active chemicals. Differences among various agents within each generation of H1-antagonists in their effects on the CNS have been noted, and with certain of the secondgeneration H1-antagonists (e.g., acrivastine and cetirizine), these differences can be clinically relevant. When given in higher than usual dosages by mouth, or even when applied topically, some subjective and/or objective CNS abnormalities have been noted with certain second-generation H1-antagonists. Given the
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availability of the safer second-generation products, the future usefulness of the older first-generation H1-antagonists used orally in allergic disease is in doubt. The need for a phase-out plan of the sedating first-generation H1-antagonists will likely become more clear as we collect further experience and information about the advantageous benefit/risk ratio of the second-generation H1-antagonists.
