Reduction of the central nervous system adverse effects associated with antihistamines in the management of allergic disorders: Strategies and progress

To reduce the risks associated with the treatment of allergic disorders, physicians should understand the benefits and risks of drugs in the antihistamine class. The risk of central nervous system adverse effects associated with antihistamine use is significant with the use of first-generation antihistamines, which show pharmacologic activity in serotonergic, α-adrenergic, dopaminergic, and muscarinic-cholinergic pathways. Adverse effects reported with the use of first-generation antihistamines most often include drowsiness, fatigue, and an inability to concentrate; these effects may result in decreased compliance with therapy. The second-generation antihistamines have the property of low lipid solubility, which slows access across the blood-brain barrier. The low sedative profile of these new drugs may also be linked to a more pronounced binding to peripheral rather than brain histamine H₁-receptors. The use of antihistamines with lower lipid solubility and greater specificity can provide an effective alternative for the relief of allergic symptoms, can improve compliance, and can reduce neurologic side effects. Because of the differences now recognized in the side effects of drugs of this class, an individualized approach to selection of antihistamine therapy is required.