Clinical pharmacology of H1-antihistamines.
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Histamine H1 Antagonists↗
Biomedical subjects
F Estelle R Simons
Publications and source records attributed to F Estelle R Simons.
H1-antihistamines and the central nervous system.
An extensive body of research exists on CNS effects of H1-antagonists. There is great interest in this area due to the well-known adverse CNS effects associated with first-generation H1-antagonists, and the many new second-generation agents claiming to have nonsedative properties. Because the CNS effects of H1-antagonists are complex and cannot be reflected in one measurement, a variety of assessments of CNS function are required. These range from the subjective (e.g., self-rating of drowsiness) to the objective (e.g. 24 h EEG sleep latency, P300), and from the simple (e.g., critical flicker fusion) to the complex (e.g., actual driving). When these tests are applied to the evaluation of the H1-antagonists currently available, it is clear that there is a real distinction between the older first-generation H1-antagonists and the newer second-generation ones. At the recommended dosages, all the second-generation H1-antagonists are clearly less sedating in more patients than their predecessors. These newer medications do not cross the blood-brain barrier readily; are highly specific for H1-receptors; have little to no anticholinergic, antiserotoninergic, or anti-alpha-adrenergic effects; and do not enhance the adverse CNS effects of alcohol or other CNS-active substances such as the benzodiazepines. Since most second-generation H1-antagonists are found to be relatively nonsedating, their benefit/risk ratios will be determined more by their other properties such as non-CNS adverse effects (e.g., potential to cause cardiac arrhythmias), potency, onset of action, duration of action, ease of administration, and cost. The future role and usefulness of the older sedating H1-antagonists, given the availability of the safer second-generation agents, are unclear at the present time. When H1-antagonist treatment is indicated, physicians should recommend an effective H1-antagonist with a favorable clinical pharmacology profile and a wide margin of safety in patients of all ages. The common, often subclinical, adverse CNS effects produced by the old H1-antagonists remain a major concern and, therefore, these compounds are no longer medications of choice in the treatment of allergic rhinitis, allergic conjunctivitis, or urticaria.
Animals↗
H1-antihistamines in children.
In children, as in adults, H1-antagonists are useful in the treatment of allergic rhinoconjunctivitis. Level 1 evidence for their efficacy in this disorder has been obtained in many well-designed pediatric studies. The widespread use of H1-antagonists in upper respiratory tract infections or otitis media in children is not supported by a strong scientific rationale. H1-antagonists are not harmful in children with asthma and, indeed, may have some beneficial effects in children with mild asthma. Their role in delaying or preventing asthma from developing in high-risk infants and toddlers is currently an important area of clinical investigation. The evidence base for their use in children with urticaria or atopic dermatitis still contains large gaps. First-generation H1-antagonists are presumed to be safe for use in infants and children. While they have undoubtedly been administered without apparent harm to millions in this age group, they impair CNS function far more commonly than is generally realized. Their use should be restricted to two uncommon situations: children with urticaria or atopic dermatitis whose pruritus is so severe that the sedation produced by an old H1-antagonist, such as hydroxyzine, is a benefit rather than a risk; and children with anaphylaxis who require intravenous diphenhydramine as adjunctive treatment to epinephrine and other modalities. Apart from these exceptions, in patients of all ages, second-generation H1-antagonists free from CNS adverse effects are clearly the medications of choice. Pediatric formulations of the new H1-antagonists cetirizine, fexofenadine, and loratadine are now available for use.
Asthma↗