H-1-RECEPTOR ANTAGONISTS - COMPARATIVE TOLERABILITY AND SAFETY

First-generation histamine H-1-receptor antagonists, such as diphenhydramine, triprolidine, hydroxyzine or chlorpheniramine (chlorphenamine), frequently cause somnolence or other CNS adverse effects. Second-generation H-1-antagonists, such as terfenadine, astemizole, loratadine and cetirizine, represent a true advance in therapeutics. In manufacturers' recommended doses, they have a more favourable benefit/risk ratio than their predecessors with regard to lack of CNS effects, and do not exacerbate the adverse CNS effects of alcohol or other CNS-active chemicals. Rarely, some of the newer H-1-antagonists may cause cardiac dysrhythmias after overdose or under other specific conditions. The concept of a risk-free H-1-antagonist is proving to be an oversimplification. An H-1-antagonist absolutely free from adverse effects under all circumstances is not yet available for use. The magnitude of the beneficial effects of each H-1-antagonist should be related to the magnitude of the unwanted effects. especially in the CNS and cardiovascular system, and a benefit-risk ratio or therapeutic index should be developed for each medication in this class.