The document discusses different generations of antihistamines and compares their sedative effects and safety profiles. First generation antihistamines are highly sedating and potentially cardiotoxic. Second generation options like cetirizine and loratadine are less sedating but loratadine may block potassium channels. Desloratadine is in the third generation and has some anticholinergic side effects while levocetirizine has a similar profile to cetirizine but causes more somnolence than placebo. Fexofenadine is noted as non-sedating, non-cardiotoxic with no anticholinergic effects and a wide therapeutic index.

1. 1 st Generation * Anticholinergic (non-selective) * Highly sedative Less sedating Cetirizine* Somnolence(%) Cetirizine 13.7 Placebo 6.3 *Zyrtec Prescribing Information Potentially sedative/ cardiotoxic ? Loratadine Potential blockage of K + channels 2 nd Generation Cetirizine, Loratadine,Fexofenadine Non-sedating Loratadine, Fexofenadine Fexofenadine *Non- cardiotoxic *No anticholinergic side effects *Wide therapeutic index Antihistamines 3rd Generation !! Desloratadine * *Anticholinergic side effects Levocetirizine * *Profile similar to cetirizine *Somnolence 4 times that of placebo *Xyzal Prescribing Information *Ellis et al, AAAAI 2002 H1 Antihistamines: Generation Concept

3. Shamsi Z, et al. Hum Psychopharmacol 2000; 15 (suppl 1): S3-S30 Welch MJ, et al. H1-Antihistamines in Allergic Disease, 2nd ed, 2002;337 HD = higher than recommended dose; +/- = exhibits effects Antihistamines: Side effects & Impairment 0 0 0 Fexofenadine +/-,+(HD) 0 +/-,+(HD) Cetrizine 0,+(HD) +/- 0,+(HD) Desloratadine 0,+(HD) 0 0,+(HD) Loratadine +++ +++ +++ Clemastine ++ +++ ++ Brompheniramine ++ +++ ++ Chlorpheniramine +++ +++ +++ Diphenhydramine Impairment Anticholinergic effect Drowsiness