Second-generation agents antihistamines

Although the antihistamines are not useful as primary agents in the treatment of asthma, a number of studies have shown that the second-generation compounds are effective as adjunctive therapies in asthmatic patients with concomitant rhinitis, urticaria, or dermatitis. Cetirizine has been used to prevent the progression from atopic dermatitis to asthma in young children. 

Antihistamines currently available for topical ophthalmic use include the first-generation agents pheniramine maleate and antazoline phosphate and the second-generation antihistamines emedastine, azelastine, ketotifen, and olopatadine. The latter three have dual action, which includes a mast cell-stabilizing effect. 

Prototypical agent Diphenhydramine. Other first-generation antihistamines include chlorpheniramine, clemastine, promethazine, and cyproheptadine. Second-generation antihistamines— loratadine, cetirizine, and fexofenadine—were developed to circumvent anticholinergic and sedative side effects. 

Also, the sedative cffecLs of these agents may potentiate the deprcssutit activity of barbiturates, alcohol, narcotic analgc-.sics. and other depressants. Recently, it was discovered that several of the second-generation antihistamines may produce life-threatening arrhythmias when coadminkstcred with drugs that inhibit their metabolism." -These interactions arc di.scussed in more detail in the. sections below. 

Terfenadine, astemizole, loratadine, and cetirizine are second-generation antihistaminic agents that are relatively nonsedating. Other Hj-receptor antagonists currently undergoing clinical trials are azelastine, ebastine, and levocabastine. 

Histaminei (Hj) receptors mediate such actions as bron-choconstriction and the contraction of smooth muscles in the gastrointestinal tract. Ebastine is a histamine,-receptor blocker. Terfenadine, astemizole, loratadine, and certirizine are second-generation antihistamine agents that are relatively nonsedating. Other H,-receptor antagonists currently undergoing clinical trials are azelastine, ebastine, and levo-cabastine (see also Figures 34 and 59). 

Second-Generation Piperidines (Prototype Terfena-dine). Terfenadine and astemizole were withdrawn from the market. Current drugs in this class include loratadine, deslor-atadine, and fexofenadine. These agents are highly selective for Hi receptors, lack significant anticholinergic actions, and penetrate poorly into the CNS. Taken together, these properties appear to account for the low incidence of side effects of piperidine antihistamines. 

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