Next generation antihistamines: therapeutic rationale, accomplishments and advances.

Antihistamines, among the most commonly prescribed drugs in the world, have evolved considerably since the first generation was introduced >50 years ago. The first generation antihistamines (e.g., chlorpheniramine, diphenhydramine, promethazine and hydroxyzine) are still widely available and in use today. These drugs have considerable sedative effects caused by their ability to cross the blood-brain barrier. The next generation of antihistamines to emerge in the market were devoid of these sedative effects; however, two (terfenadine and astemizole) have shown rare but lethal cardiotoxic side effects. The third generation antihistamines, metabolites of the earlier drugs, have demonstrated no cardiac effects of the parent drugs and are at least as potent. Many have exhibited superior pharmacokinetic and pharmacological profiles, including an improved onset of action and duration of effect. The clinical benefit of these newer oral antihistamines will clearly help improve the quality of life of patients with chronic allergies.