Question
Second generation H1 antihistaminic drugs
Answer
Second-generation H1 antihistamines were developed to overcome first-generation drugs’ major limitation — significant CNS penetration and sedation.
Examples: Cetirizine, Loratadine, Fexofenadine, Desloratadine, Levocetirizine.
Distinguishing features: relatively selective peripheral H1-receptor blockade; poor blood-brain-barrier penetration (lipophobic, and substrates for the P-glycoprotein efflux pump at the BBB) — minimal sedation and negligible anticholinergic/antiemetic action, unlike first-generation agents. Longer duration of action permits once-daily dosing.
Uses: allergic rhinitis, urticaria, allergic conjunctivitis, and other mild-to-moderate allergic conditions where sedation is undesirable (e.g. in patients who must remain alert).
Adverse effects: generally well tolerated; minimal sedation compared to first-generation agents; terfenadine and astemizole (older second-generation agents) were withdrawn for cardiotoxicity (QT prolongation, torsades de pointes) — a risk not shared by the currently used agents above.