Pharmacology Drug Classifications Practice Test

The main idea here is that first-generation H1 antihistamines, like diphenhydramine, readily cross into the brain and cause central nervous system effects. Because they penetrate the blood–brain barrier, they commonly produce sedation and drowsiness. This CNS depressant effect is the defining adverse effect of this class, especially for diphenhydramine, and it’s more prominent than nausea, headache, or dizziness. In contrast, second-generation antihistamines are much less sedating because they don’t enter the brain as readily. So, sedation is the major side effect.