Which of the following is NOT a first-generation H1 blocker?

• A. Diphenhydramine
• B. Chlorpheniramine
• C. Promethazine
• D. Loratadine

Answer: (D)

The main idea here is the difference between first-generation and second-generation H1 blockers. First-generation agents readily cross the blood-brain barrier, so they cause noticeable sedation and often anticholinergic side effects. In contrast, second-generation antihistamines are designed to limit CNS penetration, leading to little to no daytime drowsiness and fewer anticholinergic effects.

Loratadine falls into the second-generation group. It has low CNS penetration and is a substrate that tends to stay out of the brain, so it provides allergy relief with minimal drowsiness. The other three—diphenhydramine, chlorpheniramine, and promethazine—are classic first-generation blockers that readily enter the CNS and are more sedating, with a higher likelihood of anticholinergic effects. So loratadine is not a first-generation H1 blocker.