Eli5: How do antihistamines work and what is the difference between first generation and second?

Question

Eli5: How do antihistamines work and what is the difference between first generation and second?

In: 287

Answer 1

Antihistamines work by binding and preventing mast cell release of histamine, the main molecule involved in mediating allergic responses (specifically type I hypersensitivity reactions). By preventing mast cell destabilization, there is less histamine release and consequently less “symptoms” such as hives, local swelling, airway distress, etc.

First generation antihistamines (diphenhydramine or Benadryl) notoriously cross the blood brain barrier and have what we call “anticholinergic effects” – this means that the medicine alters our brains ability to use acetylcholine, a cell signaler involved in many things (salivary secretions, vestibulocochlear senses, and notably, wakefulness). By interfering with acetylcholine in the brain, we suffer side effects that are essentially the opposite of what acetylcholine does (most commonly being drowsiness and dry mouth).

Second generation antihistamines (cetirizine, fexofenadine, etc) do not cross the blood brain barrier near as effectively and therefore are much better at symptomatic relief without the side effects.