Eli5: How do antihistamines work and what is the difference between first generation and second?
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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.
Think of your body as a house with windows. When something outside, like pollen or dust, comes in through the windows, it can make you sneeze, itch, and feel uncomfortable.
Now, first-generation antihistamines are like old-fashioned window screens. They can block the things from coming inside, but they also make the room a little darker and cozy. They have this side effect of making you feel sleepy, like wanting to take a nap.
On the other hand, second-generation antihistamines are like modern window screens. They also keep the bad things out, but they let more light into the room. They do their job without making you feel sleepy or tired.
1st gen antihistamines are useful if you want the added sleepy effect or need to sedate someone, but 2nd gen are for when you need to carry on with life as normal!
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Antihistamine, like the name suggests, is a drug that blocks the effects of histamines. First gen blocks histamines and muscarinic receptors, second gen just blocks histamines. Second gen also doesn’t make you drowsy
Receptors are present on our cell surface. These are naturally used to regulate normal functions.
Histamine (naturally uccoring chemical) binds to these receptors to start inflammation (swelling)
There are 3 receptors
H1. Present in smooth muscles (promotes tightening of muscle)
H2. In the stomach (increase acid production)
H3. In the brain (increases activity)
H4. Immune cells (results in inflammation)
Anti histamines block these receptors either selectively or individually. This blockade results in the opposite effect because the rest of the body’s systems are normal.
The difference between 1st and 2nd is that
1st are able to move into the brain through a barrier called blood brain barrier. Because of this they cause drowsiness while 2nd don’t.
Another fun fact is that we have H2 blockers. They are technically antihistamines but are called H2RA’s or H2 receptor antagonists (another name for blockers)
Sauce: I’m a Pharmacist.
The window screen analogy isn’t quite right. I describe them to patients as the equivalent of paper towels.
When your allergy cells are exposed to something you are allergic to (pollen, dander, food, etc) they react by exploding and releasing a bunch of stuff including a molecule called histamine.
Histamine then binds to a receptor on other cells and causes the itchy, red, raised hives or the itchy, watery eyes or the itchy, runny, sneezy, nose or your lungs to tighten up depending on where it is released.
Antihistamines are like paper towels in that they ‘mop up’ the histamine that is released. They can’t block pollen nor the reaction of your allergy cells. All they can do is block (actually compete for the binding spot) on the receptor and then block all the symptoms.
First generation easily crossed the blood brain barrier. They make you sleepy and are shorter acting. They suck and should really never be used these days.
Second generation were made to last longer and not cross the blood brain barrier as much. Claritin was the first so got early brand name recognition but it’s too weak to do much. Zyrtec is great and cheap but makes 10% of people sleepy. Allegra is nearly as strong as Zyrtec and will not make you sleepy.
I always wondered why Benadryl made me feel like a sleepy desert. Thanks for the explainer!
They block receptors which react to things you’re allergic to, helping cut back allergies. First gen pass blood brain barrier, which can make you sleepy. 2nd gen don’t, so no sleepy
I always wondered why Benadryl made me feel like a sleepy desert. Thanks for the explainer!
They’re just drugs with active chemicals that block your body’s natural histamine production. There are several chemicals that can achieve this. Histamine is important, but sometimes overproduction can harm individuals so we have antihistamines for that. Avoid pharmaceuticals unless you absolutely have to take medicines. Basically 90% of the crap you find on shelves in the US is more harmful than good. This is why Americans are so sickly and have higher rates of cancer, diabetes, kidney and heart disease, etc….
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