How do allergy meds work, while having different side effects?

January 14, 2008 10:22 PM

How do loratadine and diphenhydramine HCI work? Specifically, how is it that both can help control allergies, yet have different side effects? I'm particularly interested in how loratadine works without causing sleepiness, while a single 25 mg capsule of diphenhydramine is able to knock me out in a matter of minutes.
posted by invisible ink to health & fitness (7 comments total)

Diphenhydramine crosses the blood-brain barrier, entering the central nervous system and making you sleepy. Loratadine does not cross the blood-brain barrier, or crosses it in only very small concentrations.

Otherwise, they have the same primary mechanism of action, blocking the histamine receptor that mediates allergic reactions.
posted by mr_roboto at 10:39 PM on January 14, 2008

Here's Wikipedia on the blood-brain barrier, for what it's worth.
posted by mr_roboto at 10:40 PM on January 14, 2008

And it's HCl, not HCI. The salt form of the molecule produced by reaction of the free base with hydrochloric acid.
posted by mr_roboto at 10:45 PM on January 14, 2008

They would both have the safe effects if they both physically made it into the brain, the way I understand it. These types of antihistamines are also anticholinergic, which means they block the effect of Acetylcholine, which as I understand it is a neurotransmitter that in addition to some other things, is produced while you sleep, and used up over the course of the day, presumably making you tired once you've been awake for 12 hours or so.
posted by floam at 11:14 PM on January 14, 2008

An excellent paper on the pharmacokinetics of Loratadine here, discussing metabolic implications of the CYP2D6 allele variation (pdf).

The CYP2D6 allele variation is extremely important in pharmacology - it explains why some people, for example, are resistant to the pain-relieving effects of codeine - whilst others are knocked out by it.

Also, Sedating Antihistamine Information here (Word Doc)

Whilst both are Histamine H1 Receptor agonists, Diphenyhydramine is very good at cross the blood-brain barrier where it basically interferes with Acetylcholine production and effect, thus leading to drowsiness. This molecule will cross the placental barrier and has been found in the breast milk of lactating women who have taken it. Loratadine can cross the B-B barrier, but only in minute quantities and it is not anticholinergenic, so does not cause drowsiness.
posted by Blacksun at 2:34 AM on January 15, 2008

A pharmacist friend mentioned that Loratadine trials showed that while standard doses will alleviate allergy symptoms in a reasonable percentage of individuals, it takes a larger dose to work in the rest of the population -- and that larger dose is enough to cause drowsiness.

In other words, in the dose required to work for many people, it does cause drowsiness.
posted by mikeh at 12:30 PM on January 15, 2008

Thank you all, for the very informative answers.
posted by invisible ink at 8:31 PM on January 15, 2008