Not really true-- the order doesn't matter all that much, except that the off-rate for diphenhydramine on the H1 and H2 receptors that it hits is much faster-- of course, even with zyrtec, it's not as slowly metabolized as it is in adults, so this is why dosing is often twice daily in children.
Mostly the reason for cetirizine as a primary therapeutic agent (with diphenhydramine added as needed) is that the former doesn't lead to CNS side-effects because of receptor selectivity, and it lasts longer.
A relatively minor reason from a pharmacokinetic standpoint is that diphenhydramine has a shorter effective window and blocks sites that would otherwise be occupied by longer-acting cetirizine, but even so, this isn't really a compelling reason. Taking zyrtec and benadryl simultaneously, for example, just means that circulating zyrtec would (hypothetically) fill histamine receptor sites as the diphenhydramine vacates them. If that makes sense.
We've very definitely used zyrtec as a fast-acting add-on therapeutic-- and come to that, so has our allergist right in front of us. Mostly, we use benadryl that way since we all use cetirizine as our first line agent.
But the dosing window for both is very wide. The safety profile of the first gen antihistamines like benadryl is not as good as it is for zyrtec, though, due to CNS depression.
So that probably goes into a lot more detail than anyone cares about, but my ultimate answer is "why on earth would anyone choose to use diphenhydramine as a FIRST agent when second-gen antihistamines exist?" In other words, I'd expect it to be a rather unusual set of circumstances to begin with, where one would be in a position to do benadryl THEN zyrtec. But there's no compelling pharmacological reason why it's unsafe or ineffective. Well, you might lose a touch of the zyrtec to metabolism as it circulates in the bloodstream doing nothing for a few hours until some H1 sites open up-- but it's not likely to make an appreciable difference.
All of this also ignores the fact that H2 sites are mostly left untouched by zyrtec, which is another reason why adding benadryl can seem "effective" whereas adding zyrtec may seemingly make little difference.
Does that help?
Last edited by HowlerKarma; 09/27/14 09:56 AM.
