Antihistamines’ Generation Gap

Are You Ready For Allergy Season?

For those of us in the Northern Hemisphere, fall will be upon us soon, and we have a few weeks to be ready for it. A common seasonal ailment is of course seasonal allergies—it’s not serious for most of us, but it can be very annoying, and can disrupt a lot of our normal activities.

Suddenly, a thing that notionally does us no real harm, is making driving dangerous, cooking take three times as long, sex laughable if not off-the-table (so to speak), and the lightest tasks exhausting.

So, what to do about it?

Antihistamines: first generation

Ye olde antihistamines such as diphenhydramine and chlorpheniramine are probably not what to do about it.

They are small molecules that cross the blood-brain barrier and affect histamine receptors in the central nervous system. This will generally get the job done, but there’s a fair bit of neurological friendly-fire going on, and while they will produce drowsiness, the sleep will usually be of poor quality. They also tax the liver rather.

If you are using them and not experiencing unwanted side effects, then don’t let us stop you, but do be aware of the risks.

See also: Long-term use of diphenhydramine ← this is the active ingredient in Benadryl in the US and Canada, but safety regulations in many other countries mean that Benadryl has different, safer active ingredients elsewhere.

Antihistamines: later generations

We’re going to aggregate 2nd gen, 3rd gen, and 4th gen antihistamines here, because otherwise we’ll be writing a history article and we don’t have room for that. But suffice it to say, later generations of antihistamines do not come with the same problems.

Instead of going in all-guns-blazing to the CNS like first-gens, they are more specific in their receptor-targetting, resulting in negligible collateral damage:

CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria

Special shout-out to cetirizine and loratadine, which are the drugs behind half the brand names you’ll see on pharmacy shelves around most of the world these days (including many in the US and Canada).

Note that these two are very often discussed in the same sentence, sit next to each other on the shelf, and often have identical price and near-identical packaging. Their effectiveness (usually: moderate) and side effects (usually: low) are similar and comparable, but they are genuinely different drugs that just happen to do more or less the same thing.

This is relevant because if one of them isn’t working for you (and/or is creating an unwanted side effect), you might want to try the other one.

Another honorable mention goes to fexofenadine, for which pretty much all the same as the above goes, though it gets talked about less (and when it does get mentioned, it’s usually by its most popular brand name, Allegra).

Finally, one that’s a little different and also deserving of a special mention is azelastine. It was recently (ish, 2021) moved from being prescription-only to being non-prescription (OTC), and it’s a nasal spray.

It can cause drowsiness, but it’s considered safe and effective for most people. Its main benefit is not really the difference in drug, so much as the difference in the route of administration (nasal rather than oral). Because the drug is in liquid spray form, it can be absorbed through the mucus lining of the nose and get straight to work on blocking the symptoms—in contrast, oral antihistamines usually have to go into your stomach and take their chances there (we say “usually”, because there are some sublingual antihistamines that dissolve under the tongue, but they are less common.)

Better than antihistamines?

Writer’s note: at this point, I was given to wonder: “wait, what was I squirting up my nose last time anyway?”—because, dear readers, at the time I got it I just bought one of every different drug on the shelf, desperate to find something that worked. What worked for me, like magic, when nothing else had, was beclometasone dipropionate, which a) smelled delightfully of flowers, which might just be the brand I got, b) needs replacing now because I got it in March 2023 and it expired July 2024, and c) is not an antihistamine at all.

But, that brings us to the final chapter for today: systemic corticosteroids

They’re not ok for everyone (check with your doctor if unsure), and definitely should not be taken if immunocompromised and/or currently suffering from an infection (including colds, flu, COVID, etc) unless your doctor tells you otherwise (and even then, honestly, double-check).

But! They can work like magic when other things don’t. Unlike antihistamines, which only block the symptoms, systemic corticosteroids tackle the underlying inflammation, which can stop the whole thing in its tracks.

Here’s how they measure up against antihistamines:

❝The results of this systematic review, together with data on safety and cost effectiveness, support the use of intranasal corticosteroids over oral antihistamines as first line treatment for allergic rhinitis.❞

~ Dr. Robert Puy et al.

Read in full: Intranasal corticosteroids versus oral H1 receptor antagonists in allergic rhinitis: systematic review of randomised controlled trials

Take care!