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penicilling t1_irb28xx wrote

First generation antihistamines (i.e diphenhydramine) cross the blood-brain barrier, and thus can affect the brain directly. While we call them "antihistamines" because they affect histaminergic receptors (which are responsible for allergic reactions , among other things), they also have other effects, such as blocking cholinergic receptors. The overall effect on the brain is sedating.

Second generation antihistamines were designed not to enter the brain as easily, and thus the brain effects, such as sedation, seen commonly in first-generation antihistamines are much less pronounced.

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WittyUnwittingly t1_irbhr6x wrote

This. 1st generation antihistamines are full-blown psychoactive drugs, usually considered "deleriants."

Eating 8-10+ Benadryl will get you high asf for 6 or so hours, but like... Not a good high: Itchy, confused, and sleepy but unable to sleep.

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shaftshaftner t1_irbtxfa wrote

To discourage the curious, benadryl is not to be messed with. People can die from overdosing. It’s rare but there have been cases of children taking 5 adult benadryl tablets and never waking up, usually due to negligence or ignorance from the caregiver.

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WittyUnwittingly t1_irbveyv wrote

Yup. Even if drugs are your thing, you're not missing much by skipping out on the Benadryl.

I think this is one of those fringe cases where the distinction between "psychoactive drug" and "recreational substance" is meaningful. Benadryl is a psychoactive drug, but it is not recreational. You would not have a "good time."

Oh yeah, there's nausea too. Lots of nausea.

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TripleXAfro t1_irbwxnt wrote

I took 450mg in a sitting , I remember passing out for an hour and waking up with the proportions of everything being extremely messed up and a weird shine on everything. I didn't have a negative experience which is interesting.

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TripleXAfro t1_irbx9aa wrote

Unlike drinking grapefruit juice and then Consuming 100mg of dmx. That was the worst experience I've ever had.

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YoureSpecial t1_irc3fao wrote

Grapefruit juice fucks all kinds of drugs up. Can make them last longer, lose effectiveness, activate the active ingredients all at once instead of over time, inhibit active ingredients, make some drugs toxic, etc.

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Blakut t1_irewtfg wrote

Yeah what is up with that?

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YoureSpecial t1_irf13av wrote

It’s true of all citrus to some degree, but grapefruit’s effects are waaaaaay more pronounced. It’s some sort of flavonoid or something. I can’t remember just now.

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loefferrafael t1_ircukr4 wrote

I appreciate and find it important that you wanted to discourage the curious because I was curious

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KanyeWaste69 t1_irbkqdp wrote

It's terrjble. Eat 30, you'll be experiencing real life terrors for the next 6 hours. Never again

It's like giving yourself full blown dementia, yet every hallucination you'll see in the dark feels as real as life

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HowRiskyIsDatClick t1_irbqgll wrote

Why are there so many spiders crawling down the wall

And also realistic hallucinations that are impossible to distinguish from reality

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CeeArthur t1_ird15ps wrote

Yeah I experimented with them a couple times with increasing dosages as I was mostly curious, and there really isn't anything fun or enjoyable to it. At best, you'll just feel a bit out of it and maybe have a good nap, but at a higher dosage it's straight up paranoia, hallucinations, twitching, pure terror, and no sleep.

The last time I took them, I thought there were people trying to break into my apartment at 4am, I had a wrench and was standing back to a corner with all the lights on just waiting. The thing is all the auditory hallucinations are so real that you can't really talk your way out of it. I thought these guys had just kicked in my neighbors door and beaten him to death, and one was waiting by my living room window for me to look away for a second so he could pounce. I eventually sort of ran how ludicrous this situation was over in my head a few times and realized it wasn't actually happening.

I did learn an important trick from this experience though, having had some scary hallucinations (not all drug induced) since then. When you start hearing things and you aren't sure if they are real or not, focus on either a phrase or maybe tv show theme song you know really well. If you start to HEAR one of those things (as if real) then odds are, you're suffering from auditory hallucinations.

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altcastle t1_irblefm wrote

Are first generation better for anxiety? I was prescribed hydroxyzine 25mg for anxiety as needed and I take it sometimes to help me sleep.

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penicilling t1_irbni7d wrote

>Are first generation better for anxiety?

1st generation are often prescribed of anxiety or insomnia because of the sedating effect. Second generation antihistamines are much less sedating, and would likely not be suitable for these uses.

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Bertensgrad t1_irbtksg wrote

Hydroxyzine is first generation isn’t it ?

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altcastle t1_irbvgtv wrote

It is according to what I looked up right before asking. Which explains why it helps with anxiety and sleep somewhat.

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Bertensgrad t1_irc3dpb wrote

Yes first generation would be the only ones with a physical effect on anxiety

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The_Scarf_Ace t1_irbfc3y wrote

If both act on acetylcholine receptors, then what would be the effect of mixing antihistamines with nicotine?

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WittyUnwittingly t1_irbhanu wrote

Anecdotally, the nicotine rush is more intense coming off a dose of Benadryl. Nicotine at the same time as Benadryl negates the drowsiness.

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StinkyBeer t1_irbuyt5 wrote

Fascinating! Which drugs are first gen and second gen antihistamines? And is there a reason to take first gen at all if second gen exists now?

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penicilling t1_irbzl51 wrote

>Which drugs are first gen and second gen antihistamines?

Commonly used 1st generation antihistamines include diphenhydramine, hydroxyzine and doxylamine.

Commonly used 2nd generation antihistamines include cetirizine and loratadine.

There are 3rd generation antihistamines as well, such as levocetirizne and fexofenadine. These may have even better efficacy and fewer side effects than the 2nd.

And is there a reason to take first gen at all if second gen exists now?

Because 1st generation antihistamines cross the blood-brain barrier, they have more effects. When we are treating allergic symptoms we call these effects "side effects" or "adverse effects". However, we might utilize these effects intentionally -- these drugs can reduce nausea, reduce anxiety, cause sedation, dry up secretions, reduce intestinal spasms, reduce the side effects of other medications. They are very useful in many clinical contexts.

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notcaffeinefree t1_irc53c9 wrote

Technically, both levocetirizne and fexofenadine are classified as second generation. While third-gen is frequently used for some of the newer antihistamines, there isn't an actual defined category yet.

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penicilling t1_irc7dqa wrote

>both levocetirizne and fexofenadine are classified as second generation.

No.

Third generation antihistamines are metabolites or enantiomers of second generation antihistamines.

Levocetirizne is the L-enantiomer of cetirizine. Fexofenadine is a metabolite of terfenadine, another second generation antihistamine. They are third generation by definition.

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[deleted] OP t1_irb6590 wrote

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[deleted] OP t1_irb6kxi wrote

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[deleted] OP t1_irb6ppd wrote

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[deleted] OP t1_irb7e92 wrote

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penicilling t1_irbasko wrote

>Are 1st gen safer ? wich do you reccommend ?

While I cannot recommend a specific medication for anyone (an interview, physical exam, and review of current and past medical issues is necessary before any such recommendations), in general, second-generation antihistamines such as cetirizine, fexofenadine, and loratadine are the first-line recommendations for symptoms of allergic rhinitis, as the side effects (such as sedation) are much less pronounced than the first-generation medications.

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[deleted] OP t1_irbg8ou wrote

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penicilling t1_irbn6c0 wrote

>Not just that, the second generation antihistamines are generally first line for anything where an actual antihistamine would be required,

This is generally true. The exception would be in patients for whom oral medications are not optimal, such as those with nausea and vomiting or with severe allergic reactions -- some 1st generation antihistamines are available in parenteral formulations, whereas, to the best of my knowledge, 2nd generation antihistamines are only available in oral form.

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GamblingTheory t1_irbk18u wrote

Fexofenadine is a third generation antihistamine and thus in many countries not freely available without prescription.

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The_RealKeyserSoze t1_irb9ouf wrote

There are pros and cons with any medication, best to consult a doctor about your specific condition/use case.

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Schip92 t1_irb9z4b wrote

Yeah I know , I use cetirizine and acupuncture :) Normally If I do multiple sets od acupuncture I don't use pharmaceuticals

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cardew-vascular t1_irbqu6d wrote

2nd generation is safer because they don't break the blood brain barrier but 1st generation are still more effective for most people for the very same reason.

That's why I have both Benedryl and prescription Citirizine at home, Citirizine to take on the daily (40mvg 2x daily during allergy season or 8 extra strength reactine a day) to try to deal and Benedryl for when things get bad and I have no other plans.

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celestiaequestria t1_irbk84s wrote

No, absolutely not. Newer antihistamines are recommended over older drugs like diphenhydramine. Benadryl can cause cardiac events, not to mention being a deliriants that is often given to children in overly large doses. Long-term use is also concerning given their correlation with dementia.

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zachtheperson t1_irboax1 wrote

Small correction, not a dissociative, but a deliriant. Deliriants tend to be a much worse experience

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cloudwalker0909 t1_irbldt0 wrote

Histamine in the brain is an excitatory neurotransmitter (it has inhibitory effects on certain neurons but is overall excitatory) and is generally wakefulness promoting. Antihistamines that cross the blood brain barrier in sufficient quantities cause sedation through the antagonism of histamine receptors in the brain.

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isblueacolor t1_irchxay wrote

Notably, there is a new narcolepsy medication called Wakix that works by acting on histamine receptors in the brain to increase wakefulness.

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CocktailChemist t1_irbdqwa wrote

As already noted, it’s a blood-brain barrier issue. The first generation antihistamines are about as ideal as you can get for penetrating the BBB - mostly non-polar molecules with a few amines. The second and subsequent generations took inspiration from first generation metabolites that also contained carboxylic acids. The additional functionality made them especially bad at getting through the BBB while retaining their activity at the target. It’s really a rather neat piece of medicinal chemistry.

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Electronic_Health22 t1_irbv419 wrote

All histamine H1 receptor antagonists that cross the blood-brain barrier make you drowsy because that is an effect of blocking the H1 receptor in the central nervous system. There are newer drugs used for allergies that don't make you sleepy because they block only peripheral H1 receptors. These newer drugs are like cetirizine, brand name Zyrtec.

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