Benzo half life vs effect life

[nTro]

Is a there a direct relationship between half-life and the speed at which dependency on a substance develops?

 

[Cotcha Yankinov]

Is a there a direct relationship between half-life and the speed at which dependency on a substance develops?

See "kindling", essentially the more often that you withdraw, the harder the successive withdrawals will be (the rebound activity strengthens every time it rebounds).

You want pretty stable drug concentrations/long half lives because you may essentially experience mini-withdrawals with some element of kindling if you're taking a short half life drug every day.

 

[Solipsis]

I don't need your input buddy if you're gonna put words into my mouth and try to be mr. Know it all . I never fixated on one reason I listed a bunch of reasons, and what you replied to me with was clearly stated before.
Looking at your comments it seems like you came here to prove everyone wrong and show how smart you are we don't need that

That's ridiculous, I don't mean to prove anyone wrong, I hope you guys are right cause I'd like to understand this better. I just don't understand how the explanations would work given apparent contradictions, at least I didn't earlier. If you can't appreciate that I'm at least just trying to help then fine suit yourself. Don't say that I 'put words into your mouth' when I tried to paraphrase an issue you raised and was apparently wrong doing so and then jump to just as wrong but pretty rude conclusions.

 

[Gorillaboy21]

Solipsis , you're the smartest and the best person on the planet ever you know more than everyone on bluelight in history

 

[Cotcha Yankinov]

I'm so confused

I'm not big on PK, but don't lipophilic molecules pass the BBB much better and tend to accumulate in CNS tissue? Thus the more lipophilic a molecule is, the less that plasma concentrations of that drug will represent CNS concentrations?

While that may help explain why, with two drugs being equal in all other respects like GABA-A affinity and plasma half life, one drug that accumulated more in the CNS would last longer relative to the other drug with equal plasma half life, it seems like that phenomenon wouldn't explain the scenario of a drug with a 24 hr half life subjectively really only lasting for 12 or whatever.

Wouldn't this latter scenario have to involve homeostatic compensation?

 

[Kdem]

Cotcha,

That's a very good question. The more lipophilic, the faster it enters the CNS. As a rule. I'm not quite sure why diazepam redistributes so quickly from the brain to other tissues ! And that whole statement about an 'equilibrium' between the brain and blood (Ashton) ... I'm not sure how that works. Lipohilicity, plasma protein binding ?

As someone said, 'pharmacokinetics is hard'.

 

[Cotcha Yankinov]

It would still be having an effect on GABA as it would still be binding to GABA A receptors in the brain - just at a very small, unnoticeable amount, as the blood level would be too low. But there would still be biointeraction, just not enough to be perceivable.

Just like 8 hours after taking a temazepam 30mg capsule you generally wouldn't feel it, but you'd still have around 15mgs in you, which is a typical dosage and enough to interact with receptors and cause an effect.

Hey Kdem, the above is a finicky dose-response range/PK explanation that I personally don't think cuts the mustard.

I think that taking 15mg of Temazepam is going to have a more perceivable effect than when you're down to the equivalent plasma concentration 8 hours after taking 30mg of Temazepam. The reason being that when you straight up just take 15mg, there aren't the acute compensations that you'd see with having a benzo in your system for 8 hrs. I can't see there being a PK explanation to this phenomenon, but I'm open to ideas