Can tolerance to a drug change its half-life?

[KissTheSky]

I was wondering if tolerant users might eliminate a drug more quickly than the non-tolerant. My understanding is that tolerance usually means only that a given amount of a drug will have a smaller effect, but are there any exceptions to that?

Would some drugs (e.g. GHB) actually have a longer effective "half-life" for the "usual dose" of a tolerant user, because the higher dose means that the drug is eliminated linearly rather than exponentially?

 

[MurphyClox]

I don't know if this counts for GHB, but tolerance can indeed lower half-life.

Not all metabolic enzymes are expressed constitutionally, or if they do, some are just expressed at a very low level. Longer exposure to a substance will induce enzyme-expression to allocate more enzyme for degradation. Thus, tolerance can lead to decreased halflife.

Peace! Murphy

 

[pallidamors]

^I think most drug metabolism is based on this, somewhat.

For example, severe alcoholics will metabolize alcohol much faster than people who are occasional drinkers. The increase of the drug concentration in the person's liver will upregulate production of the enzyme meant to metabolize that drug, right? And I dont think it matters for what order of kinetics the metabolism is based on, it should hold true for all drugs, as far as i know.

 

[MurphyClox]

IMO not all enzymes are inducible. Also, when enzyme-saturation is reached, metabolism 'stalls'.

Apart from this, I would agree. Most drugs induce this in the liver.

 

[pallidamors]

^I'm overindulging in Indian Pilsner and maybe I'm overextending the extent of my known liver knowledge.

I guess if my statement held true in all cases there'd be no instances of first or second order reactions in the liver, right? Cuz what I said only should hold true for zero order reactions (I think...but like I said...Indian Pilsner can impair your judgment and cause you to create bad BL advice)

 

[Jabberwocky]

Tolerance came about through repeated exposure. Repeated exposure can induce changes like more efficient metabolism, i.e. specific liver enzymes being at the ready. Tolerance by itself is probably not a factor.

 

[Aeon Psyche]

I was wondering if tolerant users might eliminate a drug more quickly than the non-tolerant. My understanding is that tolerance usually means only that a given amount of a drug will have a smaller effect, but are there any exceptions to that?

Would some drugs (e.g. GHB) actually have a longer effective "half-life" for the "usual dose" of a tolerant user, because the higher dose means that the drug is eliminated linearly rather than exponentially?

Yes, but I've never noticed that effect with GHB.

 

[Jabberwocky]

Tolerance came about through repeated exposure. Repeated exposure can induce changes like more efficient metabolism, i.e. specific liver enzymes being at the ready. Tolerance by itself is probably not a factor.

there is also a notion of tolerance that does not necessitate repeated exposure (ie naturally tolerant persons). This type of tolerance is relative to a 'normal' level of drug intoxication (somebody that reacts less severely than normal is said to be 'naturally tolerant').

 

[MeDieViL]

i'm wondering how big this is an issue with tolerance then actual decentisation of neuroreceptors

 

[The Monkey Mantra]

^^^ Depends on the drug, and it depends on the doses used. I know that with opioids, it tends to be more about neurological changes (not just desensitization of the receptors, but tons of other good stuff) and less about metabolism.

 

[vortex30]

Drug by drug basis. Ketamine's half life will be greatly reduced in tolerant people over intolerant people, due to tolerance being almost solely down to metabolism by the liver. LSD on the other hand, as far as I know, is not metabolized, but rather simply degrades, so specific conditions in a persons body may effect this degradation, but assuming we all have similar, healthy conditions in our body, LSD should remain in everyone's body about the same amount of time, tolerant or not.

 

[tadfish]

definately with Cannabis and also benzos. ya body just gets used to getting rid of things. except some drugs build up. but definately for valium and cannabis. also people think that with amphets but i thik they just get used to it and can then sleep on them

 

[djsim]

What the body does to the drug is defined as pharmacokinetics. I believe barbituates experience pharmacokinetic tolerance, as well as alcohol (via inducable enzyme). I've heard cannabis has reverse tolerance (can't remember where I read it though) such that a frequent user has greater stores of the drug in fat, thus less is needed to get high. Not sure how true that is though as I never got into smoking dope

 

[bcuzZ]

It´s not the psychoactive THC that is stored in the fat, but metabolites (THC-COOH,11-OH-THC,etc). A revearse tolerance would have been better for my budget