Pharmacology question - drug half-life's and duration?

[1ledzepplin1]

So I am rather confounded by the process of drug metabolism for certain compounds and it's relation to duration of action. As we all know most drugs have at least some metabolites that are pharmacologically active. Some of these metabolites have almost identical effects to their respective parent compounds while others are unique.
My question is when I research online or elsewhere how long a drug is going to last, am I finding information that applies ONLY to the parent compound or have they considered the metabolites also?
I know I was curious about DXM and it's length of action and I found that DXM polisistrex lasts 12 hours overall due to the breakdown of the plastic after 6 hours. I also know that freaking DXM is metabolised to several things like dextrorphan and this shit lasts a long time and so on and so forth.
Question 2 is how do I figure out just how long a medication is ACTUALLY going to impact me with active chemicals and their derivatives? So I don't get fucked in the ass thinking I'm not going to be forever groggy the day after when actually there's metabolites sedating me all throughout my body >

 

[tyrael]

For your first question; usual given half-lives are that of the compound and metabolites.

Second question; you'll need to gather a bit more info on the chemical. Its threshold dose or typically what's called NOEL (No Observed Effect Level) - this will tell you the dose level in an organism necessary to not observe an effect, or other words concentrations above this which will produce noticeable effects. You could work out a rough duration of action of a drug/chemical by finding this threshold dose and dividing by how many half-lives (time) it would take to be metabolised below this level.

This will be very rough however. Genetic polymorphisms, ROA, (psychological/physical) tolerances, etc. etc will all change what you're attempting to calculate. Typically medical monographs will include duration of action.

I hope that makes sense?!

 

[endotropic]

For your first question; usual given half-lives are that of the compound and metabolites.

Second question; you'll need to gather a bit more info on the chemical. Its threshold dose or typically what's called NOEL (No Observed Effect Level) - this will tell you the dose level in an organism necessary to not observe an effect, or other words concentrations above this which will produce noticeable effects. You could work out a rough duration of action of a drug/chemical by finding this threshold dose and dividing by how many half-lives (time) it would take to be metabolised below this level.

This will be very rough however. Genetic polymorphisms, ROA, (psychological/physical) tolerances, etc. etc will all change what you're attempting to calculate. Typically medical monographs will include duration of action.

I hope that makes sense?!

Keep in mind also that the no observed effect level can change while the drug is in your system. It's well known with alcohol for example, that the blood level where you can observe an effect actually DECREASES while you're drinking, so you might feel pretty loopy at .08 after your first few drinks, but later in the night .08 might feel like nothing. The same applies with cannabinoids (if it didn't potheads would be high for days), and probably other classes as well.

There's really too many variables to factor in to reliably predict how long effects will be noticeable. Your best bet is to ask a few people who've taken the same dose of the same drug and see what their experiences were, or test it yourself when you know you'll have plenty of time.

 

[Moredopamine]

Yeah, most evaluations of how long a drug's effect last consider metabolites if the metabolites exert significant (or most) of the action of the drug. E.g. many opiates have metabolites that contribute to much of the effects of the drug and it would be nonsensical to consider only the parent drug effects.

 

[1ledzepplin1]

For your first question; usual given half-lives are that of the compound and metabolites.

Second question; you'll need to gather a bit more info on the chemical. Its threshold dose or typically what's called NOEL (No Observed Effect Level) - this will tell you the dose level in an organism necessary to not observe an effect, or other words concentrations above this which will produce noticeable effects. You could work out a rough duration of action of a drug/chemical by finding this threshold dose and dividing by how many half-lives (time) it would take to be metabolised below this level.

This will be very rough however. Genetic polymorphisms, ROA, (psychological/physical) tolerances, etc. etc will all change what you're attempting to calculate. Typically medical monographs will include duration of action.

I hope that makes sense?!

Beautiful response, thank you very much for clearing that up for me. I thought myself clear on some of the many variables that contribute to the half-lives and whatnot as you were mentioning about specific physiological states but I am glad to have learned what exactly the estimated elimination times and whatnot actually meant. Thanks to the rest of y'all as well for your thoughtfulness!