The Supreme Court on Thursday rejected a controversial settlement that would have sent billions of dollars to treatment programs and victims of the nation’s opioid epidemic but that also shielded the Sackler family from future lawsuits despite the fact that it made its fortune selling prescription opioids.
I’m very surprised the pharmaceutical market hasn’t produced the opioid analogue to Vyvanse requiring enzymatic conversion as opposed to mechanical release -> long lasting natural extended release mechanism. Its a great idea that hasn’t seemed to expand to many other therapeutic agents
I don’t know vyvanse xr method of action off the top of my head…
But for opioids the difference in in enzymatic breakdown is already problematic.
Even for non XR, some people just burn thru it at different rates.
Personally I don’t have enough of a couple of the L enzymes and that means most opioids barely do anything to me. Some people have too much and will burn thru a Vicodin in half as much time, leaving them unmedicated for half the time.
There’s just too much human variation for a one sized fits all approach.
The point I’m making is, while I’m aware of people being fast or slow metabolizers, that should only factor in when it comes to active ingredient that is fully mechanically released and available for metabolism.
It cannot metabolize that which has not either been a) mechanically released or b) that which is pharmacodynamically inertt since it requires cleaving off the other binding substance (like l-lysine in Vyvanse) before the underlying active drug can be mechanically available to metabolize if that makes sense.
Vyvanse cannot be injected or administered in basically any other ROA than oral like normal dex because it (lis-dexamferamine—not dextroamphetamine) is inert until it has undergone the uncleaving of lysine from the active drug. Doesn’t matter how fast one metabolizes dextro, nobody metabolizes lis as a straight stimulant, it is inert until made not so thru the blood or whatever.
Also, doesn’t that mostly apply to codeine and morphine, wasn’t aware of that extending to oxy and hydro?
I think there is likely to still be just as large of a personal variance in the rate that lisdexamphetamine is cleaved into the active metabolite, so the same problem arises.
I think anything that delays the active metabolite from taking effect technically dampens the addictive potential; the longer the better. I also think it’s unlikely to really solve the problem though tbh. People can still tell what’s causing how they feel when they start a new medication.
You’re never gonna fully attnuate all the edge cases and it doesn’t really matter that some people end up being “allergic” or oversensitive or undersensitive to it. Thats what titration and medical supervision are for, not everything works for everyone.
Thats why choice and second/third/fourth line etc treatments exist. I sometimes do wonder if you did a double blind with folks and didn’t tell them, I would conjecture the hyper-extended nature of such things if that were so established could be sufficient to mitigate for individual differences in metabolic-polymorphism or whatever
I’m very surprised the pharmaceutical market hasn’t produced the opioid analogue to Vyvanse requiring enzymatic conversion as opposed to mechanical release -> long lasting natural extended release mechanism. Its a great idea that hasn’t seemed to expand to many other therapeutic agents
I don’t know vyvanse xr method of action off the top of my head…
But for opioids the difference in in enzymatic breakdown is already problematic.
Even for non XR, some people just burn thru it at different rates.
Personally I don’t have enough of a couple of the L enzymes and that means most opioids barely do anything to me. Some people have too much and will burn thru a Vicodin in half as much time, leaving them unmedicated for half the time.
There’s just too much human variation for a one sized fits all approach.
The point I’m making is, while I’m aware of people being fast or slow metabolizers, that should only factor in when it comes to active ingredient that is fully mechanically released and available for metabolism.
It cannot metabolize that which has not either been a) mechanically released or b) that which is pharmacodynamically inertt since it requires cleaving off the other binding substance (like l-lysine in Vyvanse) before the underlying active drug can be mechanically available to metabolize if that makes sense.
Vyvanse cannot be injected or administered in basically any other ROA than oral like normal dex because it (lis-dexamferamine—not dextroamphetamine) is inert until it has undergone the uncleaving of lysine from the active drug. Doesn’t matter how fast one metabolizes dextro, nobody metabolizes lis as a straight stimulant, it is inert until made not so thru the blood or whatever.
Also, doesn’t that mostly apply to codeine and morphine, wasn’t aware of that extending to oxy and hydro?
Morphine (not sure about codeine) are/is one of the few options that are direct acting.
Oxy, Vicodin, and all the rest first get broken down I to an active metobalite. Even if they’re not XR. XR just compounds the issue
I think there is likely to still be just as large of a personal variance in the rate that lisdexamphetamine is cleaved into the active metabolite, so the same problem arises.
I think anything that delays the active metabolite from taking effect technically dampens the addictive potential; the longer the better. I also think it’s unlikely to really solve the problem though tbh. People can still tell what’s causing how they feel when they start a new medication.
You’re never gonna fully attnuate all the edge cases and it doesn’t really matter that some people end up being “allergic” or oversensitive or undersensitive to it. Thats what titration and medical supervision are for, not everything works for everyone.
Thats why choice and second/third/fourth line etc treatments exist. I sometimes do wonder if you did a double blind with folks and didn’t tell them, I would conjecture the hyper-extended nature of such things if that were so established could be sufficient to mitigate for individual differences in metabolic-polymorphism or whatever