Surely there must be a suicidal chemist out there who is willing to share some tidbits before bidding life adieu?
I'm only a uni student and my knowledge comes primarily from reading online articles and medication information sheets. It's useful to an extent, but I'm up against a wall here what with figuring out drug interactions and timing the doses so as to create the most likely fatal outcome. There are simply too many moving parts for a lowly layperson such as myself to attempt to configure on my own.
I know the obvious solution is to reduce the number of substances, but I want to be sure this will work - as I read about interactions, I notice this and that mentioned, so I add them to my potentials list. I eventually add all the potentials because the information I do have is incomplete such that I want to be doing 'too much' work to die versus too little work and failing. For instance, most of the interactions rarely mention the doses taken, or what the ingestion schedule was relative to each other - concurrently, with 30 min difference, effects were same regardless of dose or schedule, etc - and must build up steady levels in blood over days versus taking one dose to achieve the interaction? etc so it is a lot of guessing. Obviously not ideal in this situation which is literally life and death.
And surely there are others looking for similar information. I've seen a few threads here and there, but none that gathered a large amount of data in one place such as the goal here.
So, anyone with such knowledge please drop a fun fact that could be useful to those whose methods involves a substance. That is most of us unless going with only mechanical methods and not even benzos, antiemetics, alcohol etc as aids. I'm hoping this can become akin to a megathread, or a directory of some sort organised by substance or mechanism of action. Hence the tag.
For instance, glutathione as a CYP3A4 inhibitor and weak CYP2D6 inducer - I'm focusing on those two enzymes as my method primarily involves substrates of those receptors - this study done using precursors to glutathione in rats found that 4mg/kg was effective in the former goal. They did not discuss induction, only inhibition. A complicating factor is that the precursors are themselves CYP3A4 inhibitors, so I cannot extrapolate that the glutathione itself is what caused the noted difference.
Lastly, the authors note that the rat CYP3A4 enzyme is not exactly the same for humans. And I know that dosing cannot be extrapolated cross-species either - is there some sort of chart with conversion factors? Rats tend to be hardy creatures, so require higher doses for toxins to kill them versus for a human of the same mg/kg ratio. But am unsure if this effect is seen in all substance metabolism - can it be said that they metabolise faster or less efficiently overall - and thus a comparative human dose would be closer to 0.5-2mg/kg?
Found this article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753969/ in my search. Although not related to the information I need, perhaps someone else will find it useful. The takeaway from it is that paracetamol overdose is a poor method choice. And a lot of the substances that are listed as causing interactions actually do not. (This is what concerns me, that my list of potentiators is not even relevant whatsoever. It seems drug inserts exaggerate the dangers and prefer to scare you off combining things so as to avoid financial and reputational damages when a rare thing does go wrong.)
I'm only a uni student and my knowledge comes primarily from reading online articles and medication information sheets. It's useful to an extent, but I'm up against a wall here what with figuring out drug interactions and timing the doses so as to create the most likely fatal outcome. There are simply too many moving parts for a lowly layperson such as myself to attempt to configure on my own.
I know the obvious solution is to reduce the number of substances, but I want to be sure this will work - as I read about interactions, I notice this and that mentioned, so I add them to my potentials list. I eventually add all the potentials because the information I do have is incomplete such that I want to be doing 'too much' work to die versus too little work and failing. For instance, most of the interactions rarely mention the doses taken, or what the ingestion schedule was relative to each other - concurrently, with 30 min difference, effects were same regardless of dose or schedule, etc - and must build up steady levels in blood over days versus taking one dose to achieve the interaction? etc so it is a lot of guessing. Obviously not ideal in this situation which is literally life and death.
And surely there are others looking for similar information. I've seen a few threads here and there, but none that gathered a large amount of data in one place such as the goal here.
So, anyone with such knowledge please drop a fun fact that could be useful to those whose methods involves a substance. That is most of us unless going with only mechanical methods and not even benzos, antiemetics, alcohol etc as aids. I'm hoping this can become akin to a megathread, or a directory of some sort organised by substance or mechanism of action. Hence the tag.
For instance, glutathione as a CYP3A4 inhibitor and weak CYP2D6 inducer - I'm focusing on those two enzymes as my method primarily involves substrates of those receptors - this study done using precursors to glutathione in rats found that 4mg/kg was effective in the former goal. They did not discuss induction, only inhibition. A complicating factor is that the precursors are themselves CYP3A4 inhibitors, so I cannot extrapolate that the glutathione itself is what caused the noted difference.
Lastly, the authors note that the rat CYP3A4 enzyme is not exactly the same for humans. And I know that dosing cannot be extrapolated cross-species either - is there some sort of chart with conversion factors? Rats tend to be hardy creatures, so require higher doses for toxins to kill them versus for a human of the same mg/kg ratio. But am unsure if this effect is seen in all substance metabolism - can it be said that they metabolise faster or less efficiently overall - and thus a comparative human dose would be closer to 0.5-2mg/kg?
Found this article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753969/ in my search. Although not related to the information I need, perhaps someone else will find it useful. The takeaway from it is that paracetamol overdose is a poor method choice. And a lot of the substances that are listed as causing interactions actually do not. (This is what concerns me, that my list of potentiators is not even relevant whatsoever. It seems drug inserts exaggerate the dangers and prefer to scare you off combining things so as to avoid financial and reputational damages when a rare thing does go wrong.)
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