4DQSAR
Bluelighter
- Joined
- Feb 3, 2025
- Messages
- 5,441
The two drugs they flagged as being cardiotoxic actually produce pulmonary arterial hypertension when cosumed at a fully active dose in a chronic (daily) manner. At the time CT revealed heart-valve damage BUT to be clear - the vast majority of people prescribed those medications were NOT so harmed. So there is at least some genetic element also in play. The fact they didn't note that also strikes me as wanting desperately to have some sort of way of SUGGESTING possible harm.
With both aminorex and fenfluramine, the serious damage did seem to occur quite fast in those susceptable. I actually added 4MAR because in the 1990s a family was caught producing 4MAR in a barn on their land and all three had developed severe pulmonary arterial hypertension which isn't enough to conclude that is is a genetic-bias and/or that it is dose-related but I believe when questioned they did admit to consuming a LOT of their own product thus broke RULE 1.
But it doesn't mean more evidence isn't available - only that the researchers woozled their results. But drug-induced pulmonary arterial hypertension is recognized and isn't limited to just two or three compounds.
Drug-induced pulmonary arterial hypertension: a primer for clinicians and scientists - PMC
Drug-induced pulmonary arterial hypertension (D-PAH) is a form of World Health Organization Group 1 pulmonary hypertension (PH) defined by severe small vessel loss and obstructive vasculopathy, which leads to progressive right heart failure and ...
pmc.ncbi.nlm.nih.gov
But it's always chronic use i.e. when a person is consuming a compound every day or even multiple times a day for a prolonged period. Note the paper even names the associated gene. So I'm somewhat surprised that it wasn't cited. That's what makes me think the paper was more part of the publish-or-perish culture and that presenting risk is a very good way to get funding. The correct conclusion should have been 'there is no evidence to suggest microdosing is associated with pulmonary arterial hypertension'. I do understand that a hypothesis that proves false is less likely to be published and that is a tragedy as a negative results are actually MORE valuable.
Last month I found a 2021 paper that makes 50+ years of papers utterly wrong since they used a false axiom.
But here no axioms are really presented or inferred. Explaining the details of vasular remodelleling seems oddly detailed given the paucity of data. I suppose if it isn't your field, knowing what is important is difficult. But it's already known so why would you expend space simply explaining it (badly) again? It also ignores that there is a second mode of toxicity (endothelial Injury) and quite amazing to me, totally avoids mentioning that a lot of far more commonly prescribed medications are also known to produce those same toxicities but to such a small extent that one has to look at vast samples to spot the slight increases.
But using two dihydroergolines as evidence that ergolines may be cardiotoxic - that SHOULD have been spotted by peer review. But since these are all psychologists/psychiatrists, one assumes peer-review simply did not include a medicinal chemist. I AM going to contact Retraction Watch as the paper is so deeply flawed, it's only going to cause harms.
