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, 7 tweets, 4 min read Read on Twitter
Part 5 #Tramadont #tweetorial
(in which #Tramadont remains a hilariously accurate descriptor of tramadol!)
@NarouzeMD @EMARIANOMD @toby_ashken @DavidJuurlink

CYP2D6 & tramadol is not overrated at all.
Here is a picture of the tramadol metabolism pathway (PMID 11454734) (1/7)
We can agree that M1 is the metabolite which provides opioid analgesic effects. (PMID 10961373) (2/7)
M1 is metabolized by CYP3A4 & CYP2B6 (not CYP2D6 as you suggested) to M5. (PMID 24849324) (3/7)
CYP2D6 is responsible for the vast majority of the conversion of tramadol to M1, so yes, it is quite sensitive to CYP2D6 polymorphisms. (PMID 24849324) (4/7)
While the parent compound, tramadol, is significantly less potent than other opioids, in ultrarapid metabolizers the metabolism to M1 can skyrocket, (5/7)
leading to fatal respiratory depression, significant enough to prompt an update to the package insert from the FDA with a warning for ultra-rapid metabolizers. (6/7)
...#pharmacogenomics, it’s the future!
Thanks again for the lively debate.
(7/7)
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