Xylazine and Medetomidine

"Both xylazine and medetomidine bind to alpha-2 adrenergic receptors and inhibit the release of norepinephrine, leading to profound sedation and analgesia. Addition of these adulterants to IMF may be intended to prolong or enhance the euphoric effects of IMF, but they can also cause central nervous system depression, hypotension, and bradycardia [20]. Both drugs pose a risk for individuals exposed to IMF since naloxone, an opioid antidote, does not reverse their effects. There are known antidotes for these drugs in veterinary medicine, but no approved antidotes in humans [21]. Acute overdose treatment primarily focuses on addressing sedative and cardiovascular effects, including supportive airway management [21,22]. Repeated exposure to xylazine has also been linked to severe skin ulcerations that have the potential to progress to bone involvement and amputation, and these have become recognized as a distinct clinical entity [23]. Concurrent use of xylazine and/or medetomidine with IMF potentially complicates longer term treatment but much remains unknown regarding the effects of these drugs and their potential interactions with fentanyl, or other opioids [24–26]."