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Medetomidine

By Kailyn Tomilin, MPH

Background

Medetomidine, a potent sedative-analgesic, has been found to be a contributing factor in a recent wave of overdoses across the U.S. Medetomidine is an α2-adrenoreceptor agonist often used in veterinary medicine as a sedative and anesthetic for small and large animals1. It is known for producing sedation and pain-relieving effects that last longer in duration compared to similar drugs like clonidine and xylazine1. Medetomidine is a synthetically manufactured mixture of dexmedetomidine and levomedetomidine, with dexmedetomidine being the active component2.  Dexmedetomidine was FDA approved in 1996 as a sedative for animals and approved for use in humans in 19993. Dexmedetomidine (Precedex) may be administered to patients in surgical and intensive care settings, while other forms of medetomidine are typically reserved only for veterinary use2.

Although the rate of fatal overdoses in the U.S. declined from 2022 to 2023, the recent influx of overdoses being reported can be attributed to a changing drug supply2. Researchers mention that one of the dangers associated with medetomidine is that there are currently no supplies that can be used to test for its presence among other substances, unlike with fentanyl and xylazine2. The source of medetomidine infiltration is also unknown. Researchers are unclear whether the drug is being illegally diverted from medications intended for use in hospitals, or from veterinary supplies2. To combat this, it is crucial to spread awareness and education surrounding emerging threats infiltrating the illicit drug supply and practice harm reduction.

Mechanism

Medetomidine is a specific and selective α2-adrenoreceptor agonist3. Its actions in the brain and spinal cord inhibit the firing of neurons causing its analgesia, sedation and hypotensive effects3. Medetomidine is in the same drug class as xylazine; however, its potency is 200 times greater4.

For dexmedetomidine use in clinical settings, it is often administered intravenously in a two-part infusion, with the initial loading dose being administered over a period of 10 minutes and the second over the course of several hours4. In the case of a dexmedetomidine overdose or toxicity, it is unclear whether the speed of injection compounds side effects3. Other routes of administration include intranasally and sublingually3.

Effects

Medetomidine, like other α2-agonists, can cause negative side effects when taken at high doses, with some of the cardiovascular effects being the most concerning. Side effects associated with medetomidine sedation include bradycardia, bradyarrhythmia, initial hypertension followed by prolonged hypotension, and reduced cardiac output1. Additional side effects include dry mouth, hypothermia, spontaneous muscle contractions, and respiratory depression2.

There is limited research on long-term side effects of medetomidine use in humans. According to the Philadelphia Department of Public Health, it is unclear whether prolonged medetomidine use can cause skin ulcers as seen with xylazine4.

Treatment

According to The Center for Forensic Science Research and Education, most cases of medetomidine overdose involved fentanyl and xylazine2. Medetomidine is not an opioid and does not respond to naloxone, however it is still recommended to administer naloxone in the case of a suspected medetomidine overdose as it is often combined with opioids2. Medetomidine can cause prolonged sedation, so in the event of an overdose, it is recommended to perform rescue breathing and place the individual in recovery position3.

Since most medetomidine overdoses involve opioids, treatment following a medetomidine overdose should include treating symptoms of opioid withdrawal4. The recommendation for management of opioid withdrawal is MOUD (medications for opioid use disorder)4.

Resources

Cases of medetomidine overdose are being reported in states including Pennsylvania, Missouri, Colorado and others5, emphasizing the need for increased education and awareness. To learn about other emerging adulterants, visit the MATTERS website at https://mattersnetwork.org/edu/other-drugs/. Information on naloxone and where to access it can also be found at https://mattersnetwork.org/naloxone/.

References

  1. Sinclair MD. A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice. Can Vet J. 2003;44(11):885-897.
  2. Medetomidine rapidly proliferating across USA – implicated in recreational opioid drug supply & causing overdose outbreaks. The Center for Forensic Science Research & Education. (n.d.). https://www.cfsre.org/nps-discovery/public-alerts/medetomidine-rapidly-proliferating-across-usa-implicated-in-recreational opioid-drug-supply-causing-overdose-outbreaks
  3. Jorden VS, Pousman RM, Sanford MM, Thorborg PA, Hutchens MP. Dexmedetomidine Overdose in the Perioperative Setting. Annals of Pharmacotherapy. 2004;38(5):803-807. doi:10.1345/aph.1D376
  4. Health alert. Philadelphia Department of Public Health Division of Substance Use Prevention and Harm Reduction. (n.d.). https://hip.phila.gov/document/4421/PDPH-HAN-0441A-05-13-24.pdf/
  5. Notes from the field: Detection of medetomidine among patients evaluated in emergency departments for suspected opioid overdoses – Missouri, Colorado, and Pennsylvania, September 2020–December 2023. Centers for Disease Control and Prevention. August 1, 2024. Accessed September 12, 2024. https://www.cdc.gov/mmwr/volumes/73/wr/mm7330a3.htm.