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Carfentanil (Grey death)

8/16/2017

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​Introduction
  • One of the most potent opioids created, known as Wildnil.
  • This was originally created to sedate large mammals.
  • Commonly used as positron emission tomography scan radioligand
Pharmacology
  • Carfentanil acts predominately on mu opioid receptors as a strong competitive agonist.
    • Opiate receptors are G-protein receptors in which binding of the opiate stimulates GTP -> GDP. This decreases the intracellular cAMP by inhibiting adenylate cyclase. This hyperpolarizes the cell and reduces neurotransmitter release.
  • Biological half-life 7.7 hours
  • Potency 10,000 times of morphine and 100 times of fentanyl.
  • Formulation: 10ml vial at 3mg/mL
  • 0.005-0.02 mg/kg given to animals for sedation
Picture

Clinical Toxicity
  • Altered level of consciousness -> Coma
  • Respiratory depression
  • Miosis
Case Reports               
  • Moscow theater hostage crisis
    • Russians responded by pumping “undisclosed chemical agent” into ventilation system
    • Some report naloxone was used as an antidote
    • Carfentanil was identified on the clothing of some victims

Laboratory Identification
  • Will not be positive on routine opioid drug screen
 
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  • Felt not to cross react with fentanyl immunoassays
  • Dedicated gas chromatopgraphy mass/spectrometry has been able to identify the drug as cause of death in certain case reports

Treatment/Management
  • Naloxone
    • Mu opioid receptor inverse agonist
    • IV, IM, SubQ (onset of action 2-5 mins), Intranasal (onset of action 3-5 mins)
    • Biological half life elimination: Intranasal ~2 hours, IM, IV, SubQ 0.5-1.5 hours
    • Duration = 30-120 mins (IV shorter duration than IM)
    • Adult dosing 0.4-4mg, child dosing 0.1 mg/kg/dose, re-dosing every 2-3 minutes
    • Animal studies suggest dosing adequate response to proper dosing of naloxone to carfentanil ingestion
    • Consideration of naloxone gtt especially in highly potent opioids such as carfentanil
      • Can start gtt at X mg / hour that were needed to reach GCS 15
  • Respiratory and hemodynamic support
    • Intubation
    • Vasopressors
  • Observation Period
    • 2-4 hours 
Grey Death
 
  • Looks like concrete mixing powder -> either chunky rock-like material or grey fine powder
  • Combination drug of highly potent opioids including different mixtures of heroin, fentanyl, carfentanil, and U-47700
  • Can be injected, inhaled, ingested, or absorbed through mucous membranes
    • Touching the powder does not result in direct intoxication
  • Use routine universal precautions
    • Take caution if there are any breaks in skin
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References1–7
1.             Milone MC. Laboratory testing for prescription opioids. J Med Toxicol. 2012;8(4):4086. doi:10.1007/s13181-012-0274-7.
2.             Moresco A, Larsen RS, Sleeman JM, Wild MA, Gaynor JS. USE OF NALOXONE TO REVERSE CARFENTANIL CITRATE-INDUCED HYPOXEMIA A CARDIOPULMONARY DEPRESSION IN ROCKY MOUNTAIN WAPITI (CERVUS ELAPHUS NELSONI). J Zoo Wildl Med. 2001;32(1):81-89. doi:10.1638/1042-7260(2001)032[0081:UONTRC]2.0.CO;2.
3.             Klebacher R, Harris MI, Ariyaprakai N, et al. Incidence of Naloxone Redosing in the Age of the New Opioid Epidemic. Prehospital Emerg Care. 2017:1-6. doi:10.1080/10903127.2017.1335818.
4.             Swanson DM, Hair LS, Strauch Rivers SR, et al. Fatalities Involving Carfentanil and Furanyl Fentanyl: Two Case Reports. J Anal Toxicol. 2017:1-5. doi:10.1093/jat/bkx037.
5.             Pathan H, Williams J. Basic opioid pharmacology: an update. Br J pain. 2012;6(1):11-6. doi:10.1177/2049463712438493.
6.             CARFENTANIL | C24H30N2O3 - PubChem. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/carfentanil#section=Top. Accessed August 15, 2017.
7.             Feasel MG, Wohlfarth A, Nilles JM, Pang S, Kristovich RL, Huestis MA. Metabolism of Carfentanil, an Ultra-Potent Opioid, in Human Liver Microsomes and Human Hepatocytes by High-Resolution Mass Spectrometry. AAPS J. 2016;18(6):1489-1499. doi:10.1208/s12248-016-9963-5.

 


Authored by: Katie Lupez, MD

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