Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose

Griswold, Matthew K.; Chai, Peter R.; Krotulski, Alex J; Friscia, Melissa; Chapman, Brittany P.; Boyer, Edward W.; Logan, Barry K.; Babu, Kavita M.

doi:10.1080/15563650.2017.1339889

Cited by 40 publications

(17 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the need to grow swathes of opium poppies to produce heroin), high potency (smaller quantities need to be shipped by comparison with heroin), and ease of purchase on the dark web make the fentanyls attractive to suppliers of illicit opioids (Fairbairn, Coffin, & Walley, ). Fentanyls are frequently mixed with heroin to increase its potency (Griswold et al, ; Marinetti & Ehlers, ). A recent development is the addition of fentanyls to cocaine products and to illicit prescription opioid and benzodiazepine tablets (Green & Gilbert, ; Sutter et al, ).…”

Section: Introductionmentioning

confidence: 99%

Fentanyl depression of respiration: Comparison with heroin and morphine

Hill

Santhakumar

Dewey

et al. 2019

British J Pharmacology

129

119

View full text Add to dashboard Cite

Background and Purpose: Fentanyl overdose deaths have reached "epidemic" levels in North America. Death in opioid overdose invariably results from respiratory depression. In the present work, we have characterized how fentanyl depresses respiration, and by comparing fentanyl with heroin and morphine, the active breakdown product of heroin, we have sought to determine the factors, in addition to high potency, that contribute to the lethality of fentanyl.Experimental Approach: Respiration (rate and tidal volume) was measured in awake, freely moving mice by whole body plethysmography.Key Results: Intravenously administered fentanyl produced more rapid depression of respiration than equipotent doses of heroin or morphine. Fentanyl depressed both respiratory rate and tidal volume. Fentanyl did not depress respiration in μ-opioid receptor knockout mice. Naloxone, the opioid antagonist widely used to treat opioid overdose, reversed the depression of respiration by morphine more readily than that by fentanyl, whereas diprenorphine, a more lipophilic antagonist, was equipotent in reversing fentanyl and morphine depression of respiration. Prolonged treatment with morphine induced tolerance to respiratory depression, but the degree of cross tolerance to fentanyl was less than the tolerance to morphine itself. Conclusion and Implications:We propose that several factors (potency, rate of onset, lowered sensitivity to naloxone, and lowered cross tolerance to heroin) combine to make fentanyl more likely to cause opioid overdose deaths than other commonly abused opioids. Lipophilic antagonists such as diprenorphine may be better antidotes than naloxone to treat fentanyl overdose.

show abstract

Section: Introductionmentioning

confidence: 99%

Fentanyl depression of respiration: Comparison with heroin and morphine

Hill

Santhakumar

Dewey

et al. 2019

British J Pharmacology

129

119

View full text Add to dashboard Cite

show abstract

“…the need to grow swathes of opium poppies to produce heroin), high potency (smaller quantities need to be shipped by comparison with heroin) and ease of purchase on the dark web make the fentanyls attractive to suppliers of illicit opioids. Fentanyls are frequently mixed with heroin to increase its potency (Griswold et al, 2017;Marinetti et al, 2014). A recent development is the addition of fentanyls to cocaine products and to illicit prescription opioid and benzodiazepine tablets (Green et al, 2016;Sutter et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Fentanyl depression of respiration: comparison with heroin and morphine

Hill

Santhakumar

Dewey

et al. 2019

Preprint

View full text Add to dashboard Cite

Background and Purpose:Fentanyl overdose deaths have reached 'epidemic' levels in North America. Death in opioid overdose invariably results from respiratory depression. In the present work we have characterized how fentanyl depresses respiration and by comparing fentanyl with heroin and morphine, the active breakdown product of heroin, we have sought to determine whether there are factors, in addition to high potency, that contribute to the lethality of fentanyl. Experimental Approach:Respiration (rate and tidal volume) was measured in awake, freely moving mice by whole body plethysmography Key ResultsIntravenously administered fentanyl produced more rapid depression of respiration than equipotent doses of heroin or morphine. Fentanyl depressed both respiratory rate and tidal volume, the effect on tidal volume may reflect increased respiratory muscle stiffness. Fentanyl did not depress respiration in  opioid receptor knock-out mice. Naloxone, the opioid antagonist widely used to treat opioid overdose, reversed the depression of respiration by morphine more readily than that by fentanyl whereas diprenorphine, a more lipophilic antagonist, was equipotent in reversing fentanyl and morphine depression of respiration. Prolonged treatment with morphine induced tolerance to respiratory depression but the degree of cross tolerance to fentanyl was less than the tolerance to morphine itself. Conclusion and Implications:We propose that several factors (potency, rate of onset, muscle stiffness, lowered sensitivity to naloxone and lowered cross tolerance to morphine) combine to make

show abstract

“…A user‐report cited in a World Health Organization (WHO) report describes its activity close to 2.5 times the activity of morphine. Severe poisonings have been associated with its consumption . However, little is known about pharmacokinetics in humans …”

Section: Introductionmentioning

confidence: 99%

“…Severe poisonings have been associated with its consumption. [6][7][8][9][10][11][12][13] However, little is known about pharmacokinetics in humans. 5,14 Another rapidly growing class of drugs of abuse in its own right in recent years is designer benzodiazepines.…”

Section: Introductionmentioning

confidence: 99%

Mixed intoxication by the synthetic opioid U‐47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data

Koch

Auwärter

Hermanns-Clausen

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

Novel synthetic opioids and benzodiazepines are an emerging trend on the narcotic drugs market. We present a lethal case of U-47700 and flubromazepam poisoning. A 24-year-old man suffered apnoea after the consumption of the synthetic opioid U-47700 in combination with the benzodiazepine flubromazepam. After reanimation and hospital admission, hypoxic cerebral damage and severe brain oedema were stated. Six days after admission, mechanical ventilation was discontinued, and the patient died. Seven blood serum samples and one urine sample collected during the hospitalisation were analysed by liquid chromatography-tandem mass spectrometry. In the sample collected 42 minutes after admission, the concentrations of U-47700 and flubromazepam were 370 and 830 ng/mL, respectively. Three days later, the concentrations of U-47700 and flubromazepam dropped to 4.2 and 280 ng/mL, respectively. The resulting concentration-time-curves allowed calculating a U-47700 elimination half-life of approximately six hours and confirmed the previously reported flubromazepam elimination half-life of around 100 hours. In the presented case, intoxication by the synthetic opioid U-47700 with a contribution of flubromazepam can be assumed as the cause of death. The concentration-time curves allow an estimation of the clinical course of similar cases. Flubromazepam may lead to prolonged central-nervous depressant effects.

show abstract

Self-identification of nonpharmaceutical fentanyl exposure following heroin overdose

Cited by 40 publications

References 20 publications

Fentanyl depression of respiration: Comparison with heroin and morphine

Fentanyl depression of respiration: Comparison with heroin and morphine

Fentanyl depression of respiration: comparison with heroin and morphine

Mixed intoxication by the synthetic opioid U‐47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data

Contact Info

Product

Resources

About