Fatalities caused by novel opioids: a review

Abstract

Drugs related to morphine represent not only large range of important therapeutic applications for the relief of moderate to severe pain but also give rise to a relatively large series of novel opioids that mimic the action of this naturally occurring analgesic. Most of these are based on fentanyl structures that are much more potent, and dangerous, than fentanyl itself. This publication reviews reports of fatalities attributed to 15 novel opioids with the view to assessing mortality associated with their misuse as well as reviewing published analytical procedures that would be able to detect these and other novel opioids. These drugs include reports of deaths to acetylfentanyl, acrylfentanyl, butr(yl)fentanyl, carfentanil, 2-and 4-fluorofentanyls, 4-fluorobutyrfentanyl, 4-fluoroisobutyrfentanyl, furanylfentanyl, a-and 3-methylfentanyls, 4-methoxyfentanyl, ocfentanil, as well as AH-7921, U-47700 and MT-45. Most of these cases reporting a drug-caused death involved other drugs in addition to the opioid. No obvious minimum fatal concentration was discerned for any of the opioids for which details were provided, however, the more potent members required detection limits well under 1 ng/mL and often even well below 0.1 ng/mL requiring use of the most sensitive mass spectral detection procedures, particularly when screening specimens using a non-targeted mode. Four other novel opioids have been reported in admissions to hospitals include 4-chloroisobutryfentanyl, cyclopentylfentanyl and tetrahydrofuranfentanyl, all of which are likely to have the potential to cause death. It is also likely that other analogues will appear with time.

Novel Vaccine That Blunts Fentanyl Effects and Sequesters Ultrapotent Fentanyl Analogues

“…Many deaths have been reported involving these analogues. 9 , 10 , 63 − 66 We found that immunization with TT– para -AmFenHap induced IgG capable of binding these analogues ( Figure 4 ). We also obtained the relative antibody binding site concentrations for these drugs (1.44 to 18.84 μM, Table 1 ).…”

Assessing the 2004–2018 Fentanyl Misusing Issues Reported to an International Range of Adverse Reporting Systems

“…Fentanyl is an extremely fast-acting synthetic narcotic analgesic, first approved as an anesthetic in 1963 (Drummer, 2018; Food and Drug Administration [FDA], 2018). Currently it is available for intravenous (I.V.)…”

Postmortem Toxicology of New Synthetic Opioids

“…The range of postmortem specimens (blood, urine, vitreous humor, tissues, hair), the lack of reference databases, the presence of other substances (e.g., benzodiazepines, alcohol), opioid tolerance, and postmortem phenomena (postmortem redistribution and drug instability) complicates the interpretation of the analytical findings. Pichini et al ( 2018 ) and Zawilska ( 2017 ) discussed non-fatal and lethal intoxications involving the new synthetic opioids, and Drummer ( 2018 ) focused his review on fatalities due to these compounds.…”