<p>Fentalogues</p>

Abstract

The ongoing media maelstrom regarding opioids and classification of an "opioid crisis" during the initial decade of this millennium has stirred awareness, outrage and action among regulatory and other government agencies, professional clinician organizations, community pharmacy policies, legislators, patient advocacy groups, anti-opioid advocate groups, and others. However, mass media reports often skew or misdirect the aggregate facts in a possible effort to abridge or sensationalize stories. 1 Discernable distinctions, for example, are rarely drawn between licit pharmaceutical fentanyl, illicit fentanyl analogues, and certain highly potent analogues approved only for ungulates. The omission of this information has resulted in distorted public information that has far reaching consequences in medicine and policy development, as it leads to misunderstanding and misinterpretation of the facts by politicians, lay people and many clinicians. 2 It is particularly relevant today, as pharmaceutical fentanyl is often an essential drug for intubation regularly required for ventilation procedures in declining patients that may succumb to novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These distinctions are critical in the shifting landscape of the opioid crisis as prescriptions for opioids decrease yet overdose deaths remain alarmingly prevalent and continue to rise.Licit fentanyl was first synthesized in the 1950s via manipulation of another phenylpiperidine, meperidine, in an effort to develop a novel analgesic agent and laying the groundwork for pharmaceutical fentanyl and multiple analogues. Only a small percentage of those analogues are actually approved for medical use. 2 The remainder are dangerously potent with high binding affinity to opioid receptors and rapid entry to the CNS. These characteristics make them particularly hazardous when added to other illicit substances such as heroin, unbeknownst to the end-user with potentially deadly consequences. 3 Illicit fentanyl has had a dramatically increasing impact on opioid overdose deaths in the US over the past decade. According to provisional data from the 2018 Centers for Disease Control and Prevention, over half of the opioid-related overdose deaths in 2018 involved non-methadone synthetic opioids; the most common of which was illicitly manufactured fentanyl. 4 Perhaps more telling are the annual data released by the New Hampshire Department of Justice, with the most recent of which indicating that less than 7% of 2019 opioid overdose deaths in the state were due to prescription opioids. 5 These illicit opioids have affected the landscape of opioid abuse to the extent that the Drug Enforcement Agency (DEA) chose to emergently schedule all fentanyl-related substances (FRS) to schedule I as of February 2018.

Misinterpretation of the “Overdose Crisis” Continues to Fuel Misunderstanding of the Role of Prescription Opioids

“… 14 It is well-accepted in scientific circles that current overdose deaths involve fentanyl-related compounds that are illicitly manufactured and not FDA approved pharmaceutical fentanyl (or its FDA approved chemical derivatives alfentanil, remifentanil, and sufentanil) used in both acute and chronic settings. 2 , 14 , 15 This is a distinction that must be accurately described in order to diminish untoward apprehension in prescribing pharmaceutical fentanyl and its related compounds safely in a both monitored clinical settings and for home use.…”

Pill Counting as an Intervention to Enhance Compliance and Reduce Adverse Outcomes with Analgesics Prescribed for Chronic Pain Conditions: A Systematic Review

“…The risks of opioid overdose and abuse continue to be preeminent concerns in the field of pain medicine. Although those committed to eradicating opioid analgesia from the pain management armamentarium intentionally conflate prescription opioid overdose deaths with those due to illicit fentalogues and recent data indicating that involuntary tapers of opioids actually increase the likelihood of death from overdose and suicide, the need for continued diligent focus on prescription practices by clinicians on behalf of their patient population remains a best practice [1,2]. Multiple strategies have been proposed to mitigate the risks of inappropriate medication use both wittingly and unwittingly.…”

History of Respiratory Stimulants

“…As the pattern of substance abuse and overdose death has changed over the last few decades, there has evolved the attendant realization that the current approach to overdose needs to be updated. 1 The current standard drug used in presumptive opioid-related overdoses, the opioid receptor antagonist naloxone, has a receptor binding affinity that is increasingly less competitive against the ever more-potent fentanoids (such as alfentanil, carfentanil, fentanyl, and sufentanil), and illicit “fentalogues”, 2 and is a mechanistic mismatch for respiratory depression induced by the non-opioid component in polysubstance overdoses, which unfortunately are currently the rule, not the exception. 3 , 4 This does not mean that the use of naloxone should be abandoned, quit the contrary.…”