The conundrum of polysubstance overdose

What is known and objective: Treating an opioid overdose using an opioid receptor antagonist (such as naloxone) makes mechanistic sense and can be effective. Unfortunately, the majority of current drug overdose deaths involve polysubstance use (i.e., an opioid plus a non-opioid).Comment: Respiratory depression induced by opioids results from excessive opioid molecules binding to opioid receptors. This effect can be reversed by an opioid receptor antagonist. However, the respiratory depression induced by non-opioid drugs is not due to action at opioid receptors; thus, an opioid receptor antagonist is ineffective in many of these cases. For respiratory depression induced by non-opioids, receptor antagonists are either not available (e.g., for propofol overdose) or there may be attendant risks with their use (e.g., seizures with flumazenil). This gives rise to a need for more effective ways to treat polysubstance overdose.What is new and conclusion: A new approach to treating opioid-induced respiratory depression due to drug overdose focuses on agents that stimulate respiratory drive rather than competing for opioid receptors. Such an approach is "agnostic" to the cause of the respiratory depression, so might be a potential way to treat polysubstance overdose.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Are opioid receptor antagonists adequate for "Opioid" overdose in a changing reality?

What is known and Objective: Deaths due to opioid-induced respiratory depression (OIRD) continue to rise despite intense regulatory and professional actions. COVID-19 has only worsened this situation.(1) An opioid receptor antagonist (ORA) such as naloxone is the most common intervention for OIRD. However, with increasing overdose from highly potent illicit opioids and polysubstance abuse, appraisal of the adequacy of ORA seems warranted and timely.Comment: OIRD results from the binding of an excess number of agonist molecules to opioid receptors. Mechanistically, it makes sense to reverse this by displacing agonist molecules by administering an ORA. But realistically, the trend to higher-potency agonists and polysubstance abuse diminishes the effectiveness of this approach. We are left facing a crisis without a solution.What is new and Conclusion: For the increasingly common OIRD from highly potent illicit agonists and polysubstance overdose, ORAs are correspondingly less effective. Alternatives are needed-soon.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Overdoses due to fentanyl and its analogues (F/FAs) push naloxone to the limit

What is known and Objective: Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose.Comment: Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the mu-opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up?What is new and Conclusion: As a competitive antagonist at mu-opioid receptors, naloxone is often a life-saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non-opioids.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

Benefit-risk analysis of buprenorphine for pain management

Health care providers in the United States are facing challenges in selecting appropriate medication for patients with acute and chronic pain in the midst of the current opioid crisis and COVID-19 pandemic. When compared with conventional opioids, the partial µ-opioid receptor agonist buprenorphine has unique pharmacologic properties that may be more desirable for pain management. The formulations of buprenorphine approved by the US Food and Drug Administration for pain management include intravenous injection, transdermal patch, and buccal film. A comparison of efficacy and safety data from studies of buprenorphine and conventional opioids suggests that buprenorphine may be a better-tolerated treatment option for many patients that provides similar or superior analgesia. Our benefit-risk assessment in this narrative review suggests that health care providers should consider that buprenorphine may be an appropriate alternative for pain management over other opioids. © 2021 Hale et al.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]