The conundrum of polysubstance overdose

Journal of Clinical Pharmacy and Therapeutics, vol. 46, pp. 1189–1193

Abstract

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.

Authors 4

1. Joseph V. Pergolizzi Aachen

   Leiden University Medical Center · Nema Research (United States)

   Affiliation as printed

   Enalare Therapeutics Inc. Princeton New Jersey USA

   Leiden University Medical Center Leiden The Netherlands

   NEMA Research Inc. Naples Florida USA

   Neumentum Inc. Morristown New Jersey USA

2. Albert Dahan Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center Leiden The Netherlands

3. Jo Ann LeQuang

   Nema Research (United States)

   Affiliation as printed

   NEMA Research Inc. Naples Florida USA

4. Robert B. Raffa corresponding

   University of Arizona · Temple University

   Affiliation as printed

   College of Pharmacy (Adjunct) University of Arizona Tucson Arizona USA

   Enalare Therapeutics Inc. Princeton New Jersey USA

   Neumentum Inc. Morristown New Jersey USA

   Temple University School of Pharmacy (Prof. emer.) Philadelphia Pennsylvania USA