We would like to congratulate CODA’s Associate Director of Research and Associate Professor of Psychiatry at OHSU, Dr. Randy Torralva, and Dr. Aaron Janowsky, Professor of Psychiatry and Behavioral Neuroscience at OHSU and of the Veterans Administration Portland Health Care on their recent publication in the Journal of Pharmacology and Experimental Therapeutics entitled, “Noradrenergic Mechanisms in Fentanyl-Mediated Rapid Death Explain the Failure of Naloxone in the Opioid Crisis.”
The article is one of the first in-depth reviews of the pharmacology and underlying mechanisms of fentanyl, describing how fentanyl-induced severe respiratory distress is resistant to naloxone intervention and therefore more likely than heroin and other opioids to lead to overdose death. Their research can lead to a significant reduction in opioid overdose deaths related to fentanyl.
In the article, Dr. Torralva, an anesthesiologist, and Dr. Janowsky, a neuropharmacologist, point out that unlike other opioids, fentanyl has the unique ability to cause the rapid onset of respiratory failure via chest wall rigidity and closure of the vocal cords in a clinical phenomenon called “wooden chest syndrome”. Patients, in recounting their experiences, have shared feeling like their chest is being crushed or squeezed, like they can’t physically talk or lose consciousness very quickly.
“Wooden chest syndrome” can occur within 1-2 minutes of injection containing fentanyl and is routinely fatal without medical intervention. The article suggests underlying mechanisms of “wooden chest syndrome” involve both opioid receptors and adrenaline receptors and as a result, fentanyl-induced “wooden chest syndrome” is resistant to reversal by naloxone as a single agent. The article suggests “wooden chest syndrome” may be the cause of the ongoing rise in deaths from fentanyl despite the availability and wide awareness of naloxone. Drs. Torralva and Janowsky describe how these insights could inform the development of next-generation opioid reversal drugs that could simultaneously reverse the effects of both fentanyl and morphine based drugs.
Dr. Torralva would like to express his deep gratitude and appreciation of CODA for all of its support in this endeavor and to the CODA Research Dept. (Dr. Katharina Wiest, PhD, MSPH, Nicole Abraham, M.S. and Adam Gott M.A.) for their tremendous support and assistance in the preparation of the manuscript. CODA is proud to support the work of Dr. Torralva and all its researchers!
Funding for the authors and this work was provided by: The Dept. of Veterans Affairs Merit Review [I01BX002758] and Career Scientist programs, the U.S. Food and Drug Administration, U.S. Department of Justice Drug Enforcement Administration [D-15-OD-0002], and National Institutes of Health/National Institute on Drug Abuse [ADA12013]. The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. Additional funding support was provided by CODA, Inc. and Torralva Medical Therapeutics, LLC.
Read the complete article here