In the ever-evolving terrain of opioid addiction and overdose, there are new synthetic versions of the drug that are becoming more popular, more potent, and more deadly.
One such class of opioids are nitazenes. First developed in the 1950s by pharmaceutical companies as analgesics, they never came to market and so were largely unknown outside of the laboratory. However, they have officially escaped the lab and are increasingly popular on the street – with most compounds hundreds to thousands of times more potent than morphine and ten times more potent than fentanyl. Carfentanil – an analogue of fentanyl – was initially used in the mid-1980s as a general anesthetic for elephants.
The presentation of overdose, though, remains the same: altered mental status, pinpoint pupils, and respiratory depression that can lead to coma and death. But, besides being more potent, these nitazenes, as well as other synthetic opioids that have now hit the streets, can last much longer. Often, one dose of naloxone is not enough – especially if opioids have been mixed with other drugs (see the DEA announcement put out this May).
Nevertheless, even though one dose of naloxone may not be enough, it should not be given indiscriminately, and ventilation should continue to be the immediate intervention when it comes to severe hypoventilation or respiratory failure.
It takes a full two minutes for naloxone to work, as it binds to opioid receptors in the body, displacing the opioids themselves. When treating a patient who has overdosed, this can feel like a lifetime, which is why giving a second or third dose before the first has had time to work, can be so tempting. However, naloxone induced opioid withdrawal can be severe – and the longer the patient has been using, the more painful it is. The severity of the withdrawal can actually compel further opioid use and foster a mistrust of naloxone or refusal to carry it.
In fact, a recent update on naloxone administrations from the Joint Royal Colleges Ambulance Liaison Committee in the UK advocates titrating naloxone to achieve spontaneous respiration – not complete arousal (interestingly, Nyxoid – the European version of Narcan – delivers 1.8 mg of naloxone as opposed to the 4 mg). Also, because the half-life of naloxone is about 1.5 hours, they recommend that the patient be monitored for at least 4 hours after the last dose of naloxone.
In other words, naloxone still works. But first responders need to know that not all opioids are created equal and, unfortunately, expect to see versions or mixtures of the drug being used that are even more potent than fentanyl.
References:
Edinoff AN, Martinez Garza D, Vining SP, Vasterling ME, Jackson ED, Murnane KS, Kaye AM, Fair RN, Torres YJL, Badr AE, Cornett EM, Kaye AD. New Synthetic Opioids: Clinical Considerations and Dangers. Pain Ther. 2023 Apr;12(2):399-421. doi: 10.1007/s40122-023-00481-6. Epub 2023 Feb 24. PMID: 36826742; PMCID: PMC9950705.
Pergolizzi J Jr, Raffa R, LeQuang JAK, Breve F, Varrassi G. Old Drugs and New Challenges: A Narrative Review of Nitazenes. Cureus. 2023 Jun 21;15(6):e40736. doi: 10.7759/cureus.40736. PMID: 37485167; PMCID: PMC10361140.
https://www.medpagetoday.com/emergencymedicine/emergencymedicine/104824
