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Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse. Naloxone is the main treatment used to reverse OIRD and is available as nasal sprays, prefilled naloxone injection devices, and generic naloxone for injection. An overdose needs to be treated as soon as possible to avoid death, and synthetic opioids such as fentanyl are up to 50 times more potent than heroin, so the availability of new, higher-dose, 5-mg prefilled injection or 8-mg intranasal spray naloxone preparations are important additions for emergency treatment of OIRDs, especially by lay people in the community. Higher naloxone doses are expected to reverse a synthetic overdose more rapidly and the current formulations are ideal for use by untrained lay people in the community. There are potential concerns about severe withdrawal symptoms, or pulmonary edema from treatment with high-dose naloxone. However, from the perspective of first responders, the balance of risks would point to administration of naloxone at the dose required to combat the overdose where the risk of death is very high. The presence of xylazines as an adulterant complicates the treatment of OIRDs, as naloxone is probably ineffective, although it will reverse the respiratory depression due to the opioid. For these patients, hospitalization is particularly vital. Education about the benefits of naloxone remains important not only in informing people about how to treat emergency OIRDs but also how to obtain naloxone. A call to emergency services is also essential after administering naloxone because, although the patient may revive, they may overdose again later because of the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs.<\/jats:p>","DOI":"10.3389\/fpubh.2024.1346109","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:20:44Z","timestamp":1709079644000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Fact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids"],"prefix":"10.3389","volume":"12","author":[{"given":"Albert","family":"Dahan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Franko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Carroll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Craig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callie","family":"Crow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Galinkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin C.","family":"Garrity","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Rausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"B1","unstructured":"Provisional Data Shows U.S. Drug Overdose Deaths Top 100,000 in 20222023"},{"key":"B2","doi-asserted-by":"publisher","first-page":"290","DOI":"10.15585\/mmwr.mm6911a4","article-title":"Drug and opioid-involved overdose deaths - United States, 2017-2018","volume":"69","author":"Wilson","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.3389\/fphar.2018.01210","article-title":"Postmortem toxicology of new synthetic opioids","volume":"9","author":"Concheiro","year":"2018","journal-title":"Front Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"293","DOI":"10.15585\/mmwr.mm7211a7","volume":"72","year":"2023","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1213\/ANE.0000000000002496","article-title":"Risk factors for opioid-use disorder and overdose","volume":"125","author":"Webster","year":"2017","journal-title":"Anesth Analg."},{"key":"B6","unstructured":"Identifying Risks When Prescribing Opioids"},{"key":"B7","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1176\/appi.ajp.2017.17070808","article-title":"Service use preceding opioid-related fatality","volume":"175","author":"Olfson","year":"2018","journal-title":"Am J Psychiatry."},{"key":"B8","unstructured":"Chronic Pain Management and Opioid Misuse: A Public Health Concern (Position Paper)2020"},{"key":"B9","unstructured":"Fentanyl Tainted Pills Bought on Social Media Cause Youth Drug Deaths to Soar"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e0000769","DOI":"10.1371\/journal.pgph.0000769","article-title":"Fentanyl-driven acceleration of racial, gender and geographical disparities in drug overdose deaths in the United States","volume":"3","author":"D'Orsogna","year":"2023","journal-title":"PLOS Glob Public Health."},{"key":"B11","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1177\/00027162231154348","article-title":"Demographic and geographic variation in fatal drug overdoses in the United States, 1999-2020","volume":"703","author":"Monnat","year":"2022","journal-title":"Ann Am Acad Pol Soc Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0290416","DOI":"10.1371\/journal.pone.0290416","article-title":"Examining sociodemographic correlates of opioid use, misuse, and use disorders in the All of Us Research Program","volume":"18","author":"Yeh","year":"2023","journal-title":"PLoS ONE"},{"key":"B13","unstructured":"Drug Overdose Death Rates2023"},{"key":"B14","volume-title":"Full Prescribing Information","year":"2020"},{"key":"B15","volume-title":"Kloxxado (Naloxone HCl). 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