Bankstown Hospital - Grand Rounds - Further Reading

Welcome to the Grand Rounds Further Reading List, Drug Health edition, brought to you by the Clinical Library, on Level 4, next to the Auditorium.

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“Managing novel short acting Nitazene

withdrawal syndrome: a case series from Australia.”

Isoardi, K. Z., et al. "Clinical toxicity of nitazene detections in two Australian emergency department toxicosurveillance systems." Drug and Alcohol Review n/a(n/a): https://onlinelibrary.wiley.com/doi/abs/10.1111/dar.13998

 PDF AVAILABLE AT LINK.

                Abstract: Introduction: Nitazenes are a group of potent synthetic opioids that have had increasing prominence as novel psychoactive drugs in the last 5 years. We describe emergency department nitazene-related presentations. Methods: This is a prospective series of patients with analytically confirmed nitazene presentations identified by the Emerging Drugs Network of Australia and Emerging Drugs Network of Australia Victoria. Both studies' databases were searched between July 2020 and February 2024 with clinical data and blood nitazene concentrations abstracted. Results: There were 32 presentations, 23 (72%) males, with a median age of 31 years (range 18–63 years). Only five (16%) intentionally ingested a nitazene, with most (12, 38%) believing they had taken alternative opioids. Co-exposures occurred in 31 (97%), mostly metamfetamine. Naloxone was administered in 23 (72%) presentations, with a median total dose of intravenous naloxone within 1 h post hospital presentation of 400 μg (interquartile range [IQR] 160–450 μg). Four (13%) received a naloxone infusion. Thirteen (41%) were admitted to the intensive care unit. The median length of stay was 17 h (IQR 7–39 h). Protonitazene was the commonest nitazene detected in 23 (72%) presentations with a median concentration of 2.0 mg/L (range 0.7–15 mg/L). The lowest concentration of protonitazene in a patient that received naloxone was 0.7 mg/L. Discussion and Conclusions: Most patients were unaware they were using nitazenes. Given their potency, this has important implications for harm, particularly in those not intentionally using opioids. Nitazene exposure was mostly unintentional. Naloxone use was common and standard dosing regimens appeared effective in most cases.

Meyer, M., et al. (2023). "Shifting drug markets in North America - a global crisis in the making?" International Journal of Mental Health Systems 17(1): 36: https://doi.org/10.1186/s13033-023-00601-x

 PDF AVAILABLE AT LINK.

                Understanding drug market dynamics and their underlying driving factors is paramount to developing effective responses to the overdose crisis in North America. This paper summarises the distinct drug market trends observed locally and internationally over the past decade to extrapolate future drug market trajectories. The emergence of fentanyl on North American street markets from 2014 onwards led to a shift of street drug use patterns. Previously perceived as contaminants, novel synthetic opioids became the drugs of choice and a trend towards higher potency was observed across various substance classes. The diversification of distribution strategies as well as the regionalisation and industrialisation of production followed basic economic principles that were heavily influenced by prosecution and policy makers. Particularly, the trend towards higher potency is likely most indicative of what to expect from future illicit drug market developments. Nitazenes and fentanyl-analogues, several times more potent than fentanyl itself, are increasingly detected in toxicological testing and have the potential of becoming the drugs of choice in the future. The dynamic of drug import and local production is less clear and influenced by a multitude of factors like precursor availability, know-how, infrastructure, and the success of local drug enforcement strategies. Drug market dynamics and the current trajectory towards ultrapotent opioids need to be recognised by legislation, enforcement, and the health care system to prepare effective responses. Without significant improvements in treatment access, the implementation of preventative approaches and early warning systems, the mortality rate will continue to increase. Furthermore, there is no mechanism in place preventing the currently North American focused overdose crisis to spread to other parts of the globe, particularly Europe. A system of oversight, research, and treatment is needed to address mortality rates of historic proportions and prevent further harm.

Partridge, E., et al. (2025). "A cluster of multi-drug intoxications involving xylazine, benzimidazole opioids (nitazenes) and novel benzodiazepines in South Australia." Emergency Medicine Australasia 37(1): e14512: https://onlinelibrary.wiley.com/doi/abs/10.1111/1742-6723.14512

Abstract: Objective: To highlight the detection of xylazine and nitrazolam in conjunction with benzimidazole opioids (nitazenes) and other novel benzodiazepines in a cluster of patients after putative heroin use. Methods: Deidentified clinical and analytical data were gathered from patients enrolled in the Emerging Drugs Network of Australia system. Results: In December 2023, three adults presented to the ED with sedation following putative use of heroin. Toxicological analysis of blood samples identified xylazine, protonitazene, metonitazene, bromazolam and nitrazolam. Local health authorities subsequently issued an alert. Conclusion: This is the first signal of xylazine and nitrazolam use in Australia. These results demonstrate toxico-surveillance programmes with analytical confirmation of drugs are invaluable in monitoring illicit drug use.

Pergolizzi, J., Jr., et al. (2023). "Old Drugs and New Challenges: A Narrative Review of Nitazenes." Cureus 15(6): e40736: https://pmc.ncbi.nlm.nih.gov/articles/PMC10361140/

 FULLTEXT AVAILABLE AT LINK.

                Nitazenes are a group of compounds developed in the 1950s as opioid analgesics, but they were never approved to market. As such, they are not well known outside of academic research laboratories. A characteristic of nitazenes is their high potency (e.g., hundreds to thousands fold more potent than morphine and other opioids and tenfold more potent than fentanyl). In the past few years, several nitazenes, including "designer analogs," have been detected in the illicit drug supply and have been implicated in overdose mortality, primarily due to their exceptionally high potency. In the street drug supply, nitazenes are often found mixed with fentanyl or other agents but their presence is not always disclosed to drug buyers, who may not even be familiar with nitazenes. These drugs pose a particular challenge since there is little experience in how to reverse a nitazene overdose or potential drug-drug or drug-alcohol interactions. Public health efforts are needed to better inform street drug consumers, first responders, healthcare professionals, and the general public about these "new old drugs" that are infiltrating the recreational drug supply.

Piatkowski, T., et al. (2025). "‘The gear could be cut with fentanyl which is starting to happen more in Australia’: exploring overdose survivors’ perspectives on toxic supply and safe consumption." Drugs: Education, Prevention and Policy 32(1): 42-50: https://doi.org/10.1080/09687637.2024.2392520

                The widespread proliferation of high-potency synthetic opioids, particularly fentanyl, has precipitated a severe public health crisis in North America, with escalating overdose fatalities. Emerging concerns are observed in Australia, where recent incidents underscore the global impact of these substances. This study aimed to explore the role of synthetic opioids in overdoses among people in Queensland, Australia, and identify appropriate harm reduction responses from their perspective. Semi-structured interviews with 27 people who used opioids and who had experienced overdose in their lifetime were conducted. An iterative coding process, incorporating deductive and inductive codes, was employed. Participants emphasised the unpredictability and toxicity of the drug supply, especially with the presence of fentanyl. They highlighted the heightened risks due to decreased tolerance if there were periods of abstinence, and the challenges of using drugs in unsafe environments. There was strong support for safe consumption rooms to mitigate overdose risks. There are risks faced by people who use opioids due to an unpredictable and toxic drug supply, particularly with the presence of fentanyl. These findings underscore the importance of implementing proactive harm reduction strategies, including safe consumption spaces, to address the harms of synthetic opioids.