China 
Africa 
Explore chapters and articles related to this topic
Designer Benzodiazepines
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Peter D. Maskell, Nathan E. Wilson
There have been discussions of the use of the GABA-A receptor benzodiazepine antagonist flumazenil in the treatment of benzodiazepine overdose. It is a drug like naloxone that is used as an antidote for opioid overdose, because of it being an opioid receptor antagonist that has a rapid onset and a short duration of action (Sivilotti, 2016). Unlike naloxone, which is widely used in the clinical setting, the use of flumazenil differs from country to country. In the United Kingdom, flumazenil is not licenced for the treatment of benzodiazepine overdose (Anon, 2018a), despite the NICE guideline suggesting that flumazenil should be considered in patients presenting with a benzodiazepine overdose (NICE, 2016), with doses of 0.2 mg (IV) every one to two minutes, until the reversal of excess sedation or a 1 mg total dose (Sivilotti, 2016). The concerns with the use of flumazenil are that it may precipitate benzodiazepine withdrawal, inducing seizures and agitation. The other contraindications include a history of epilepsy, co-ingestion of drugs such as tricyclic antidepressants and stimulants, as flumazenil lowers the seizure threshold, and long-term benzodiazepine use because of a risk of withdrawal symptoms. Precise risk estimations for the use of flumezanil have been determined from a large meta- analysis investigating the administration of flumezanil for benzodiazepine overdose in 994 patients (13 different trials). The results suggested that adverse events, mainly agitation and gastrointestinal symptoms, were significantly more common in the flumezanil group than the placebo group (risk ratio 2.85; 95% CI 2.11–3.84), with serious adverse events, supraventricular arrhythmia, and convulsions again significantly more common in the flumezanil group than in the placebo group (risk ratio 3.81; 95% CI 1.28–11.39) (Penninga, Graudal, Ladekar, & Jürgens, 2016). The study concluded that flumazenil should not be routinely used, and the risk benefits of any administration should be weighed up in each patient. It is important to appreciate that a thorough history may allow for its safe administration. It is important to note that as flumazenil has shorter t½ than many benzodiazepines, particularly NPS benzodiazepines, re-sedation may occur. In the case of flubromazolam overdose, in the literature, flumezanil was used as an antidote following the positive identification of benzodiazepine use by an immunoassay screen. An improvement in the clinical situation was observed on the administration of flumezanil with GCS improvement from three to ten and spontaneous breathing (the consciousness, however, deteriorated after 30 minutes presumably due to the short t½ of flumezanil and the long (~10–20h t½) of flubromazolam (Lukasik-Glebocka et al., 2016). In this case, noradrenaline (IV central line) was used to increase blood pressure throughout. The patient was moved from the intensive care unit nine days after admission after supportive ventilation. Full case details can be found in the publication (Lukasik-Glebocka et al., 2016). The indication in the case was that flumezanil was of little use apart from confirming the overdose of a benzodiazepine.
Detection of flubromazolam in patients with suspected non-medical drug use attending emergency departments in the United Kingdom
Published in Clinical Toxicology, 2022
Mark Haden, Josephine Cashman, Andrew Ketchin, Rebecca Macfarlane, Shabana Issa, Michael Eddleston, Selina Hines, Simon Hudson, Simon L. Hill, Simon H. L. Thomas
Flubromazolam (8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1, 2, 4]triazolo-[4,3a] [1, 4]benzodiazepine) is a triazole analogue of flubromazepam structurally related to midazolam and alprazolam (Figure 1). It was patented in 1978 [1], but is not licensed as a medicine anywhere in the world. Non-medical use was first reported in Europe (Sweden) in 2014 and flubromazolam is now a controlled drug in many European countries including the UK [6]. The main feature of flubromazolam toxicity is sedation, which occurs at oral doses less than 0.5 mg and may be protracted [6–8] as a result of prolonged elimination and/or the presence of active metabolites. Hypotonia, amnesia, disorientation, miosis, mydriasis, tachycardia, and bradycardia have also been reported [7,9–12].
Occurrence and time course of NPS benzodiazepines in Sweden – results from intoxication cases in the STRIDA project
Published in Clinical Toxicology, 2019
Matilda Bäckberg, Madeleine Pettersson Bergstrand, Olof Beck, Anders Helander
This study presented a case series of 217 analytically confirmed acute intoxications involving 15 different NPS BZD that were detected in Sweden in 2012–2016. The results demonstrated that use of NPS BZD was common, with flubromazolam being especially prevalent and hazardous, but also revealed frequent use of multiple drugs. The results emphasized the importance of including NPS BZD in routine drug analysis.