Drugs and health
Sally Robinson in Priorities for Health Promotion and Public Health, 2021
Counterfeit and illegal drugs, especially those in pill or powder form, can be dangerous because the dose of the active substance is unknown. They can include potentially poisonous adulterants such as lead (metal), strychnine (pesticide), clenbuterol (decongestant), local anaesthetics, levamisole (worm treatment), aluminium and glass (DH, 2011). One woman said: I’m seeing more diversity in drugs and quality of drugs due to the darknet markets … we’re injecting drugs that we don’t know exactly what they are or the strength any more. So called ‘liquid Xanax’ for example – it’s clearly not etizolam when it has floaties in it.(Australian woman, quoted in Peacock et al., 2019 p.1679)
Designer Benzodiazepines
Ornella Corazza, Andres Roman-Urrestarazu in Handbook of Novel Psychoactive Substances, 2018
The lack of pharmacological testing of the NPS benzodiazepines to date either using functional in vitro or in vivo testing has made it difficult to determine the potency of the NPS benzodiazepines. Quantitative structure activity relationship (QSAR), which relates the structure of the molecules to biological activity using a known model, allows some initial prediction of potency. triazolobenzodiazepines (such as etizolam) are generally more potent than 1,4-benzodiazepines (such as diazepam), although individual potency will depend on the functional groups present (Hester, Duchamp, & Chidester, 1971; Meguro & Kuwada, 1970) and so does not allow more than a rudimentary determination of the potency. Recent work by Waters et al. has developed a QSAR model to determine the biological activity of NPS benzodiazepines (Waters, Manchester, Maskell, Haegeman, & Haider, 2018) that show the strength of binding of the drugs to the GABA-A receptor but not the pharmacological potency. The best current method to develop some idea of the potency of the NPS benzodiazepines is to look at the common dose of NPS benzodiazepines taken by users—the scale being from the most potent drugs (+++++) to the least potent drugs (+) (Table 19.3), with the potency of the individual NPS benzodiazepines shown in Table 19.2. This assumes that the common dose of the drug gives a similar level of effect in an individual, which may not be true. To give an idea of the potency, diazepam would score (+/++), whereas clonazolam, flubromazolam, and flunitrazolam would be the most potent drugs (+++++) correlating with user reports (Huppertz et al., 2018; Anon n.d.; Theis 2017.; Andersson & Kjellgren, 2017). Because of the very low dose (~0.5 mg) that is needed for these drugs, it is possible that the user may easily overdose because of the difficulty in measuring the dose if using the powder form. If taking tablets, as the quality control of the illicit manufacturers is poor, it is highly likely the users will take a dose that they did not intend to. The NPS benzodiazepines are, however, the NPS grouping that have the lowest risk of fatal toxicity of the NPS compounds. This should, however, not be taken as meaning that they are safe compounds to take (King & Corkery, 2018).
Non-fatal intoxications involving the novel benzodiazepine clonazolam: case series from the Emerging Drugs Network of Australia – Victoria project
Published in Clinical Toxicology, 2023
Rebekka Syrjanen, Shaun L. Greene, Jared W. Castle, Matthew Di Rago, Sarah E. Hodgson, Rachelle Abouchedid, Andis Graudins, Jennifer L. Schumann
The blood clonazolam concentration range identified in our cases (0.2–2.1 µg/L) was substantially lower than concentrations previously reported. The female who ingested 10 mg of clonazolam had a serum clonazolam concentration of 77 µg/L 4 h post ingestion [5]. Similarly, a patient who had used both etizolam and clonazolam (one tablet containing clonazolam 1.1 mg) had a maximum serum clonazolam concentration of 10.2 µg/L [11]. However, the concentration of the active metabolite, 8-aminoclonazolam, in all four cases was substantially higher, suggesting peak clonazolam concentration had passed at the time of sampling. Ultimately, it is difficult to draw conclusions without knowledge of the concentration of clonazolam per tablet, and the exact time between tablet ingestion and blood sampling. In addition, although comprehensive drug screening was utilised, there may have been undetected substances which could further explain the presenting toxidromes.
Designer benzodiazepines: a report of exposures recorded in the National Poison Data System, 2014–2017
Published in Clinical Toxicology, 2019
Joseph E. Carpenter, Brian Patrick Murray, Camille Dunkley, Ziad N. Kazzi, Melissa H. Gittinger
The term “designer benzodiazepine” is actually a bit of a misnomer, as the class includes benzodiazepine relatives and derivatives, namely thienodiazepines, triazolobenzodiazepines, and thienotriazolodiazepines (Figure 1) [8]. Notable members of this drug family include clonazolam, diclazepam, flubromazepam, flubromazolam, and pyrazolam [9]. None of these chemicals are approved by the United States Food and Drug Administration (FDA) for therapeutic use. Another benzodiazepine relative, etizolam, is approved for therapeutic use in some countries, but remains unapproved in the United States and has been reported to be a drug of abuse alongside other more novel agents [9,10].
Blepharospasm in Japan: A Clinical Observational Study From a Large Referral Hospital in Tokyo
Published in Neuro-Ophthalmology, 2018
M. Wakakura, A. Yamagami, M. Iwasa
Our findings further highlight the need for clinicians to remain aware of the risk of blepharospasm when prescribing etizolam (a thienodiazepine) and benzodiazepines. However, the second most common medication prescribed to patients in the present study was zolpidem. Although zolpidem is a non-benzodiazepine with an unrelated chemical structure, it produces its effects via the benzodiazepine binding site at α1-containing GABAA receptors.33 Therefore, the mechanism underlying the development of blepharospasm in patients treated with zolpidem may be consistent with that for other forms of drug-induced blepharospasm.