John R. H. Archer

Heavy metal poisoning from Ayurvedic traditional medicines: an emerging problem?

The use of Ayurvedic medicines is common in both adults and children and is increasing in many areas of the world. This paper will discuss the risks of heavy metal poisoning associated with the use of Ayurvedic medicines and illustrate this with some cases managed by the authors. Many Ayurvedic medicines contain heavy metals, including lead, mercury and arsenic, and there have been numerous reports of clinically significant heavy metal poisoning related to their use. However, there have been few studies that allow quantification of the incidence of this problem. There is limited regulation of these products in most areas of the world. Recent European legislation may help to improve safety of products bought in shops, but it is likely to have a relatively limited overall impact as it will not cover personal imports or products prescribed by traditional medicine practitioners. There is an urgent need for studies to quantify the frequency and potential risk of heavy metal poisoning from Ayurvedic medicines and for culturally appropriate education to inform the public of the potential for toxicity associated with these products.

Analysis of anonymous pooled urine from portable urinals in central London confirms the significant use of novel psychoactive substances

AIM Analysis of urine samples collected across a city centre, for the detection of novel psychoactive substances (NPS). DESIGN Cross-sectional study of anonymized urine samples used for the analysis of classical recreational drugs, NPS and metabolites. METHODS Pooled urine samples collected from portable stand-alone four-person urinals across a city centre were analysed using full-scan accurate-mass high-resolution liquid chromatography coupled to tandem mass spectrometry. Data were processed against compound databases containing >1700 drug compounds and metabolites. RESULTS Seven established recreational drugs (3,4-methylenedioxyamphetamine, cocaine, cannabis, ketamine, 3,4-methylenedioxy-N-methylamphetamine, methamphetamine and amphetamine) and six potential NPS [hordenine (all 12 urinals), cathine (11), methylhexaneamine (9), 4-methylmethcathinone (6), methiopropamine and metabolites (2) and methoxetamine and metabolites (1)] were detected. Methylhexaneamine, methiopropamine and hordenine are currently uncontrolled in the UK, whereas methoxetamine is currently subject to a Temporary Class Drug Order. Metabolites of the anabolic steroid nandrolone were found in two urinals and trenbolone metabolites and clenbuterol in one urinal. CONCLUSION Analysis of pooled urine samples collected anonymously from stand-alone urinals in a large inner city can detect the use of recreational drugs, NPS and anabolic steroids. Metabolite detection indicates actual drug use, metabolism and elimination rather than simply discarded drugs in the urinals. This technique by confirming the actual drug(s) used has the potential to be additive to currently used datasets/key indicators providing more robust information for healthcare authorities, legislative and law enforcement on the drugs actually being used.

Trend analysis of anonymised pooled urine from portable street urinals in central London identifies variation in the use of novel psychoactive substances

Abstract Context. There is increasing interest in the analysis of waste water at sewage treatment plants to monitor recreational drug use. This technique is limited for novel psychoactive substances (NPS) due to limited knowledge on their human and bacterial metabolism and stability in waste water. Small studies have reported the detection of NPS using pooled anonymous urine samples, which eliminates some of these potential confounders. Objective. To determine patterns of recreational drug, including NPS, use by confirming their presence in analysis of pooled urine from portable street urinals across a wide geographical area in central London over a 6-month period. Materials and methods. Pooled anonymous urine samples were collected from 12 four-bay stand-alone portable urinals distributed once a month across central London for six consecutive months. Samples were analysed using high-performance liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM-MS); acquired data were processed against target compound databases. Results. With regards to Classical Recreational Drugs, there was consistency of detection of cathine, cocaine, morphine, MDMA over the 6 months, with variability of detection of amphetamine, ketamine and cannabis. With regards to NPS, a total of 13 NPS were detected during the six months. Mephedrone and methylhexaneamine were detected consistently each month. Other commonly detected NPS included methiopropamine (5 months), pipradrol (4 months), cathinone (4 months), 5-(2-aminopropyl)benzofuran (3 months) and 4-methyethcathinone (3 months). Of note, methoxetamine and the synthetic cannabinoid receptor agonists were not detected in any samples. Discussion. Previous studies using the same method detected three and five NPS in a nightclub and pissoir setting, respectively, on a single night. The longer sampling time of 6 months has allowed detection of 13 NPS. Of note, mephedrone showed the least month-to-month variation in detection over the 6-month sampling period. With regards to classical recreational drugs, those detected were consistent with use-data from UK population surveys. The only exception is amphetamine which these surveys have shown a steady decline in use since 1996 but our study showed some variation in the frequency of its detection. However, the sampling period was too short and a longer study is needed to detect the trend in decreasing use. Conclusion. This study demonstrates that analysis of anonymous pooled urine samples from stand-alone urinals can be used to detect and monitor trends in the use of classical recreational drugs and NPS in a large city centre over time. This technique has the potential to be a novel key indicator alongside other existing indicators to provide a more robust picture of the use of recreational drugs including NPS.

What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient

Abstract Context. Intravenous lipid emulsion (ILE) and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) are being used together or in close succession in the management of circulatory failure secondary to cardiotoxic drug poisoning. There have been reports of mechanical problems, including fat emulsion agglutination, clogging, increased blood clot formation and even cracking of parts of the machine, in patients concurrently receiving VA-ECMO and ILE as part of parenteral nutrition. Objective. To ascertain the adverse effects associated with the combined use of ILE and ECMO in the poisoned patient. Methods. PubMed and OVID (1966 to 9 June 2014) and EMBASE (1947 to 9 June 2014) were searched to identify publications relating to studies and/or case reports where ILE had been used at the same time when VA-ECMO was used – 7 were identified. In addition, the abstracts published between 2006 and 2013 inclusive of those from the North American Congress of Clinical Toxicology and the congresses of the European Association of Poisons Centres and Clinical Toxicologists were searched to identify additional cases and 2 were found. Finally all cases posted on lipidrescue.org were reviewed to determine if they related to the use of ILE with VA-ECMO and no new cases were identified. In vitro study. An in vitro study involving the continuous infusion of 20% ILE at 3 mL/h for 24 h demonstrated layering (separation of intact fat emulsion from blood) and agglutination (clumping resulting in little or no flow of fat emulsion through the circuit) in all circuits within 30 min of starting the fat emulsion infusion. Clinical studies. An observational study based in 42 centres that regularly used ‘fat emulsion’ during VA-ECMO treatment reported cracking of stopcocks (the valve which restricts flow in the VA-ECMO tubing) (n = 10, 23.8%); fat emulsion agglutination (n = 11, 26.2%); clogging and associated malfunction of the membrane oxygenator (n = 2, 4.8%); and increased blood clot formation in the circuits (n = 2, 4.8%). In a prospective observational study of 9 neonates on VA-ECMO receiving intravenous nutrition, layering and agglutination were seen in four sets of VA-ECMO tubing and blood clots were found in seven circuits. Nine case reports were identified where ILE was used with VA-ECMO for the management of circulatory failure/instability secondary to cardiotoxic drug poisoning. In two of these case reports, the authors specifically stated that ILE did not cause any mechanical complications with the VA-ECMO; the other seven reports made no comment as to whether there were any complications or not. Conclusions. There is in vitro and clinical evidence that the combined use of ILE and extracorporeal membrane oxygenation may be associated with fat deposition in the VA-ECMO circuits and increased blood clot formation. Clinicians managing poisoned patients with both of these novel treatment modalities should be aware of these potential complications.

Safety of Metformin in Patients with Chronic Obstructive Pulmonary Disease and Type 2 Diabetes Mellitus

Abstract Type 2 diabetes mellitus (T2DM) is commonly associated with chronic obstructive pulmonary disease (COPD). Metformin is a valuable treatment for T2DM, and may offer additional benefits in COPD. However, due to its rare association with lactic acidosis, its safety in COPD is uncertain. We retrospectively identified patients with T2DM who had been admitted to hospital for COPD exacerbations. We compared those who were taking metformin with those who were not, with respect to their lactate concentration (primary endpoint) and survival (secondary endpoint). The study cohort (n = 130) had a mean (±standard deviation) age of 73.0 ± 9.8 years and 47 (36%) were female. Arterial blood gases were recorded in 120 cases: 88 (73%) were hypoxemic, 45 (38%) were in respiratory failure and 33 (28%) had respiratory acidosis. The 51 patients (39%) in the metformin group had a median (interquartile range) lactate concentration of 1.45 mmol/L (1.10–2.05) versus 1.10 mmol/L (0.80–1.50) in the non-metformin group (p = 0.012). Median survival was 5.2 years (95% CI 4.5–5.8) versus 1.9 years (1.1–2.6), respectively (hazard ratio 0.57; 95% CI 0.35–0.94). This remained significant in a multivariate model adjusted for measurable confounders. In conclusion, among patients with COPD at high risk for lactate accumulation, metformin therapy was associated with a minor elevation of lactate concentration of doubtful clinical significance. Metformin was associated with a survival benefit, but this must be interpreted cautiously due to possible effects from unmeasured confounders. Viewed collectively, the results suggest that COPD should not present a barrier to the investigational or clinical use of metformin.

An Internet snapshot study to compare the international availability of the novel psychoactive substance methiopropamine

Abstract Context. With the increased use of novel psychoactive substances, there is an increasing availability of these substances from Internet-based suppliers. Methiopropamine, first reported in 2011, is a recreational drug available over the Internet. The aim of this study was to investigate availability and cost of methiopropamine in three different countries: the UK, France, and Canada. Methods. Using the European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, this study, conducted in June 2013, was undertaken in two different languages: in English (the UK and Canada) and in French (France and Canada), using three Internet searching engines: “google.co.uk”, “google.fr” and “google.ca”. Results. A total of 62 sites were found, most of them were found from the English searches. 45% of the suppliers seemed to originate from the UK. The prices of methiopropamine were comparable between suppliers, no matter which search engine or language was used. The cost of a unit of methiopropamine was inversely related to the purchased quantity, going from 19.49 ± 0.15 GBP per gram for a purchase amount of 500 mg to 3.54 ± 0.13 GBP per gram for a purchase amount of 1 kg. Discussion. The results of the present study demonstrate that the sale of methiopropamine has the potential to reach users across the world. It also appears to support that snapshot studies could be used for toxicovigilance across different countries, by studying the Internet market of novel psychoactive substances. Conclusion. To date, snapshot studies, used to monitor the Internet novel psychoactive substances market, have only been undertaken in Europe. We have shown that the flexibility of this methodology enables comparison of the online activity of drug sellers between different countries and continents and that, at least for methiopropamine, the UK is the predominant source for Internet supply.

Running an unknown risk: a marathon death associated with the use of 1,3-dimethylamylamine (DMAA).

Keywords: 1,3 dimethylamylamine (DMAA); sports supplement; Marathon; fatality; 4-methylhexane-2-amine; recreational drug

Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity.

INTRODUCTION AND AIMS There has been a global increase in the availability and use of novel psychoactive substances (NPS) over the last decade. Phenibut (β-phenyl-γ-aminobutyric acid) is a GABAB agonist that is used as an NPS. Here, we bring together published scientific and grey information sources to further understand the prevalence of use, desired effects and acute toxicity of phenibut. DESIGN AND METHODS Using European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, we undertook an English language Internet snapshot survey in May 2015 to gather information on the availability and price of phenibut from Internet NPS retailers. To gather information on prevalence of use, desired effects and/or adverse effects, we searched grey literature (online drug discussion forums) and medical literature (PubMed and abstracts from selected International Toxicology conferences). RESULTS We found 48 unrelated Internet suppliers selling phenibut in amounts ranging from 5 g (US

Nopaine no gain: recreational ethylphenidate toxicity.

1.60, £1.01/g) to 1000 kg (US

Analysis of anonymized pooled urine in nine UK cities: variation in classical recreational drug, novel psychoactive substance and anabolic steroid use

0.23, £0.14/g). Capsules containing 200-500 mg of phenibut were available in packs of between 6 (US