Suicidal attempt with eliglustat overdose.

Eliglustat is an orphan medicine used for long-term treatment of Gaucher disease type 1 (GD1) in adults. GD1 is a genetic condition, in which glucosylceramide builds up in the body, typically in liver, spleen, and bone. Clinical signs and symptoms of the disease are anemia, tiredness, easy bruising, hepatosplenomegaly, bone pain, and fractures. Eliglustat works by blocking glucosylceramide synthase (substrate reduction therapy). This medicine is subject to additional safety monitoring by regulatory authorities in the European Union. Scientific literature on eliglustat overdose is not available. We herein describe successful treatment of a suicidal attempt with massive eliglustat overdose. A 29-year-old female with GD1, a poor metabolizer of cytochrome P450 2D6 on a recommended daily dose of 84 mg of eliglustat, had taken 94 capsules of eliglustat (84 mg per capsule). One hour after ingestion of almost 8 g of eliglustat, the patient suffered from somnolence, severe bradycardia (37 bpm), and hypotension (systolic blood pressure of 70 mm Hg). After intravenous administration of atropine (1 mg) and cafedrine/theoadrenaline (100 mg/5 mg) by the called emergency physician, the patient resolved gradually. She remained 24 h with stable hemodynamics at a nearby intensive care unit. During continuous ECG monitoring, increased frequency of supraventricular ectopic activity and a first-degree atrioventricular block were observed. To our knowledge, this is the first case report on a suicidal attempt with eliglustat.

Effect of new legislation in Germany on prevalence and harm of synthetic cannabinoids.

CONTEXT: New psychoactive substances (NPS) have become an ongoing threat to public health. To prevent the emergence and spread of NPS, a new German law, the 'NpSG' took effect in November 2016. This study presents an overview of analytically confirmed synthetic cannabinoid (SC) intoxications from January 2015 to December 2018. In order to demonstrate effects of the NpSG, the results of 23 month before and 25 month after the introduction of the law were compared. METHODS: Within the scope of a prospective observational study blood and urine samples were collected from emergency patients with suspected NPS intoxication. Comprehensive drug analyses were performed by LC-MS/MS analysis. RESULTS: In the period considered, 138 patients were included. Within these, SC intake was verified in 65 patients (73%) in the period before the law change, and in 30 patients (61%) after. The median age increased significantly from 19.5 to 26 years. Seizures and admission to the ICU were reported significantly less frequently (seizures 29% versus 6.7%, p = 0.0283; ICU admission 42% versus 13%, p = 0.0089). 34 different SCs were detected, including four SCs (Cumyl-PEGACLONE, 5 F-MDMB-P7AICA, EG-018, 5 F-Cumyl-P7AICA) not covered by the NpSG at the time of detection. In the first period the most prevalent SC was MDMB-CHMICA (n = 24). 5 F-ADB was the most prevalent SC overall, detected in 7 patients (11%) in the first, and in 24 patients (80%) in the second period. CONCLUSION: The number of SC intoxications decreased overall after the implementation of the NpSG. The shift in the detected SCs can be considered a direct effect of the NpSG but unfortunately the market supply does not appear to have been reduced. Although changes in the age distribution and in the severity of intoxications may be seen as secondary effects of the law, the main objectives of the new law to prevent the emergence and spread of further chemical variations of known scheduled drugs, have apparently not been achieved from the perspective of this study.

Acute severe intoxication with cyclopropylfentanyl, a novel synthetic opioid.

BACKGROUND: Since 2016 an increase has been observed in the availability of new synthetic opioids (NSO) in Europe. Cyclopropylfentanyl is a very potent and selective µ-opioid agonist, which was reported for the first time in August 2017 in Europe. METHODS: The case was included in a prospective observational study of patients treated in emergency departments after the intake of novel psychoactive substances (NPS). Clinical features were acquired using a structured questionnaire for physicians. Serum and/or urine samples of ED patients were analyzed using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) screening methods for NPS. CASE REPORT: Within 10 min after intranasal intake of fentanyl, a 25-year-old male developed nausea, profuse sweating and dyspnoe. Because soon afterwards coma and respiratory insufficiency was noticed, the patient was admitted to hospital. After administration of naloxone (0.8 mg) breathing stabilized. However, the patient displayed recurrent decreases of oxygen saturation for 12 h. The intake of cyclopropylfentanyl was analytically confirmed. CONCLUSION: The constantly growing diversity of NSO still poses a high risk for drug users and can be a challenging task for clinicians and forensic toxicologists. Clinicians treating opioid overdoses should be aware of the potentially long lasting respiratory depression induced by fentanyl analogs.

[Health damages after ingestion of button batteries in childhood]. / Gesundheitsschäden nach Ingestion von Knopfzellbatterien im Kindesalter.

BACKGROUND: Exposure of children under 5 years to button batteries may result in severe corrosive injury, especially when they get stuck in the oesophagus. The injury is caused by the discharge current of the batteries. An increasing number of button battery ingestions have been described worldwide. OBJECTIVES: The aim of this study was to describe incidence and complications after battery ingestion in children in Germany. MATERIALS AND METHODS: Paediatric gastroenterologists and paediatric surgeons were asked to report complicated battery ingestions in children between 2011 and 2016 retrospectively. The survey was done using a structured questionnaire. In addition, button battery ingestion calls to a German poison centre were analysed retrospectively. RESULTS: In 116 cases the button battery was located in the oesophagus. Severe complications developed in 47 patients and 5 of these children died. Serious complications occurred also in children with removal of the button batteries within less than 3 h after the intake. The Freiburg poison centre received 258 paediatric ingestions of button batteries. Out of these, seven button batteries were stuck in the oesophagus and five in the nose causing corrosion injury. CONCLUSIONS: Serious complications and even death after button battery ingestion are described in Germany. Button batteries impacted in the oesophagus should be removed emergently to minimize corrosive injury. Because no symptoms or only slight discomfort are developed initially, awareness of button batteries as a unique corrosive hazard among the public and clinicians is an important requirement for prompt diagnosis and treatment resulting in a satisfactory outcome.

[Poisonous plants-a new approach for assessing the risk of poisoning in small children]. / Risiko Pflanze ­ Ein neuer Ansatz zur Einschätzung des Vergiftungsrisikos für Kleinkinder.

BACKGROUND: Plant poisoning in small children (from 0.5 to <6 years of age) is the third most frequent cause for phone contact with a poison center. For prevention of poisonings, a list of poisonous plants that should not be planted close to playgrounds or other places frequently visited by children was published in 2000 by the Bundesanzeiger. This list has been reevaluated and updated by the "Toxicity of Plants" working group of the Committee of the Assessment of Intoxications at the Federal Institute of Risk Assessment (BfR). MATERIALS AND METHODS: Relevant plants were taken from a recent publication. A literature search was conducted in PubMed concerning all plant poisonings in children and the toxic ingredients of plants. Also, monographs and the database POISINDEX were integrated in the evaluation. A classification was made for plants that after oral, dermal, or ocular contact of small quantities could cause severe, moderate, mild, or no intoxications in small children. RESULTS: Based on data of exposure and potentially toxic ingredients of the involved plants, a risk assessment was executed, which diverges from other publications because it concerns the actual basic risk of an intoxication. In total, 251 plants were reevaluated. For 11 plants, there was a high risk, for 32 a moderate, for 115 a mild, and for 93 plants no risk of intoxication could be determined. CONCLUSION: The new assessment of evaluating a toxicity risk for small children on the basis of exposure data and including the toxicity of ingredients allows for a more realistic assessment of the risk of poisoning with outdoor plants. In this way, infant exposure carrying a high risk of intoxication can be identified.

[Poisoning by exotic pets]. / Vergiftungen durch exotische Haustiere.

Exotic poisonous animals such as snakes, marine animals, spiders, and scorpions are a rarity in Central Europe, but are kept as pets by some people. Poisoning caused by these animals is a particular challenge in medical care.Over a period of six years (2001-2006), a total of 202 cases of poisoning with exotic animals were registered and evaluated at four poison information centers in Germany and France. Of the accidents, 91% happened in the home environment; the rest in pet stores. The poisonings were caused by snakes (38%), marine animals (31%), arthropods (spiders and scorpions, 27%), and other poisonous animals (4%). Severe poisoning was involved in 8% of the cases, all caused by snake bites. The severe poisonings were in the form of coagulopathies, severe local symptoms, and a respiratory insufficiency requiring intubation. In six cases of severe poisoning, an immune serum (antivenom) was administered and in three cases a surgical procedure was needed. Deaths did not occur.After the bite of a poisonous animal, the affected limb should usually be immobilized and disinfected, but not tied, cut, or sucked. The exact biological name of the species should be identified. In addition to hospitalization, it is recommended to consult a poison information center.

Validation of an LC-MS/MS method for the quantitative analysis of 1P-LSD and its tentative metabolite LSD in fortified urine and serum samples including stability tests for 1P-LSD under different storage conditions.

A variety of hallucinogens of the lysergamide type has emerged on the drug market in recent years and one such uncontrolled derivative of lysergic acid diethylamide (LSD) is 1-propionyl-LSD (1P-LSD). Due to the high potency of LSD and some of its derivatives (common doses: 50-200 µg), sensitive methods are required for the analysis of biological samples such as serum and urine. The occurrence of an intoxication case required the development of a fully validated, highly sensitive method for the quantification of 1P-LSD and LSD in urine and serum using LC-MS/MS. Given that LSD is unstable in biological samples when exposed to light or elevated temperatures, we also conducted stability tests for 1P-LSD in urine and serum under different storage conditions. The validation results revealed that the analysis method was accurate and precise with good linearity over a wide calibration range (0.015-0.4 ng mL-1). The limit of detection (LOD) and the lower limit of quantification (LLOQ) of 1P-LSD and LSD in serum and urine were 0.005 ng mL-1 and 0.015 ng mL-1, respectively. The stability tests showed no major degradation of 1P-LSD in urine and serum stored at -20 °C, 5 °C or at room temperature for up to five days, regardless of protection from light. However, LSD was detected in all samples stored at room temperature showing a temperature-dependent hydrolysis of 1P-LSD to LSD to some extent (up to 21% in serum). Serum samples were particularly prone to hydrolysis possibly due to enzymatically catalyzed reactions. The addition of sodium fluoride prevented the enzymatic formation of LSD. The method was applied to samples obtained from the intoxication case involving 1P-LSD. The analysis uncovered 0.51 ng mL-1 LSD in urine and 3.4 ng mL-1 LSD in serum, whereas 1P-LSD remained undetected. So far pharmacokinetic data of 1P-LSD is missing, but with respect to the results of our stability tests and the investigated case rapid hydrolysis to LSD in-vivo seems more likely than instabilities of 1P-LSD in urine and serum samples.

MAGAM II - prospective observational multicentre poisons centres study on eye exposures caused by cleaning products.

Objective: Local effects on the eye following cleaning product exposures are frequently reported. According to EU chemicals legislation many cleaning products are labelled with Hazard Phrase 318 indicating risk of irreversible eye damage. The objectives of this study were to identify cleaning products with potential for irreversible eye damage by collecting human exposure data from poisons centres (PC), and to clarify to what degree exact product identification is possible during a PC telephone call. Methods: MAGAM II was a multicentre binational prospective observational PC study. All human eye exposures to detergents or maintenance products reported to nine PCs taking calls from the public and medical professionals during an 18-month period were included. The severity of eye effects was rated according to the WHO Poisoning Severity Score. Results: Five hundred and eighty-six cases were included. Product identification by name leading to formula information was successful in 533 cases (91%). Follow-up was successful in 528 exposures. Irrigation was performed in 94% of cases. Duration of symptoms was ≥24 hours in 73 patients (25%). 33 (6%) patients developed moderate eye injury. Healing was reported in all cases. The percentage of moderate cases was highest in the group of drain cleaners (25%), toilet cleaners (18%) and oven cleaners (15%). Products intended for professional use caused relatively more moderate eye injuries than products also intended for consumer use. Conclusion: MAGAM II has shown that PCs are able to identify formulas in sufficiently high quality as needed for product-directed toxicovigilance. The results underline the potential of PC exposure case data for product safety monitoring. The results indicate that irreversible eye damage is very rare after cleaning product exposure.

[Accidental intoxication by outdoor and garden plants : Data from two German poison centres]. / Akzidentelle Vergiftungen mit Gartenpflanzen und Pflanzen in der freien Natur : Daten aus zwei deutschen Giftinformationszentren.

BACKGROUND AND OBJECTIVES: Accidental exposure of children to plants occurs often and results in numerous calls to poison centres. The aim of this study was to identify outdoor plants that led to moderate or severe poisoning after accidental exposure and to identify patterns of paediatric plant exposures. MATERIALS AND METHODS: Human exposure data on accidental exposures provided by two German poison centres were retrospectively evaluated regarding the number and the routes of exposure. Special attention was turned to the kind and severity of symptoms. Based on these data a modified Litovitz factor was calculated. RESULTS: Out of 42,344 confirmed exposures to 227 plant species, 39,346 (93%) were asymptomatic, 2415 (5.7%) experienced minor, 580 (1.3%) moderate and 3 (0.007%) severe symptoms. Twenty-six plant genera were responsible for 70% of all exposures. Only eight of these plants (Arum spec., Laburnum anagyroides, Narcissus spec., Phaseolus vulgaris/coccineus, Prunus laurocerasus, Sambucus spec., Taxus baccata, Thuja spec.) led to at least moderate symptoms. Accidental exposure of children aged 0.5-5 years was mainly by oral ingestion (98%) and involved mostly fruits (60%). CONCLUSIONS: Exposure data collected by poison centres are very useful for hazard identification of outdoor plants. The data give a comprehensive overview of observed symptoms, which offers valuable instruments for use in clinical practice.

Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine flubromazepam with lethal outcome: Pharmacokinetic data.

Novel synthetic opioids and benzodiazepines are an emerging trend on the narcotic drugs market. We present a lethal case of U-47700 and flubromazepam poisoning. A 24-year-old man suffered apnoea after the consumption of the synthetic opioid U-47700 in combination with the benzodiazepine flubromazepam. After reanimation and hospital admission, hypoxic cerebral damage and severe brain oedema were stated. Six days after admission, mechanical ventilation was discontinued, and the patient died. Seven blood serum samples and one urine sample collected during the hospitalisation were analysed by liquid chromatography-tandem mass spectrometry. In the sample collected 42 minutes after admission, the concentrations of U-47700 and flubromazepam were 370 and 830 ng/mL, respectively. Three days later, the concentrations of U-47700 and flubromazepam dropped to 4.2 and 280 ng/mL, respectively. The resulting concentration-time-curves allowed calculating a U-47700 elimination half-life of approximately six hours and confirmed the previously reported flubromazepam elimination half-life of around 100 hours. In the presented case, intoxication by the synthetic opioid U-47700 with a contribution of flubromazepam can be assumed as the cause of death. The concentration-time curves allow an estimation of the clinical course of similar cases. Flubromazepam may lead to prolonged central-nervous depressant effects.

Acute side effects after consumption of the new synthetic cannabinoids AB-CHMINACA and MDMB-CHMICA.

INTRODUCTION: In 2014, the "European Monitoring Centre for Drugs and Drug Addiction" (EMCDDA) reported on 30 novel synthetic cannabinoids (SCs). Among these were indole- and indazole-based valine derivatives with a cyclohexylmethyl side chain (e.g., AB-CHMINACA and MDMB-CHMICA), which represent a new class of SCs. METHODS: A prospective observational study of patients treated in emergency departments (EDs) after the intake of SCs was conducted. Clinical and laboratory data were combined and reported to a poison control centre. Serum and/or urine samples of ED patients were analyzed using LC-MS/MS. RESULTS: Forty four patients (39 male, five female, 12-48 years) were included. AB-CHMINACA (MDMB-CHMICA) was identified in 20 (19) serum samples, and in 21 (25) urine samples, respectively. In 19 of the cases, more than one SC was present. Other psychoactive substances (mainly amfetamines) were identified in seven cases, but in five out of these in urine samples only. Based on the Poison Severity Score, severity of poisoning was minor (4), moderate (31) or severe (9). Most frequently reported neuropsychiatric symptoms were CNS-depression (n = 21, 61%), disorientation (n = 20, 45%), generalized seizures (n = 12, 27%), combativeness (n = 8, 18%) and extreme agitation (n = 7, 16%). Duration of symptoms lasting 24 hours or longer occurred in 15 cases (34%). DISCUSSION: The prevalence of certain neuropsychiatric symptoms was higher in our study than in former reports after the intake of SCs of the aminoalkylindole-type (first generation) SCs. In addition, severe poisoning and duration of symptoms were also higher. CONCLUSIONS: In this study, the valine derivative AB-CHMINACA and the tert-leucine derivative MDMB-CHMICA ("third generation of SCs") seem to be associated with more severe clinical toxicity than was previously reported in patients exposed to earlier generation SCs such as JWH-018. However, this observation needs to be confirmed with a larger cohort of patients with analytically confirmed abuse of third generation SCs. The rapid turnover of SCs on the drug market together with the occurrence of SCs such as AB-CHMINACA and MDMB-CHMICA is alarming, especially because of the unexpectedly high frequency of neuropsychiatric symptoms.

Bad trip due to 25I-NBOMe: a case report from the EU project SPICE II plus.

OBJECTIVE: The potent hallucinogenic drug 25I-NBOMe has recently emerged on the drug market. We present a case with analytically confirmed 25I-NBOMe intoxication from the prospective study "SPICE II Plus". CASE REPORT: Because of a severe headache a 42-year-old man took one sip of a pediatric analgesic syrup, which had been refilled with a self-made solution of 25I-NBOMe in ethanol. Thirty minutes later restlessness occurred. On arrival in the emergency department mydriasis, strong sweating, disorientation, and agitation were noticed. Within short time the patient developed severe agitation, coenesthesia, and complex hallucinations. In blood serum samples obtained at admission revealed the presence of 25I-NBOMe (34 ng/mL), 2C-I (12 ng/mL) and 25I-NBOH (<1 ng/mL) (LC-ESI-MS/MS). The presumed analgesic syrup contained 25I-NBOMe (2800 µg/mL), and besides ethanol no other compounds were detected. After six hours, the symptoms resolved without further complications. CONCLUSIONS: This is a unique case of an analytically confirmed, accidental ingestion of 25I-NBOMe in a drug naïve adult. The finding of 2C-I in the serum sample 50 minutes after intake indicates a fast metabolic breakdown of 25I-NBOMe due to first-pass metabolism.

[Desoxypipradrol - a new (already well known) designer drug]. / Desoxypipradrol - eine neue (alte) Designerdroge.

Novel psychoactive substances (NPS) are easily accessible and the consumption has increased in recent years. New compounds as well as compounds derived from pharmaceutical research or the patent literature are provided, mostly without any declaration. As a consequence, severe adverse reactions may occur after consumption of unknown doses of these drugs, in particular after mixed intake of different psychoactive substances or co-medication. The toxic effects in such cases are not predictable. We report cases of rhabdomyolysis in patients after consumption of desoxipipradrol in combination with other NPS. Particularly in case of synergistic serotonergic effects a distinct stimulation of 5-HT2A-receptors (or 5-HT1A-receptors) should be considered which may lead to serotonergic syndrome.

Metabolites of synthetic cannabinoids in hair--proof of consumption or false friends for interpretation?

The detection of drug metabolites in hair is widely accepted as a proof for systemic uptake of the drug, unless the metabolites can be formed as artefacts. However, regarding synthetic cannabinoids, not much is known about mechanisms of incorporation into hair. For a correct interpretation concerning hair findings of these compounds and their metabolites, it is necessary to identify the different routes of incorporation and to assess their contribution to analytical findings. This study presents the results of the LC-ESI-MS/MS analysis of an authentic hair sample taken from a patient with a known history of heavy consumption of synthetic cannabinoids. In the authentic hair sample, 5F-PB-22 and AB-CHMINACA as well as their main metabolites 5F-PB-22 3-carboxyindole, PB-22 5-OH-pentyl, and AB-CHMINACA valine were detected in all segments, comprising segments grown in a time period where the substances had not been distributed on the 'legal high' market. To enable interpretation of the results regarding the distribution of the detected analytes along the hair shaft, the stability of 5F-PB-22 and AB-CHMINACA in hair matrix and under thermal stress was assessed. The stability tests revealed that the three 'metabolites' are also formed in externally contaminated hair after storage of the samples under different conditions. In addition, 5F-PB-22 3-carboxyindole and AB-CHMINACA valine were identified as degradation products in smoke condensate. Therefore, interpretation of 'metabolite' findings of compounds comprising chemically labile amide/ester bonds or 5-fluoro-pentyl side chains should be carried out with utmost care, taking into account the different mechanisms of formation and incorporation into hair.

Adverse effects after the use of JWH-210 - a case series from the EU Spice II plus project.

Since 2009, more than 140 different synthetic cannabinoids (SC) have been identified in herbal mixtures consumed as recreational drugs. Knowledge of the acute toxicity of each individual compound remains sparse. Here we present a retrospective observational case series of patients presenting to emergency departments with analytically confirmed intake of JWH-210 as the only SC detected in serum samples. Cases were selected from a poison centre database from March 2011 to June 2014. In total, 22 patients were included (aged 12-25 years, median 17.5; 18 males 4 female). JWH-210 was identified in the serum samples in concentrations ranging from 0.18 to 90 ng/mL. Tachycardia, nausea, somnolence, hypokalemia, hypertension, restlessness, and/or agitation were most frequently reported. Diplopia, seizures, syncope, and ECG changes such as T-wave inversion and bradycardia were also noted. Acute adverse effects of JWH-210 typically include central nervous system depression or cerebral seizures, but also signs of sympathomimetic toxicity. Nausea was reported in 80% and typically shows a sudden onset shortly after inhalation, suggesting a central nervous effect possibly mediated by CB1 receptors. Cardiovascular effects are reported in up to 80% of the patients and might not only include alterations in blood pressure and heart rate, but also changes in the electrocardiogram (ECG). JWH-210 as a representative of a strong CB1 receptor agonist confirms previous reports about adverse effects of SC, but shows a distinct quantitative pattern of symptoms, compared to several other SC. Copyright © 2016 John Wiley & Sons, Ltd.

Prolonged hypoglycemia after a suicidal ingestion of repaglinide with unexpected slow plasma elimination.

CONTEXT: Repaglinide is a short-acting insulin secretagogue with high interindividual variability in pharmacokinetics due to genetic polymorphisms. Little is known about repaglinide overdoses, both with respect to pharmacokinetics and appropriate management. Given its short serum half-life of less than 1 h, hypoglycemic effects of repaglinide are expected to cease within a few hours post-ingestion. CASE DETAILS: A 15-year-old girl ingested 10.5 mg of repaglinide in a suicide attempt. Few hours later, she developed a strong food craving, nausea, abdominal pain, and a headache. The lowest recorded serum glucose was 44 mg/dl (2.4 mmol/l) 14 h post-ingestion. Using liquid chromatography-mass spectrometry, we detected repaglinide serum levels of 5.3, 2.6, and 1.0 ng/ml at 14, 20, and 26 h post-ingestion, respectively. DISCUSSION: This case illustrates that in the context of overdose, repaglinide can lead to prolonged hypoglycemia. We therefore recommend glucose monitoring and observation for 24 h in all patients who remain hypoglycemic or show symptoms of hypoglycemia for an unusually long period of time.