Katharina E. Hofer

Acute toxicity associated with the recreational use of the novel dissociative psychoactive substance methoxphenidine

Abstract Introduction. Methoxphenidine is a novel dissociative designer drug of the diarylethylamine class which shares structural features with phencyclidine (PCP), and is not at present subject to restrictive regulations. There is very limited information about the acute toxicity profile of methoxphenidine and the only sources are anonymous internet sites and a 1989 patent of the Searle Company. We report a case of analytically confirmed oral methoxphenidine toxicity. Case details. A 53-year-old man was found on the street in a somnolent and confusional state. Observed signs and symptoms such as tachycardia (112 bpm), hypertension (220/125 mmHg), echolalia, confusion, agitation, opisthotonus, nystagmus and amnesia were consistent with phencyclidine-induced adverse effects. Temperature (99.1°F (37.3°C)) and peripheral oxygen saturation while breathing room air (99%) were normal. Laboratory analysis revealed an increase of creatine kinase (max 865 U/L), alanine aminotransferase (72 U/L) and gamma-glutamyl transpeptidase (123 U/L). Methoxphenidine was identified by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction in plasma and urine samples collected on admission. The clinical course was favourable and signs and symptoms resolved with symptomatic treatment. Conclusion. Based on this case report and users’ web reports, and compatible with the chemical structure, methoxphenidine produces effects similar to those of the arylcyclohexylamines, as PCP.

Massive human rivaroxaban overdose

Thomas Lehmann; Katharina E. Hofer; Michael Baumann; Karin Hasler; Alessandro Ceschi; Hugo Kupferschmidt; Gabriele Rohde; Wolfgang Korte Center of Laboratory Medicine and Hemostasis and Hemophilia Center St. Gallen, St. Gallen, Switzerland; Swiss Toxicological Information Centre, Associated Institute of the Zurich University, Zurich, Switzerland; Department of Emergency, Kantonsspital St. Gallen, Switzerland; Bioanalytik, Bayer Pharma AG, Leverkusen, Germany

Gastric pharmacobezoars in quetiapine extended-release overdose: A case series

Abstract Objective. Although extended-release (XR) formulations are recognized to bear some risk of pharmacobezoar formation in overdose, there are no previously documented reports of this phenomenon with quetiapine. We describe nine cases of pharmacobezoar formation in acute quetiapine XR overdose. Methods. Observational case series of all patients who underwent gastroscopy after quetiapine XR overdose, which were reported by physicians to the Swiss Toxicological Information Centre between January 2010 and December 2012, with detailed analysis of cases with documented pharmacobezoar. Results. Gastric pharmacobezoars were detected in 9 out of 19 gastroscopic evaluations performed during the study period. All these patients ingested a large dose of quetiapine XR (10–61 tablets; 6–24.4 g quetiapine). All patients but one also coingested at least one other substance, and in three cases another XR drug formulation. Gastroscopic pharmacobezoar removal was achieved without complications in all patients, but was difficult due to the particular “gelatinous-sticky-pasty” consistency of the concretion. The subsequent clinical course was favorable. Conclusions. The possibility of pharmacobezoar formation following a large quetiapine XR overdose should be considered, as this may influence acute patient management. Complete endoscopic pharmacobezoar removal may be a promising approach in selected cases, but further studies are needed to define its role.

Paracetamol orodispersible tablets: a risk for severe poisoning in children?

PurposeChildhood paracetamol (acetaminophen) ingestion with subsequent risk of hepatotoxicity is a major medical problem. The aim of this study was to investigate the risk of high-dose ingestion of orodispersible, fast-disintegrating paracetamol tablets in children.MethodsA retrospective single-center case study of all accidental selfadministrations of solid or orodispersible 500-mg paracetamol tablets occurring in children ≤ 6 years, reported to the Swiss Toxicological Information Centre between June 2003 and August 2009.Results We found 187 cases with ingestion of solid 500-mg paracetamol tablets and 16 cases with ingestion of orodispersible 500-mg tablets. The mean ingested dose in the orodispersible-tablet group was 59% higher than in the solid-tablet group (p = 0.085). Administration of activated charcoal and/or N-acetylcysteine because of ingestion of a potentially hepatotoxic paracetamol dose ( ≥ 150 mg/kg body weight) was recommended in 32 patients (17.1%) in the solid-tablet group and in five (31%) in the orodispersible-tablet group.ConclusionsOrodispersible paracetamol formulations may represent an important risk factor for severe paracetamol poisoning in children. Over-the-counter availability may contribute to increasing the use of this galenic formulation and eventually the number of poisonings in children.

Moderate toxic effects following acute zonisamide overdose

Zonisamide is an antiepileptic drug that acts on voltage-sensitive sodium and calcium channels, with a modulatory effect on GABA-mediated neuronal inhibition and an inhibitory effect on carbonic anhydrase. It is used mainly for the treatment of partial seizures, and is generally well tolerated at therapeutic doses. The most common reported adverse effects are somnolence, anorexia, dizziness, and headache. There are limited data on zonisamide overdose in the literature, and no case of zonisamide mono-intoxication has been published to date. We describe the first case of zonisamide mono-intoxication in a 25-year-old woman who ingested 12.6 g of this substance with suicidal intent. Despite a plasma zonisamide concentration of 182 mg/L on admission, the patient exhibited a benign clinical course with vomiting and central nervous system depression, requiring brief intubation. Somnolence persisted for 50 hours, and normal-anion-gap metabolic acidosis and polyuria for several days. Complete recovery may be expected with supportive care, even after ingestion of large zonisamide overdoses.

Acute toxicity profile of tolperisone in overdose: Observational poison centre-based study.

Abstract Introduction. Tolperisone is a centrally acting muscle relaxant that acts by blocking voltage-gated sodium and calcium channels. There is a lack of information on the clinical features of tolperisone poisoning in the literature. The aim of this study was to investigate the demographics, circumstances and clinical features of acute overdoses with tolperisone. Methods. An observational study of acute overdoses of tolperisone, either alone or in combination with one non-steroidal anti-inflammatory drug in a dose range not expected to cause central nervous system effects, in adults and children (< 16 years), reported to our poison centre between 1995 and 2013. Results. 75 cases were included: 51 females (68%) and 24 males (32%); 45 adults (60%) and 30 children (40%). Six adults (13%) and 17 children (57%) remained asymptomatic, and mild symptoms were seen in 25 adults (56%) and 10 children (33%). There were nine adults (20%) with moderate symptoms, and five adults (11%) and three children (10%) with severe symptoms. Signs and symptoms predominantly involved the central nervous system: somnolence, coma, seizures and agitation. Furthermore, some severe cardiovascular and respiratory signs and symptoms were reported. The minimal dose for seizures and severe symptoms in adults was 1500 mg. In 11 cases the latency between the ingestion and the onset of symptoms was known and was reported to be 0.5–1.5 h. Conclusions. The acute overdose of tolperisone may be life-threatening, with a rapid onset of severe neurological, respiratory and cardiovascular symptoms. With alternative muscle relaxants available, indications for tolperisone should be rigorously evaluated.

Acute neurotoxicity associated with recreational use of methylmethaqualone confirmed by liquid chromatography tandem mass spectrometry

Methylmethaqualone is a sedative designer drug created by adding a methyl group to the 3-phenyl ring of methaqualone, and is at present not subject to restrictive regulation in many countries. To our knowledge, no case of methylmethaqualone abuse has been published to date in the scientific literature, and the only sources of information are users’ reports on Web discussion forums and data from preclinical animal studies. We report a case of oral methylmethaqualone abuse confirmed by liquid chromatography tandem mass spectrometry in a 24-year-old previously healthy Caucasian male. Observed symptoms and signs such as central nervous system depression alternating with excitation, psychomotor agitation, muscle hyperactivity, and tachycardia were compatible with methaqualone-induced adverse effects. Except for the mild tachycardia (115 beats/min), other vital signs were normal: blood pressure 134/89 mmHg, body temperature 36.2°C (97.16°F), and peripheral oxygen saturation 99% while breathing room air. The ECG showed no prolongation of the QT interval and the QRS duration was normal. Laboratory analysis revealed a slight increase in creatine kinase (368 U/L) and alanine aminotransferase (90 U/L) serum concentrations. Blood alcohol concentration was 0.32 g/L. Methylmethaqualone was identified in a serum sample collected on admission which was analyzed by a liquid chromatography tandem mass spectrometry toxicological screening method using turbulent flow online extraction. After a few days the patient ingested the same amount of substance with identical symptoms. Based on the chemical structure and animal data, and according to this case report and users’ Web reports, methylmethaqualone appears to have a similar acute toxicity profile to methaqualone, with marked psychomotor stimulation. Symptoms of acute toxicity can be expected to resolve with supportive care.