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Although paediatric patients frequently suffer from intoxications with atypical antipsychotics, the number of studies in young children, which have assessed the effects of acute exposure to this class of drugs, is very limited. The aim of this study was to achieve a better characterization of the acute toxicity profile in young children of the atypical antipsychotics clozapine, olanzapine, quetiapine, and risperidone. We performed a multicentre retrospective analysis of cases with atypical antipsychotics intoxication in children younger than 6 years, reported by physicians to German, Austrian, and Swiss Poisons Centres for the 9-year period between January 1, 2001 and December 31, 2009. One hundred and six cases (31 clozapine, 29 olanzapine, 12 quetiapine, and 34 risperidone) were available for analysis. Forty-seven of the children showed minor, 28 moderate, and 2 severe symptoms. Twenty-nine cases were asymptomatic. No fatalities were recorded. Symptoms predominantly involved the central nervous and cardiovascular systems. Minor reduction in vigilance (Glasgow Coma Scale score >9) (62 %) was the most frequently reported symptom, followed by miosis (12 %) and mild tachycardia (10 %). Extrapyramidal motor symptoms were observed in one case (1 %) after ingestion of risperidone. In most cases, surveillance and supportive care were sufficient to achieve a good outcome, and all children made full recovery. Conclusions: Paediatric antipsychotic exposure can result in significant poisoning; however, in most cases only minor or moderate symptoms occurred and were followed by complete recovery. Symptomatic patients should be monitored for central nervous system depression and an electrocardiogram should be obtained.

Purpose: Childhood 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. Methods: A 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. Conclusions: Orodispersible 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

Sir,Reports of bites by theraphosid spiders are infrequent [1,2], and the composition and toxicity of most of their venoms are still poorly understood. While most theraphosid spiders can be conside...

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.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.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.

Objective Poison centres offer rapid and comprehensive support for emergency physicians managing poisoned patients. This study investigates institutional, case-specific and poisoning-specific factors which influence the decision of emergency physicians to contact a poison centre. Methods Retrospective, consecutive review of all poisoning-related admissions to the emergency departments (EDs) of a primary care hospital and a university hospital-based tertiary referral centre during 2007. Corresponding poison centre consultations were extracted from the poison centre database. Data were matched and analysed by logistic regression and generalised linear mixed models. Results 545 poisonings were treated in the participating EDs (350 (64.2%) in the tertiary care centre, 195 (35.8%) in the primary care hospital). The poison centre was consulted in 62 (11.4%) cases (38 (61.3%) by the tertiary care centre and 24 (38.7%) by the primary care hospital). Factors significantly associated with poison centre consultation included gender (female vs male) (OR 2.99; 95% CI 1.69 to 5.29; p1 vs 1) (OR 2.84; 95% CI 1.65 to 4.9; p Conclusions We found low rates of poison centre consultation by emergency physicians. It appears that intensive care unit admission and other factors reflecting either complexity or uncertainty of the clinical situation are the strongest predictors for poison centre consultation. Hospital size did not influence referral behaviour.

N-methyl-5-(2 aminopropyl)benzofuran (5-MAPB) is a novel psychoactive benzofuran, created by N-methylation of 5-(2-aminopropyl)benzofuran (5-APB), which shares structural features with methylenedioxymethamphetamine (MDMA). To our knowledge, no case of 5-MAPB-related toxicity has been published in the scientific literature. We report a case of oral 5-MAPB exposure confirmed by liquid chromatography-tandem mass spectrometry in a 24-year-old previously healthy white man. Observed symptoms and signs such as paleness, cold and clammy skin, hypertension, elevated high-sensitive troponin T level, tachycardia, ECG change, diaphoresis, mild hyperthermia, mydriasis, tremor, hyperreflexia, clonus, agitation, disorientation, hallucinations, convulsions, reduced level of consciousness, and creatine kinase level elevation (305 IU/L) were compatible with undesired effects related to 5-APB or MDMA exposure. Signs and symptoms resolved substantially within 14 hours with aggressive symptomatic treatment, including sedation with benzodiazepines, external cooling, analgesia and sedation with fentanyl-propofol, and treatment with urapidil, an α-receptor-blocking agent. 5-MAPB showed first-order elimination kinetics with a half-life of 6.5 hours, comparable to the half-life of MDMA. According to the chemical structure, this case report, and users' Web reports, 5-MAPB appears to have an acute toxicity profile similar to that of 5-APB and MDMA, with marked vasoconstrictor effect.

OBJECTIVES: To describe clinical effects, circumstances of occurrence, management and outcomes of cases of inadvertent administration of medications by an incorrect parenteral route. METHODS: Retrospective single-center consecutive review of parenteral route errors of medications, reported to our center between January 2006 and June 2010. We collected demographic data and information on medications, route and time of administration, severity of symptoms/signs, treatment, and outcome. RESULTS: Seventy-eight cases (68 adults, 10 children) were available for analysis. The following wrong administration routes were recorded: paravenous (51%), intravenous (33%), subcutaneous (8%), and others (8%). Medications most frequently involved were iodinated x-ray contrast media (11%) and iron infusions (9%). Twenty-eight percent of the patients were asymptomatic and 54% showed mild symptoms; moderate and severe symptoms were observed in 9% and 7.7%, respectively, and were mostly due to intravenous administration errors. There was no fatal outcome. In most symptomatic cases local nonspecific treatment was performed. CONCLUSIONS: Enquiries concerning administration of medicines by an incorrect parenteral route were rare, and mainly involved iodinated x-ray contrast media and iron infusions. Most events occurred in adults and showed a benign clinical course. Although the majority of exposures concerned the paravenous route, the occasional severe cases were observed mainly after inadvertent intravenous administration.

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.

Aims: To analyse the clinical features of trimipramine poisoning, identify a minimal toxic dose, and the dose bearing a 50% risk of developing a moderate, severe or fatal outcome. Methods: All acute adult trimipramine monointoxications reported by physicians to the Swiss Toxicological Information Centre between January 1992 and December 2009 were identified. Results: 230 cases (26 confirmed and 204 probable) were analysed; the mean age was 35.7 years, 74% were females. 137 patients showed mild, 54 moderate, and 21 severe symptoms. 3 cases were fatal due to refractory cardiovascular collapse. 93% of the events were attempted or completed suicides. The most common symptoms were central nervous system depression (79.2%), tachycardia (19.1%), and QTc prolongation (13.9%). The severity of poisoning depended significantly on the ingested dose (p Language: en

Sir,The world of antivenom production is described as in crisis, characterized by shortages, producers leaving the market, high prices and unsustainability [1]. To our knowledge, there is only spar...

Clozapine is an atypical antipsychotic drug used in the treatment of resistant schizophrenia. Intoxications with this drug are frequently observed. The aim of the present study was to identify a minimal dose and the dose bearing a 50% risk of developing moderate or severe intoxication symptoms. We also investigated the influence of age, sex, effect of decontamination measures, and pretreatment with clozapine on the severity of poisoning.A retrospective case study of 73 acute clozapine monointoxications reported by physicians to the Swiss Toxicological Information Centre between 1995 and 2007.The most common symptoms were central nervous system depression (63.1%), tachycardia (39.7%), restlessness/agitation (16.4%), confusion/disorientation (15.1%), dysarthria (15.1%), arterial hypertension (10.9%), bradykinesia (9.6%), respiratory depression (9.6%), and QTc prolongation (8.2%). We found a significant correlation between ingested clozapine dose and severity of poisoning. The minimal dose for both moderate and severe intoxications was 0.1 g. The dose for a 50% risk of developing moderate or severe intoxications was 0.9 g in patients older than 50 years and 14.5 g in patients younger than 50 years. Patients older than 50 years had a significantly increased risk for a severe clinical course (odds ratio, 6.41; 95% confidence interval, 1.88-21.90). We found no significant correlation between pretreatment, sex or decontamination, and the severity of the intoxication.Moderate and severe clozapine intoxications can already occur after ingestion of doses in the low therapeutic range, especially in patients older than 50 years. Poisoned patients have to be monitored for central nervous system depression, tachycardia, blood pressure abnormalities, respiratory depression, and QTc prolongation.

Introduction. White or false hellebore (Veratrum album) has a toxicological relevance because of the potential for misidentification of this plant as yellow gentian (Gentiana lutea). Case series. We report a retrospective case series of 11 children (8–12 years) with accidental intake of V. album at a youth camp where they had collected herbs for preparing fresh herb tea. Two children (18%) remained asymptomatic. Nine (82%) developed mild gastrointestinal symptoms, six (55%) presented neurological symptoms, and three (27%) showed bradycardia. All children recovered completely within 10 h of ingestion. The plant was identified at the emergency department; however, detection of veratridine and cevadine by means of high-performance liquid chromatography–Mass spectrometry from the blood of the child with the most severe symptoms was negative (limit 0.01 ng/mL). Discussion. Veratrum species contain more than 200 different alkaloids, which are the principal toxins and are responsible for most clinical symptoms. There are likely multiple mechanisms of toxicity and some of them are only partially understood. The opening of voltage-gated sodium channels is probably one of the most relevant pathophysiological mechanisms. Conclusions. Veratrum album intoxication in children demonstrated the same clinical course as observed in adults. Accidental ingestion of a low dose of the plant had a favorable outcome with supportive care.

Bei akuten Vergiftungen ist die Erhaltung oder Wiederherstellung der Vitalfunktionen die erste und wichtigste Maßnahme. Jede weitere spezifische Therapie und die Prognose im akuten Notfall ist danach abhängig von der Noxenidentifikation und der Ermittlung der substanzspezifischen Toxizität. Obwohl die Evidenz lückenhaft ist, gilt heute noch immer das Konzept, dass eine Reduktion der Giftabsorption und die Verkürzung des Vergiftungsverlaufes durch eine beschleunigte Elimination der Noxen günstig sind. Diese Maßnahmen sind jedoch in den Kontext der Prognose und des zeitlichen Verlaufes der Intoxikation zu setzen. Methoden zur Reduktion der Giftabsorption sind (in absteigender Bedeutung) die einmalige orale Verabreichung von Aktivkohle, die Ganzdarmspülung und die Magenspülung; das induzierte Erbrechen mittels Ipecac wird nicht mehr praktiziert. Methoden zur beschleunigten Elimination sind die wiederholte Verabreichung von Aktivkohle, die Alkalinisierung des Urins und extrakorporelle Eliminationsverfahren (Hämodialyse, Hämoperfusion). Eine beschleunigte Elimination macht nur Sinn bei Noxen mit langer Verweildauer im Körper. Die Gabe von Antidoten ist immer spezifisch auf bestimmte Noxen ausgerichtet und kommt nur bei einer begrenzten Anzahl Giften in Frage. Die Beschaffung spezifischer Antidote wird erleichtert durch eine übersichtlich und einheitlich organisierte Versorgung dieser oft schwer erhältlichen und nicht zugelassenen Präparate.

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.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 2013.75 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.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.

Methoxetamine, the N -ethyl derivative of ketamine, is a novel recreational drug that is not at present subject to restrictive regulations in most countries. To our knowledge, no case of methoxetamine abuse has been published to date in the scientific literature, and the only sources of information are illegal drug users' Web discussion forums. We report the first case of analytically confirmed intravenous methoxetamine abuse in a 19-year-old man. Observed signs and symptoms such as tachycardia, hypertension, confusion, agitation, stupor, ataxia, mydriasis, and nystagmus were consistent with ketamine-induced adverse effects and resolved with symptomatic treatment. According to this case report, user Web reports, and the chemical structure, methoxetamine produces ketamine-like effects. Complete recovery can be expected with supportive care.

Maleic acid (MA) is a common component of descaling products and is widely used in daily life. Accidental ingestion in relevant amounts does not play a major role in human beings; however, it seems to be highly toxic for dogs. It has been commonly used experimentally to induce Fanconi syndrome in dogs or small rodents. Two dogs were presented for acute kidney injury (AKI) after accidental ingestion of a descaling agent containing MA at an estimated amount of 70 mg/kg each. The third dog involved was euthanased by the referring veterinarian, and postmortem pathological analysis revealed severe acute tubular necrosis consistent with toxic nephropathy. The other dogs received symptomatic therapy for AKI including treatment with haemodialysis and showed complete normalisation of serum creatinine at a follow-up after five months. Renal damage can be very severe, but seems to be at least partially reversible and an attempt to treatment is warranted.

Seizures during intoxications with pharmaceuticals are a well-known complication. However, only a few studies report on drugs commonly involved and calculate the seizure potential of these drugs.To identify the pharmaceutical drugs most commonly associated with seizures after single-agent overdose, the seizure potential of these pharmaceuticals, the age-distribution of the cases with seizures and the ingested doses.A retrospective review of acute single-agent exposures to pharmaceuticals reported to the Swiss Toxicological Information Centre (STIC) between January 1997 and December 2010 was conducted. Exposures which resulted in at least one seizure were identified. The seizure potential of a pharmaceutical was calculated by dividing the number of cases with seizures by the number of all cases recorded with that pharmaceutical. Data were analyzed using descriptive statistics.We identified 15,441 single-agent exposures. Seizures occurred in 313 cases. The most prevalent pharmaceuticals were mefenamic acid (51 of the 313 cases), citalopram (34), trimipramine (27), venlafaxine (23), tramadol (15), diphenhydramine (14), amitriptyline (12), carbamazepine (11), maprotiline (10), and quetiapine (10). Antidepressants were involved in 136 cases. Drugs with a high seizure potential were bupropion (31.6%, seizures in 6 of 19 cases, 95% CI: 15.4-50.0%), maprotiline (17.5%, 10/57, 95% CI: 9.8-29.4%), venlafaxine (13.7%, 23/168, 95% CI: 9.3-19.7%), citalopram (13.1%, 34/259, 95% CI: 9.5-17.8%), and mefenamic acid (10.9%, 51/470, 95% CI: 8.4-14.0%). In adolescents (15-19y/o) 23.9% (95% CI: 17.6-31.7%) of the cases involving mefenamic acid resulted in seizures, but only 5.7% (95% CI: 3.3-9.7%) in adults (≥ 20y/o; p0.001). For citalopram these numbers were 22.0% (95% CI: 12.8-35.2%) and 10.9% (95% CI: 7.1-16.4%), respectively (p = 0.058). The probability of seizures with mefenamic acid, citalopram, trimipramine, and venlafaxine increased as the ingested dose increased.Antidepressants were frequently associated with seizures in overdose, but other pharmaceuticals, as mefenamic acid, were also associated with seizures in a considerable number of cases. Bupropion was the pharmaceutical with the highest seizure potential even if overdose with bupropion was uncommon in our sample. Adolescents might be more susceptible to seizures after mefenamic acid overdose than adults. "Part of this work is already published as a conference abstract for the XXXIV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 27-30 May 2014, Brussels, Belgium." Abstract 8, Clin Toxicol 2014;52(4):298.

Literature regarding acute human toxicity of thiopurines is limited to a handful of case reports. Our objectives were to describe all cases of overdose with thiopurines reported to the Swiss Toxicological Information Centre between 1995-2013. A retrospective analysis was performed to determine circumstances, magnitude, management and outcome of overdose with these substances. A total of 40 cases (14 paediatric) were reported (azathioprine, n = 35; 6-mercaptopurine, n = 5). Of these, 25 were with suicidal intent, 12 were accidental and 3 were iatrogenic errors. The magnitude of overdose ranged from 1.5 to 43 (median 8) times the usual dose in adults. Twelve cases (30%) had attributable symptoms. The majority of these were minor and included gastrointestinal complaints and liver function test and blood count abnormalities. Symptoms were experienced by patients who took at least 1.5-times their usual daily thiopurine dose. Overdoses over two or more consecutive days, even if of modest size, were less well tolerated. One case of azathioprine and allopurinol co-ingestion over consecutive days led to agranulocytosis. Decontamination measures were undertaken in 11 cases (10 activated charcoal, 1 gastric lavage) and these developed fewer symptoms than untreated patients. This study shows that acute overdoses with thiopurines have a favourable outcome in the majority of cases and provides preliminary evidence that gastrointestinal decontamination with activated charcoal may reduce symptom development after overdose of these substances if patients present to medical services soon after ingestion.

Literature regarding acute human toxicity of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) is limited.Our objectives were to describe all cases of overdose with MMF or EC-MPS reported to the Swiss Toxicological Information Centre (STIC) or in the literature between 1995 and 2013. Therefore, we performed an observational case-series and systematic literature search to determine circumstances, magnitude, management and outcome of overdose with MMF or EC-MPS.Of 152,762 reports to STIC, 15 (7 pediatric) involved overdose with MMF (n = 13) or EC-MPS (n = 2). Three cases from other centers were identified from a systematic literature search. The magnitude of overdose ranged from 1.2 to 16.7 (median 2.9) times usual dose. Six (33%) MMF overdoses had attributable symptoms, which included abdominal pain, vomiting, headache and dizziness. The majority of findings were minor, although a 9-fold MMF overdose caused hypotension 8 h after ingestion and a 12.5-fold overdose caused leukopenia after 5 days. Symptoms did not occur in patients who took 2.5 times or less of their usual MMF dose. Gastrointestinal decontamination measures with activated charcoal were undertaken in one-third of cases.Acute MMF and EC-MPS overdoses had a favorable outcome in all cases reported to STIC and in the literature.

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 diffi cult 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 infl uence acute patient management. Complete endoscopic pharmacobezoar removal may be a promising approach in selected cases, but further studies are needed to defi ne its role.

Transplant recipients and other patients requiring immunosuppression with calcineurin inhibitors or their household contacts may be exposed to overdose. This study investigated the circumstances, pharmacokinetics and outcomes of overdose with cyclosporine and tacrolimus reported to the Swiss Toxicological Information Centre between 1995 and 2011. Of 145,396 reports by healthcare professionals, 28 (0.02%) concerned enteral or parenteral overdose with these calcineurin inhibitors. Thirteen (46%) were iatrogenic errors, 12 (43%) were with suicidal intent and 3 (11%) were accidental. Iatrogenic overdoses usually involved noncapsule drug formulations. Acute enteral overdoses caused symptoms in a dose-dependent fashion but were generally well tolerated; the mean multiple of patient's usual dose was 20.8 ± 28.8 for symptomatic versus 4.4 ± 3.4 for asymptomatic cases (p = 0.037). The most common symptoms were nausea, headache, somnolence, confusion, hypertension and renal impairment. In contrast, acute intravenous overdoses were often poorly tolerated and resulted in one fatality due to cerebral edema after a cyclosporine overdose. Enteral decontamination measures were performed in six cases involving oral ingestion and appeared to reduce drug absorption, as shown by pharmacokinetic calculations. In the one case where it was used, pharmacoenhancement appeared to accelerate tacrolimus clearance after intravenous overdose.

To analyze the clinical features of trimipramine poisoning, identify a minimal toxic dose, and the dose bearing a 50% risk of developing a moderate, severe or fatal outcome.All acute adult trimipramine monointoxications reported by physicians to the Swiss Toxicological Information Centre between January 1992 and December 2009 were identified.Two hundred and thirty cases (26 confirmed and 204 probable) were analyzed, the mean age was 35.7 years and 74% were females. One hundred and thirty-seven patients showed mild, 54 moderate and 21 severe symptoms. Three cases were fatal due to refractory cardiovascular collapse. Ninety-three per cent of the events were attempted or completed suicides. The most common symptoms were central nervous system depression (79.2%), tachycardia (19.1%) and QT(c) prolongation (13.9%). The severity of poisoning depended significantly on the ingested dose (P0.001). The minimal dose for moderate symptoms was 250 mg (median dose 1.2 g) and 850 mg for severe symptoms (median dose 2.7 g). The dose for a 50% risk of developing a moderate, severe or fatal outcome was 5.11 g. In 38 patients early gastrointestinal decontamination was performed. Overall, these patients ingested higher trimipramine doses than the late- or not-decontaminated patients (P = 0.113). The median doses were also higher in the decontaminated group within each severity category except in the fatal cases.We demonstrated that moderate trimipramine poisoning can already occur after ingestion of doses in the high therapeutic range. Poisoned patients have to be monitored for central nervous system depression, dysrhythmias and QT(c) prolongation. Early decontamination might be beneficial.

Background Picking wild mushrooms is a popular pastime in Switzerland. Correct identification of the species is difficult for laypersons. Ingestion of toxic mushrooms may result in serious toxicity, including death. The aim of the study is to analyze and describe the circumstances of exposure to mushrooms, and to define the clinical relevance of mushroom poisoning for humans in Central Europe. Materials and methods We performed a retrospective case study and analyzed all inquiries concerning human exposures to mushrooms (n = 5638, 1.2% of all inquiries) which were reported to the Swiss Toxicological Information Centre between January 1995 and December 2009. Results The most frequent reason for contacting the poison center in cases of adult exposure was toxicity resulting from edible species. Pediatric exposure predominantly occurred from mushrooms found around the home. Severe symptoms have not only been observed after ingestion of non-amatoxin-containing toxic mushrooms, i.e. Boletus sp. and Cortinarius sp., but also after meals of edible species. The mortality of confirmed amatoxin poisonings was high (5/32) compared to other reports. Conclusions Inquiries regarding mushroom poisoning were a relatively infrequent reason for contacting the poison center. Nevertheless, accidental ingestion of toxic mushrooms can be responsible for severe or fatal poisonings. Although pediatric exposure to mushrooms found around the home has not led to serious toxicity in this study, prevention of exposure is warranted. Inspection of wild mushrooms by a certified mushroom expert or a mycologist seems to be a safe procedure which should be recommended.

Introduction. Human contact with potentially toxic plants, which may occur through abuse or by accident or attempted suicide, is frequent and sometimes results in clinically significant toxicity. Objective. The aim of the present study was to identify which plants may lead to severe poisoning, and to define the clinical relevance of plant toxicity for humans in Switzerland. Methods. We analyzed 42 193 cases of human plant exposure and 255 acute moderate, severe, and lethal poisonings, which were reported to the Swiss Toxicological Information Centre between January 1995 and December 2009. Results. Plant contact was rarely responsible for serious poisonings. Lethal intoxications were extremely rare and were caused by plants with cardiotoxic (Taxus baccata) or mitosis-inhibiting (Colchicum autumnale) properties. Conclusions. Most often, plant contact was accidental and patients remained asymptomatic or developed mild symptoms, which fully resolved within a short time.

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.

Exposure to household products is very common, but in industrialized countries severe or fatal poisoning with household products is rare today, due to the legal restriction of sale of hazardous household products. The big challenge for physicians, pharmacologists and toxicologists is to identify the few exceptional life-threatening situations where immediate intervention is needed. Among thousands of innocuous products available for the household only very few are hazardous. Substances found in these products include detergents, corrosives, alcohols, hydrocarbons, and some of the essential oils. The ingestion of batteries and magnets and the exposure to cyanoacrylates (super glue) can cause complications in exceptional situations. Among the most dangerous substances still present in household products are ethylene glycol and methanol. These substances cause major toxicity only through their metabolites. Therefore, initial symptoms may be only mild or absent. Treatment even in asymptomatic patients has to be initiated as early as possible to inhibit production of toxic metabolites. For all substances not only the compound itself but also the route of exposure is relevant for toxicity. Oral ingestion and inhalation generally lead to most pronounced symptoms, while dermal exposure is often limited to mild irritation. However, certain circumstances need special attention. Exposure to hydrofluoric acid may lead to fatal hypocalcemia, depending on the concentration, duration of exposure, and area of the affected skin. Accidents with hydrocarbon pressure injectors and spray guns are very serious events, which may lead to amputation of affected limbs. Button batteries normally pass the gastrointestinal tract without problems even in toddlers; in rare cases, however, they get lodged in the esophagus with the risk of localized tissue damage and esophageal perforation.

The use of complementary and alternative medicine (CAM) in Switzerland is rather high, and therefore, the occurrence of accidental intakes of CAM remedies by children and associated intoxications is to be expected. In the present study, the inquiries to the Swiss Toxicological Information Centre that took place from 1998 until 2007 and concerned accidental, unintended intakes of CAM remedies by children were analysed. Inquiries for information were performed by concerned care-givers, physicians, pharmacists and others in case of acute accidental intake of CAM remedies. Feedbacks from physicians about paediatric patients with acute intoxication possibly associated with the accidental ingestion of CAM remedies were as well considered. During the study period, 3,158 accidental intakes of CAM remedies (1,015 of herbal and 2,143 of homeopathic remedies) were reported, corresponding to 8.6% of all reported accidental intakes of pharmaceutical products by children. No significant increase of the yearly number of accidental intakes of CAM remedies was detected during the study period. There was no accidental intake of CAM remedies leading to severe signs or symptoms. Concerning the herbal remedies, three intoxications of moderate and 28 of minor severity were reported. Nine children with intoxication from homeopathic remedies were reported, with minor symptoms only. All other accidental intakes of CAM remedies did not lead to intoxications and evolved without manifestations. The data show that accidental, unintended intake of CAM remedies happened in children, but developed mostly harmlessly. Comparing herbal with homeopathic remedies, accidental intakes with homeopathic remedies were more common, but intoxications associated with manifestations were observed more frequently with herbal remedies.

Exposure to household products is very common, but in industrialized countries severe or fatal poisoning with household products is rare today, due to the legal restriction of sale of hazardous household products. The big challenge for physicians, pharmacologists and toxicologists is to identify the few exceptional life-threatening situations where immediate intervention is needed. Among thousands of innocuous products available for the household only very few are hazardous. Substances found in these products include detergents, corrosives, alcohols, hydrocarbons, and some of the essential oils. The ingestion of batteries and magnets and the exposure to cyanoacrylates (super glue) can cause complications in exceptional situations. Among the most dangerous substances still present in household products are ethylene glycol and methanol. These substances cause major toxicity only through their metabolites. Therefore, initial symptoms may be only mild or absent. Treatment even in asymptomatic patients has to be initiated as early as possible to inhibit production of toxic metabolites. For all substances not only the compound itself but also the route of exposure is relevant for toxicity. Oral ingestion and inhalation generally lead to most pronounced symptoms, while dermal exposure is often limited to mild irritation. However, certain circumstances need special attention. Exposure to hydrofluoric acid may lead to fatal hypocalcemia, depending on the concentration, duration of exposure, and area of the affected skin. Accidents with hydrocarbon pressure injectors and spray guns are very serious events, which may lead to amputation of affected limbs. Button batteries normally pass the gastrointestinal tract without problems even in toddlers; in rare cases, however, they get lodged in the esophagus with the risk of localized tissue damage and esophageal perforation.

Seizures are a recognized complication of acute overdose with the racemic (1:1 ratio of R- and S-enantiomers) selective serotonin reuptake inhibitor antidepressant citalopram.We tested the hypothesis that escitalopram (the therapeutically active S-enantiomer of citalopram) causes fewer seizures in overdose than citalopram at comparable doses of the S-enantiomer.Multicenter retrospective review of cases with citalopram and escitalopram overdose reported to German, Austrian, and Swiss Poisons Centers between 1997 and 2006.316 citalopram and 63 escitalopram cases were analyzed. Somnolence, nausea, vomiting, tachycardia, QT prolongation, and tremor occurred with similar frequency in both groups. There was a striking difference in the frequency of single and multiple seizures: 43 cases (13.5%) in the citalopram group and 1 case (1.6%) with a single seizure in the escitalopram group (p=0.0065).At comparable ingested doses of the S-enantiomer, the symptom profile for citalopram and escitalopram intoxications is similar except for seizures that occur more frequently in citalopram than in escitalopram poisoning.

In acute poisoning the maintenance or reconstitution of vital functions is the first and most critical action. All subsequent therapies and the prognosis depend on the identification of the causative agent and on information about substance-specific toxicity. Despite incomplete evidence the concept of harm reduction by decreased absorption of the toxicants and by shortening the course of illness is consistent with toxicokinetic-dynamic principles and is therefore still used by clinical toxicologists. All these treatment options have to be seen within the context of the prognosis and the time course of an individual case of poisoning. Treatment options of gastrointestinal decontamination are (in decreasing order of importance) single-dose activated charcoal, whole bowel irritation, and gastric lavage. Induced emesis by ipecac syrup is not practiced anymore. Enhanced elimination techniques are multiple-dose activated charcoal, urine alkalinization, and extracorporeal techniques such as hemodialysis and hemoperfusion. Enhanced elimination is only beneficial in toxicants with long half-life. Antidotes are directed against specific agents and therefore may be used only in a limited number of cases. The procurement of specific antidotes, often hardly available and not approved, is facilitated if the supply is organized in a transparent and standardized manner.

Poisoning in children with household products are common. The majority of these accidents are of low severity and resolve without complications. The big challenge for physicians is to reveal the few situations that could be life-threatening where immediate interventions is needed. The most commonly encountered substances in household products are detergents, alcohols (ethanol, isopropanol), hydrocarbons, as well as irritants (bleach, limescale removers). Rare but dangerous chemicals are for example "toxic alcohols" (methanol, ethylene glycol) and strong acids and alkalis. Also in case of ingestion of button batteries or magnets severe cases are uncommon but each case must be judged carefully to identify the cases where complications could appear.

Kindervergiftungen sind häufig, verlaufen aber nur selten schwer oder gar tödlich. Die Herausforderung für Ärzte/Ärztinnen ist es, bei der Vielzahl der Kinderintoxikationen die wenigen lebensbedrohlichen rasch zu erfassen und den Kindern unverzüglich die entsprechende Therapie zukommen zu lassen. Unter den Haushaltprodukten sind Detergentien, Alkohole (Ethanol, Isopropylalkohol), Kohlenwasserstoffe, sowie leicht ätzende Substanzen weit verbreitet. Seltene, aber gefährliche Inhaltstoffe können “toxische Alkohole“ (Ethylenglykol, Methanol), sowie starke Säuren und Laugen sein. Auch bei Vergiftungsunfällen mit Knopfbatterien und Magneten gilt es, die vielen unproblematischen Fälle von den seltenen mit Gefährdungspotenzial abzugrenzen.

An 11-month-old Swiss boy was brought to his paedi-atrician. He had been in good health and had developednormally until then, but his parents mentioned that overthe previous 2 weeks, the child no longer laughed orplayed, was becoming more and more restless, and sleptonly 1 to 2 h a night. He was no longer able to crawl andto stand up, and he had lost weight. Clinical examina-tion revealed swollen hands and feet with skin desqua-mation, axial hypotonia and brisk reflexes. The childsweated profusely, refused to crawl or stand, showedstereotypic movements of the hands (kneading) andrepeatedly bit objects or his own hands.Upon admission to the regional hospital, blood cellcount, electrolytes, blood gas analysis, thyroid hormonesand cerebrospinal fluid were normal. Liver and kidneyparameters were normal, but plasma LDH and CK wereincreased to 724 U/l (normal

e92 Volume 35 Number 8S Results: Of 152,762 reports to STIC, 55 involved OD with thiopurines (n = 39), MMF (n = 14), or SIR (n = 2). Of these, 32 were with suicidal intent, 19 accidental, and 4 iatrogenic errors. Eleven (31%) thiopurine, 4 (31%) MMF, and 1 (50%) SIR ODs had attributable symptoms. The majority of symptoms were minor, although 1 case of sustained thiopurine OD caused agranulocytosis, 1 case of a 9-fold MMF OD caused biphasic hypotension (possibly reflecting enterohepatic circulation), and 1 case of SIR OD in a child caused tremor, raised liver enzymes, and gastroenteritis. Symptoms were observed in patients taking 1.5 and 2.4 times or greater than their usual dose (or the maximum licensed dose in patients not usually taking medication) for thiopurines and MMF, respectively. Decontamination measures were undertaken in 10 thiopurine ODs (9 activated charcoal, 1 gastric lavage). The OR for the development of symptoms after gastrointestinal decontamination in these ODs was 0.14 (95% CI, 0.01–1.5) compared with cases without decontamination. Charcoal was given primarily to children. The mean age of cases managed with charcoal was 8 (10) versus 30 (15) years for cases managed without (P < 0.0001). Conclusion: Acute toxicity with thiopurines appears to only be significant with a prolonged exposure to high drug concentrations. MMF ODs seem to be well tolerated. Physicians should be aware, however, that patients who develop hypotension shortly after oral OD may relapse some hours later. It seems that SIR is highly toxic in young children even at modest degrees of overdose. Gastrointestinal decontamination with activated charcoal appeared to reduce symptom development after overdose of thiopurines. Thiopurine, MMF, and SIR OD patterns, outcomes, and management require continued study and transplant and poisons centers should be encouraged to actively seek follow-up data on the cases with which they are involved. Acknowledgement: C.G and A.C contributed equally. Disclosure of Interest: None declared.