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BACKGROUND: Atomoxetine uses a novel nonstimulant approach to the treatment of attention deficit hyperactivity disorder. There is limited information on overdose of atomoxetine in children or adults. OBJECTIVE: To provide information on atomoxetine in overdose. METHODS: Case series were conducted at 3 regional poison centers for atomoxetine ingestion in children (age ⩽17 y). Exclusion criteria were polypharmacy or lack of follow-up. RESULTS: Forty patients were included (25 boys; 63%) in the study. The mean ± SD age was 6.1 ± 4.9 years (range 9 mo–17 y). Twenty-five patients were managed at home, 14 in hospital emergency departments (3 children were admitted), and 1 patient was managed in a physician's office. Symptoms reported were tachycardia, drowsiness, nausea, hypertension, and vomiting. A seizure was reported in one child who had recently started atomoxetine therapy. No arrhythmias beyond sinus tachycardia were reported. Mean maximum heart rate in patients with tachycardia was 131 ± 14 beats/min. The mean dose ingested, categorized by medical outcome, was: no effect (n = 22), 40 ± 32 mg; minor effect (n = 14), 167 ± 221 mg; and moderate effect (n = 4), 249 ± 326 mg. There were no major outcomes or fatalities. The lowest dose ingested that resulted in hypertension was 480 mg, in a 14-year-old girl (BP 136/95 mm Hg). CONCLUSIONS: In this case series, clinically significant cardiovascular effects requiring direct intervention did not occur. Activated charcoal and/or observation appear to be sufficient for accidental ingestion. Further investigation may be needed to indicate whether seizures occur from atomoxetine ingestion.

Valproic acid exposures reported to poison centers have increased more than 4-fold over the last 5 years. There are no large case series published on valproic acid ingestion.A prospective multicenter case series of all patients reporting an ingestion of valproic acid. Data collected included: age, gender, dose ingested, concomitant medications, symptoms and vital signs, laboratory values, length of hospital stay, and medical outcome. Entrance into the study required a serum valproic acid concentration above the therapeutic threshold of 100 microg/mL. Statistical analysis was by Fisher's exact test.A total of 335 patients were reported to participating centers of which 186 (55%) had serum valproic acid concentrations greater than 100 microg/mL. Of the 186 cases, 53 were multiple drug exposures leaving 133 cases of sole valproic acid ingestion for evaluation. Age ranged from 2 to 66 years with a mean of 30.1 years +/- 12. Peak serum valproic acid concentrations ranged from 110 microg/mL to 1840 microg/mL with a mean of 378.3 microg/mL +/- 310.2 microg/mL. Time from postingestion to the peak measured valproic acid concentration ranged from 1 to 18 hours, with a mean of 7.4 hours +/- 3.9. Symptoms included lethargy (n = 94), coma (n = 19), tachycardia (n = 24), aspiration (n = 8), metabolic acidosis (n = 8), and hypotension (n = 4). A peak concentration of450 microg/mL was more likely to be associated with a moderate or major adverse outcome (p0.005). A peak concentration850 microg/mL was more likely to be associated with coma (p0.005) and acidosis (p0.005). Eleven patients experienced transient thrombocytopenia (platelets150,000) and all had peak valproic acid concentrations450 microg/mL. Four patients experienced transient leukopenia (WBC3,500). The mean hospital stay for all patients was 42 +/- 33.1 hours. A hospital stay48 hours was more likely to be associated with a peak valproic acid concentration450 microg/mL (p0.05). There were 2 fatalities.In this case series, patients with peak valproic acid concentrations above 450 microg/mL were more likely to develop significant clinical effects and have longer hospital stays. A peak valproic acid concentration above 850 microg/mL was more likely to be associated with coma, respiratory depression, aspiration, or metabolic acidosis.

A mechanism of induction of canine benign prostatic hyperplasia (BPH) by androgen-stimulated growth of prostatic cells exposed to estrogen-induced toxicity. Estrogen is thought to be activated by redox cycling of catechol metabolites, a mechanism of generation of active radicals. Mongrel dogs, 4 animals/group, were sham-operated (controls) or were treated for 60 days with implants of 5 alpha-dihydrotestosterone and/or estradiol-17 beta. The activities of drug and hormone metabolizing enzymes (aryl hydrocarbon hydroxylase, 7-ethoxycoumarin O-deethylase, and estradiol-17 beta-2- and -4-hydroxylase) in prostate were significantly elevated by chronic treatment with either estradiol-17 beta or 5 alpha-dihydrotestosterone plus estradiol-17 beta, but not in kidney or liver which are not targets of hormone-induced hyperplasia. Activities of the detoxifying enzymes catalase and glutathione peroxidase I in prostate were increased by estradiol-17 beta treatment, whereas in kidney or liver they were not affected or changed to a lesser degree than observed in prostate. Free radial-induced damage (carbonyl content) of proteins was observed in prostate of dogs treated with either estradiol-17 beta or 5 alpha-dihydrotestosterone plus estradiol-17 beta and in liver protein by treatment with either 5 alpha-dihydrotestosterone or 5 alpha-dihydrotestosterone plus estradiol-17 beta. It was concluded that the patterns of estradiol-17 beta- or 5 alpha-dihydrotestosterone plus estradiol-17 beta-induced increases in activities of catechol estrogen synthase and of other drug metabolizing enzymes were consistent with the postulated free radical generation by redox cycling of catechol estrogen specifically in the prostate. The increases in activities of detoxifying enzymes may represent an (albeit insufficient) response to prostatic free radical damage to protein in prostate is consistent with a postulated induction of BPH via injury by estrogen metabolites followed by 5 alpha-dihydrotestosterone-stimulated growth of altered prostatic cells.

Cyclobenzaprine (CBP) has a cyclic structure similar to amitriptyline. In overdose, CBP has been suggested to produce the cardiovascular and neurologic toxicity found with the cyclic antidepressants. To examine this possibility, a retrospective chart review of all cases of CBP exposure reported to five regional poison centers was performed for the years 1989-93. There were a total of 750 charts identified for CBP exposure, of which 523 had data sufficient for evaluation. There were 121 polydrug ingestions leaving 402 pure CBP ingestions. Ages ranged from 7 mo to 77 yrs, with a mean of 20 yrs; 26% were 6 yrs or less. Females comprised 63% of the patient group. No deaths occurred. Dysrhythmias beyond sinus tachycardia were infrequent, and none were life-threatening. No seizures occurred. Common effects were lethargy, sinus tachycardia, and agitation, and both hypertension and hypotension were seen. All symptomatic cases with a known time of ingestion were symptomatic within 4 h of ingestion. Doses ingested ranged from 5-1000 mg, with a mean of 133 mg. Asymptomatic and symptomatic patients had a mean dose ingested of 45 mg and 183 mg, respectively. Treatment was primarily gastrointestinal (GI) decontamination and supportive care. Other therapies required were mechanical ventilation, dopamine, fluid bolus, sedation, and foley catheter. Symptoms requiring treatment beyond GI decontamination did not occur with ingestions less than 100 mg. In conclusion, cyclobenzaprine does not appear to produce the life-threatening cardiovascular or neurologic effects of the cyclic antidepressants in doses less than 1 g. Lethargy and anticholinergic effects are prominent, though serious toxicity is infrequent.

Little has been published on benzonatate ingestion, with the few case reports suggesting significant risk of seizures after poisoning. A 7-year retrospective review of all single substance ingestion of benzonatate reported to the National Poison Center Database System (NPDS) from 2000 to 2006. In this review, there were 2,172 patients, of which 1,280 (58%) were female. Mean age was 20 years, with 676 (30%)

Tiagabine is an anticonvulsant that blocks reuptake of the inhibitory neurotransmitter GABA. There are no published studies or case series of tiagabine overdoses.The records of six poison centers and one statewide poison center network were searched for all exposures to tiagabine for the years 2000-2002. Inclusion criterion was a human tiagabine exposure with follow-up to a known outcome; exclusion criterion was multiple drug ingestion.57 cases met the inclusion criterion. Thirty-seven patients were female (67%). Mean and median ages were 30.5 years (S.D. +/- 18.5) and 31 years, respectively, with a range of 2 to 80 years. Seven patients wereor = 6 years. Neurologic symptoms were common: lethargy, seizures (multiple), status epilepticus, seizure (single), coma, confusion, agitation, tremors, dizziness, dystonias/abnormal posturing, and hallucinations. Other symptoms included respiratory depression, tachycardia, hypertension, and hypotension. Therapies included benzodiazepines, mechanical ventilation, phenytoin, phenobarbital, diphenhydramine, and dopamine. The mean onset and duration of symptoms were 1.3 hours (+/- 0.5, range 1-2 hours) and 9.1 hours (+/- 3.8, range 4-24 hours), respectively. Dose ingested by history was known for 38 patients (67%). The lowest dose with the development of multiple seizures and coma was 96 mg. This occurred in a 36-year-old female with a history of epilepsy. The lowest dose with symptoms in a child was 8 mg, in a 6-year-old with drowsiness. Mean dose of those with and without symptoms was 102 mg and 10 mg, respectively. The mean dose for patients experiencing seizures was 224 mg (+/- 172, range 96 to 680 mg). The mean dose for patients experiencing coma and respiratory depression was 270 mg (+/- 204, range 96 to 680 mg). Fifty-two patients (91%) were evaluated in the ED of whom 43 were admitted for medical care.Seizures and altered mental status were common with tiagabine overdose, with rapid onset and resolution of symptoms. In this series, seizures did not occur until the ingestion was greater than three times the maximum recommended daily dose.

To evaluate whether administration of activated charcoal, in addition to standard N-acetylcysteine (NAC) therapy, after acetaminophen overdose provides additional patient benefit over NAC therapy alone, a 1-year non-randomized prospective, multi-center, observational case series was performed at three poison centers and one poison center system. Entrance criteria were all acute acetaminophen overdoses with: 1) an acetaminophen blood concentration determined to be in the toxic range by the RumackMatthew nomogram; and 2) all therapies, including NAC and activated charcoal, initiated between 4 and 16 h post-ingestion. There were 145 patients meeting entrance criteria, of whom 58 patients (40%) received NAC only and 87 patients (60%) received NAC and activated charcoal. Overall, 23 patients had elevations of AST or ALT greater than 1000 IU/L, of which 21 patients received NAC only (38% of total NAC only group) and 2 patients received NAC and activated charcoal (2% of total NAC + AC group). Administration of activated charcoal in this series of patients with toxic acetaminophen concentrations treated with NAC was associated with reduced incidence of liver injury, as measured by elevated serum transaminases and prothrombin times.

OBJECTIVE:There are no large studies, case series, or case reports of metformin ingestion in children. This study summarizes the clinical course and outcomes of metformin ingestion in children reported to the American Association of Poison Control Centers– Certified regional poison centers.METHODS:This was a case series of all metformin ingestions in patients RESULTS:Fifty-five cases were collected. Ages ranged from 15 months to 17 years, with a mean (±SD) of 4.2 ± 4.4 years. The dose ingested, by history, ranged from 250 mg to 16.5 g, with a mean and median of 1710 ± 3391 and 500 mg, respectively. Forty-one children (76%) ingested a maximum of two tablets (=1700 mg). In the children younger than six years, dosage ranged from 9 to 196 mg/kg, with a mean and median of 60 ± 41.1 and 40 mg/kg, respectively. Thirty-seven children were evaluated in a healthcare facility. Clinical effects were limited to nausea (2), diarrhea (2), and dizziness (1). None of the 38 children who had serial glucose measurements experienced hypoglycemia. Arterial blood gas and electrolyte measurements were performed in three and 19 children, respectively. No evidence of acidosis was demonstrated. Two children had lactate concentrations measured and were determined to be in the normal range. Twenty-nine patients received activated charcoal. Five patients received parenteral glucose and one adolescent with a history of diabetes received insulin for hyperglycemia.CONCLUSIONS:Unintentional ingestion of ≤1700 mg of metformin in the healthy pediatric population does not appear to pose a significant health risk of hypoglycemia or detrimental outcome. In the 21 children who were tested for either blood glucose, electrolyte, or lactate concentrations, no evidence of lactic acidosis was seen.