First case of acute respiratory distress syndrome and alimentary tract hemorrhage following mass ingestion of methylisothiazolinone.

The frequency of methylisothiazolinone (MIT)-related health concerns regarding allergic contact dermatitis with a spongiotic reaction pattern and restrictive lung function indicating peripheral airway dysfunction caused by the use of humidifier disinfectant is increasingly rising. There is a limited number of evidences supporting the environmentally acute and mass exposure to MIT resulting in acute respiratory distress syndrome (ARDS). Here, we report the first case of ARDS and alimentary tract hemorrhage following mass ingestion of methylisothiazolinone.

Mirabegron Toxicosis in Dogs: a Retrospective Study.

Mirabegron is a selective beta (B)3 adrenoreceptor agonist marketed for human treatment of an overactive bladder (OAB). It has a wide margin of safety in humans, but in dogs, severe adverse effects have occurred. We sought to determine the effects and outcome of mirabegron toxicosis in dogs. A retrospective review of all calls within the Pet Poison Helpline (PPH), an international animal poison control center, database was performed for mirabegron exposures between 2013 and 2015. Potential ingested doses ranging from 1.31 to 8.3 mg/kg. Many dogs remained asymptomatic and no fatalities occurred in any dogs. The most commonly reported signs were tachycardia and erythema. While mirabegron was found to have a very narrow margin of safety and high toxicity risk to dogs during preclinical trials, effects appear to differ greatly in the nonclinical field environment and further study is needed.

Treatment of meloxicam overdose in a dog via therapeutic plasma exchange.

OBJECTIVE: To describe the treatment of a meloxicam overdose in a dog with therapeutic plasma exchange (TPE). CASE SUMMARY: A 6-month-old female Bulldog, presented for routine laparoscopic ovariectomy. Postoperatively the dog received an accidental overdose of meloxicam (1 mg/kg IV [intravenously]). The patient was treated with supportive medical therapy and TPE over 210 minutes achieving 1.2 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Meloxicam concentrations were determined in the samples by high pressure liquid chromatography. Post TPE, the dog continued to receive supportive medical therapy and was discharged 48 hours after the overdose. The dog remained asymptomatic for meloxicam intoxication. Follow-up rechecks at 1 and 6 weeks were unremarkable with no further treatment required. NEW OR UNIQUE INFORMATION: This report describes the successful use of TPE adjunctively following an acute meloxicam overdose. An 82% reduction of plasma meloxicam concentration was achieved over 210 minutes. Twenty-four hours after therapy, a 47% sustained reduction of plasma meloxicam was measured after redistribution of drug between body compartments.

[Stevens-Johnson syndrome and toxic epidermal necrolysis (SJSTEN) related to insecticide: Second case in the literature and potential implications]. / Le syndrome de Stevens-Johnson-toxic epidermal necrolysis (SJSTEN) lié à un insecticide : second cas dans la littérature et implications potentielles.

INTRODUCTION: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJSTEN) is a rare acute drug reaction characterized by the brutal destruction of the superficial layer of the skin and mucosa. SJSTEN is favoured by some drugs (90 % of cases) and genetic factors. It occurs at any age in both sexes. The pathophysiology is not completely understood. To our knowledge, only one case linked to an insecticide has been described. We present the second case involving a combination of lambdacyhalothrin and thiamethoxam. OBSERVATION: A 34-year-old farmer was admitted in emergency for a severe allergic reaction occurring few days after the use of an insecticide to treat his field with no particular precaution. The disease progression was swift: deterioration of general condition, generalized itching, blisters, bubbles, hyperthermia, tachycardia, significant oral pain and oral lesions and dysphagia. Hands, feet were concerned and external genitalia was responsible for burning urination. Oral lesions have rapidly evolved from edema to infected lesions. The diagnosis of SJSTEN was confirmed by histopathology. After complete assessment and adequate treatment, the patient was discharged after 17 days of hospitalization. The etiological research concluded to a probable poisoning by lambdacyhalothrin and thiamethoxam. DISCUSSION: This is the second published case of a SJSTEN linked to an insecticide combining lambdacyhalothrin and thiamethoxam. Manufacturers, users, regulators and physicians should take these data into account.

Digital Holter measurement of QT prolongation in ziprasidone overdose.

OBJECTIVE: QT prolongation is an important complication in drug overdose, particularly with some antidepressants and antipsychotics. There are problems with the accurate measurement of the QT interval and determining for what QT interval patients should be monitored, because of the risk of torsades des pointes (TdP). We report a case of ziprasidone overdose with QT prolongation, demonstrating different methods of measuring the QT interval. CASE REPORT: A 47-year-old female presented after taking 1.2 g of ziprasidone and 250 mg of diazepam. She was taking propranolol and venlafaxine therapeutically. She developed bradycardia and QT prolongation (540 msec). She was transferred to a telemetry bed and observed for 48 h until her QT interval returned to normal (460 msec). QT intervals were extracted from (1) 12-lead digital Holter recordings (gold standard); (2) automated measurements on standard electrocardiograms (ECGs); and (3) manual measurements on standard ECGs, and compared on a QT versus time plot. An abnormal QT was determined based on the QT nomogram. Manual QT measurements showed a clear temporal association between ziprasidone overdose and a long QT, consistent with accurate QT measurements using continuous 12-lead Holter recordings with automatic QT measurements. However, standard automated measurements did not indicate an abnormal QT. CONCLUSIONS: Manual measurement of the QT interval appeared to be similar to the more accurate measurement of the QT by automated digital Holter recordings and better than standard automated measurements. Manual QT measurements would be more appropriate in clinical assessment of patients.

Respiratory failure following isolated ziprasidone ingestion in a toddler.

Ziprasidone is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar mania in adults and is used off label in children and adolescents. Despite increasing use of ziprasidone in both adult and pediatric populations, there remains a paucity of reports describing unintentional pediatric exposures. The following report describes a patient with isolated ziprasidone ingestion who required intubation secondary to respiratory failure. A 15-month-old previously healthy boy presented to the emergency department shortly after his father found him with approximately five partially dissolved 80-mg ziprasidone tablets in his mouth. The child was flaccid and lethargic with no eye opening, withdrawing from pain only. Two hours after arrival, he developed worsening CNS depression with inability to protect his airway and underwent endotracheal intubation. A serum ziprasidone level was 330 ng/mL by LC/MS. The patient was extubated approximately 14 h later and was discharged from the hospital shortly thereafter in good health without neurological sequelae. Isolated pediatric ingestion of ziprasidone resulting in the need for significant medical intervention has not been previously reported. We report a case of respiratory failure requiring intubation following accidental ziprasidone ingestion with confirmatory serum levels.

Unintentional ingestion of ziprasidone in a 22-month-old.

Unintentional ingestions are a common presentation to the emergency department in the pediatric population. However, very few ingestions of an atypical antipsychotic, such as ziprasidone, have been described in the emergency medicine literature. While the prevalence of these newer antipsychotics increases in the general population, emergency physicians can expect to see more patients with accidental or intentional overdoses. Many emergency physicians may be unfamiliar with the presentation, initial workup, and expected clinical course of such an overdose. We describe a case of an unintentional ingestion of ziprasidone tablets in a 22-month-old girl who presented to the emergency department with somnolence, drooling, and poor tone.

A systematic review of cardiovascular effects after atypical antipsychotic medication overdose.

As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.

Pediatric ziprasidone overdose.

We describe the first ziprasidone overdose with quantitative serum levels of a pediatric patient in coma and with pinpoint pupils. This case is an important contribution to the pediatric ziprasidone literature because it illustrates that ingestion of just 1 pill may result to profound mental status and respiratory depression in a child. H.C., a 30-month-old girl, presented to the emergency department approximately 30 minutes after an accidental ingestion of an adult family member's medication. The child was found on the floor surrounded by numerous pills and was witnessed to have ingested at least 1 tablet by a caregiver. After finding the child with the pills, the family observed the child for a brief period but transported her to the hospital after she became lethargic and unresponsive. The child received 2 doses of 0.4 mg of intravenous naloxone without change in her neurologic status. The child then underwent a rapid sequence intubation for airway protection and subsequently received gastrointestinal decontamination with 15 g of activated charcoal via the orogastric tube. Ziprasidone is an atypical antipsychotic drug that was approved by the Food and Drug Administration in February 2001 for the general treatment of schizophrenia in adults. Previously reported pediatric ziprasidone overdoses describe a syndrome of sedation, tachycardia, hypotonia, and coma consistent with that of the patient described in this paper. In pediatric ziprasidone overdose, QTc prolongation and hypotension have also been illustrated, but seizures have not been reported. An interesting aspect of this case is the development of pinpoint pupils unresponsive to naloxone. This phenomenon has been reported before with overdose of olanzapine, a similar atypical antipsychotic. The mechanism of miosis associated with overdose of atypical antipsychotics is unclear but is likely related to interference with central innervation of the pupil. Pupil size is maintained by a balance between sympathetic and parasympathetic neurohumeral tones. We propose that an overdose of an alpha-1 receptor blocking agent, such as ziprasidone, results in unopposed parasympathetic stimulation resulting in miosis.

Pattern of ziprasidone exposures reported to Texas poison centers, 2001-2005.

Information on potentially adverse exposures to the atypical antipsychotic drug ziprasidone is limited. This study described the pattern of exposures involving only ziprasidone (isolated exposures) reported to Texas poison control centers during 2001-2005. The mean dose was 666 mg. The patient age distribution was or=20 years (60%). The exposures were intentional in 53% of the cases. Seventy-five percent of the exposures were managed at health care facilities. The final medical outcome was classified as no effect for 39% of the cases and minor effects for 40% of the cases. Adverse clinical effects were listed for 53% of the patients; the most frequently reported being neurological (42%), cardiovascular (13%), and gastrointestinal (5%). The most frequently listed treatment was decontamination by charcoal (34%) or cathartic (28%). Potentially adverse ziprasidone exposures reported to poison control centers are likely to involve management at a health care facility and involve some sort of adverse clinical effect. With proper treatment, the outcomes of such exposures are generally favorable.

Prospective observational multi-poison center study of ziprasidone exposures.

BACKGROUND: Ziprasidone is an atypical antipsychotic associated with QTc prolongation during therapeutic use. We characterized the clinical manifestations associated with ziprasidone overdoses, in particular the incidence and severity of QTc prolongation. METHODS: Four regional poison centers prospectively collected ziprasidone overdose data from August 1, 2003 to October 1, 2005. Cases were included if they were followed to known medical outcome and comprised single-substance ziprasidone exposures or with co-ingestants not associated with prolongation of the QTc interval. RESULTS: Fifty-six ziprasidone exposures met inclusion criteria. The most common clinical effects were drowsiness (N=38, 67.9%) and tachycardia (N=19, 33.9%). QTc prolongation (>0.500 second) occurred in only one patient. Seven patients had QTc intervals of 0.450 to 0.500 second. Medical outcomes were coded as no effect (13, 23.2%), minor effect (21, 35.5%), moderate effect (20, 35.7%), or major effect (2, 3.4%). CONCLUSION: Common clinical effects following ziprasidone overdose are drowsiness and tachycardia. Clinically significant QTc prolongation occurs infrequently.

Seguridad de ziprasidona en intoxicación: a propósito de un caso / Ziprasidone security in overdose: one case report

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[Pharmacokinetics of perospirone hydrochloride at an excessive dose and changes in the serum prolactin level].

A 36-year-old female, in whom 8 mg perospirone hydrochloride tablets had been prescribed, took 178 tablets (corresponding to 1,424 mg) as a single dose. After 4.5 hours, she was admitted under a diagnosis of acute drug intoxication. We investigated her clinical course and medical records including the laboratory data, and measured serial changes in the serum levels of perospirone hydrochloride and prolactin by HPLC and ELISA. Concerning the clinical course, the consciousness level on admission was JCS II-10, but normalized 18 hours after dosing. Thereafter, there were no intoxication symptoms or sequelae related to massive administration of this agent, and the patient was discharged 3 days after admission. There were no abnormalities in the laboratory data obtained on admission and 2 days after admission. The serum levels of perospirone hydrochloride were 695 ng/mL 4.5 hours after dosing and approximately 60 ng/mL 18 hours after dosing, when consciousness became clear. The t1/2 beta value was 8 hours, similar to that in healthy adults. Furthermore, the serum level of prolactin 4.5 hours after dosing was 49.5 ng/mL, but returned to the normal range 18 hours after dosing, when consciousness became clear.

Ziprasidone overdose: cases recorded in the database of Pfizer-Spain and literature review.

Ziprasidone is an atypical antipsychotic with a highly specific receptorbinding profile that has been shown to be effective for both positive and negative symptoms of schizophrenia. The agent has been associated with a low frequency of extrapyramidal symptoms and sedative and anticholinergic effects. Four cases of acute ziprasidone overdose were recorded in the database of the department of pharmacovigilance of Pfizer-Spain from January 2003 (when ziprasidone was first marketed in Spain) to October 2004. The doses taken were 780, 1120, 4400, and 4480 mg. In two cases, an excessive ingestion of other drugs such as benzodiazepines and sedative hypnotics was also noted. None of the four cases showed cardiac adverse effects, and the QTc interval was within the normal range in all patients. No relevant neurologic clinical signs were observed, except for mild drowsiness in three cases. Evaluation of these four cases, as well as review of the literature, showed that an overdose of ziprasidone alone, in patients without risk factors that contraindicate its use, is relatively safe.