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1.
BMC Psychiatry ; 24(1): 123, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355481

RESUMEN

BACKGROUND: Clozapine is a highly effective second-generation antipsychotic with few extrapyramidal reactions, making it a preferred choice among clinicians. However, instances of acute clozapine poisoning resulting from suicide attempts and misuse have been reported. Through our review of existing literature, we identified that we believe to be the highest recorded overdose of clozapine in elderly patients, resulting in a nonfatal outcome. CASE PRESENTATION: The case report involves a 71-year-old female with a history of depression who ingested a dose of 10,000 mg of clozapine. Approximately 6 h after the overdose, the clozapine level was 5,200 µg/L, significantly surpassing the recommended therapeutic concentration range of 350-600 µg/L. After gastric lavage and hemoperfusion, the blood level dropped to 1847.11 µg/L. Notably, during therapeutic drugs monitoring (TDM), we found a perplexing spike in the patient's blood level to 5554.15 µg/L after the second hemoperfusion. CONCLUSION: In this case we mainly focused on the abnormal fluctuations in the concentration of clozapine. We conducted a comprehensive analysis of potential factors contributing to this abnormal phenomenon in terms of the patient's age, clinical symptoms, various laboratory test indexes, and the pharmacokinetics of clozapine. Our findings underscore the importance of timely TDM and the precision of results in managing elderly patients experiencing high-dose clozapine poisoning.


Asunto(s)
Antipsicóticos , Clozapina , Sobredosis de Droga , Anciano , Femenino , Humanos , Antipsicóticos/envenenamiento , Clozapina/envenenamiento , Monitoreo de Drogas/métodos , Intento de Suicidio
2.
Drug Chem Toxicol ; 47(4): 386-403, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38348658

RESUMEN

Worldwide, acute antipsychotic poisoning results in high morbidities and mortalities. Though extrapyramidal syndromes are commonly associated, the extent of extrapyramidal syndromes in relation to the severity of antipsychotic poisoning has not been addressed yet. Thus, this study aimed to assess the Global Dystonia Rating Scale (GDRS) as an unfavorable outcomes predictive tool in acute antipsychotic poisoning. A cross-sectional study included 506 antipsychotic-poisoned patients admitted to Tanta University Poison Control Center, Egypt, over three years was conducted. The mean GDRS was 9.1 ± 16.7 in typical antipsychotic poisoning, which was significantly higher than that of atypical antipsychotics (4.2 ± 11.5) (p = 0.003). Patients with GDRS> 20 showed significantly higher liability for all adverse outcomes (p < 0.05). However, poisoning with typical antipsychotics was associated with significantly more cardiotoxicity (p = 0.042), particularly prolonged QRS (p = 0.005), and intensive care unit (ICU) admission (p = 0.000). In contrary to the PSS, which failed to predict the studied adverse outcomes, GDRS significantly predicted all adverse outcomes (p < 0.000) for all antipsychotic generations. In atypical antipsychotics, GDRS above three accurately predicted cardiotoxicities, prolonged QTc interval, and respiratory failure with Area under curves (AUC) of 0.937, 0.963, and 0.941, respectively. In typical antipsychotic poisoning, at higher cutoffs (7.5, 27.5, 18, and 7.5), cardiotoxicities, prolonged QTc interval, and respiratory failure were accurately predicted (AUC were 0.974, 0.961, and 0.960, respectively). GDRS is an objective, substantially useful tool that quantifies dystonia and can be used as an early reliable predictor of potential toxicity in acute antipsychotic poisoning.


Asunto(s)
Antipsicóticos , Distonía , Humanos , Antipsicóticos/envenenamiento , Antipsicóticos/efectos adversos , Masculino , Femenino , Estudios Transversales , Adulto , Distonía/inducido químicamente , Egipto , Adulto Joven , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adolescente , Valor Predictivo de las Pruebas
3.
J Clin Psychopharmacol ; 41(6): 650-657, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34668874

RESUMEN

BACKGROUND: Deaths from antipsychotic (AP) poisoning have increased in England and Wales despite restriction of the use of thioridazine in 2000. METHODS: We analyzed data from the Office for National Statistics drug-related death database, England and Wales, 1993-2019, to investigate fatal AP poisoning. RESULTS: There were 2286 deaths (62% male patients). Annual numbers of intentional AP-related fatal poisonings (suicides) were relatively stable (1993, 35; 2019, 44; median, 44; range, 30-60). Intentional overdose deaths involving clozapine (96 male, 25 female) increased from 1 in 1994 to 5 in 2003 and have since remained relatively constant (median, 6; range, 3-10 per annum). Unintentional second-generation AP-related fatal poisonings have increased steadily since 1998, featuring in 828 (74%) of all unintentional, AP-related fatal poisonings in the period studied (2019, 89%). There were 181 unintentional clozapine-related deaths, (107 [59%] alone without other drugs ± alcohol) as compared with 291 quetiapine-related deaths (86 [30%] alone without other drugs ± alcohol) and 314 unintentional olanzapine-related deaths (77 [25%] alone without other drugs ± alcohol). Some 75% of all unintentional clozapine- and olanzapine-related deaths were of male patients (78% and 73%, respectively) as compared with 58% of unintentional quetiapine-related fatal poisonings. Clozapine now features prominently in intentional and in unintentional AP-related fatal poisoning in England and Wales. Deaths of male patients predominate in both categories. There were also 77 and 86 deaths attributed to unintentional poisoning with olanzapine and with quetiapine, respectively, in the absence of other drugs. CONCLUSIONS: More effort is needed to prevent unintentional deaths not only from clozapine but also from olanzapine and quetiapine.


Asunto(s)
Antipsicóticos/envenenamiento , Clozapina/envenenamiento , Sobredosis de Droga/mortalidad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/mortalidad , Olanzapina/envenenamiento , Intoxicación/mortalidad , Adulto , Inglaterra/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Gales/epidemiología
4.
J Biochem Mol Toxicol ; 34(10): e22546, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32583942

RESUMEN

The purpose of this study was to investigate the mutual effect of systemic inflammatory response syndrome (SIRS) accompanied with fibrinolysis, endotoxemia, and coagulation in severe cases of antipsychotic poisoning. A total of 199 patients were examined, of which 71 were men and 128 were women. The age of the patients was from 22 to 63 years, (45.3 ± 6.1 years on average). According to the results of the course of therapy, the patients were divided into two groups. In the blood plasma, the content of C-reactive protein, fibrinogen and its proteolysis products (oligopeptides, D-dimers), interleukin-6 were determined. In the first 1 to 3 days, in group 1, the level of interleukin-6 decreased and approached the normal level (P ≤ .05). The opposite trend continued throughout the observation of patients from group 2-their levels of interleukin-6 increased day by day (P ≤ .05). The concentration of D-dimer already in 1 day after admission to intensive care in patients from group 2 exceeded the norm by 14 times (P ≤ .05). The level of D-dimer correlated with the level of oligopeptides in blood plasma upon admission, as well as for 3 and 5 days after admission to intensive care: 0.36, 0.76 at P ≤ .05, 0.94 at P ≤ .01, respectively. Similar correlations were obtained for the content of oligopeptides in urine and the level of D-dimer: 0.55, 0.85 at P ≤ .05, 0.93 at P ≤ .01. In this regard, the most pronounced correlation is that between the SIRS score, plasma D-dimer level, and the plasma level of the D-dimer derivatives, oligopeptides.


Asunto(s)
Antipsicóticos/envenenamiento , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Enfermedad Aguda , Adulto , Estudios de Casos y Controles , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Oligopéptidos/sangre , Oligopéptidos/orina , Sepsis/etiología , Análisis de Supervivencia , Síndrome de Respuesta Inflamatoria Sistémica/complicaciones , Adulto Joven
5.
Aust N Z J Psychiatry ; 54(6): 591-601, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31957465

RESUMEN

BACKGROUND: Hospital-treated deliberate self-poisoning is common, with a median patient age of around 33 years. Clinicians are less familiar with assessing older adults with self-poisoning and little is known about their specific clinical requirements. OBJECTIVE: To identify clinically important factors in the older-age population by comparing older adults (65+ years) with middle-aged adults (45-64 years) during an index episode of hospital-treated deliberate self-poisoning. METHODS: A prospective, longitudinal, cohort study of people presenting to a regional referral centre for deliberate self-poisoning (Calvary Mater Newcastle, Australia) over a 10-year period (2003-2013). We compared older-aged adults with middle-aged adults on demographic, toxicological and psychiatric variables and modelled independent predictors of referral for psychiatric hospitalisation on discharge with logistic regression. RESULTS: There were (n = 157) older-aged and (n = 925) middle-aged adults. The older-aged group was similar to the middle-aged group in several ways: proportion living alone, reporting suicidal ideation/planning, prescribed antidepressant and antipsychotic drugs, and with a psychiatric diagnosis. However, the older-aged group were also different in several ways: greater proportion with cognitive impairment, higher medical morbidity, longer length of stay, and greater prescription and ingestion of benzodiazepines in the deliberate self-poisoning event. Older age was not a predictor of referral for psychiatric hospitalisation in the multivariate model. CONCLUSION: Older-aged patients treated for deliberate self-poisoning have a range of clinical needs including ones that are both similar to and different from middle-aged patients. Individual clinical assessment to identify these needs should be followed by targeted interventions, including reduced exposure to benzodiazepines.


Asunto(s)
Hospitales , Evaluación de Necesidades , Intoxicación/prevención & control , Intoxicación/terapia , Anciano , Antidepresivos/envenenamiento , Antipsicóticos/envenenamiento , Australia , Benzodiazepinas/envenenamiento , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Ideación Suicida
6.
Pediatr Emerg Care ; 36(10): 468-472, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31790070

RESUMEN

OBJECTIVES: Extrapyramidal symptoms (EPS) induced by pharmacologic agents can cause patient discomfort and lead to emergency department visits. Analyzing these cases at a pediatric emergency department may help to elucidate the characteristic features of extrapyramidal syndrome in children. METHODS: This retrospective study was conducted at Chang Gung Memorial Hospital in Taiwan. Pediatric patients with drug-induced extrapyramidal syndrome seeking treatment at our emergency department from January 2001 to December 2010 were enrolled. The patients' clinical features, drug history, demographic data, and treatment data were collected and analyzed. RESULTS: One hundred nineteen patients (61 females, 58 males) were enrolled. Ninety-six patients could provide their drug history; all of whom took dopamine antagonists and 90% of whom took dopamine antagonists as antiemetic agents, with only 9 patients taking them for antipsychotic purposes. Metoclopramide syrup overdose was the main cause of extrapyramidal syndrome in patients under 2 years old. The average emergency room stay of the patients who could provide their drug history was shorter than that of those who could not. CONCLUSIONS: It is not uncommon for patients with drug-induced EPS to present to a pediatric emergency room owing to the use of dopamine antagonists as antiemetic agents. Clinical symptoms with a clear drug history are helpful for the diagnosis and management. Emphasizing the correct usage of liquid medications will reduce the risk of EPS.


Asunto(s)
Antieméticos/envenenamiento , Antipsicóticos/envenenamiento , Enfermedades de los Ganglios Basales/inducido químicamente , Antagonistas de Dopamina/envenenamiento , Servicio de Urgencia en Hospital , Adolescente , Enfermedades de los Ganglios Basales/tratamiento farmacológico , Niño , Preescolar , Sobredosis de Droga , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Taiwán
7.
Nervenarzt ; 91(1): 57-63, 2020 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-30941458

RESUMEN

Despite unlimited access to therapeutic drug monitoring lithium poisoning is still a common and potentially life-threatening but in most cases preventable complication of lithium treatment; however, it is still considered to be the gold standard in the treatment of affective disorders. The necessity of drug monitoring and potential lithium toxicity substantiate the skepticism of many therapists with respect to this often very effective treatment. This therefore limits the use of lithium although the unique therapeutic effects and high efficiency are well known. This retrospective data analysis of risk factors and etiology of lithium poisoning cases identified 58 cases of lithium poisoning, which were treated internally in this hospital between 2010 and 2014. Of the patients 67.2% were female and the majority were classified as chronic poisoning (66.1%). The most relevant patient-related risk factor seemed to be insufficient self-management as 26% of cases of lithium poisoning occurred during febrile infections or exsiccosis. Regarding practitioner-related risk factors, an insufficient consideration of drug interactions, insufficient therapeutic drug monitoring after dose increase and a paucity of experience and knowledge concerning lithium treatment were most relevant. This study illustrates the most important risk factors for lithium poisoning and their frequencies and contributes to raise awareness for this highly relevant topic. These data can help to prevent further cases of lithium poisoning. Furthermore, the results enable a comparison between the actual treatment reality and currently available evidence for the treatment of lithium poisoning.


Asunto(s)
Antidepresivos , Antipsicóticos , Compuestos de Litio , Antidepresivos/envenenamiento , Antipsicóticos/envenenamiento , Enfermedad Crónica , Femenino , Humanos , Compuestos de Litio/envenenamiento , Masculino , Estudios Retrospectivos , Factores de Riesgo
8.
J Clin Psychopharmacol ; 39(4): 312-317, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31205192

RESUMEN

PURPOSE/BACKGROUND: Quetiapine is a relatively new atypical antipsychotic with fewer adverse effects. It is increasingly prescribed to patients. The purpose of this study was to describe the cases of poisoning observed at the western France Poison Control Centre and identify potential risk factors that increase the severity of the cases. METHODS: This was a retrospective study of self-poisoning with quetiapine as reported by the western France Poison Control Centre between 2007 and 2017. RESULTS: There were 372 cases of quetiapine poisoning. Circumstances are known in 367 of 372 cases. There were 75 cases of null severity (grade 0), 133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2), and 79 cases of high severity (grade 3). Five deaths were listed in this series. The most commonly observed symptoms were neurological and cardiovascular in nature (drowsiness, coma, tachycardia, hypotension). Of these cases, 79.8% included voluntary ingestions. Among 302 cases with coagents, the most common coagents were benzodiazepines (56%), other psychotropic drugs (41%), and antidepressants (37%). An evaluated ingested dose 1500 mg or greater and 2 or more coagents increase the risk of severe poisoning. In particular, concomitant ingestion of benzodiazepines and antidepressants with quetiapine was associated with high severity (odds ratio, 2.478 [confidence interval, 1.3-4.723]; odds ratio, 1.820 [confidence interval, 1.010-3.316]). CONCLUSIONS: Quetiapine may lead to severe poisoning for which there is currently no specific treatment. Patients and practitioners should be aware of this when quetiapine is prescribed, particularly when used in combination with other medications, and in order to deal with cases of poisoning.


Asunto(s)
Antipsicóticos/envenenamiento , Dibenzotiazepinas/envenenamiento , Fumarato de Quetiapina/envenenamiento , Adulto , Antipsicóticos/uso terapéutico , Coma/inducido químicamente , Dibenzotiazepinas/uso terapéutico , Sobredosis de Droga/mortalidad , Femenino , Francia , Humanos , Hipotensión/inducido químicamente , Masculino , Centros de Control de Intoxicaciones , Fumarato de Quetiapina/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Taquicardia/inducido químicamente
9.
Forensic Sci Med Pathol ; 15(1): 110-113, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30498933

RESUMEN

Kratom is a plant with dose-dependent mixed stimulant and opioid properties whose pharmacologic characteristics and social impact continue to be described. The main active isolate of kratom is mitragynine, an indole-containing alkaloid with opioid-like effects. Kratom toxicity and kratom-associated fatalities have been described, including those in association with additional drugs. In this paper we describe the case of a 27-year-old man who was found deceased with a toxic blood concentration of quetiapine in conjunction with the qualitative presence of mitragynine. Investigative and autopsy findings suggested perimortem hyperthermia and seizure-like activity. Kratom toxicity and kratom-associated fatalities are being increasingly reported. Experiments with kratom extracts have shown inhibitory effects upon hepatic CYP enzymes, leading to previous speculation of the potential for clinically significant interactions between kratom and a wide array of medications. Herein is described a fatal case of quetiapine toxicity complicated by mitragynine use. The potential ability of mitragynine to alter the pharmacokinetics of a prescription medication via inhibition of its hepatic metabolism is discussed.


Asunto(s)
Antipsicóticos/envenenamiento , Interacciones de Hierba-Droga , Fumarato de Quetiapina/envenenamiento , Alcaloides de Triptamina Secologanina/sangre , Adulto , Antipsicóticos/sangre , Sobredosis de Droga , Humanos , Masculino , Fumarato de Quetiapina/sangre
10.
Ther Drug Monit ; 39(6): 581-583, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29135905

RESUMEN

To the best of our knowledge, no case has been published in the literature that reports an overdose of tiapride, either alone or in combination with other drugs. We report a self-poisoning case in an 18-year-old girl, with approximately 10 times the usual daily dose (ie, 2.5 g). Although the blood concentration was 20/30-fold higher than usually observed after therapeutic drug intakes (17,300 mcg/L), the patient remained almost asymptomatic.


Asunto(s)
Antipsicóticos/envenenamiento , Intento de Suicidio , Clorhidrato de Tiaprida/envenenamiento , Adolescente , Ansiolíticos/administración & dosificación , Ansiolíticos/envenenamiento , Antipsicóticos/administración & dosificación , Antipsicóticos/farmacocinética , Diazepam/administración & dosificación , Diazepam/envenenamiento , Monitoreo de Drogas , Sobredosis de Droga , Femenino , Humanos , Clorhidrato de Tiaprida/administración & dosificación , Clorhidrato de Tiaprida/farmacocinética
11.
Am J Emerg Med ; 35(9): 1387.e1-1387.e2, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28705742

RESUMEN

Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy for schizophrenia and mood disorders formulated as an ester for intramuscular injection. Cases of oral haloperidol decanoate intoxications have not been described in literature. In this report, we present for the first time a case of an oral ingestion of haloperidol decanoate of a young woman who presented to the emergency department following an intentional oral ingestion of 1 ampoule of haloperidol decanoate 100mg. At presentation, she had a bilateral rest tremor of both hands and mild hypothermia. No other obvious signs of an intoxication were observed. She was treated with a single dose of activated charcoal and laxative and was admitted to the intensive care for rhythm monitoring and observation. During the night the QTc interval increased to 453ms, but stayed within the normal range. Haloperidol plasma levels increased as well, but also stayed within therapeutic ranges. These findings indicate that treatment with oral activated charcoal was sufficient to prevent any serious events.


Asunto(s)
Antipsicóticos/envenenamiento , Carbón Orgánico/uso terapéutico , Haloperidol/análogos & derivados , Laxativos/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Administración Oral , Arritmias Cardíacas/inducido químicamente , Electrocardiografía , Femenino , Haloperidol/envenenamiento , Humanos , Masculino , Adulto Joven
12.
Australas Psychiatry ; 25(4): 391-394, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28168881

RESUMEN

OBJECTIVE: In cases of drug overdose, clinicians often find it challenging to predict serum drug level and decide the optimum time for recommencing the overdosed drug. METHOD: This paper describes how to predict serum drug level using the principles of pharmacokinetics. RESULTS: The proposed method and recommencement of the overdosed drug is demonstrated using a clinical case of lithium overdose. CONCLUSION: The proposed method can assist clinicians in predicting serum drug levels and deciding the optimum time for recommencing the overdosed drug safely. Therefore, it may reduce unnecessary repeat serum drug level procedures.


Asunto(s)
Antipsicóticos , Sobredosis de Droga , Litio , Antipsicóticos/sangre , Antipsicóticos/farmacocinética , Antipsicóticos/envenenamiento , Predicción , Humanos , Litio/sangre , Litio/farmacocinética , Litio/envenenamiento
13.
Br J Clin Pharmacol ; 82(1): 249-54, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26945707

RESUMEN

AIMS: Morbidity and mortality from drug overdose has decreased over three decades. This is credited to safer drugs and therefore better outcomes in overdose. We aimed to investigate changing prescriptions of antipsychotic medications and associated changes in antipsychotic overdoses over a 26-year period. METHODS: All antipsychotic poisoning presentations to a tertiary referral toxicology unit between 1987 and 2012 were reviewed. Data were collected prospectively on demographics, ingestion information, clinical effects, complications and treatment. Rates of antipsychotic drug use in Australia were obtained from Australian government publications for 1990-2011 and linked to overdose admissions by postcode. RESULTS: There were 3180 antipsychotic overdoses: 1235 first generation antipsychotics, 1695 'atypical' second generation antipsychotics and 250 lithium overdoses. Over 26 years, antipsychotic overdoses increased 1.8-fold, with first generation antipsychotics decreasing to one-fifth of their peak (≈80/year to 16) and second generation antipsychotics increasing to double this (≈160/year), olanzapine and quetiapine accounting for 78%. All antipsychotic overdoses had a median length of stay of 18.6 h, 15.7% admitted to intensive care unit, 10.4% ventilated and 0.13% died in hospital, which was the same for first generation compared to second generation antipsychotics. There was a 2.3-fold increase in antipsychotic prescriptions over the same period; first generation antipsychotics declined whereas there was a dramatic rise in second generation antipsychotics, mainly olanzapine, quetiapine and risperidone (79%). CONCLUSION: Over 26 years there was an increase in antipsychotic prescribing associated with an increase in antipsychotic overdoses. Although the type of antipsychotics changed, the morbidity and mortality remained the same, so that antipsychotics are an increasing proportion of overdose admissions.


Asunto(s)
Antipsicóticos/administración & dosificación , Sobredosis de Droga/epidemiología , Hospitalización/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Adulto , Anciano , Antipsicóticos/envenenamiento , Australia/epidemiología , Sobredosis de Droga/mortalidad , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/normas , Estudios Prospectivos , Adulto Joven
14.
Nihon Ronen Igakkai Zasshi ; 53(3): 244-9, 2016.
Artículo en Japonés | MEDLINE | ID: mdl-27535187

RESUMEN

Lithium carbonate is considered to be a first-line treatment for bipolar disorder; however, this drug has a narrow therapeutic window, and lithium intoxication is commonly induced by various drugs interaction and situations. We herein report a case of lithium intoxication induced by the administration of an antihypertensive agent targeting the angiotensin 1 (AT1) subtype of the angiotensin II receptor in a 65-year-old woman with a 40-year history of bipolar disorder type 1, and 1-year history of essential hypertension. Her bipolar disorder had been well-controlled with 600 mg/day of lithium carbonate for more than 10 years. She was later diagnosed with hypertension and the AT1 receptor blocker, azilsartan was thereafter administrated on a daily basis. After 3 weeks of azilsartan administration, she presented with progressive action tremor and showed a gradual deterioration of her physical state. Four months after the start of azilsartan administration, she presented with alternating episodes of diarrhea and constipation. Two weeks before admission to our hospital, she presented with mild consciousness disturbances, myoclonus, truncal ataxia, and appetite loss. She was diagnosed to have lithium intoxication based on an elevated serum lithium concentration of 3.28 mEq/l.It is therefore important to evaluate the serum lithium concentration after the administration of antihypertensive agents, and consider lithium-antihypertensive agent interactions when selecting antihypertensive agents in elderly patients receiving long-term lithium carbonate treatment.


Asunto(s)
Antipsicóticos/envenenamiento , Carbonato de Litio/envenenamiento , Anciano , Antagonistas de Receptores de Angiotensina/farmacocinética , Antihipertensivos , Antipsicóticos/farmacocinética , Trastorno Bipolar/tratamiento farmacológico , Interacciones Farmacológicas , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Litio , Carbonato de Litio/farmacocinética
15.
Ann Emerg Med ; 66(2): 154-64, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25639523

RESUMEN

STUDY OBJECTIVE: Antipsychotic drugs are frequently reported to cause QT prolongation and torsade de pointes. We aim to investigate the potential risk of torsade de pointes in antipsychotic overdose by assessing the QT interval with the QT nomogram. METHODS: All presentations to a toxicology service between January 1987 and May 2013 were reviewed. Admissions with single ingestions of an antipsychotic greater than maximum daily dose were extracted. Demographics, dose, ECG, and outcomes (arrhythmias and death) were obtained. QT intervals in multiple leads were manually measured and the median taken. QT-heart rate (QT-HR) pairs were plotted on the QT nomogram and defined as prolonged if above the abnormal line. The QTcF (Fridericia's HR correction) was calculated and compared with dose. RESULTS: From 2,356 antipsychotic overdoses, 494 were included. There were no abnormal QT-HR pairs in 4 aripiprazole, 31 pericyazine, 14 trifluoperazine, and 7 haloperidol overdoses. Abnormal QT intervals occurred in 9 of 16 amisulpride overdoses (56%; 95% confidence interval [CI] 31% to 79%), 16 of 57 thioridazine overdoses (28%; 95% CI 17% to 42%), and 5 of 29 chlorpromazine overdoses (17%; 95% CI 7% to 36%). Abnormal QT intervals occurred in 5 of 41 risperidone overdoses (12%; 95% CI 5% to 27%), 10 of 202 quetiapine overdoses (5%; 95% CI 3% to 9%), and 2 of 76 olanzapine overdoses (3%; 95% CI 0.5% to 10%), but there was no correlation between dose and QTcF, and most abnormal QT intervals were at fast HR. An additional 186 single antipsychotic ingestions with noncardiotoxic coingestants had similar proportions of abnormal QT. There was 1 case of torsade de pointes in a thioridazine overdose. CONCLUSION: There appeared to be significant risk of QT prolongation with amisulpride and thioridazine overdoses. Although there were abnormal QT intervals for quetiapine, olanzapine, and risperidone overdoses, they were associated with tachycardia and not dose dependent, and so were unlikely to be associated with increased torsade de pointes risk.


Asunto(s)
Antipsicóticos/envenenamiento , Sobredosis de Droga/diagnóstico , Electrocardiografía/métodos , Síndrome de QT Prolongado/inducido químicamente , Nomogramas , Adolescente , Adulto , Anciano , Amisulprida , Sobredosis de Droga/fisiopatología , Femenino , Humanos , Síndrome de QT Prolongado/diagnóstico , Síndrome de QT Prolongado/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo/métodos , Sulpirida/análogos & derivados , Sulpirida/envenenamiento , Taquicardia/inducido químicamente , Taquicardia/diagnóstico , Taquicardia/fisiopatología , Tioridazina/envenenamiento , Torsades de Pointes/inducido químicamente , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatología , Adulto Joven
18.
Am J Emerg Med ; 33(10): 1541.e1-2, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26314213

RESUMEN

No specific treatment exists for poisoning with most fat-soluble drugs. Intravenous lipid emulsion (ILE) may be effective therapy against such drugs, but effects of ILE treatment are unclear. A 24-year-old woman with depression seen sleeping in the morning was found comatose in the evening, and an emerging lifesaving technologies service was called. After emerging lifesaving technologies departure to hospital, she stopped breathing, became pulseless, and cardiopulmonary life support was started immediately. Electrocardiographic monitoring showed asystole during resuscitation even after arrival at hospital. Empty packaging sheets of 60-tablet chlorpromazine (CPZ) (50 mg/tablet) and 66-tablet mirtazapine (MZP) (15 mg/tablet) found at the scene suggested drug-related cardiopulmonary arrest. Along with conventional administration of adrenaline (total dose, 5 mg), 20% Intralipid 100 mLwas given intravenously 8 minutes after hospital arrival and readministered 27 minutes after hospital arrival because of continued asystole. Return of spontaneous circulation occurred 29 minutes after arrival (70 minutes after cardiac arrest). The patient recovered without any major complications and was transferred to another hospital for psychiatric treatment 70 days after admission. Concentrations of CPZ and MZP were still high when return of spontaneous circulation was achieved with ILE. This case suggested the possible benefit of ILE in treating life threatening cardiotoxicity from CPZ and MZP overdose.


Asunto(s)
Antidepresivos Tricíclicos/envenenamiento , Antipsicóticos/envenenamiento , Reanimación Cardiopulmonar/métodos , Clorpromazina/envenenamiento , Sobredosis de Droga/terapia , Emulsiones Grasas Intravenosas/uso terapéutico , Paro Cardíaco/inducido químicamente , Paro Cardíaco/terapia , Mianserina/análogos & derivados , Fosfolípidos/uso terapéutico , Aceite de Soja/uso terapéutico , Depresión/tratamiento farmacológico , Emulsiones/uso terapéutico , Femenino , Humanos , Mianserina/envenenamiento , Mirtazapina , Adulto Joven
19.
Toxicol Mech Methods ; 25(1): 1-12, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25264211

RESUMEN

CONTEXT: Olanzapine is widely used in the treatment of schizophrenia and it is becoming more frequently responsible for overdoses. Standard pharmacokinetic models do not fit to the toxic concentration data. OBJECTIVE: The aim of present study is to investigate the reasons for an abnormal olanzapine plasma concentration time curve in the range of toxic concentrations. Two hypotheses were verified: entering the enterohepatic cycle, and drug deposition and its desorption from activated charcoal used for gastrointestinal decontamination. MATERIALS AND METHODS: One-hundred thirty-five plasma concentration data from 21 patients hospitalized for acute olanzapine poisoning were analyzed with the use of the population pharmacokinetic approach. A non-linear mixed-effects modeling approach with Monolix 4.3.1 was employed. RESULTS: A model assuming gallbladder emptying at irregular intervals was developed. Also, a model that describes desorption of olanzapine from the charcoal surface, in which the dose is divided into two absorbed fractions, was constructed. The analysis has found gastrointestinal decontamination and previous olanzapine treatment, as the significant covariates for toxicokinetic parameters of olanzapine. CONCLUSION: Our study provides interesting models for investigation of toxic concentration of olanzapine, which may also be used as the basis for further model development for other drugs as well. The investigated population was not large enough to reliably confirm any of the proposed models. It would be well worth continuing this study with more substantial data. Also, any additional information about olanzapine metabolite concentration could be vital.


Asunto(s)
Antipsicóticos/farmacocinética , Benzodiazepinas/farmacocinética , Modelos Biológicos , Absorción Fisicoquímica , Adolescente , Adulto , Anciano , Antipsicóticos/sangre , Antipsicóticos/envenenamiento , Benzodiazepinas/sangre , Benzodiazepinas/envenenamiento , Carbón Orgánico/uso terapéutico , Sobredosis de Droga/sangre , Sobredosis de Droga/terapia , Circulación Enterohepática , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Dinámicas no Lineales , Olanzapina , Procesos Estocásticos , Toxicocinética , Adulto Joven
20.
Eur J Pediatr ; 173(6): 743-50, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24370666

RESUMEN

UNLABELLED: 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.


Asunto(s)
Antipsicóticos/envenenamiento , Centros de Control de Intoxicaciones/estadística & datos numéricos , Austria , Preescolar , Femenino , Alemania , Humanos , Lactante , Masculino , Estudios Retrospectivos , Suiza
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