Clozapine Intoxication Mimicking Acute Stroke

Lebin, Jacob A.; Villarreal, Joshua; Chen, Betty C.; Hall, M. Kennedy

doi:10.5811/cpcem.2018.1.36734

Cited by 7 publications

(11 citation statements)

References 12 publications

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“…Most adverse effects disappear during the initial 4–6 weeks of treatment due to the development of tolerance [ 8 , 9 ]. Based on this clinical experience, some authors postulate greater toxicity in patients with acute clozapine poisoning who have not been exposed to it previously [ 4 , 10 ]. The evidence and pathophysiology of this hypothesis remain uncertain.…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment of an Acute High-Dose Clozapine Poisoning without Detoxication

et al. 2021

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Patient: Male, 28-year-old Final Diagnosis: Clozapine poisoning Symptoms: Drowsiness • hyperventilation • impaired consciousness • respiratory insufficiency • tachycadia Medication: — Clinical Procedure: — Specialty: Critical Care Medicine • Psychiatry Objective: Management of emergency care Background: Clozapine is a well-proven atypical antipsychotic drug used for therapy of treatment-resistant schizophrenia. Over the last decades only a few cases of clozapine poisoning have been reported. Hence, guidelines for inhospital management are currently not available. Most of the reported cases underwent detoxication measures as charcoal therapy and/or gastric lavage. However, there is no evidence for primary detoxication to improve clinical outcome. In contrast, use of therapy with intravenous physostigmine in the case of anticholinergic syndrome is restricted due to concerns about safety and dosing. We present a case of acute high-dose clozapine poisoning without detoxication and complete recovery supported by physostigmine. Case Report: We report the case of a 28-year-old man with prior diagnosed schizophrenia who presumably ingested 8 g (regular maximum daily dose 900 mg/d) of clozapine with uncertain intent. Initial computed tomography (CT) showed pulmonary infiltrates and widespread pneumomediastinum and soft-tissue emphysema of unknown genesis. The patient developed a progressive impairment of vigilance and respiratory insufficiency requiring invasive artificial ventilation for 31 h. Afterwards, an anticholinergic syndrome led again to impaired vigilance, tachycardia, and hyperventilation. To avoid risks associated with artificial ventilation, we applied physostigmine. Subsequently, the anticholinergic syndrome and the pneumomediastinum completely regressed and no further artificial ventilation was needed. Conclusions: Based on the presumably ingested dosage, we present the likely highest reported nonfatal overdose of clozapine without detoxication. Additionally, we observed widespread pneumomediastinum as an uncommon complication. Our approach was to refrain from detoxication to minimize complications and to treat early with physostig-mine because of anticholinergic syndrome to minimize its impact and to avoid artificial ventilation due do vigilance impairment.

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Section: Discussionmentioning

confidence: 99%

Successful Treatment of an Acute High-Dose Clozapine Poisoning without Detoxication

et al. 2021

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“…Stock solutions of each drug having concentrations of 1.0 mg/mL for PHY and 0.66 mg/mL for CLZ were prepared in order to attain their toxic dose in blood as reported previously in the literature [7,8]. The pharmaceuticals were dissolved in a mixture of propylene glycol: 0.9% sodium chloride (40: 60, v/v).…”

Section: In Vivo Analysis Of Clozapine and Phenytoinmentioning

confidence: 99%

“…Further application of the proposed method to in vivo experiment was attained by injecting experimental rats with the reported toxic doses of CLZ and PHY (0.66 and 1 mg/mL) respectively [7,8], so as to mimic the stroke syndrome accompanied with their toxicity. The drugs were injected in three rats to take the average response, where the mean concentration of CLZ and PHY were 61.73 and 25.0 µg/mL respectively.…”

Section: In Vivo Analysismentioning

confidence: 99%

A diagnostic intoxication tool for clozapine and phenytoin using hybrid micelle liquid chromatography

Ayman

El-Shabrawy

Zeid

et al. 2021

Journal of Taibah University for Science

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Micellar liquid chromatography was employed for the quantification and separation of the antidepressant drug clozapine (CLZ) and antiepileptic agent phenytoin (PHY). This mixture was separated using C8 column operating at 40°C using a mobile phase consisting of 0.075 M sodium dodecyl sulphate (SDS), 10% acetonitrile, 0.3% triethylamine (TEA), adjusted to pH 2.5 by 2 M ortho-phosphoric acid and applying a simple gradient program starting with a flow rate of 0.8 mL/min for the first 10 min of analysis applying 220 nm as detection wavelength, followed by raising the flow rate to 1.5 mL/min till end of analysis, adopting UV detection wavelength of 250 nm. The proposed method was used to quantify the concentration of both (CLZ) and (PHY) in rat whole blood whether spiked or in vivo suggesting its utility as a diagnostic tool for intoxication with either drugs in emergency rooms.

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“…Клозапин -атипичный нейролептик, применяемый для лечения заболеваний центральной нервной системы. В литературе описаны многочисленные осложнения, связанные с приемом клозапина: агранулоцитоз [1], миокардит [2-4], кататония [5], альвеолит [6], усиление токсичности клозапина при развитии инфекционных осложнений [7][8][9], рабдомиолиз [10], имитация инсульта [11], отсроченные осложнения при тяжелой клозапиновой интоксикации [12][13], кома [14].…”

Section: ◊ введениеunclassified

Purkinje Cells of the Cerebellum in Clozapine and Clozapine Ethanol Poisoning (Experimental Research)

Голубев

Сундуков

Churilov

et al. 2019

Russian Journal of Forensic Medicine

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Objectives. Systematization of cerebellar Purkinje cell injuries to clarify the pathogenesis of combined clozapine-alcohol poisoning and to substantiate the immediate cause of death. Material and methods. Experimental studies were performed on 25 white outbreed rats divided into 5 groups: control, group I (clozapine 3 hours), group II (clozapine 24 hours), group III (clozapine + alcohol 3 hours), group IV (clozapine+alcohol 24 hours). Te assessment of Purkinje cell injury was performed using the classifcation of neuronal damage.Results. In the control group of animals reversible changes in Purkinje cells prevailed: primary irritation and acute swelling (15-20%). Irreversible changes were detected in 2-5%. In case of clozapine poisoning the number of Purkinje cells with irreversible changes (shrinking, karyocytolysis, severe changes, Ghost-like cells) was increased. Te percentage of Purkinje cells with such changes was 30-40%. In case of combined clozapine-alcohol poisoning the percentage of irreversible Purkinje cells injury increased to 40-60% (especially 24 hours afer starting the study). Quantitative diferences in irreversible changes in Purkinje cells in the experimental groups were statistically signifcant if compared to the controls (p<0.05). Conclusion. As a result of the study the most commonly detected injuries of Purkinje cells of cerebellum in clozapine poisoning were revealed. Te most prominent damage to Purkinje cells with predominance of irreversible changes were found in cases of combined clozapine-alcohol poisoning. 24-hour duration of the experiment led to the more severe Purkinje cell injuries if compared to the 3-hour duration.

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Clozapine Intoxication Mimicking Acute Stroke

Cited by 7 publications

References 12 publications

Successful Treatment of an Acute High-Dose Clozapine Poisoning without Detoxication

Successful Treatment of an Acute High-Dose Clozapine Poisoning without Detoxication

A diagnostic intoxication tool for clozapine and phenytoin using hybrid micelle liquid chromatography

Purkinje Cells of the Cerebellum in Clozapine and Clozapine Ethanol Poisoning (Experimental Research)

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