The redistribution of selected psychiatric drugs in post-mortem cases

Rodda, Kabrena E; Drummer, Olaf H.

doi:10.1016/j.forsciint.2006.02.013

Cited by 65 publications

(31 citation statements)

References 19 publications

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“…Moreover, post-mortem material is known to pose difficulties for the interpretation of toxicology results [52]. In the present study, only femoral venous blood samples were included, which minimizes the risk of post-mortem redistribution [53,54]. The extent to which the vast number of interacting drugs interferes with the metabolic ratios in relation to genotype remains uncertain, but the result portrays the real situation in patients on VEN.…”

Section: Discussionmentioning

confidence: 99%

Fatal venlafaxine poisonings are associated with a high prevalence of drug interactions

et al. 2010

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Venlafaxine (VEN) is an antidepressant found to possess a higher fatal toxicity index (FTI, i.e., deaths in proportion to consumption) than other newer antidepressants and selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to elucidate using post-mortem cases whether the apparent high toxicity of VEN is associated with adverse drug interactions, pharmacogenetic factors and/or the manner of death. Within a 2-year period, a comprehensive post-mortem database and death certificates were searched for cases with laboratory findings of VEN, findings of other drugs, associated background information and the cause and manner of death. In 123 cases, the concentrations of VEN and its two metabolites, O-desmethylvenlafaxine (O-VEN) and N-desmethylvenlafaxine (N-VEN), and the CYP2D6 genotype were determined in post-mortem blood. The median concentrations of VEN, O-VEN and N-VEN were 560, 420 and 49 µg/l, respectively. A prominent feature of the VEN-positive cases was the high abundance of interacting drugs (46%), being more common with higher VEN concentrations. Compared to other common antidepressants, VEN-positive cases showed the highest suicide frequency, but also the proportion of suicidal VEN poisonings of all suicides was substantially higher than that of mirtazapine or SSRIs. Relative CYP2D6 activity did not predispose to high VEN concentrations, and the frequency of the extreme phenotypes followed the general population. In conclusion, the high suicide potential of VEN in combination with the high prevalence of drugs causing adverse interactions could be the reason for the observed high FTI.

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Section: Discussionmentioning

confidence: 99%

Fatal venlafaxine poisonings are associated with a high prevalence of drug interactions

et al. 2010

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“…The pharmacological and toxicological information obtained from the drug distribution in tissues and cells is important for understanding and predicting both drug reaction and toxicity [3,4]. Oral doses of antipsychotics for the treatment of schizophrenia patients are on the order of a few milligrams per day.…”

Section: Introductionmentioning

confidence: 99%

Screening and quantification of antipsychotic drugs in human brain tissue by liquid chromatography–tandem mass spectrometry: Application to postmortem diagnostics of forensic interest

Sampedro

Unceta

Gómez‐Caballero

et al. 2012

Forensic Science International

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“…The article suggests that postmortem therapeutic concentrations that were not related to overdose occur with blood levels between 0.15 and 2.7 mg/L [5]. Drugs with increased lipophilicity, low protein binding, and increased diffusion across gastrointestinal tract into tissues as well as drugs with volumes of distribution >3 L/kg may contribute to increased postmortem redistribution [11]. According to Parker and McIntyre, the volume of distribution of 8-10 L/kg indicates variability of quetiapine concentration among specimen types, and overall mean data suggests that its postmortem redistribution is small [12].…”

Section: Discussionmentioning

confidence: 99%

Late-onset seizures associated with quetiapine poisoning

Young

Kleinschmidt²,

Wax³

2009

J. Med. Toxicol.

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Introduction: Quetiapine, a second-generation antipsychotic, acts at multiple brain neurotransmitter receptors and has the potential for serious complications. Although seizures have been described in the literature, delayed seizure onset has not been reported. We report the first case of delayed seizures after a significant quetiapine overdose.Case Report: A 27-year-old female presented to the emergency department following an overdose of approximately 30 g of quetiapine. Twenty-four hours after arrival, the patient had 2 seizures. The patient was then intubated and remained in the ICU for four days. EEG was negative for epileptiform activity. The serum quetiapine levels (MedTox, St. Paul, MN) were 8.67 mg/L on hospital day one and 3.28 mg/L on hospital day three.Discussion: Quetiapine poisoning, with serum levels, associated with seizures has been reported in one prior case. Our case report represents late-onset seizures with serum levels above therapeutic range (>1 mg/L). The serum concentrations of quetiapine in this case were consistent with those in postmortem case reports. Toxicology Observations

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The redistribution of selected psychiatric drugs in post-mortem cases

Cited by 65 publications

References 19 publications

Fatal venlafaxine poisonings are associated with a high prevalence of drug interactions

Fatal venlafaxine poisonings are associated with a high prevalence of drug interactions

Screening and quantification of antipsychotic drugs in human brain tissue by liquid chromatography–tandem mass spectrometry: Application to postmortem diagnostics of forensic interest

Late-onset seizures associated with quetiapine poisoning

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