Introduction Olanzapine is an atypical antipsychotic of the thienobenzodiazepine class. The chlorobutane was separated, concentrated under nitrogen and injected onto the gas chromatograph GC with nitrogen—phosphorus detection NPD. This website also contains material copyrighted by 3rd parties. Time from death to discovery is variable and may be unknown. Am J Med Pathol ; Selling or giving away this medicine is against the law. Selling or giving away clonazepam is against the law. This is what happens to your brain when you take Xanax
The findings have clinical relevance, but the significance, particularly for olanzapine, is unclear given the lack of comparative data at this point. The inherent difficulties in collecting these data include lack of computerized databases, toxicology findings not systematically recorded by drug, and cause of death not recorded as an overdose. Interpretation of postmortem concentrations of new drugs is particularly difficult because no postmortem database exists and perimortem details are usually unavailable.
Postmortem concentrations are usually compared with therapeutic or pharmacokinetic data because this is the only information available and, consequently, high concentrations are interpreted as consistent with overdose. Furthermore, the number of cases detected is not only a function of the frequency of drug use in that particular jurisdiction but also of the analytical procedures used by the investigating laboratory.
However, risperidone and pimozide are not detected by the screening procedures used in most postmortem toxicology laboratories, and their overdose occurrence is thus likely to be under-reported. The relative safety of the atypical antipsychotics has been comprehensively reviewed elsewhere. Also, a review of inquiries to the UK National Poisons Information Service over 9 months revealed no fatalities after overdoses of atypical antipsychotics.
However, the outcome of treated overdoses in hospital settings likely differs from outcomes for individuals who do not receive active intervention, and, as the authors comment, patients who die outside of hospital are unlikely to be revealed by inquiries to a poison centre. Gardner et al 31 reported rapid recovery with the use of activated charcoal in a year-old woman from an overdose of mg of olanzapine that was associated with initial tachypnea, tachycardia, unstable blood pressure and hypoxemia.
The findings of this review suggest an adverse outcome for patients often with pre-existing undetected physical pathology such as cardiovascular disease who take overdoses of multiple medications and do not receive intervention. Olanzapine has a high volume of distribution i. After death, significant redistribution from liver to central blood specimens occurs, and the higher range of olanzapine concentrations in postmortem blood is consistently observed independent of any assay differences.
Higher concentrations are also observed in central heart blood specimens than in peripheral femoral blood specimens. Postmortem olanzapine blood concentrations may not represent true antemortem or perimortem levels and should be interpreted cautiously. In only 1 case of our series 17 was an antemortem specimen available for comparison. The patient died approximately 2 hours after admission to hospital, and the postmortem olanzapine heart blood concentration was elevated 5-fold over the antemortem level.
Thus, because of olanzapine's instability in blood, sample concentrations should be measured as soon as possible after death. Compounds with a heterocyclic sulfur atom, such as chlorpromazine and perphenazine, are readily oxidized to sulfoxides and sulfones and are unstable in liver homogenates; 34 olanzapine may be similarly subject to in vitro degradation. The significant variation in blood concentrations of olanzapine in clinical practice makes it difficult to interpret postmortem findings.
Olanzapine is extensively metabolized in the liver, 39 and an impairment of enzyme-mediated metabolism may lead to variable blood concentrations. However, the existence of multiple pathways for olanzapine metabolism suggests that an alteration of one route of metabolism may not necessarily result in significant change in the clearance of olanzapine in vivo.
In many overdose situations, there is often limited information concerning concomitant medications that were recently prescribed but not necessarily taken at the time of overdose. Furthermore, in clinical practice, antipsychotics are frequently taken in conjunction with other drugs and at greater than recommended doses. Although the specific pathophysiology remains undetermined at this time, it has been suggested that the most likely mechanism of death in an overdose of olanzapine involves cardiac toxicity at the cellular membrane level.
Sudden death is more common in patients with psychiatric problems, particularly those receiving antipsychotic drugs. An analysis of 85 fatal intoxications found that pimozide and olanzapine were less likely to be associated with death in overdose than prothipendyl and chlorprothixene, 45 which is surprising given pimozide's known cardiotoxicity. Similarly, diabetes mellitus and obesity both additional risk factors for cardiovascular disease are more prevalent in patients with schizophrenia, and an increased risk of these disorders has been reported in patients taking olanzapine.
In summary, although olanzapine has been associated with toxicity in certain overdose situations, evidence of any direct relation remains limited. The adverse consequences of overdose are compounded in psychiatric populations because of frequent, yet often undiagnosed or untreated physical illnesses, complex polypharmacy with high doses of psychotropic drugs and delayed or absent interventions.
Infrequent, serious adverse effects can occur, and early signal detection and effective notification processes are crucial when they do occur. It is recommended that similar toxicology data reviews be conducted for commonly prescribed psychotropic drugs. None declared for Dr. Pierre Chue, 3rd Floor, St. National Center for Biotechnology Information , U.
Journal List J Psychiatry Neurosci v. Pierre Chue and Peter Singer. This article has been cited by other articles in PMC. Abstract Objective Given the increasing use of atypical antipsychotics in psychiatric populations and the very limited data concerning the safety of such drugs, we examined the available data on olanzapine in untreated overdose situations. Methods Available toxicity data concerning olanzapine were obtained from the Offices of the Medical Examiners of Canada, the Canadian Adverse Drug Reaction Monitoring Program and a review of the literature.
Results Despite the complexities and limitations of postmortem data analysis, 29 deaths were identified where an overdose of olanzapine was either the principal cause of toxicity or a significant contributor in combined toxicity. Conclusions Olanzapine is associated with toxicity in certain overdose situations, but evidence of any relation is limited and likely influenced by the higher rates of cardiovascular disease and sudden death in subjects with schizophrenia.
Recommendations Similar toxicity data reviews should be conducted for all commonly prescribed psychotropics. Introduction Olanzapine is an atypical antipsychotic of the thienobenzodiazepine class. Results Of the 29 toxicology cases with recorded olanzapine levels, 11 were reported in the literature Table 1 , 15 by medical examiners Table 2 , Table 3 and 1 in the Canadian Adverse Drug Reaction Monitoring Programme Table 3.
Discussion Given the limitations of autopsy material, a causal relation cannot be inferred from the data presented. J Clin Psychiatry ; The safety of olanzapine compared with other antipsychotic drugs: Adult and pediatric olanzapine overdose [abstract A]. J Toxicol Clin Toxicol ; A new atypical antipsychotic. Psychiatric times' advances in psychopharmacology.
Olanzapine overdose with serum concentrations. Ann Emerg Med ; Am J Psychiatry ; Overdose with olanzapine Zyprexa , a new antipsychotic agent [abstract A]. Olanzapine overdose mimicking opioid intoxication. Ann Emerg Med ; Pupillary effects of olanzapine overdose mimic opiate and alpha-2 agonists [abstract]. Fogel J, Diaz JE. Olanzapine overdose cause of acute extrapyramidal symptoms.
Yip L, Graham K. Olanzapine toxicity in a toddler [letter]. Olanzapine overdose in an month-old child. J Child Adolesc Psychopharmacol ;9: Olanzapine overdose in a 1-year-old male. Pediatr Emerg Care ; Anderson DT, Kuwahara T. Thirty-five case studies involving postmortem tissue distribution of olanzapine Zyprexa [abstract A95]. Eli Lilly Canada Inc. Olanzapine concentrations in clinical serum and postmortem blood specimens — when does therapeutic become toxic?
J Forensic Sci ; Fatal overdose of olanzapine. Forensic Sci Int ; Gerber JE, Cawthon B. Overdose and death with olanzapine. Am J Forensic Med Pathol ; Olanzapine concentrations in forensic investigations [abstract A]. Am J Emerg Med ; Can Adverse Drug React Newsl ; The pharmacology and toxicology of atypical antipsychotic agents. Lower mortality in geriatric patients receiving atypical antipsychotics compared to haloperidol [abstract A].
Overdose profiles of new antipsychotic agents. Int J Neuropsychopharmacol ;3: Site dependence of drug concentrations in postmortem blood — a case study. J Ann Toxicol ; The stability of some drugs and poisons in putrefying human liver tissues. J Forensic Soc ; Use all medications as directed by your doctor.
Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Keep track of the amount of medicine used from each new bottle. Clonazepam is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription. Dosage Information in more detail. Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose.
Do not take extra medicine to make up the missed dose. Clonazepam may impair your thinking or reactions. Avoid driving or operating machinery until you know how this medicine will affect you. Dizziness or severe drowsiness can cause falls or other accidents. Get emergency medical help if you have signs of an allergic reaction to clonazepam: Report any new or worsening symptoms to your doctor, such as: The sedative effects of clonazepam may last longer in older adults.
Accidental falls are common in elderly patients who take benzodiazepines. Use caution to avoid falling or accidental injury while you are taking clonazepam. This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. Side effects in more detail. Up to 10 years of age or 30 kg of body weight: See adult dosing Comments: Taking this medicine with other drugs that make you sleepy or slow your breathing can cause dangerous side effects or death.
Ask your doctor before taking a sleeping pill, an opioid medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures. Other drugs may interact with clonazepam, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.
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