Suspected Opioid Overdose Case Resolved by CYP2D6 Genotyping

Division of Translational Therapeutics, Department of Paediatrics, Faculty of Medicine, University of British Columbia, Canada.
Therapeutic drug monitoring (Impact Factor: 2.38). 03/2012; 34(2):121-3. DOI: 10.1097/FTD.0b013e31824a1e21
Source: PubMed


A 14-year-old female with suspected narcotic overdose had CYP2D6 genotyping performed to verify opiate intoxication. The role of pharmacogenetics in pain management and individualization of opiate pharmacotherapy is discussed.

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    ABSTRACT: The advances in high-throughput genomic technologies have improved the understanding of disease pathophysiology and have allowed a better characterization of drug response and toxicity based on individual genetic make up. Pharmacogenomics is being recognized as a valid approach used to identify patients who are more likely to respond to medication, or those in whom there is a high probability of developing severe adverse drug reactions. An increasing number of pharmacogenomic studies are being published, most include only adults. A few studies have shown the impact of pharmacogenomics in pediatrics, highlighting a key difference between children and adults, which is the contribution of developmental changes to therapeutic responses across different age groups. This review focuses on pharmacogenomic research in pediatrics, providing examples from common pediatric conditions and emphasizing their developmental context.
    Pharmacogenomics 11/2013; 14(15):1889-905. DOI:10.2217/pgs.13.193 · 3.22 Impact Factor
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    ABSTRACT: Background The non-medical use of pharmaceutical opioids such as codeine is of increasing public health concern. The aim of the study was to describe codeine intoxication experiences amongst recreational drug users, as posted on public internet forums. Methods Internet searches were carried out by using the specific key word ‘codeine’ and in combination with ‘experience’, ‘report’, ‘trip’ and ‘forum’. 96 Trip reports and 156 thread discussions relating to the sole use of codeine were analysed using the empirical phenomenological psychological (EPP) method. Nine themes and 72 categories emerged. Results Narratives illustrated transitions between medical and non-medical use of codeine for dulling of emotional and/or physical pain, opiate withdrawal management and for intoxication. Codeine's appeal centred on access via family medicine cabinets, prescribers and pharmacies. Discussion and dissemination of indigenous harm reduction tactics included the learning to appreciate codeine's effect via moderated use in optimal settings, avoidance of tolerance by use of informed dosing schedules, cold water extraction of codeine, and using codeine as an alternative to stronger opioids. Oral and rectal routes were favoured, with awareness on forums of the harms of intravenous and subcutaneous injection. 250 mg was recommended to optimise recreational outcomes. Forum users describe potentiating practices and using over-the-counter medications to improve intoxication experiences and reduce unpleasant side effects. Dissociative effects, ability to ignore physical and emotional pain, codeine induced synaesthesia and altered states of consciousness were described. Overdose was characterised by anaesthesia, severe chest and stomach pain, respiratory depression, panic and fear of death. Conclusions Efforts to ensure legitimate codeine use for pain and reduction of aberrant behaviours centre on evidence based screening, risk minimisation, prescription monitoring and specific treatment protocols. This study shows that internet drug forums drive communal knowhow and indigenous harm reduction strategies, and warrant consideration as viable public health mechanisms for informing users.
    International Journal of Drug Policy 12/2014; 26(1). DOI:10.1016/j.drugpo.2014.06.016 · 2.40 Impact Factor
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    ABSTRACT: Cytochrome P450 2D6 (CYP2D6) is a member of the cytochrome P450 (CYP) superfamily involved in the biotransformation of drugs and substances of abuse encountered in clinical toxicology. Among the CYP superfamily, the CYP2D6 gene is considered as the most polymorphic as more than 105 different alleles have been identified so far. CYP2D6 genetic polymorphisms have the potential to affect the toxicity of their substrates. This review will focus specifically on CYP2D6 genetic polymorphisms and their relevance for poisoning due to amphetamines, opioid analgesics and antidepressants in humans. PubMed (up to August 2013) was searched with the following selection criteria: 'CYP2D6 AND (toxicology OR poisoning OR intoxication OR overdose)'. Of the 454 citations retrieved, only 46 papers dealt with the impact of CYP2D6 polymorphisms on poisoning due to amphetamines, opioid analgesics and antidepressants. Amphetamines. While some in vitro studies suggest that CYP2D6-mediated metabolites of 3,4-methylenedioxymethamphetamine (MDMA) are substantially more cytotoxic compared with unchanged MDMA, it is not yet confirmed in human cases of MDMA intoxication that extensive/ultra-rapid CYP2D6 metabolisers could be at higher risk. This would also apply to methamphetamine exposure and the related cardiac and central nervous system toxicity. Opioid analgesics. CYP2D6 ultra-rapid metabolisers are more likely to experience the adverse effects of codeine and tramadol. Opioid analgesics that do not rely on CYP2D6 for therapeutic activity, such as morphine and hydromorphone, may therefore be a better alternative to codeine and tramadol, with the limitation that these drugs have their own set of adverse reactions. Antidepressants. CYP2D6 poor metabolisers are generally more prone to adverse effects. Among them, the four drugs with the highest level of evidence are amitriptyline, nortriptyline, venlafaxine and fluoxetine. Further data are needed, however, for doxepin and paroxetine, while citalopram adverse effects seem definitely less influenced by CYP2D6 genetic polymorphisms. Either poor or extensive/ultra-rapid CYP2D6 metabolisers may be exposed to toxic effects of amphetamines, opioid analgesics and antidepressants. In these three categories, the level of evidence is substance dependent, with differences within the same pharmacological class.
    Clinical Toxicology 05/2015; 53(6):1-10. DOI:10.3109/15563650.2015.1049355 · 3.67 Impact Factor

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