Pharmacological data science perspective on fatal incidents of morphine treatment

Noufal, Yazan; Kringel, Dario; Toennes, Stefan W.; Dudziak, R.; Lötsch, Jörn

doi:10.1016/j.pharmthera.2022.108312

Cited by 4 publications

(9 citation statements)

References 191 publications

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“…In the case of oral administration, the maximum daily dose can reach as high as 30 mg, considering the effects of first-pass metabolism [ 133 ]. It is worth noting that there is not a well-defined toxic dose or specific plasma/blood concentration for morphine [ 44 ]. However, its use carries a substantial risk of addiction and misuse, contributing to a range of serious health complications [ 134 ].…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, the administration of higher doses of morphine can lead to respiratory depression and potentially life-threatening health issues [ 135 ]. The use of morphine for analgesia has been associated with a significant number of drug-related deaths, with estimated incidence rates ranging from 0.3% to 4% [ 44 , 136 ]. Additionally, morphine can be detected in trace amounts not only in biological fluids but also in aqueous environments [ 137 ].…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, this interaction with the dopamine-reward pathway is responsible for the pain-relieving properties of morphine, as it alters the perception of pain signals in the brain [ 41 , 42 ]. Intentionally administered morphine or morphine generated through the metabolism of other drugs, such as heroin, may potentially cause respiratory depression and even lead to fatal outcomes when taken in high doses [ 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

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Unveiling Morphine: A Rapid and Selective Fluorescence Sensor for Forensic and Medical Analysis

Boroujerdi,

Butt,

Paul

et al. 2024

Sensors

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Opioid use, particularly morphine, is linked to CNS-related disorders, comorbidities, and premature death. Morphine, a widely abused opioid, poses a significant global health threat and serves as a key metabolite in various opioids. Here, we present a turn-off fluorescent sensor capable of detecting morphine with exceptional sensitivity and speed in various samples. The fluorescent sensor was developed through the dimerization process of 7-methoxy-1-tetralone and subsequent demethylation to produce the final product. Despite morphine possessing inherent fluorophoric properties and emitting light in an approximately similar wavelength as the sensor’s fluorescent blue light, the introduction of the target molecule (morphine) in the presence of the sensor caused a reduction in the sensor’s fluorescence intensity, which is attributable to the formation of the sensor–morphine complex. By utilizing this fluorescence quenching sensor, the chemo-selective detection of morphine becomes highly feasible, encompassing a linear range from 0.008 to 40 ppm with an impressive limit of detection of 8 ppb. Consequently, this molecular probe demonstrates a successful application in determining trace amounts of morphine within urine, yielding satisfactory analytical results. The study also explores the effect of several variables on the sensor’s response and optimizes the detection of morphine in urine using a response surface methodology with a central composite design.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Unveiling Morphine: A Rapid and Selective Fluorescence Sensor for Forensic and Medical Analysis

Boroujerdi,

Butt,

Paul

et al. 2024

Sensors

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“…In contrast, for codeine, studies concluded that there was a large variability in the calculated post-mortem concentration ratios of codeine to its metabolite, morphine, which was not explained by the CYP2D6 genotypes alone [ 16 , 24 , 28 ]. A recent systematic review has shown that the reliability and validity of measuring morphine concentrations in post-mortem samples are low [ 37 ]. This is because there are post-mortem changes, including post-mortem morphine metabolism and redistribution, that could result in a wide range of morphine blood concentrations reported in deaths [ 37 ].…”

Section: Resultsmentioning

confidence: 99%

“…A recent systematic review has shown that the reliability and validity of measuring morphine concentrations in post-mortem samples are low [ 37 ]. This is because there are post-mortem changes, including post-mortem morphine metabolism and redistribution, that could result in a wide range of morphine blood concentrations reported in deaths [ 37 ]. Morphine is mainly metabolized into morphine-3-glucuronide (M3G, inactive metabolite) and morphine-6-glucuronide (M6G, equal or greater affinity at the mu-opioid receptor than morphine) by the UDP-glucuronosyltransferase 2B7 (UGT2B7) enzyme ( Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study

Magarbeh

Gorbovskaya

Wells

et al. 2023

JPM

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There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case–controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids.

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Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS

Dai,

Dou,

Chen

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Pharmacological data science perspective on fatal incidents of morphine treatment

Cited by 4 publications

References 191 publications

Unveiling Morphine: A Rapid and Selective Fluorescence Sensor for Forensic and Medical Analysis

Unveiling Morphine: A Rapid and Selective Fluorescence Sensor for Forensic and Medical Analysis

Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study

Strong opioids-induced cardiac, neurologic, and respiratory disorders: a real-world study from 2004 to 2023 based on FAERS

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