Blood free morphine levels vary with concomitant alcohol and benzodiazepine use

Stenhouse, Grant; Stephen, Duncan W.S.; Grieve, J.

doi:10.1016/j.jcfm.2004.04.008

Cited by 12 publications

(7 citation statements)

References 9 publications

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“…Even in low doses, death may occur, and severe respiratory impairment may persist long after the peak blood morphine concentration has passed [12]. Moreover, consistent with previous research [14,[21][22][23][24][25][26][27], substances in addition to heroin metabolites were detected in almost all cases. Hypnosedatives in particular were highly prevalent, as was alcohol and the gabapentinoids.…”

Section: Discussionsupporting

confidence: 86%

“…Case series provide valuable insights into the circumstances of death and the toxicology of overdose [14,[22][23][24][25][26][27][28][29][30][31][32][33][34]. In many cases, blood morphine (the primary metabolite of heroin) concentrations are low, which may reflect the concomitant role of other drugs, low tolerance in some cases, or persistent respiratory depression after concentrations have declined.…”

Section: Introductionmentioning

confidence: 99%

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A descriptive coronial study of heroin toxicity deaths in Australia, 2020–2022: Characteristics, toxicology and survival times

Darke,

Duflou,

Peacock

et al. 2023

Addiction

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Background and aimsMortality rates among people who use heroin are estimated to be 15 times that of the general population. The study aimed to determine (1) the case characteristics and circumstances of death of heroin‐related toxicity deaths in Australia, 2020–2022; (2) their toxicological profile and major autopsy findings; (3) the proportion of cases in which blood 6‐acetyl morphine (6AM) was detected, as a proxy measure of survival times; and (4) compare 6AM positive and negative cases on toxicology, circumstances of death and acute clinical presentation.DesignRetrospective study of heroin toxicity deaths in Australia, 2020–2022, retrieved from the National Coronial Information System.SettingThis study was conducted Australia‐wide.CasesThere were 610 cases of fatal heroin‐related drug toxicity.MeasurementsInformation was collected on characteristics, manner of death, toxicology and autopsy results.FindingsThe mean age was 42.6 years (range 18–73 years), 80.5% were male and 7.5% were enrolled in a drug treatment programme. The circumstances of death were as follows: unintentional drug toxicity (86.2%), combined unintentional drug toxicity/disease (11.3%) and intentional drug toxicity (2.5%). The median free morphine concentration was 0.17 mg/L (range 0.00–4.20 mg/L). Psychoactive drugs other than heroin were present in 95.2% (Confidence Interval 93.1%–96.8%), most commonly hypnosedatives (62.3%, 58.2%–66.4%) and psychostimulants (44.8%, 40.7%–49.1%). Major autopsy findings of clinical significance included acute bronchopneumonia (14.8%, 11.3%–18.8%), emphysema (16.9%, 13.2%–21.1%), cardiomegaly (30.1%, 12.7%–28.2%), coronary artery disease (27.4%, 23.0%–32.3%), coronary replacement fibrosis (13.4%, 10.1%–17.3%), hepatic cirrhosis (8.8%, 6.6%–12.2%) and renal fibrosis (10.3%, 7.3%–14.0%). In 47.0% (42.3%–51.2%), 6AM was present in blood.ConclusionsThe ‘typical’ heroin overdose case in Australia from 2020 to 2022 was a male who injected heroin, aged in the 40s, not enrolled in a treatment programme and had used multiple drugs. In over half of cases, there had been a sufficient survival time for 6‐acetyl morphine to have been metabolised, which may indicate times in excess of 20–30 min.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

A descriptive coronial study of heroin toxicity deaths in Australia, 2020–2022: Characteristics, toxicology and survival times

Darke,

Duflou,

Peacock

et al. 2023

Addiction

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“…Interestingly, the median concentration of free morphine in blood was lower in people also drinking alcohol (median 0.20 mg/l) and highest when heroin users had taken a benzodiazepine (median 0.30 mg/l). This result agrees with an earlier study showing lower free morphine when alcohol was coingested [28]. The mechanism accounting for this finding is not obvious because both ethanol and benzodiazepines act as depressants of the central nervous system and interact with the GABA A receptor complex [29].…”

Section: Discussionsupporting

confidence: 92%

Heroin poisoning deaths with 6-acetylmorphine in blood: demographics of the victims, previous drug-related offences, polydrug use, and free morphine concentrations in femoral blood

2011

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This article discusses cases of drug-poisoning death in which 6-acetylmorphine (6-AM) was identified in blood as evidence for recent use of heroin. We report the demographics of the victims, previous drug-related offences, polydrug use, and the concentrations of free morphine in peripheral blood. After solid-phase extraction, morphine, codeine, and 6-AM were determined in blood samples by isotope-dilution gas chromatography-mass spectrometry (GC-MS) using limits of quantitation of 0.005 mg/l for each opiate. The victims of heroin poisoning were mainly men (88%), with a mean age of 35.4 ± 8.4 years (±SD) and no significant gender difference in age (men 35 ± 8.4 years; women 35 ± 8.6 years). The median concentration of free morphine in blood (n = 671) was 0.25 mg/l (66% [ 0.20 mg/l) and women had a higher concentration (0.30 mg/l) than men (0.24 mg/l) (P \ 0.05). No significant difference (P [ 0.05) was found for the concentration of free morphine in blood when heroin was the only drug taken (median 0.26 mg/l, n = 53) compared with multidrug deaths (median 0.24 mg/l, n = 618) (P [ 0.05). The coingested drugs most commonly identified in heroin-related deaths were ethanol (44%), diazepam (27%), cannabis (20%), and flunitrazepam (19%). We found that 61% of victims had previous drugrelated offences ranging from 1 to 48 times. The close agreement between the concentrations of free morphine in blood when heroin was the only drug taken and multidrug deaths suggests that differences in tolerance to opiates is more important in causing death than adverse drug-drug interactions.

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“…To my knowledge, this was the first time this was asserted. History would prove him right . The main drugs he identified were other central nervous system (CNS) depressants, notably alcohol and the barbiturates.…”

Section: The Classicsmentioning

confidence: 99%

“…Many heroin ‘overdose’ deaths appear to involve quite low morphine concentrations [2–4,6–10]. What we term ‘heroin’ overdoses involve predominantly polydrug toxicity [2–4,10–13]. Drug purity has only moderate influence, and is not an overwhelmingly important factor [14,15].…”

Section: Introductionmentioning

confidence: 99%