Opioid-induced respiratory depression in humans: a review of pharmacokinetic-pharmacodynamic modelling of reversal.

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Abstract

Opioids are potent painkillers but come with serious adverse effects ranging from addiction to potentially lethal respiratory depression. A variety of drugs with separate mechanisms of action are available to prevent or reverse opioid-induced respiratory depression (OIRD).

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Most cited references 62

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Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene.

H Matthes, R. Maldonado, F Simonin … (1996)

Despite tremendous efforts in the search for safe, efficacious and non-addictive opioids for pain treatment, morphine remains the most valuable painkiller in contemporary medicine. Opioids exert their pharmacological actions through three opioid-receptor classes, mu, delta and kappa, whose genes have been cloned. Genetic approaches are now available to delineate the contribution of each receptor in opioid function in vivo. Here we disrupt the mu-opioid-receptor gene in mice by homologous recombination and find that there are no overt behavioural abnormalities or major compensatory changes within the opioid system in these animals. Investigation of the behavioural effects of morphine reveals that a lack of mu receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence. We observed no behavioural responses related to delta- or kappa-receptor activation with morphine, although these receptors are present and bind opioid ligands. We conclude that the mu-opioid-receptor gene product is the molecular target of morphine in vivo and that it is a mandatory component of the opioid system for morphine action.

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A flood of opioids, a rising tide of deaths.

Susan Okie (2010)

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Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016

Hawre Jalal, Jeanine M. Buchanich, Mark Roberts … (2018)

Better understanding of the dynamics of the current U.S. overdose epidemic may aid in the development of more effective prevention and control strategies. We analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System in which accidental drug poisoning was identified as the main cause of death. By examining all available data on accidental poisoning deaths back to 1979 and showing that the overall 38-year curve is exponential, we provide evidence that the current wave of opioid overdose deaths (due to prescription opioids, heroin, and fentanyl) may just be the latest manifestation of a more fundamental longer-term process. The 38+ year smooth exponential curve of total U.S. annual accidental drug poisoning deaths is a composite of multiple distinctive subepidemics of different drugs (primarily prescription opioids, heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with its own specific demographic and geographic characteristics.

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Author and article information

Journal

Journal ID (iso-abbrev): Br J Anaesth

Title: British journal of anaesthesia

Publisher: Elsevier BV

ISSN (Electronic): 1471-6771

ISSN (Print): 0007-0912

Publication date (Electronic): Jun 2019

Volume: 122

Issue: 6

Affiliations

[1 ] Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.

[2 ] Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: a.dahan@lumc.nl.

Article

Publisher Item ID: S0007-0912(19)30008-X

DOI: 10.1016/j.bja.2018.12.023

PubMed ID: 30915997

SO-VID: 33270aa2-5b0d-47da-9047-53505218e599

History

Keywords: naloxone,breathing,respiratory depression,pharmacokinetics,pharmacodynamics,opioids

Data availability:

Keywords: naloxone, breathing, respiratory depression, pharmacokinetics, pharmacodynamics, opioids

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Opioid-induced respiratory depression in humans: a review of pharmacokinetic-pharmacodynamic modelling of reversal.

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Abstract

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Dermal Microdialysis in Pharmacokinetics

Most cited references 62

Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene.

A flood of opioids, a rising tide of deaths.

Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016

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