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Anesthesiology Sep 2023Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the... (Review)
Review
Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed. Long-acting opioids, and those with a high affinity at the µ-opioid receptor and/or slow receptor dissociation kinetics, are particularly resistant to the effects of naloxone. In this review, the authors examine the pharmacology of naloxone and its safety and limitations in reversing opioid-induced respiratory depression under different circumstances, including its ability to prevent cardiac arrest.
Topics: Humans; Naloxone; Analgesics, Opioid; Narcotic Antagonists; Opiate Overdose; Respiratory Insufficiency; Drug Overdose; Heart Arrest
PubMed: 37402248
DOI: 10.1097/ALN.0000000000004622 -
Pharmacological Reviews Nov 2023Oxycodone, a semisynthetic derivative of naturally occurring thebaine, an opioid alkaloid, has been available for more than 100 years. Although thebaine cannot be used... (Review)
Review
Oxycodone, a semisynthetic derivative of naturally occurring thebaine, an opioid alkaloid, has been available for more than 100 years. Although thebaine cannot be used therapeutically due to the occurrence of convulsions at higher doses, it has been converted to a number of other widely used compounds that include naloxone, naltrexone, buprenorphine, and oxycodone. Despite the early identification of oxycodone, it was not until the 1990s that clinical studies began to explore its analgesic efficacy. These studies were followed by the pursuit of several preclinical studies to examine the analgesic effects and abuse liability of oxycodone in laboratory animals and the subjective effects in human volunteers. For a number of years oxycodone was at the forefront of the opioid crisis, playing a significant role in contributing to opioid misuse and abuse, with suggestions that it led to transitioning to other opioids. Several concerns were expressed as early as the 1940s that oxycodone had significant abuse potential similar to heroin and morphine. Both animal and human abuse liability studies have confirmed, and in some cases amplified, these early warnings. Despite sharing a similar structure with morphine and pharmacological actions also mediated by the -opioid receptor, there are several differences in the pharmacology and neurobiology of oxycodone. The data that have emerged from the many efforts to analyze the pharmacological and molecular mechanism of oxycodone have generated considerable insight into its many actions, reviewed here, which, in turn, have provided new information on opioid receptor pharmacology. SIGNIFICANCE STATEMENT: Oxycodone, a -opioid receptor agonist, was synthesized in 1916 and introduced into clinical use in Germany in 1917. It has been studied extensively as a therapeutic analgesic for acute and chronic neuropathic pain as an alternative to morphine. Oxycodone emerged as a drug with widespread abuse. This article brings together an integrated, detailed review of the pharmacology of oxycodone, preclinical and clinical studies of pain and abuse, and recent advances to identify potential opioid analgesics without abuse liability.
Topics: Animals; Humans; Oxycodone; Thebaine; Analgesics, Opioid; Opioid-Related Disorders; Morphine; Receptors, Opioid
PubMed: 37321860
DOI: 10.1124/pharmrev.121.000506 -
The Journal of Clinical Investigation Sep 2023The nucleus accumbens (NAc) is the most promising target for drug use disorder treatment. Deep brain stimulation (DBS) of NAc is effective for drug use disorder...
The nucleus accumbens (NAc) is the most promising target for drug use disorder treatment. Deep brain stimulation (DBS) of NAc is effective for drug use disorder treatment. However, the mechanisms by which DBS produces its therapeutic effects remain enigmatic. Here, we define a behavioral cutoff criterion to distinguish depressive-like behaviors and non-depressive-like behaviors in mice after morphine withdrawal. We identified a basolateral amygdala (BLA) to NAc D1 medium spiny neuron (MSN) pathway that controls depressive-like behaviors after morphine withdrawal. Furthermore, the paraventricular nucleus of thalamus (PVT) to NAc D2 MSN pathway controls naloxone-induced acute withdrawal symptoms. Optogenetically induced long-term potentiation with κ-opioid receptor (KOR) antagonism enhanced BLA to NAc D1 MSN signaling and also altered the excitation/inhibition balance of NAc D2 MSN signaling. We also verified that a new 50 Hz DBS protocol reversed morphine withdrawal-evoked abnormal plasticity in NAc. Importantly, this refined DBS treatment effectively alleviated naloxone-induced withdrawal symptoms and depressive-like behaviors and prevented stress-induced reinstatement. Taken together, the results demonstrated that input- and cell type-specific synaptic plasticity underlies morphine withdrawal, which may lead to novel targets for the treatment of opioid use disorder.
Topics: Mice; Animals; Analgesics, Opioid; Nucleus Accumbens; Receptors, Dopamine D2; Morphine; Naloxone; Substance Withdrawal Syndrome; Receptors, Dopamine D1; Mice, Inbred C57BL
PubMed: 37561576
DOI: 10.1172/JCI163266 -
Revue Medicale Suisse Aug 2023
Topics: Humans; Opiate Alkaloids; Low Back Pain; Neck Pain; Acute Pain
PubMed: 37610198
DOI: 10.53738/REVMED.2023.19.838.1530 -
Revue Medicale Suisse Oct 2023
Topics: Humans; Opiate Alkaloids; Neck Pain
PubMed: 37850812
DOI: 10.53738/REVMED.2023.19.846.1959 -
Revue Medicale Suisse Jan 2024
Topics: Humans; Opiate Alkaloids; Pain Management
PubMed: 38268354
DOI: 10.53738/REVMED.2024.20.858.130 -
CJEM Oct 2023
Topics: Humans; Buprenorphine, Naloxone Drug Combination; Buprenorphine; Emergency Service, Hospital; Analgesics, Opioid
PubMed: 37805957
DOI: 10.1007/s43678-023-00594-z -
Current Opinion in Psychiatry Jul 2023Opioid overdose events are a time sensitive medical emergency, which is often reversible with naloxone administration if detected in time. Many countries are facing... (Review)
Review
PURPOSE OF REVIEW
Opioid overdose events are a time sensitive medical emergency, which is often reversible with naloxone administration if detected in time. Many countries are facing rising opioid overdose deaths and have been implementing rapid opioid overdose response Systems (ROORS). We describe how technology is increasingly being used in ROORS design, implementation and delivery.
RECENT FINDINGS
Technology can contribute in significant ways to ROORS design, implementation, and delivery. Artificial intelligence-based modelling and simulations alongside wastewater-based epidemiology can be used to inform policy decisions around naloxone access laws and effective naloxone distribution strategies. Data linkage and machine learning projects can support service delivery organizations to mobilize and distribute community resources in support of ROORS. Digital phenotyping is an advancement in data linkage and machine learning projects, potentially leading to precision overdose responses. At the coalface, opioid overdose detection devices through fixed location or wearable sensors, improved connectivity, smartphone applications and drone-based emergency naloxone delivery all have a role in improving outcomes from opioid overdose. Data driven technologies also have an important role in empowering community responses to opioid overdose.
SUMMARY
This review highlights the importance of technology applied to every aspect of ROORS. Key areas of development include the need to protect marginalized groups from algorithmic bias, a better understanding of individual overdose trajectories and new reversal agents and improved drug delivery methods.
Topics: Humans; Opiate Overdose; Artificial Intelligence; Naloxone; Drug Overdose; Analgesics, Opioid; Narcotic Antagonists; Opioid-Related Disorders
PubMed: 37185583
DOI: 10.1097/YCO.0000000000000870 -
Brain, Behavior, and Immunity Oct 2023Chronic morphine exposure causes the development of addictive behaviors, accompanied by an increase in neuroinflammation in the central nervous system. While previous...
Chronic morphine exposure causes the development of addictive behaviors, accompanied by an increase in neuroinflammation in the central nervous system. While previous researches have shown that astrocytes contribute to brain diseases, the role of astrocyte in morphine addiction through induced neuroinflammation remain unexplored. Here we show that morphine-induced inflammation requires the crosstalk among neuron, astrocyte, and microglia. Specifically, astrocytes respond to morphine-induced neuronal activation by increasing glycolytic metabolism. The dysregulation of glycolysis leads to an increased in the generation of mitochondrial reactive oxygen species and causes excessive mitochondrial fragmentation in astrocytes. These fragmented, dysfunctional mitochondria are consequently released into extracellular environment, leading to activation of microglia and release of inflammatory cytokines. We also found that blocking the nicotinamide adenine dinucleotide salvage pathway with FK866 could inhibit astrocytic glycolysis and restore the mitochondrial homeostasis and effectively attenuate neuroinflammatory responses. Importantly, FK866 reversed morphine-induced addictive behaviors in mice. In summary, our findings illustrate an essential role of astrocytic immunometabolism in morphine induced neural and behavioral plasticity, providing a novel insight into the interactions between neurons, astrocytes, and microglia in the brain affected by chronic morphine exposure.
Topics: Mice; Animals; Morphine Dependence; Astrocytes; Neuroinflammatory Diseases; Morphine; Microglia; Mitochondria
PubMed: 37543246
DOI: 10.1016/j.bbi.2023.07.030 -
American Journal of Surgery Oct 2023
Topics: Humans; Opium; Opiate Alkaloids; Opioid-Related Disorders
PubMed: 37336710
DOI: 10.1016/j.amjsurg.2023.06.007