{"title":"Hypoxic Effects of Heroin and Fentanyl and Their Basic Physiological Mechanisms.","authors":"Eugene A Kiyatkin","doi":"10.1152/ajplung.00251.2024","DOIUrl":null,"url":null,"abstract":"<p><p>Respiratory depression that diminishes oxygen delivery to the brain is the most dangerous effect of opioid drugs. While plethysmography is a valuable tool to examine drug-induced changes in respiration, the primary cause of brain abnormalities induced by opioids is the global decrease in brain oxygen levels. The primary goal of this review is to provide an overview and discussion on fluctuations in brain oxygen levels induced by opioids, with a focus on heroin and fentanyl. To evaluate fluctuations in brain oxygen levels we used oxygen sensors coupled with high-speed amperometry in awake, freely moving rats. First, we provide an overview of brain oxygen responses induced by natural physiological stimuli and discuss the mechanisms regulating oxygen entry into brain tissue. Then, we present data on brain oxygen responses induced by heroin and fentanyl and review their underlying mechanisms. These data allowed us to compare the effects of these drugs on brain oxygen regarding their latency, potency, time-dependency, and potential lethality at high doses as well as their relationships with peripheral oxygen responses. We also discuss data on the effects of naloxone on brain oxygen responses induced by heroin and fentanyl in the paradigms of both the pre-treatment and treatment, when naloxone is administered at different times after the primary opioid drug. Although most data discussed were obtained in rats, they may have clinical relevance for understanding the mechanisms underlying the physiological effects of opioids and developing rational treatment strategies to decrease acute lethality and long-term health complications of opioid misuse.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Lung cellular and molecular physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/ajplung.00251.2024","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Respiratory depression that diminishes oxygen delivery to the brain is the most dangerous effect of opioid drugs. While plethysmography is a valuable tool to examine drug-induced changes in respiration, the primary cause of brain abnormalities induced by opioids is the global decrease in brain oxygen levels. The primary goal of this review is to provide an overview and discussion on fluctuations in brain oxygen levels induced by opioids, with a focus on heroin and fentanyl. To evaluate fluctuations in brain oxygen levels we used oxygen sensors coupled with high-speed amperometry in awake, freely moving rats. First, we provide an overview of brain oxygen responses induced by natural physiological stimuli and discuss the mechanisms regulating oxygen entry into brain tissue. Then, we present data on brain oxygen responses induced by heroin and fentanyl and review their underlying mechanisms. These data allowed us to compare the effects of these drugs on brain oxygen regarding their latency, potency, time-dependency, and potential lethality at high doses as well as their relationships with peripheral oxygen responses. We also discuss data on the effects of naloxone on brain oxygen responses induced by heroin and fentanyl in the paradigms of both the pre-treatment and treatment, when naloxone is administered at different times after the primary opioid drug. Although most data discussed were obtained in rats, they may have clinical relevance for understanding the mechanisms underlying the physiological effects of opioids and developing rational treatment strategies to decrease acute lethality and long-term health complications of opioid misuse.
期刊介绍：
The American Journal of Physiology-Lung Cellular and Molecular Physiology publishes original research covering the broad scope of molecular, cellular, and integrative aspects of normal and abnormal function of cells and components of the respiratory system. Areas of interest include conducting airways, pulmonary circulation, lung endothelial and epithelial cells, the pleura, neuroendocrine and immunologic cells in the lung, neural cells involved in control of breathing, and cells of the diaphragm and thoracic muscles. The processes to be covered in the Journal include gas-exchange, metabolic control at the cellular level, intracellular signaling, gene expression, genomics, macromolecules and their turnover, cell-cell and cell-matrix interactions, cell motility, secretory mechanisms, membrane function, surfactant, matrix components, mucus and lining materials, lung defenses, macrophage function, transport of salt, water and protein, development and differentiation of the respiratory system, and response to the environment.
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