Restoring The Mechanical Properties of the Respiratory System as a Treatment of Fentanyl Overdose-Induced Hypoventilation using Kappa Agonists

使用 Kappa 激动剂恢复呼吸系统的机械特性来治疗芬太尼过量引起的通气不足

基本信息

项目摘要

ABSTRACT Mu-opioid agonist overdose is associated with immediate and prolonged tetanic and rhythmic contractions of the inspiratory and expiratory muscles that impede respiratory movements for hours. This effect, referred to as opioid induced chest wall rigidity, is a critical mechanism contributing to the lethality of opioid-induced hypoventilation. Mu-opioid-induced muscle “rigidity” is produced by neurons in the locus coeruleus and can be suppressed by kappa-opioid receptor agonists, but not by current ventilatory stimulants. The objective of our proposal is to demonstrate, following an overdose by the mu-opioid receptor agonist fentanyl, that kappa-opioid receptor agonists 1- restore the alteration of passive respiratory mechanics and suppress the hypermetabolism produced by fentanyl induced muscle rigidity, 2- prevent a fatal outcome in unsedated rats. We will test nalfurafine, the only commercially available kappa agonist, and show that it counteracts the ventilatory effects of a fentanyl overdose. If efficacy is demonstrated in rodents, we will pursue these efficacy studies in non-anesthetized large mammal models and will test intravenous as well as intranasal route. Our ultimate goal is to obtain FDA approval for nalfurafine as a treatment of mu-opioid receptor agonist-induced hypoventilation, treatment that could be used in indications ranging from mass casualty to individual victims of opioid intoxication.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Philippe A Haouzi其他文献

Philippe A Haouzi的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Philippe A Haouzi', 18)}}的其他基金

Restoring The Mechanical Properties of the Respiratory System as a Treatment of Fentanyl Overdose-Induced Hypoventilation using Kappa Agonists
使用 Kappa 激动剂恢复呼吸系统的机械特性来治疗芬太尼过量引起的通气不足
  • 批准号:
    10766378
  • 财政年份:
    2022
  • 资助金额:
    $ 20.3万
  • 项目类别:
Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine
小剂量右美托咪定治疗芬太尼过量所致呼吸衰竭
  • 批准号:
    10828679
  • 财政年份:
    2020
  • 资助金额:
    $ 20.3万
  • 项目类别:
Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine
小剂量右美托咪定治疗芬太尼过量所致呼吸衰竭
  • 批准号:
    10595421
  • 财政年份:
    2020
  • 资助金额:
    $ 20.3万
  • 项目类别:
Treatment of Fentanyl Overdose-Induced Respiratory Failure by Low-Dose Dexmedetomidine
小剂量右美托咪定治疗芬太尼过量所致呼吸衰竭
  • 批准号:
    10701905
  • 财政年份:
    2020
  • 资助金额:
    $ 20.3万
  • 项目类别:
The cyclic redox dye Azure B as a novel cyanide antidote: in vivo efficacy studies
环状氧化还原染料 Azure B 作为新型氰化物解毒剂:体内功效研究
  • 批准号:
    10223544
  • 财政年份:
    2019
  • 资助金额:
    $ 20.3万
  • 项目类别:
Methylene blue as an antidote against hydrogen sulfide intoxication
亚甲蓝作为硫化氢中毒的解毒剂
  • 批准号:
    9324057
  • 财政年份:
    2016
  • 资助金额:
    $ 20.3万
  • 项目类别:
Methylene blue as an antidote against hydrogen sulfide intoxication
亚甲蓝作为硫化氢中毒的解毒剂
  • 批准号:
    9144894
  • 财政年份:
    2016
  • 资助金额:
    $ 20.3万
  • 项目类别:
Effects of acute administration of the Phenothiazinium Chromophore Methylene blue during life threatening cyanide intoxication
在危及生命的氰化物中毒期间急性施用吩噻嗪发色团亚甲蓝的影响
  • 批准号:
    9357397
  • 财政年份:
    2016
  • 资助金额:
    $ 20.3万
  • 项目类别:
Methylene Blue, A Novel Treatment of H2S Poisoning-induced Brain Injury
亚甲蓝,一种治疗硫化氢中毒脑损伤的新方法
  • 批准号:
    8796074
  • 财政年份:
    2014
  • 资助金额:
    $ 20.3万
  • 项目类别:
Crystalline hydroxocobalamin and methemoglobin as a treatment of H2S intoxication
结晶羟钴胺和高铁血红蛋白治疗 H2S 中毒
  • 批准号:
    8551778
  • 财政年份:
    2012
  • 资助金额:
    $ 20.3万
  • 项目类别:

相似海外基金

Novel Digital Methods to Evaluate Functional and Pulmonary Outcomes following Pediatric Acute Respiratory Failure
评估小儿急性呼吸衰竭后功能和肺部结果的新型数字方法
  • 批准号:
    10724042
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Optimizing Time-Limited Trials of Mechanical Ventilation in Acute Respiratory Failure: A Mixed Methods Observational Study
优化急性呼吸衰竭机械通气的限时试验:混合方法观察研究
  • 批准号:
    10633823
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Use of Inter-Hospital Transfer Services in Critical Illness and Acute Respiratory Failure
在危重疾病和急性呼吸衰竭中使用医院间转运服务
  • 批准号:
    10739060
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Strengthening implementation science in Acute Respiratory Failure using multilevel analysis of existing data
利用现有数据的多级分析加强急性呼吸衰竭的实施科学
  • 批准号:
    10731311
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Identifying patient subgroups and processes of care that cause outcome differences following ICU vs. ward triage among patients with acute respiratory failure and sepsis
确定急性呼吸衰竭和脓毒症患者在 ICU 与病房分诊后导致结局差异的患者亚组和护理流程
  • 批准号:
    10734357
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Respiratory Drive in Acute Respiratory Failure
急性呼吸衰竭中的呼吸驱动
  • 批准号:
    10637245
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Health expectations after acute respiratory failure in survivor-care partner dyads
幸存者护理伙伴二人组急性呼吸衰竭后的健康期望
  • 批准号:
    10732929
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Temporal trends in quality indicators of palliative care for patients with chronic illness hospitalized with acute respiratory failure
因急性呼吸衰竭住院的慢性病患者姑息治疗质量指标的时间趋势
  • 批准号:
    10622756
  • 财政年份:
    2023
  • 资助金额:
    $ 20.3万
  • 项目类别:
Association of patient characteristics and antibiotic timing with the development of acute respiratory failure in hospital-acquired sepsis
患者特征和抗生素使用时机与医院获得性脓毒症急性呼吸衰竭发展的关系
  • 批准号:
    10313769
  • 财政年份:
    2022
  • 资助金额:
    $ 20.3万
  • 项目类别:
Financial Hardship among Patients with Acute Respiratory Failure and their Family Member Caregivers: Understanding the Impact on Patient- and Family- Centered Outcomes
急性呼吸衰竭患者及其家庭成员护理人员的经济困难:了解对以患者和家庭为中心的结果的影响
  • 批准号:
    10413457
  • 财政年份:
    2022
  • 资助金额:
    $ 20.3万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了