Dataset Information

Fentanyl-Induced Respiratory Depression: A Narrative Review on the Possible Single-Nucleotide Polymorphism.

ABSTRACT: Opioid-related respiratory depression is a serious clinical problem as it can cause multiple deaths and anoxic brain injury. Genetic variations influence the safety and clinical efficacy of fentanyl. Pharmacogenetic studies help in identifying single-nucleotide polymorphisms (SNPs) associated with fentanyl causing respiratory depression and aid clinician in personalized pain medicine. This narrative review gives an insight of the common SNPs associated with fentanyl.

SUBMITTER: Udayakumar P

PROVIDER: S-EPMC8462425 | biostudies-literature | 2021 Jan-Mar

REPOSITORIES: biostudies-literature

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Fentanyl-Induced Respiratory Depression: A Narrative Review on the Possible Single-Nucleotide Polymorphism.

Udayakumar Prabha P Udayakumar Srisruthi S

Anesthesia, essays and researches 20210101 1

Opioid-related respiratory depression is a serious clinical problem as it can cause multiple deaths and anoxic brain injury. Genetic variations influence the safety and clinical efficacy of fentanyl. Pharmacogenetic studies help in identifying single-nucleotide polymorphisms (SNPs) associated with fentanyl causing respiratory depression and aid clinician in personalized pain medicine. This narrative review gives an insight of the common SNPs associated with fentanyl. ...[more]

PMID: 34667340

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Project description:Introduction: Overdose fatalities associated with the opioid epidemic are predictably attributable to drug-induced respiratory depression. In terms of illicit opioid abuse, fentanyl is the synthetic opioid responsible for the largest number of overdose deaths. There is, therefore, an urgent need to identify safe and effective therapeutics that can attenuate fentanyl-induced respiratory depression. Identification of effective alternate analgesic strategies that lessen the respiratory depression associated with narcotics would also help improve current strategies for pain management. Our laboratory recently reported that the G protein-biased CB2 cannabinoid receptor agonist LY2828360 suppressed chemotherapy-induced neuropathic nociception and attenuated both morphine tolerance and physical dependence in paclitaxel-treated mice. However, the impact of LY2828360 on other undesirable side effects of opioids, such as opioid-induced respiratory depression, remains unknown. Materials and Methods: We used whole-body plethysmography to assess the impact of the CB2 cannabinoid agonist LY2828360 on fentanyl-induced respiratory depression using wild-type (WT) and CB2 knockout (CB2KO) mice. Results: Fentanyl reduced minute ventilation and respiratory frequency without altering tidal volume in both WT and CB2KO mice. In WT mice, the high dose of fentanyl (0.2 mg/kg intraperitoneal [i.p.]) produced a greater suppression of respiratory parameters compared with the low dose of fentanyl (0.1 mg/kg i.p.). Coadministration of a behaviorally active dose of LY2828360 (3 mg/kg i.p.) with fentanyl (0.2 mg/kg i.p.) attenuated fentanyl-induced respiratory depression in WT mice. Notably, LY2828360 (3 mg/kg i.p.) did not attenuate fentanyl-induced respiratory depression in CB2KO mice, consistent with mediation by CB2 receptors. Moreover, LY2828360 (3 mg/kg i.p.) alone lacked intrinsic effects on respiratory parameters in either WT or CB2KO mice. Conclusion: The combination of a CB2 agonist with fentanyl may represent a safer adjunctive therapeutic strategy compared with a narcotic analgesic alone by attenuating the development of opioid-induced respiratory depression. Moreover, the CB2 agonist, administered alone, did not alter respiration. Our findings suggest that the CB2 cannabinoid agonist LY2828360 may provide CB2-mediated protection against fentanyl-induced respiratory depression, a detrimental and unwanted side effect of opioid use and abuse.

Dataset Information

Fentanyl-Induced Respiratory Depression: A Narrative Review on the Possible Single-Nucleotide Polymorphism.

Publications

Fentanyl-Induced Respiratory Depression: A Narrative Review on the Possible Single-Nucleotide Polymorphism.

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