Chamoun Karam, Chevillard Lucie, Hajj Aline, Callebert Jacques, Mégarbane Bruno
Inserm, UMR-S1144, Paris Cité University, 75006 Paris, France.
Faculty of Pharmacy, Saint-Joseph University, Beirut 1100, Lebanon.
Pharmaceuticals (Basel). 2023 Mar 2;16(3):382. doi: 10.3390/ph16030382.
In 2020, fentanyl and its analogs contributed to ~65% of drug-attributed fatalities in the USA, with a threatening increasing trend during the last ten years. These synthetic opioids used as potent analgesics in human and veterinary medicine have been diverted to recreational aims, illegally produced and sold. Like all opioids, central nervous system depression resulting from overdose or misuse of fentanyl analogs is characterized clinically by the onset of consciousness impairment, pinpoint miosis and bradypnea. However, contrasting with what observed with most opioids, thoracic rigidity may occur rapidly with fentanyl analogs, contributing to increasing the risk of death in the absence of immediate life support. Various mechanisms have been proposed to explain this particularity associated with fentanyl analogs, including the activation of noradrenergic and glutamatergic coerulospinal neurons and dopaminergic basal ganglia neurons. Due to the high affinities to the mu-opioid receptor, the need for more elevated naloxone doses than usually required in morphine overdose to reverse the neurorespiratory depression induced by fentanyl analogs has been questioned. This review on the neurorespiratory toxicity of fentanyl and analogs highlights the need for specific research focused on these agents to better understand the involved mechanisms of toxicity and develop dedicated strategies to limit the resulting fatalities.
2020年，芬太尼及其类似物在美国约65%的药物所致死亡中起了作用，且在过去十年呈威胁性上升趋势。这些在人类和兽医学中用作强效镇痛药的合成阿片类药物已被转用于娱乐目的，被非法生产和销售。与所有阿片类药物一样，芬太尼类似物过量或滥用导致的中枢神经系统抑制在临床上表现为意识障碍、针尖样瞳孔和呼吸减慢。然而，与大多数阿片类药物不同的是，芬太尼类似物可能会迅速出现胸廓强直，在没有立即生命支持的情况下增加死亡风险。人们提出了各种机制来解释与芬太尼类似物相关的这种特殊性，包括去甲肾上腺素能和谷氨酸能蓝斑脊髓神经元以及多巴胺能基底神经节神经元的激活。由于对μ-阿片受体具有高亲和力，对于逆转芬太尼类似物引起的神经呼吸抑制，是否需要比吗啡过量时通常所需剂量更高的纳洛酮剂量存在疑问。这篇关于芬太尼及其类似物神经呼吸毒性的综述强调了针对这些药物进行具体研究的必要性，以便更好地理解所涉及的毒性机制，并制定专门策略来减少由此导致的死亡。
