Tan Hon Sen, Habib Ashraf S
Department of Women's Anesthesia, KK Women's and Children's Hospital, 229899, Singapore.
Department of Anesthesiology, Division of Women's Anesthesia, Duke University Medical Center, Durham, NC, 27710, USA.
J Pain Res. 2021 Apr 14;14:969-979. doi: 10.2147/JPR.S278279. eCollection 2021.
Optimal pain relief requires a balance between adequate analgesia and risk of adverse effects. Opioids remain the cornerstone for managing moderate to severe pain, but are associated with opioid-induced respiratory depression (OIRD) and gastrointestinal complications. Opioids exert their analgesic effects predominantly via G-protein signaling, however, adverse effects including OIRD are mediated by the β-arrestin pathway. Oliceridine is the first of a new class of biased opioid agonists that preferentially activate G-protein signaling over β-arrestin, which would theoretically improve analgesia and reduce the risk of adverse effects. Oliceridine is approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe acute pain. The efficacy of Oliceridine was mainly established in two randomized controlled Phase III clinical trials of patients experiencing moderate to severe pain after bunionectomy (APOLLO-1) and abdominoplasty (APOLLO-2). The results of the APOLLO studies demonstrate that Oliceridine, when administered via patient-controlled analgesia (PCA) demand boluses of 0.35mg and 0.5mg, provides superior analgesia compared to placebo, and is equianalgesic to PCA morphine 1mg demand boluses, without significant difference in the incidence of respiratory complications. In a more pragmatic trial of surgical and non-surgical patients, the ATHENA observational cohort study reported rapid onset of analgesia with Oliceridine given with or without multimodal analgesia. However, these studies were designed to evaluate analgesic efficacy, and it is still uncertain if Oliceridine has a better safety profile than conventional opioids. Although several post hoc analyses of pooled data from the APOLLO and ATHENA trials reported that Oliceridine was associated with lower OIRD and gastrointestinal complications compared to morphine, prospective studies are needed to elucidate if biased agonists such as Oliceridine reduce the risk of adverse effects compared to conventional opioids.
最佳的疼痛缓解需要在充分镇痛和不良反应风险之间取得平衡。阿片类药物仍然是治疗中度至重度疼痛的基石，但与阿片类药物引起的呼吸抑制（OIRD）和胃肠道并发症相关。阿片类药物主要通过G蛋白信号传导发挥镇痛作用，然而，包括OIRD在内的不良反应是由β-抑制蛋白途径介导的。奥里替丁是一类新型偏向性阿片类激动剂中的首个药物，它优先激活G蛋白信号传导而非β-抑制蛋白，理论上这将改善镇痛效果并降低不良反应风险。奥里替丁已获美国食品药品监督管理局（FDA）批准用于治疗中度至重度急性疼痛。奥里替丁的疗效主要在两项针对拇囊炎切除术后（APOLLO-1）和腹部整形术后（APOLLO-2）出现中度至重度疼痛患者的随机对照III期临床试验中得到确立。APOLLO研究结果表明，当通过患者自控镇痛（PCA）按需推注0.35mg和0.5mg奥里替丁时，与安慰剂相比，其镇痛效果更佳，且与按需推注1mg PCA吗啡的镇痛效果相当，呼吸并发症发生率无显著差异。在一项针对手术和非手术患者的更具实用性的试验中，ATHENA观察性队列研究报告称，无论是否联合多模式镇痛，使用奥里替丁均可快速起效镇痛。然而，这些研究旨在评估镇痛效果，奥里替丁是否比传统阿片类药物具有更好的安全性仍不确定。尽管对APOLLO和ATHENA试验汇总数据的几项事后分析报告称，与吗啡相比，奥里替丁与更低的OIRD和胃肠道并发症相关，但仍需要前瞻性研究来阐明与传统阿片类药物相比，像奥里替丁这样的偏向性激动剂是否能降低不良反应风险。
