Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.
Department of Surgery, Emory University School of Medicine, Atlanta, Georgia.
Pharmacotherapy. 2018 Mar;38(3):390-401. doi: 10.1002/phar.2090. Epub 2018 Feb 23.
Cancer-related pain continues to be a significant therapeutic challenge, made more difficult by contemporary opioid use and diversion concerns. Conventional treatment using a tiered approach of nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and adjuvant agents is limited; and alternatives are needed for patients with rapidly progressing pain and those who develop hyperalgesia and tolerance to opioids. Ketamine, an N-methyl-d-aspartate (NMDA) selective antagonist, has historically been used for anesthesia in adult and pediatric populations but has also been investigated for depression, bipolar disorder, and general and postoperative pain management. As an analgesic, low-dose ketamine decreases morphine requirements and rates of nausea and vomiting, suggesting a potentially beneficial role in cancer-related pain. Ketamine is typically administered intravenously and has a rapid onset of action with a relatively short half-life (2-3 hours) but is inconvenient for use in an ambulatory setting. Oral bioavailability is low and erratic, limiting application of this route for chronic use. Intranasal administration has a number of potential advantages, including avoidance of first-pass hepatic metabolism, no need for venous access, ability to repeat doses quickly, and rapid absorption. Although early studies of intranasal ketamine are promising in a number of indications, information is more limited in its use as an adjunct in cancer-related pain. We review the background, rationale, pharmacokinetics, and clinical and safety data using intranasal ketamine as an adjunctive agent and its potential in cancer-related pain.
癌症相关疼痛仍然是一个重大的治疗挑战，由于当代阿片类药物的使用和滥用问题而变得更加困难。使用非甾体抗炎药（NSAIDs）、阿片类药物和辅助药物的分层方法进行常规治疗受到限制；对于疼痛迅速进展的患者以及对阿片类药物产生痛觉过敏和耐受的患者，需要替代品。氯胺酮是一种 N-甲基-D-天冬氨酸（NMDA）选择性拮抗剂，历史上用于成人和儿科人群的麻醉，但也被用于治疗抑郁症、双相情感障碍以及一般和术后疼痛管理。作为一种镇痛药，小剂量氯胺酮可减少吗啡的需求和恶心呕吐的发生率，表明其在癌症相关疼痛中可能具有有益作用。氯胺酮通常静脉给药，起效迅速，半衰期相对较短（2-3 小时），但在门诊环境中使用不方便。口服生物利用度低且不稳定，限制了其在慢性使用中的应用。鼻内给药有许多潜在的优势，包括避免首过肝代谢、无需静脉通路、能够快速重复剂量以及快速吸收。尽管鼻内氯胺酮在许多适应症的早期研究中很有前景，但在癌症相关疼痛的辅助治疗中的信息更为有限。我们回顾了鼻内氯胺酮作为辅助药物的背景、原理、药代动力学以及临床和安全性数据，及其在癌症相关疼痛中的潜在应用。
