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阿片类拮抗剂用于晚期癌症患者的临床研究:在2443例接受阿片类药物治疗的晚期癌症患者中,有7例在使用阿片类药物后接受了阿片类拮抗剂治疗。

A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids.

作者信息

Uekuzu Yoshihiro, Higashiguchi Takashi, Futamura Akihiko, Ito Akihiro, Mori Naoharu, Murai Miyo, Ohara Hiroshi, Awa Hiroko, Chihara Takeshi

机构信息

Department of Pharmacy, Fujita Health University Nanakuri Memorial Hospital.

出版信息

Biol Pharm Bull. 2017 Mar 1;40(3):278-283. doi: 10.1248/bpb.b16-00715. Epub 2016 Dec 16.

Abstract

There have been few detailed reports on respiratory depression due to overdoses of opioids in terminal cancer patients. We investigated the situation of treatment with opioid antagonists for respiratory depression that occurred after administration of opioid at optimal doses in terminal cancer patients, to clarify pathological changes as well as causative factors. In 2443 terminal cancer patients receiving opioids, 7 patients (0.3%) received opioid antagonists: 6, morphine (hydrochloride, 5; sulfate, 1); 1, oxycodone. The median dosage of opioids was 13.3 mg/d, as converted to morphine injection. Respiratory depression occurred on this daily dose in 4 patients and after changed dose and route in 3 patients. Opioids were given through the vein in 6 patients and by the enteral route in 1 patient. Concomitant drugs included nonsteroidal anti-inflammatory drugs in 3 patients and zoledronic acid in 2 patients. In morphine-receiving patients, renal functions were significantly worsened at the time of administration of an opioid antagonist than the day before the start of opioid administration. These findings indicate that the proper use of opioids was safe and acceptable in almost all terminal cancer patients. In rare cases, however, a risk toward respiratory depression onset is indicated because morphine and morphine-6-glucuronide become relatively excessive owing to systemic debility due to disease progression, especially respiratory and renal dysfunctions. At the onset of respiratory depression, appropriate administration of an opioid antagonist mitigated the symptoms. Thereafter, opioid switching or continuous administration at reduced dosages of the same opioids prevented the occurrence of serious adverse events.

摘要

关于晚期癌症患者因过量使用阿片类药物导致呼吸抑制的详细报告很少。我们调查了晚期癌症患者在以最佳剂量使用阿片类药物后发生呼吸抑制时使用阿片类拮抗剂的治疗情况,以阐明病理变化及致病因素。在2443例接受阿片类药物治疗的晚期癌症患者中,7例(0.3%)接受了阿片类拮抗剂治疗:6例使用吗啡(盐酸吗啡5例;硫酸吗啡1例);1例使用羟考酮。阿片类药物的中位剂量经换算相当于吗啡注射液13.3mg/d。4例患者在该日剂量时发生呼吸抑制,3例在剂量和给药途径改变后发生。6例患者通过静脉给药,1例通过肠内途径给药。同时使用的药物包括3例患者使用非甾体抗炎药,2例患者使用唑来膦酸。在接受吗啡治疗的患者中,使用阿片类拮抗剂时的肾功能较开始使用阿片类药物前一天显著恶化。这些发现表明,在几乎所有晚期癌症患者中,正确使用阿片类药物是安全且可接受的。然而,在罕见情况下,由于疾病进展导致全身虚弱,尤其是呼吸和肾功能障碍,吗啡和吗啡-6-葡萄糖醛酸相对过量,提示存在呼吸抑制发作的风险。在呼吸抑制发作时,适当使用阿片类拮抗剂可缓解症状。此后,更换阿片类药物或降低相同阿片类药物的剂量持续给药可预防严重不良事件的发生。

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