Santillán R, Maestre J M, Hurlé M A, Flórez J
Department of Anesthesiology (Pain Unit), University Hospital M. de Valdecilla, Spain Department of Physiology and Pharmacology, University of Cantabria, SantanderSpain.
Pain. 1994 Jul;58(1):129-132. doi: 10.1016/0304-3959(94)90192-9.
The ability of nimodipine, a calcium-channel blocker, to enhance morphine analgesia and/or modify the development of tolerance was studied in patients with cancer pain who had needed successive increments of morphine for periods ranging from 21 to 780 days. Assessment of daily morphine consumption was the primary effect parameter. Nimodipine succeeded in reducing the daily dose of morphine in 16 of 23 patients (oral, n = 13; intrathecal, n = 3), and failed to modify it in 2 patients. Total oral daily dose was reduced by nimodipine (120 mg/day) from 282.6 +/- 47.7 mg to 158.7 +/- 26.2 mg (n = 15, P < 0.001). Intrathecal morphine was also reduced by 1-5 mg/day. Nimodipine was withdrawn in 5 patients during the first week of treatment due to intolerance (n = 3) or aggravation of the disease (n = 2). These preliminary results support experimental findings showing that pharmacological interference with Ca(2+)-related events may modify chronic opioid effects, including the expression of tolerance.
在癌症疼痛患者中,研究了钙通道阻滞剂尼莫地平增强吗啡镇痛作用和/或改变耐受性发展的能力,这些患者连续增加吗啡剂量达21至780天。评估每日吗啡消耗量是主要效应参数。23例患者中,16例(口服给药13例,鞘内给药3例)尼莫地平成功减少了吗啡日剂量,2例患者未出现剂量改变。尼莫地平(120mg/天)使口服吗啡日总剂量从282.6±47.7mg降至158.7±26.2mg(n = 15,P < 0.001)。鞘内注射吗啡剂量也减少了1 - 5mg/天。治疗第一周内,5例患者因不耐受(3例)或病情加重(2例)停用尼莫地平。这些初步结果支持实验研究结果,表明对与Ca(2+)相关事件的药理学干预可能改变慢性阿片类药物的作用,包括耐受性的表达。