Kissin I, Brown P T, Bradley E L
Department of Anesthesiology, University of Alabama School of Medicine, Birmingham 35294.
Anesthesiology. 1991 Nov;75(5):813-6. doi: 10.1097/00000542-199111000-00013.
It was suggested that for a given analgesic effect, more potent opioids may produce smaller degrees of tolerance than those with lower analgesic potency. The use of opioids with high analgesic potency to reduce the rate of tolerance development would be an important therapeutic consideration. This study tested the hypothesis that the degree of acute tolerance to the analgesic effect of opioids is inversely related to their potency. In the experiments on rats, the analgesic effects of morphine, alfentanil, and sufentanil given by a continuous 8-h infusion at a constant rate, were determined by measuring the threshold of motor response to noxious pressure on the tail. The comparative degree of acute tolerance was determined on the basis of the decline in the level of analgesia at the end of the infusion period. Morphine 4 mg.kg-1.h-1, alfentanil 0.45 mg.kg-1.h-1, and sufentanil 0.0085 mg.kg-1.h-1 caused approximately similar increases in the pain threshold. The peak of analgesia could not be maintained; it declined by 74 +/- 6% (P less than 0.0001) with morphine, 86 +/- 6% (P less than 0.0001) with alfentanil, and 92 +/- 2% (P less than 0.0001) with sufentanil. The results indicate that the infusion of alfentanil and sufentanil, which differ from morphine by higher analgesic potency (by 10-fold and more than 100-fold, respectively), results in a decline in the degree of analgesia during infusion similar to that of morphine. These data reject the hypothesis that the magnitude of acute tolerance to the analgesic action of opioid drugs following their systemic administration is inversely related to their potency.
有人提出，在产生相同镇痛效果的情况下，强效阿片类药物产生的耐受性程度可能比镇痛效力较低的药物更小。使用高镇痛效力的阿片类药物来降低耐受性发展速度将是一个重要的治疗考量因素。本研究检验了以下假设：对阿片类药物镇痛作用的急性耐受程度与其效力呈负相关。在大鼠实验中，通过测量对尾部有害压力的运动反应阈值，确定以恒定速率连续8小时输注吗啡、阿芬太尼和舒芬太尼的镇痛效果。根据输注期结束时镇痛水平的下降来确定急性耐受的比较程度。吗啡4mg·kg-1·h-1、阿芬太尼0.45mg·kg-1·h-1和舒芬太尼0.0085mg·kg-1·h-1引起的痛阈升高大致相似。镇痛峰值无法维持；吗啡组下降了74±6%（P<0.0001），阿芬太尼组下降了86±6%（P<0.0001），舒芬太尼组下降了92±2%（P<0.0001）。结果表明，与吗啡相比，镇痛效力更高（分别高10倍和100倍以上）的阿芬太尼和舒芬太尼在输注过程中导致的镇痛程度下降与吗啡相似。这些数据否定了以下假设：全身性给予阿片类药物后，对其镇痛作用的急性耐受程度与其效力呈负相关。
