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两药同用时,哌替定可导致氯丙嗪的镇静、降血压、呼吸抑制作用加强,可能需要减少哌替定的剂量。
相关药物:大量报道表明,哌替定和其他吩噻嗪类衍生物之间存在相似的相互作用。吗啡和哌替定的降血压及镇静作用被氯丙嗪延长[1~3]。丙氯拉嗪[4]、异丙嗪[5]、丙酰马嗪[6,7]均被报道与哌替定存在相互影响。基于药理学的相似性,可以预测其他吩噻嗪类药物(丙嗪、硫利达嗪、三氟拉嗪等)、硫杂蒽类药物(如氯普噻吨、替沃噻吨)、丁酰苯类(氟哌啶醇)、二氢吲哚酮类(吗啉酮)和二苯丙氧氮杂卓类(洛沙平)与哌替定也存在相似的相互作用。已报道与氯丙嗪存在相互作用的其他麻醉性镇痛药包括酚太尼、二氢吗啡酮和羟氢吗啡酮。[5,8]虽然缺乏其他麻醉性镇痛药(如可待因、左啡诺等)相互作用的资料,但由于其药理作用与哌替定相似,相似的相互作用也可能发生。
机制:氯丙嗪增加哌替定毒性代谢物去甲哌替定的生成速度[8],这也是两药合用相比于各自单独使用呼吸抑制增加的原因[9]。此外,氯丙嗪可减慢麻醉性镇痛剂的代谢,延长其半衰期[5]。
建议:哌替定与氯丙嗪联合广泛应用于术前准备,但与氯丙嗪同时使用时,哌替定的剂量应当减少25~50%。
参考文献:1、Sadove, M.S., and others: Chlorpromazine and narcotics in the management of pain of malignat lesions, J.A.M.A. 155:626, 1954.
2、Dripps, R.D., and others: Use of chlorpromazine in anesthesia and surgery, Ann. Surg. 142:774, 1955.
3、Dobkin, A.B., and others: Chlorpromazine: review and investigation as premedicant in anesthesia, Anesthesiology 17:135, 1956.
4、Steen, S.N., and Yates M.: The effects of benzquinamide and prochlorperazine separately and combined, on the human respiratory center, Anesthesiology 36:519, 1972.
5、Keeri-Szanto, M.: The mode of action of promethazine in potentiating narcotic drugs, Br.J.Anaesth. 46:918, 1974.
6、Hoffman, J.C., and Smith, T.C.: The respiratory effects of meperidine and propiomazine in man. Anesthesiology 32:325, 1970.
7、Reier, C.E., and Johnstone, R.E.: Respiratory depression: narcotic versus narcotic-tranquilizer combinations, Anesth, Analg. (Cleve.) 49:119, 1970.
8、Stambaugh, J.E. and Wainer, I.W.: Drug interaction: meperidine and chlorpromazine, a toxic combination, J. Clin. Pharmacol. 21:140 1981.
9、Lambertsen, C.L., and others: The separate and combined respiratory effects of chlorpromazine and meperidine in normal men controlled at 46 mm Hg alveolar Pco2, J. Pharmacol. Exp. Ther. 131:381, 1961.
10、McGee, J.L., and Alexander, M.R.: Phenothiazine analgesia-fact or fantasy? Am. J. Hosp. Pharm. 36:633, 1979.
11、Demerol, Product information, Winthrop Laboratories, New York, N.Y., 1983.
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