Amouzadeh H R, Sangiah S, Qualls C W
Department of Physiological Sciences, Oklahoma State University, Stillwater 74078.
Vet Hum Toxicol. 1989 Dec;31(6):532-4.
Various inducers and inhibitors of hepatic microsomal enzymes were studied for their effects on xylazine-ketamine anesthesia. Pretreatment of Sprague-Dawley rats with chloramphenicol (100 mg/kg, ip), cimetidine (100 mg/kg, ip), ketoconazole (40 mg/kg, po), and SKF 525-A (25 mg/kg, ip) significantly (p less than 0.05) increased the duration of anesthesia in rats injected with ketamine (45 mg/kg, im) and xylazine (21 mg/kg, im). Pretreatment with phenobarbital (40 mg/kg, ip, once daily for 4 days) did not affect the duration of anesthesia significantly. The increase in duration of anesthesia in animals pretreated with SKF 525-A and ketoconazole was accompanied by secondary respiratory distress about 6 hr following recovery from anesthesia, often leading to death within 24 hr. Lesions consisting of extensive serous pleural effusion, alveolar edema rich in macrophages and extensive pulmonary hilar edema with hemorrhage were found at necropsy. These results indicate that inhibition of hepatic microsomal enzymes by commonly used therapeutic agents during xylazine-ketamine anesthesia to prolong the anesthetic effect, or as a result of concurrent pharmacotherapy, could have deleterious effects.
研究了各种肝微粒体酶诱导剂和抑制剂对赛拉嗪-氯胺酮麻醉的影响。用氯霉素（100毫克/千克，腹腔注射）、西咪替丁（100毫克/千克，腹腔注射）、酮康唑（40毫克/千克，口服）和SKF 525-A（25毫克/千克，腹腔注射）预处理斯普拉格-道利大鼠，显著（p小于0.05）延长了注射氯胺酮（45毫克/千克，肌肉注射）和赛拉嗪（21毫克/千克，肌肉注射）大鼠的麻醉时间。用苯巴比妥（40毫克/千克，腹腔注射，每天一次，共4天）预处理对麻醉时间没有显著影响。用SKF 525-A和酮康唑预处理的动物麻醉时间延长，麻醉恢复后约6小时出现继发性呼吸窘迫，常导致24小时内死亡。尸检发现病变包括广泛的浆液性胸腔积液、富含巨噬细胞的肺泡水肿以及广泛的肺门水肿伴出血。这些结果表明，在赛拉嗪-氯胺酮麻醉期间，常用治疗药物抑制肝微粒体酶以延长麻醉效果，或由于同时进行药物治疗，可能会产生有害影响。
