可卡因乙烯醚与可卡因一样具有心脏毒性，但毒性比可卡因加乙醇小。

Cocaethylene is as cardiotoxic as cocaine but is less toxic than cocaine plus ethanol.

作者信息

Henning R J, Wilson L D

机构信息

Department of Medicine, University of South Florida College of Medicine, Tampa, USA.

出版信息

Life Sci. 1996;59(8):615-27. doi: 10.1016/0024-3205(96)00227-5.

DOI:10.1016/0024-3205(96)00227-5

PMID:8761012

Abstract

Cocaethylene is a pharmacologically active cocaine metabolite that is produced in the liver by the transesterification of cocaine only in the presence of ethanol. The acute cardiovascular effects of cocaethylene are not known. We compared the acute cardiovascular effects of cocaethylene with cocaine and with cocaine plus ethanol in 18 dogs. We administered cocaethylene 7.5 mg/kg to 6 dogs, cocaine 7.5 mg/kg to 6 dogs, and cocaine 7.5 mg/kg plus ethanol 1 gm/kg to 6 dogs. The dose of each drug was chosen to produce in dogs the concentrations of cocaethylene or cocaine that have been measured in patients who have experienced cardiotoxic reactions to cocaine or cocaine plus ethanol. Arterial, left ventricular (LV), pulmonary artery wedge pressures (PAWP), the maximum rate of LV pressure rise [(dP/dt)max] and fall [(dP/dt)min], and heart rate (HR) were continuously measured. Stroke volume was determined 3 times during the first hour after drug administration then hourly for four hours. The concentrations of cocaethylene and cocaine peaked in the serum at 3717 +/- 651 ng/ml and 4140 +/- 459 ng/ml, respectively, two minutes after each bolus. The median half-life of cocaethylene was 144.3 minutes whereas the median half-life of cocaine was 96.7 minutes (p < 0.01). Cocaethylene maximally decreased (dP/dt)max by 44%, (dP/dt)min by 29%, and stroke volume by 28% (all p < 0.01) and increased the PAWP by 50% (p < 0.02) and the HR by 13% (p = NS) during the first hour. Cocaine maximally decreased (dP/dt)max by 40%, (dP/dt)min by 31%, and the stroke volume by 26% and increased the PAWP by 100% and the HR by 46% (all p < 0.01) during the first hour. Ethanol plus cocaine maximally decreased (dP/dt)max by 68%, (dP/dt)min by 78% and the stroke volume by 49% and increased the PAWP by 118% and the HR by 74% (all p < 0.01) during the first hour. In this last group, (dP/dt)max and stroke volume remained depressed by approximately 20% (p < 0.01) for five hours. We conclude that cocaethylene is as toxic as cocaine to the myocardium but is less toxic than ethanol plus cocaine.

摘要

可卡因乙烯酯是一种具有药理活性的可卡因代谢产物，仅在有乙醇存在的情况下，由肝脏中的可卡因酯交换反应产生。可卡因乙烯酯的急性心血管效应尚不清楚。我们比较了可卡因乙烯酯与可卡因以及可卡因加乙醇在18只狗身上的急性心血管效应。我们给6只狗注射7.5毫克/千克的可卡因乙烯酯，给6只狗注射7.5毫克/千克的可卡因，给6只狗注射7.5毫克/千克的可卡因加1克/千克的乙醇。选择每种药物的剂量是为了使狗体内产生在对可卡因或可卡因加乙醇有心脏毒性反应的患者中所测得的可卡因乙烯酯或可卡因浓度。连续测量动脉压、左心室（LV）、肺动脉楔压（PAWP）、左心室压力上升的最大速率[(dP/dt)max]和下降速率[(dP/dt)min]以及心率（HR）。在给药后的第一个小时内三次测定每搏输出量，然后在接下来的四个小时内每小时测定一次。每次推注后两分钟，血清中可卡因乙烯酯和可卡因的浓度分别达到峰值，为3717±651纳克/毫升和4140±459纳克/毫升。可卡因乙烯酯的中位半衰期为144.3分钟，而可卡因的中位半衰期为96.7分钟（p<0.01）。在第一个小时内，可卡因乙烯酯最大程度地使(dP/dt)max降低了44%，(dP/dt)min降低了29%，每搏输出量降低了28%（所有p<0.01），并使PAWP升高了50%（p<0.02），使HR升高了13%（p=无统计学意义）。可卡因在第一个小时内最大程度地使(dP/dt)max降低了40%，(dP/dt)min降低了31%，每搏输出量降低了26%，并使PAWP升高了100%，使HR升高了46%（所有p<0.01）。乙醇加可卡因在第一个小时内最大程度地使(dP/dt)max降低了68%，(dP/dt)min降低了78%，每搏输出量降低了49%，并使PAWP升高了118%，使HR升高了74%（所有p<0.01）。在最后一组中，(dP/dt)max和每搏输出量在五个小时内仍大约降低20%（p<0.01）。我们得出结论，可卡因乙烯酯对心肌的毒性与可卡因相同，但比乙醇加可卡因的毒性小。