Schindler C W
Preclinical Pharmacology Laboratory, National Institutes of Health/National Institute on Drug Abuse, Division of Intramural Research, Addiction Research Center, Baltimore 21224, USA.
Addict Biol. 1996;1(1):31-47. doi: 10.1080/1355621961000124676.
Over the past 10 years a great deal has been learned about the cardiovascular effects of cocaine. In particular, the acute effects of cocaine have been studied extensively. Upon acute administration cocaine increases blood pressure and heart rate, primarily through an action on the sympathetic nervous system. Cocaine also suppresses the baroreflex response and vagal tone, further contributing to its effects on heart rate. At the same time cocaine is increasing the work-load on the heart it induces coronary artery vasoconstriction, potentially leading to cardiac ischemia. At higher doses cocaine can depress ventricular function and slow electrical conduction in the heart. Both these effects appear to be mediated by cocaine's local anesthetic action. The effects of cocaine mediated by the sympathetic nervous system are greatly reduced in anesthetized animals. Further, when cocaine is administered repeatedly over a short period of time, acute tolerance can develop to the sympathomimetic effects of cocaine. In contrast, the effects of cocaine mediated by its local anesthetic action do not appear blunted by anesthesia or susceptible to acute tolerance. With chronic administration, higher doses appear to induce tolerance while lower doses may induce sensitization to cocaine's sympathomimetic effects. Cocaine also induces a variety of pathological changes in the heart, including myocardial contraction band necrosis and ventricular hypertrophy. These effects of cocaine on the heart can all contribute to potentially lethal cardiovascular events. In addition to the effects of cocaine alone, the metabolites of cocaine may also contribute to cocaine's cardiovascular toxicity, and both licit and illicit drugs used in combination with cocaine might potentially alter its cardiovascular effects.
在过去十年里，人们对可卡因的心血管效应有了很多了解。特别是，可卡因的急性效应已得到广泛研究。急性给药时，可卡因主要通过作用于交感神经系统来升高血压和心率。可卡因还会抑制压力反射反应和迷走神经张力，进一步影响其对心率的作用。同时，可卡因在增加心脏工作负荷的同时会诱发冠状动脉血管收缩，可能导致心肌缺血。高剂量时，可卡因会抑制心室功能并减缓心脏的电传导。这两种效应似乎都由可卡因的局部麻醉作用介导。在麻醉动物中，由交感神经系统介导的可卡因效应会大大降低。此外，当在短时间内反复给予可卡因时，会对可卡因的拟交感神经效应产生急性耐受性。相比之下，由可卡因局部麻醉作用介导的效应似乎不会因麻醉而减弱，也不易产生急性耐受性。长期给药时，高剂量似乎会诱导耐受性，而低剂量可能会诱导对可卡因拟交感神经效应的敏化。可卡因还会在心脏中诱发多种病理变化，包括心肌收缩带坏死和心室肥大。可卡因对心脏的这些效应都可能导致潜在的致命心血管事件。除了可卡因本身的效应外，可卡因的代谢产物也可能导致其心血管毒性，并且与可卡因联合使用的合法和非法药物都可能改变其心血管效应。
