Schenck N L
Ann Otol Rhinol Laryngol. 1975 Jan-Feb;84(1 Pt 1):65-72. doi: 10.1177/000348947508400110.
Almost a half century following attempts to ban its use, cocaine remains at the pinnacle of topical anesthesia in otolaryngology. To understand how nonaddicting synthetic substitutes such as procaine, dibucaine, tetracaine and lidocaine have not totally supplanted cocaine, requires an in-depth analysis of its unique pharmological properties, untoward effects and potential substitutes. Almost all of the reported cocaine deaths occurred after subcutaneous injection; when used topically, cocaine's toxicity has been confined to an occasional reaction. Certain variables under physician control may be manipulated to reduce the chance of reaction to a minimum. For example, intermittent application of a particular dosage results in lower blood levels, and allowing sufficient time between doses reduces the amount necessary to obtain the desired anesthesia. If total dosage is kept below 200 mg there are few reactions. A singular advantage of cocaine over other topical anesthetics is its inherent ability to cause vasoconstriction, thus retarding its own absorption. The addition of a topical vasoconstrictor such as epinephrine is thus redundant, and may actually be harmful as cocaine sensitizes the patient to exogenous epinephrine. Finally, the usual preoperative dosages of barbiturates are entirely inadequate to prevent or treat cocaine reactions. Why, then, have synthetic local anesthetics not replaced cocaine? Inherent differences in topical effectiveness, duration of anesthesia and toxicity provide the answer. Of other local anesthetics possessing topical effectiveness tetracaine is about six times more toxic than cocaine. Dibucaine is as toxic as tetracaine, and lidocaine, while relatively nontoxic, provides only a 15 minute duration of topical anesthesia. A review of cocaine and its potential substitutes thus leads to the conclusion that cocaine is still a vital and necessary instrument in the otolaryngologist's armamentarium, singularly providing excellent topical anesthesia of usable duration, vasoconstriction, and shrinkage of mucous membranes, all with a quite acceptable margin of safety.
在试图禁止使用可卡因近半个世纪后,它在耳鼻喉科局部麻醉领域仍占据着巅峰地位。要理解像普鲁卡因、丁卡因、丁哌卡因和利多卡因等非成瘾性合成替代品为何没有完全取代可卡因,需要深入分析其独特的药理特性、不良反应及潜在替代品。几乎所有报道的可卡因致死案例都发生在皮下注射之后;当局部使用时,可卡因的毒性仅限于偶尔出现的反应。医生可控制的某些变量可加以调整,将反应几率降至最低。例如,间歇性应用特定剂量会使血药浓度降低,且两次给药之间留出足够时间可减少达到所需麻醉效果所需的剂量。如果总剂量保持在200毫克以下,很少会出现反应。可卡因相对于其他局部麻醉剂的一个独特优势是其具有引起血管收缩的内在能力,从而减缓自身吸收。因此添加诸如肾上腺素之类的局部血管收缩剂是多余的,而且实际上可能有害,因为可卡因会使患者对外源性肾上腺素敏感。最后,通常的术前巴比妥类药物剂量完全不足以预防或治疗可卡因反应。那么,为什么合成局部麻醉剂没有取代可卡因呢?局部麻醉效果、麻醉持续时间和毒性方面的内在差异给出了答案。在具有局部麻醉效果的其他局部麻醉剂中,丁卡因的毒性比可卡因大约高六倍。丁哌卡因与丁卡因毒性相当,而利多卡因虽然相对无毒,但仅能提供15分钟的局部麻醉持续时间。对可卡因及其潜在替代品的综述得出的结论是,可卡因在耳鼻喉科医生的装备中仍然是一种至关重要且必要的工具,它能单独提供具有可用持续时间的出色局部麻醉、血管收缩以及黏膜收缩,且安全 margin 相当可接受。