Sinner B, Graf B M
Zentrum für Anaesthesie, Rettungs- und Intensivmedizin, Georg August Universität Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
Handb Exp Pharmacol. 2008(182):313-33. doi: 10.1007/978-3-540-74806-9_15.
There are two optical isomers of the 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone ketamine: S(+) ketamine and R(-) ketamine. Effects of this drug are mediated by N-methyl-d-aspartate (NMDA), opioid, muscarinic and different voltage-gated receptors. Clinically, the anaesthetic potency of the S(+)-isomer is approximately three to four times that of the R(-)-isomer, which is attributable to the higher affinity of the S(+)-isomer to the phencyclidine binding sites on the NMDA receptors. Ketamine is water- and lipid-soluble, allowing it to be administered conveniently via various routes and providing extensive distribution in the body. Ketamine metabolism is mediated by hepatic microsomal enzymes. It causes bronchodilation and stimulation of the sympathetic nervous system and cardiovascular system. In clinics, ketamine and particularly S(+)-ketamine are used for premedication, sedation, and induction and maintenance of general anaesthesia, which is than termed "dissociative anaesthesia". Ketamine and its S(+)-isomer are ideal anaesthetic agents for trauma victims, patients with hypovolemic and septic shock and patients with pulmonary diseases. Even subanaesthetic doses of this drug have analgesic effects, so ketamine is also recommended for post-operative analgesia and sedation. The combination of ketamine with midazolam or propofol can be extremely useful and safe for sedation and pain relief in intensive care patients, especially during sepsis and cardiovascular instability. In the treatment of chronic pain ketamine is effective as a potent analgesic or substitute together with other potent analgesics, whereby it can be added by different methods. There are some important patient side-effects, however, that limit its use, whereby psycho-mimetic side-effects are most common.
2-(2-氯苯基)-2-(甲氨基)环己酮氯胺酮有两种光学异构体:S(+)氯胺酮和R(-)氯胺酮。该药物的作用是由N-甲基-D-天冬氨酸(NMDA)、阿片样物质、毒蕈碱和不同的电压门控受体介导的。临床上,S(+)异构体的麻醉效力约为R(-)异构体的三到四倍,这归因于S(+)异构体对NMDA受体上苯环己哌啶结合位点的更高亲和力。氯胺酮具有水溶性和脂溶性,使其能够通过各种途径方便地给药,并在体内广泛分布。氯胺酮的代谢由肝脏微粒体酶介导。它会引起支气管扩张,并刺激交感神经系统和心血管系统。在临床上,氯胺酮尤其是S(+)氯胺酮用于术前用药、镇静以及全身麻醉的诱导和维持,这种麻醉方式被称为“分离麻醉”。氯胺酮及其S(+)异构体是创伤患者、低血容量性和感染性休克患者以及肺部疾病患者的理想麻醉剂。即使是亚麻醉剂量的这种药物也有镇痛作用,因此氯胺酮也被推荐用于术后镇痛和镇静。氯胺酮与咪达唑仑或丙泊酚联合使用对于重症监护患者的镇静和止痛可能极其有用且安全,尤其是在脓毒症和心血管不稳定期间。在慢性疼痛的治疗中,氯胺酮作为一种强效镇痛药或与其他强效镇痛药联合使用时可作为替代品有效,可通过不同方法添加。然而,有一些重要的患者副作用限制了其使用,其中拟精神副作用最为常见。