Hendrickx Jan F A, Eger Edmond I, Sonner James M, Shafer Steven L
Department of Anesthesia, Onze Lieve Vrouw Hospital, Moorselbaan 164, 9300 Aalst, Belgium.
Anesth Analg. 2008 Aug;107(2):494-506. doi: 10.1213/ane.0b013e31817b859e.
Drug interactions may reveal mechanisms of drug action: additive interactions suggest a common site of action, and synergistic interactions suggest different sites of action. We applied this reasoning in a review of published data on anesthetic drug interactions for the end-points of hypnosis and immobility.
We searched Medline for all manuscripts listing propofol, etomidate, methohexital, thiopental, midazolam, diazepam, ketamine, dexmedetomidine, clonidine, morphine, fentanyl, sufentanil, alfentanil, remifentanil, droperidol, metoclopramide, lidocaine, halothane, enflurane, isoflurane, sevoflurane, desflurane, N2O, and Xe that contained terms suggesting interaction: interaction, additive, additivity, synergy, synergism, synergistic, antagonism, antagonistic, isobologram, or isobolographic. When available, data were reanalyzed using fraction analysis or response surface analysis.
Between drug classes, most interactions were synergistic. The major exception was ketamine, which typically interacted in either an additive or infra-additive (antagonistic) manner. Inhaled anesthetics typically showed synergy with IV anesthetics, but were additive or, in the case of nitrous oxide and isoflurane, possibly infra-additive, with each other.
Except for ketamine, IV anesthetics acting at different sites usually demonstrated synergy. Inhaled anesthetics usually demonstrated synergy with IV anesthetics, but no pair of inhaled anesthetics interacted synergistically.
药物相互作用可能揭示药物作用机制：相加相互作用提示作用位点相同，协同相互作用提示作用位点不同。我们在一项关于催眠和制动终点的麻醉药物相互作用的已发表数据综述中运用了这一推理。
我们在Medline中检索了所有列出丙泊酚、依托咪酯、甲己炔巴比妥、硫喷妥钠、咪达唑仑、地西泮、氯胺酮、右美托咪定、可乐定、吗啡、芬太尼、舒芬太尼、阿芬太尼、瑞芬太尼、氟哌利多、甲氧氯普胺、利多卡因、氟烷、恩氟烷、异氟烷、七氟烷、地氟烷、N2O和氙气且包含提示相互作用的术语（相互作用、相加、相加性、协同、协同作用、协同的、拮抗、拮抗的、等效应线图或等效应线的）的手稿。如有可用数据，则使用分数分析或反应表面分析重新进行分析。
在不同药物类别之间，大多数相互作用是协同的。主要例外是氯胺酮，其通常以相加或亚相加（拮抗）方式相互作用。吸入麻醉药通常与静脉麻醉药表现出协同作用，但彼此之间是相加的，或者在氧化亚氮和异氟烷的情况下可能是亚相加的。
除氯胺酮外，作用于不同位点的静脉麻醉药通常表现出协同作用。吸入麻醉药通常与静脉麻醉药表现出协同作用，但没有一对吸入麻醉药表现出协同相互作用。
