Inhaled Anesthetics Do Not Combine to Produce Synergistic Effects Regarding Minimum Alveolar Anesthetic Concentration in Rats

Abstract

Such results are consistent with the notion that inhaled anesthetics act on a single site to produce immobility in the face of noxious stimulation.

HCN1 Channels as Targets for Anesthetic and Nonanesthetic Propofol Analogs in the Amelioration of Mechanical and Thermal Hyperalgesia in a Mouse Model of Neuropathic Pain

“…The alkylphenols are hydrophobic, with calculated octanol/water partition coefficients (expressed as cLog P) of approximately 5 , comparable with that of potent bilayer modifiers (Rusinova et al, 2011). General anesthetics have been shown to exert many, but perhaps not all, of their effects via specific interactions with ion channels (Eger et al, 2008), thereby leaving open the possibility that those that are lipophiles (such as the alkylphenols) may also alter embedded membrane protein function via interactions with the lipid bilayer (Lundbaek et al, 2010) (Fig. 6A).…”

Dexmedetomidine and hydroxyzine synergistically potentiate the hypnotic activity of propofol in mice

“…Thus, another analytical technique should be required. A comparison using the sum of ''normalized dose'' provides theoretical evidence for an interaction of the combination of drugs, one of which shows a ceiling effect [1,7]. In practical settings, limiting the conclusion that a ceiling effect implies synergy to those cases in which a 10% reduction is observed at clinically relevant doses seems reasonable [1].…”

“…However, many popular anesthetic agents follow conventional pharmacokinetics, depending primarily on hepatic metabolism and clearance [25]. Thus, managing anesthesia with a single drug is complex, and a combination of drugs may provide preferable solutions in clinical settings [4,7]. When the hypnotic activities of each drug are synergistic without clearance interference, titration of dosing for each agent may result in a faster reduction to a basal level in the blood and the effector site [4].…”

“…Recently, Hendrickx et al [1] extensively reviewed anesthetic interactions using the definitions developed in two former investigations [6,7]. The new definition of synergy in terms of the sum of the normalized doses could be used to evaluate the interaction of drugs showing a ceiling effect [1].…”

“…The new definition of synergy in terms of the sum of the normalized doses could be used to evaluate the interaction of drugs showing a ceiling effect [1]. Thus, comparative studies of almost all anesthetics, including intravenous and inhalational compounds [7], could be discussed. Although that review [1] may further our understanding of anesthetic interactions, a few uncertainties remain as exceptions or unsolved cases.…”