The solubility of volatile anaesthetics in oil

The oil solubility of an anaesthetic is of interest, not only because it governs the passage of the anaesthetic into and out of the fat depots of the body, but also because there is a well-established correlation between anaesthetic potency and oil solubility. Figure 2.10 shows a linear inverse relationship between log narcotic concentration and log solubility in oleyl alcohol for a series of common anaesthetic gases. The ordinate of the graph represents the minimum alveolar concentration (MAC), which is that concentration of anaesthetic at which 50% of the patients cease to move in response to a stimulus. The abscissa shows the solubility expressed in terms of the oil/gas partition coefficient. Partition coefficients are widely used to express solubility and are the ratios of the concentration of the gas in the two phases in equilibrium at a given temperature. When, as in this case, one of the phases is the gas itself, the partition coefficient expressed as the liquid/gas (note the order of the phases) concentration ratio is equal to the

Ostwald solubility coefficient. The graph shows that an anaesthetic gas with a high oil solubility is effective at a low alveolar concentration and has a high potency. This relationship is the basis of the Meyer-Overton hypothesis of anaesthesia.

The correlation between anaesthetic potency and lipid solubility shown in Fig. 2.10 is valid for most inhaled anaesthetics and the product MAC x oil/gas partition coefficient (which should of course be a constant) varies by only a factor of 2 or 3 for potencies ranging over 100 000-fold. This constancy implies that inhaled anaesthetics act in the same manner at a specific hydrophobic site (the so-called unitary theory of anaesthesia). This has been challenged by more recent work that has identified compounds, including alkanes7 and poly-halogenated and perfluorinated compounds,8 which do not obey the Meyer- Overton hypothesis. It has been suggested that a contributory cause of deviation from this hypothesis may be the choice of lipid to represent the anaesthetic site of action of these compounds, implying that there may be multiple sites of action for inhaled anaesthetics.

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