Update in Anaesthesia Pharmacology of Inhalational Anaesthetics John Myatt Correspondence Email:
[email protected] MODE OF ACTION Summary importance in lower brain centres and the spinal The molecular basis of inhalational anaesthesia is not cord. Potentiation of glycine receptors is seen at low Inhalational anaesthetics fully understood. Historically, the first observation concentrations for all the volatile agents. produce loss of consciousness, but may that had a significant impact was the Meyer-Overton Two-pore-domain potassium channels have other effects including hypothesis which demonstrated that the potency - these analgesia (nitrous oxide) (expressed as minimum alveolar concentration, MAC have subunits that are activated by volatile and gaseous or muscle relaxation - see below) of an anaesthetic agent increased in direct anaesthetics and may modulate membrane excitability (isoflurane). They are proportion to its oil:gas partition coefficient (see and have a complex distribution within the CNS. presented as liquefied gases Figure 1). This led to the interpretation that the site of Other possible targets may include NMDA receptors, under pressure or as volatile action of general anaesthetics was the lipid bilayer of HCN channels and some subtypes of the sodium liquids. nerve membranes and that when a sufficient amount channel. of drug was dissolved in this layer, then anaesthesia occurred. There were several theories as to the molecular POTENCY mechanism, but each with its own limitations. The potency of an inhalational anaesthetic agent can be More recent research suggests that inhalational agents measured by its MAC. This is defined as the minimum may act on specific membrane proteins and alter ion alveolar concentration at steady-state that prevents flux or receptor function.