The principal molecular targets of anesthetic action that have been studied are neuronal ion channels that mediate impulse conduction in the CNS. Chloride channels (γ-aminobutyric acid-A [GABAA] and glycine receptors) and potassium channels (K2P, possibly KV, and KATP channels) remain the primary inhibitory ion channels considered legitimate candidates of anesthetic action. Excitatory ion channel targets include those activated by acetylcholine (nicotinic and muscarinic receptors), by glutamate (amino3-hydroxy-5-methyl-4-isoxazol-propionic acid [AMPA], kainate, and N-methyl-d-aspartate [NMDA] receptors), or by serotonin (5-HT2 and 5-HT3 receptors). Figure 25–1 depicts the relation of these inhibitory and excitatory targets of anesthetics within the context of the nerve terminal.
Recently, researchers using powerful new investigational tools such as extended array electroencephalograms and functional magnetic resonance imaging have focused on neural networks within the brain that are altered by general anesthetics (see Box: What Does Anesthesia Represent & Where Does It Work? for more details).
A clear distinction should be made between volatile and gaseous anesthetics, both of which are administered by inhalation. Volatile anesthetics (halothane, enflurane, isoflurane, desflurane, sevoflurane) have low vapor pressures and thus high boiling points so that they are liquids at room temperature (20°C) and sea-level ambient pressure, whereas gaseous anesthetics (nitrous oxide, xenon) have high vapor pressures and low boiling points so that they are in gas form at room temperature. The characteristics of volatile anesthetics make it necessary that they be administered using precision vaporizers. Figure 25–2 shows the chemical structures of important, clinically used, inhaled anesthetics.
Inhaled anesthetics, both volatile and gaseous, are taken up through gas exchange in the alveoli of the lung. Uptake from the alveoli into the blood and distribution and partitioning into the effect compartments within the body are important determinants of the kinetics of these agents. As stated previously, an ideal anesthetic should have a rapid onset (induction) and offset (emergence). To achieve this, the effect site concentration within the CNS (brain and spinal cord) will need to change rapidly. Several factors determine how quickly the CNS concentration changes.