Inhaled anesthetics: Mech of action

Basic, Basic Sciences

The mechanism of action for volatile anesthetics that produce immobility and amnesia is not entirely understood. Current evidence supports the idea that response to noxious stimuli is ablated by inhaled anesthetics at the level of the spinal cord, while the amnestic effects are mediated within the brain. General anesthesia using volatile anesthetics decreases the transmission of noxious information being transmitted from the spinal cord to the brain, and as a result, supraspinal arousal is decreased. In the brain, inhaled anesthetics decrease cerebral blood flow and metabolism, as well as decrease activation in selected distinct regions. Some recent studies have demonstrated that the tuberomammilary nucleus, a GABA-modulated region of the hypothalamus linked to sleep states, is implicated in the sedative action of some IV anesthetics, and potentially inhaled agents as well. 

Volatile anesthetics have activity at various ion channels including nicotinic acetylcholine, serotonin type 3, GABAa, glycine, and glutamate receptors. At high concentrations, inhaled anesthetics also have activity at some voltage gated channels, though not at clinically used concentrations. The current theory is that inhaled anesthetics enhance inhibitory postsynaptic channel activity (GABAa and glycine receptors) and inhibit excitatory synaptic channel activity (nicotinic acetylcholine, serotonin, and glutamate). GABAa receptors are the most numerous inhibitory neurotransmitter receptors in the brain. Volatile anesthetics increase the sensitivity of these receptors and prolong their inhibitory effect. In the spinal motor neurons, the volatile anesthetics also augment activity of the inhibitory glycine receptors and inhibit post-synaptic AMPA and NMDA receptors, leading to immobility. 

Nitrous oxide is unique in that its primary site of action is at the NMDA-sensitive glutamate channels via inhibitory effects and neuronal nicotinic acetylcholine receptors.

Sources

    Basics of Anesthesia, 6th edition. Miller.

    N Engl J Med. 2003 Aug 28;349(9):909-10; author reply 909-10

    [PubMed: 12761368]

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Answered correctly

2018

Year asked

Author
Caitlin Tourjé, MD