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Section IICoredrugs in anaesthetic practiceenantiopure preparation of the R(+)isomer, supports the protein-based action of
anaesthetics. The S(−)form of etomidate is clinically inactive and at the GABAA
receptor there is a 30-fold difference in activity.
Anaesthetics increase channel opening time, so allowing for increased chloride
entry resulting in hyperpolarisation. The effect is seen for etomidate, propofol
and barbiturates, as well as halogenated volatiles. Etomidate is selective for the
GABAAreceptor but propofol will also increase glycine channel opening time and
is inhibitory at neuronal nicotinic and 5HT 3 receptors. The site(s) on the GABAA
receptor associated with anaesthetic action are associated with theβsubunit and
are distinct from the benzodiazepine receptor site. There are at least 30 types of
GABAAreceptor, each with different subunit composition;β 2 andβ 3 subunits are
more sensitive to the effects of etomidate than is theβ 1 subunit.Glycine receptor
The major inhibitory transmitter in the spinal cord and brainstem is glycine, which
is associated with a chloride channel similar to the GABAAreceptor. The volatile
anaesthetics all markedly potentiate the action of glycine, although there is no evi-
dence of stereoselectivity. It has been suggested that the spinal cord is an important
site of action for volatile rather than intravenous anaesthetic agents. Efficacy here
correlates more with immobility than awareness.NMDA receptor
Neuronal signalling may also be reduced by inhibition of excitatory pathways. The
NMDA receptor is involved in long-term signal potentiation associated with learning
and memory; it is activated by glutamate, modulated by magnesium and inhib-
ited in a non-competitive manner by ketamine, nitrous oxide and xenon. This
glutamate-mediated mechanism represents an additional pathway for anaesthe-
sia. Other anaesthetic agents, such as barbiturates, can reduce the effectiveness of
glutamate but at a lower potency than for inhibition of GABAAreceptor function.Intravenous anaesthetic agents
Intravenous anaesthetics have been defined as agents that will induce loss of con-
sciousness in one arm–brain circulation time.
The introduction of barbiturates in the 1930s was a significant advance in anaes-
thesia. Their rapid onset and relatively short duration of action made them differ-
ent from previously used agents. Hexobarbitone was introduced first, followed by
thiopental and subsequently methohexitone. Phencyclidine (angel dust) was with-
drawn due to serious psychotomimetic reactions, but the chemically related com-
pound ketamine is still used. The imidazole ester, etomidate, is useful due to its car-
diovascular stability but side-effects limit its use. The phenolic derivative propofol
has become the most popular agent in recent years due to its ready-to-use formula-
tion, favourable recovery profile and use in target-controlled anaesthesia. Steroidal