Pharmacology for Anaesthesia and Intensive Care

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8 General anaesthetic agents

Table 8.1.General anaesthetic effects at central receptors.

Inhibitory Neurotransmitters Excitatory Neurotransmitters

GABAA Glycine NMDA Neuronal nACh

propofol ++++ ++ 0 −

thiopental +++++ ++ 0 −

R-etomidate +++++ 000

S-etomidate 0 0 0 0

Ketamine 0 0 − 0

Isoflurane ++++ +++ 0 −

Nitrous Oxide 0 0 − 0

Xenon 0 0 − 0

+: enhances effect of neurotransmitter;−:reduces effect of neurotransmitter; 0: no effect on neuro-

transmitter. nACh: central nicotinic acetylcholine receptor.

GABAAreceptor

The GABAAreceptor, like the nicotinic acetylcholine receptor, belongs to the pen-

tameric family of ligand-gated ion-channel receptors. It has binding sites for GABA

associated withαsubunits and modulatory sites at theα/γinterface for benzodi-

azepines and on theβsubunit for etomidate, barbiturates, propofol and volatile

agents (Figure8.2). The stereospecificity of the action of etomidate, presented as an

β

γ (^) Cl−
ionophore^
General Anaesthetic Site
Benzodiazepine
Receptor Site
α
α
β
Figure 8.2.The GABAAreceptor.
The GABAAReceptor Complex, from above.The grey triangles show the two agonist sites
for gamma amino butyric acid (GABA). Diazepam, temazepam and midazolam are agonists
and flumazenil is an antagonist at the benzodiazepine site. Propofol, etomidate, barbiturates
and halogenated volatile agents are agonists at the general anaesthetic site. Both sites
produce positive allosteric modulation.