Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

35

Na conductance

K conductance

Action potential

70

0

Trans-membrane

potential

difference

(mV)

012 345

Time (msecs)

0

10

20

30

Conductance

(mmho/cm^2 )

Figure 10.1.Changes in Na+and K+conductance during the action potential.

Local anaesthetics

Preparations

Local anaesthetics are formulated as the hydrochloride salt to render them water-

soluble. They often contain the preservative sodium metabisulphite and a fungi-

cide. Multi-dose bottles contain 1 mg.ml−^1 of the preservative methyl parahydrox-

ybenzoate. Only the single-dose ampoules without additives (apart from glucose at

80 mg.ml−^1 used in ‘heavy’ bupivacaine) are suitable for subarachnoid adminis-

tration as the preservatives carry the risk of producing arachnoiditis. Adrenaline

or felypressin (a synthetic derivative of vasopressin with no antidiuretic effect) are

added to some local anaesthetic solutions in an attempt to slow down absorption

from the site of injection and to prolong the duration of action. Lidocaine is available

in a large range of concentrations varying from 0.5% to 10%. The high concentrations

are used as a spray to anaesthetize mucous membranes (note 1%=10 mg.ml−^1 ).

Mechanism of action

Local anaesthetic action is dependent on blockade of the Na+channel. Unionized

lipid-soluble drug passes through the phospholipid membrane where in the axo-

plasm it is protonated. In this ionized form it binds to the internal surface of a Na+

channel, preventing it from leaving the inactive state. The degree of blockade in vitro

is proportional to the rate of stimulation due to the attraction of local anaesthetic to

‘open’ Na+channels (Figure10.2).

Alternatively, ‘membrane expansion’ may offer an additional mechanism of action.

Unionized drug dissolves into the phospholipid membrane and may cause swelling

of the Na+channel/lipoprotein matrix resulting in its inactivation.