Pharmacology for Anaesthesia and Intensive Care

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10 Local anaesthetics

Table 10.1.Classification of local anaesthetics.

Esters−CO.O− Amides−NH.CO−

Procaine Lidocaine

Amethocaine Prilocaine

Cocaine Bupivacaine

Ropivacaine

Dibucaine

Physiochemical characteristics

Local anaesthetics are weak bases and exist predominantly in the ionized form at

neutral pH as their pKaexceeds 7.4. They fall into one of two chemical groupings, ester

or amide, which describes the linkage between the aromatic lipophilic group and

the hydrophilic group that each group possesses. Esters are comparatively unstable

in solution, unlike amides that have a shelf-life of up to 2 years (Table10.1,Figure

10.3).

The individual structures confer different physiochemical and clinical character-

istics.


Potencyis closely correlated tolipid solubilityin vitro, but less so in vivo. Other fac-

tors such as vasodilator properties and tissue distribution determine the amount

of local anaesthetic that is available at the nerve.


Theduration of actionis closely associated with the extent ofprotein binding.

Local anaesthetics with limited protein binding have a short duration of action,

and conversely those with more extensive protein binding have a longer duration

of action.


Theonset of actionis closely related topKa. Local anaesthetics are weak bases

and exist mainly in the ionized form at normal pH. Those with a high pKahave

agreater fraction present in the ionized form, which is unable to penetrate the

phospholipid membrane, resulting in a slow onset of action. Conversely, a low

Local anaesthetic

Cytoplasm

H

Na Na

Phospholipid

membrane

Na channel

Figure 10.2.Mechanism of action of local anaesthetics.