Lipid Solubility

The higher the lipid solubility the greater the penetration of the nerve membrane by the agent, so that higher lipid solubility results in greater potency. It also results in more toxicity and local irritancy. High lipid solubility also increases the rate of onset and duration of action of local anaesthetic agents.

Figure LA.3

Mechanism of action of local anaesthetic agents using lidocaine as an example

Figure LA.3

Mechanism of action of local anaesthetic agents using lidocaine as an example

PHYSICOCHEMICAL AND PHARMACOKINETIC PROPERTIES OF LOCAL

ANAESTHETIC AGENTS

Molecular weight

pKa (250C)

Partition coefficient

Protein binding

(%)

Onset

Potency (relative to lidocaine)

Duration

Esters

Amethocaine

2ó4

B.5

4.1

Slow

4

Long

Procaine

236

B.9

G.G2

ó

Slow

1/2

Short

Amides

Bupivacaine

2BB

B.1

27.5

Medium

4

Long

Lidocaine

234

7.9

2.9

ó4

Rapid

1

Medium

Prilocaine

22G

7.9

G.9

55

Rapid

1

Medium

Ropivacaine

274

B.G

27.5

95

Medium

4

The lower the pKa, the lower the degree of ionization for any given pH and so the more rapid the speed of onset of the block. Increasing pKa increases the ionized proportion of the drug so that intracellularly a higher proportion is in the active state. However, this also means that less is in the non ionized, diffusible state so the onset and offset of action are also slower. Figure LA.5 shows the effect of differences in pH and pKa on the proportion of ionized and non ionized local anaesthetic agents.

Figure LA.5 Effect of pH on the ionization of local anaesthetic agents

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