4. Local Anaesthetics: Influences on Onset and Duration

Question 1

Action

Answer 1

the axoplasmic part of the sodium channel is blocked by the ionized
part of the local anaesthetic molecule, but a charged moiety will not traverse the lipid
and connective tissue membranes. It is only when existing in the uncharged form
that the drug can gain access to the axoplasm.

Question 2

Alkalinization:

Answer 2

the addition of bicarbonate will raise the pH of the weakly acidic
solution nearer the pKa

The addition of 1.0 ml
NaHCO3 8.4% to 10.0 ml of lidocaine 2% will raise its pH from 6.5 to 7.2

More drug will exist in the non-ionized
form, and so penetration will be more rapid. NaHCO3 significantly reduces the
latency of lidocaine, although its effect on bupivacaine is less impressive, with some
studies reporting only a 2–3-minute improvement

Question 3

Carbonation:

Answer 3

After infiltration of the drug, it is believed that the increased amount of CO2 moves into the axoplasm, where it increases the levels of the weak carbonic acid.

Question 4

Methods of Extending the Duration of Local Anaesthetic Blocks

Answer 4

Dexamethasone: the addition of this glucocorticoid to local anaesthetics for plexus and
peripheral nerve anaesthesia is a popular current technique, and there are a number of
systematic reviews to confirm that doses up to 8 mg can almost double the duration of
some blocks.

so it
is as likely that the effect seen may simply be the consequence of systemic absorption.

Question 5

Clonidine

Answer 5

Clonidine: this does appear to have a direct action on peripheral nerves, mediated
via the hyperpolarization of cation channels, and is effective in increasing the
duration of neuraxial blocks, at least partly by spinal α2-agonism.

Question 6

Buprenorphine

Answer 6

: this is a partial μ-agonist which may also block voltage-gated Na+
channels and thereby exert a local anaesthetic effect. It also acts on κ- and δ-opioid
receptors. It can in some reports almost double the duration of plexus blocks, and
studies suggest that the effect is not due to systemic absorption.

Question 7

Adrenaline

Answer 7

Adrenaline (epinephrine): the addition of adrenaline is of very modest benefit, and
when added to local anaesthetic for peripheral nerve block

Question 8

Extending an obstetric epidural for operative delivery

Answer 8

depending on operative urgency.
Typical regimens include levobupivacaine 0.5% 20 ml, lidocaine 2% 20 ml, and
levobupivacaine 0.5% 10 ml plus lidocaine 2% 10 ml. It is common to add
adrenaline 100 μg (5 μgml−1 is 1 in 200,000), and many anaesthetists add an opioid
such as fentanyl or diamorphine. Some also alkalinize the solutions by adding
sodium bicarbonate 8.4%, 1.0 ml per 10 ml

Question 9

Inflammatory modulation

Answer 9

Local anaesthetics have been shown to interact with
some of these proteins to modify the physiological response.

Question 10

Protein binding and lipid solubility:

Answer 10

protein binding influences the duration of action
of a compound, and lipid solubility is a prime determinant of intrinsic anaesthetic
potency. Lidocaine has low lipid solubility, whereas that of bupivacaine is high.

Question 11

Newer local anaesthetic formulations

Answer 11

Liposomes are one alternative formulation. A liposome is formed when amphipathic
lipid molecules (i.e. ones which have both hydrophobic and hydrophilic properties)
encounter an aqueous medium, and become so orientated as to form a phospholipid
bilayer which is similar to a cell membrane

Their release varies according to the
characteristics of the particular liposome