Local Anaesthetics
A 30-year old woman presents to the office for treatment of
an ingrown toenail. For the past 3 weeks she has had
progressively worsening redness, swelling, and pain from the
area around the right great toenail. On examination you find
that the distal, medial corner of the right great toenail is in
growing. The skin on the medial or the nail is red and tender.
There is a visible purulent drainage as well. You place her on
a 1-week course of oral cephalexin and have her return to the
office. On follow-up the redness is markedly improved, and
there is no further drainage. You surgically correct the
ingrown toenail after achieving local anesthesia with 2 percent
lidocaine injected to infiltrate the digital nerves.
I.What is the mechanism of action of lidocaine as an
anesthetic agent?
II.Why does the treatment of infection increase the
effectiveness of the local anesthetic?
III.After effective nerve block before tooth
extraction, patients do not feel pain but can
chew. Why this is the case?
Chemical aspects
• Molecules of local anaesthetics consist of
an aromatic part linked by an ester or
amide bond to a basic side chain.
Figure 44-1 Structures of local anaesthetics. The
general structure of local anaesthetic molecules
consists of aromatic group (left), ester or amide
group (shaded) and amine group (right).
• They are weak bases with pKa values in
the range 8 - 9 thus mainly, but not
completely ionised at physiological pH
(Important for penetrating nerve sheath
and axon membranes).
• Benzocaine, an atypical local anaesthetic
has no basic group.
• Ester – containing compounds are usually
inactivated in the plasma and tissues
(mainly liver) by non-specific esterases.
• Amides are more stable, and generally
have longer plasma half-lives.
Mechanism of action
• Local anaesthetics block the initiation and
propagation of action potential by preventing
voltage dependent increase in Na+
conductance.
• Their main action is to block sodium channels by
physically plugging the trans-membrane pore,
interacting with residue of S6 helical domain of
the channel protein.
• In general, local anaesthetics block conduction
in small-diameter nerve fibres more readily than
large fibres.
• Because nociceptive impulses are carried by Aδ
and C fibres pain sensation is blocked more
readily than other sensory modalities (touch,
proprioception).
• Local anaesthetics as their name implies are
mainly used to produce local nerve block.
• In concentrations too low to cause nerve block
they are able to suppress spontaneous
discharge in sensory neurons, believed to be
responsible for neuropathic pain.
• Lidocaine iv can be used to control
neuropathic pain and some
antidysrhythmic drugs (e.g. mexiletine,
tocainide, flacainides can be used orally
(but not licensed for this indication).
• Local anaesthetics probably act in their
cationic form but must reach their site of
action by penetrating the nerve sheath and
axonal membrane as unionised.
Figure 44-2 Interaction of local anaesthetics with
sodium channels. The blocking site within the
channel can be reached via the open channel
gate on the inner surface of the membrane by the
charged species BH+ (hydrophilic pathway), or
directly from the membrane by the uncharged
species B (hydrophilic pathway).
Table: 44.1 Properties of individual local
anaesthetics
Refer to Rang and Dale’s Page 641
CONT..
Some properties of local anaesthetics
Drug Onset Duration Tissue Plasma
penetrati half-life
on (h)
Cocaine Medium Medium Good Appox. 1
Procaine Medium Short Poor <1
Lidocaine Rapid Medium Good Approx. 2
Tetracaine Very Long Moderate Approx. 2
slow
Bupivacai Slow Long Moderate Approx. 2
ne
Unwanted effects and
pharmacokinetics
• Unwanted effects are due mainly to escape of
local anaesthetics into the systemic circulation.
• Main unwanted effects are:
– Central nervous system effects: agitation, confusion,
tremors progressing to convulsions and respiratory
depression.
– Cardiovascular effects namely myocardial depression
and vasodilatation leading to fall in blood pressure.
– Occasional hypersensitivity reactions.
• Local anaesthetics vary in the rapidity with
which they penetrate tissues, and in their
duration of action.
– Lidocaine (Lignocaine) penetrates tissues
readily and is suitable for surface application.
– Bupivacaine has a particularly long duration of
action.
Table: 44.2 Methods of administration, uses and
adverse effects of local anaesthetics.
Refer to Rang and Dale’s Page 643
Clinical use of local anaesthetics
•Local anaesthetics may be infiltrated into soft tissue (e.g.
of gums) or to block a nerve or nerve plexus.
•Coadministration of a vasoconstrictor (e.g. adrenaline)
prolongs the local effect.
•Lipid-soluble drugs (e.g. lidocaine [lignocaine]) are
absorbed from mucous membranes and are used as
surface anaesthetics.
•Bupivacaine has a slow onset but long duration. It is
often used for epidural blockade (e.g. to provide
continuous epidural blockade during labour) and spinal
anaesthesia. Its isomer levobupivacaine is less
cardiotoxic if it is inadvertently administered into a blood
vessel
