LOCAL ANAESTHETIC

AGENTS
Local anaesthetic agents:

Local anaesthetic drug act by producing a

reversible block to the transmission of peripheral
nerve impulses.
A reversible block may also be produce by
physical factors, including pressure and cold.
All those local anaesthetic have originated
from cocaine- the alkaloid found in the leaves of local
South American bush- Erythroxylum coca.
This drugs are not used widely other then as a
tropical agent because of its systemic toxicity-
Central nervous stimulant and addictive properties.
 The demonstration of the physical structure of
cocaine as an ester of benzoic acid permitted the
production of safer agents.

The subsequent production of amide agents

with varying clinical profiles has greatly extended the
scope of modern local anaesthesia.
Mode of action:

Neural transmission- During the resting phase,

the interior of a peripheral nerve fiber has a
potential difference of about –70mv, relative to the
outside.
When the nerve is stimulated, there is a rapid
increase in the membrane potential to
approximately +20mv, followed by immediate
restoration to the resting level.
This depolarization /repolarization sequence
lasts 1-2 ms and produce the familiar action
potential associated with the passage of a nerve
impulse.
 Depolarization of the fibre is the result of a
sudden increase in membrane permeability to
sodium, thus sodium diffuse down to both
electrochemical and concentration gradients
Sodium ions enter into the cell through a large
protein molecules in the membrane- the channels.
This was closed during the resting phase. But
stimulation if the nerve change the configuration of
the protein so that the channels open.
The membrane potential increase to +20mv, and
the channels close. Then it favors movement of
potassium out through specific channels, potassium
exits from the cell. The resting potential is restored.
 At sensory nerve endings – the initial opening of
Na channels is produce by the appropriate
physiological stimulus, which may be medicated
chemically.
By action-potential, it produce a current flow
between the depolarized(+) segment of nerve and
the next segment(-) .

A similar sequence is induced when

transmitter substance act- this current causes the
change of the Na channels , so that the action-
potential is propagated along the nerve.
Effects of local anaesthetic drugs:
Local anaesthetics are usually injected in an acid solution as
the hydrochloride salt . Thus soluble in water and suitable for
injection.

Systemic toxicity:

If significant amounts of local anaestheic drug reach

the issue of heart and brain, they exert the same membrane-
stabilizing effect as on peripheral nerve, Resulting in
progressive depression of function.
The earliest feature of systemic toxicity is numbness
or tingling of the tongue and and circumoral area, this is the
result of a rich blood supply to these tissue depositing
enough drug to have an effect on the nerve endings.
 The pt may become light-headed, anxious,
drowsy and complain of tinnitus.
If the concentration continue to increase,
consciousness is lost and this may be followed by
convulsion.
Coma and apnoea may develop
subsequently.
Cardiovascular collapse may result from
direct myocardial depression and vasodilatation.
Factor affecting toxicity:

The most common cause of life threatening

systemic toxicity is an inadvertent intravascular
injection, but it may result also from absolute over
dosage.

Absorption:
Absorption from the site of injection
depends on the blood flow- the higher the blood
flow, the more rapid is the increase in plasma
concentration and the greater the resultant peak.
Distribution:

After absorption , local anaesthetic drug are

distributed rapidly, and taken up by organs with a
large blood supply and high affinity- brain , heart ,
liver and lungs.
Muscle and fat with low blood supplies,
equilibrate more slowly.
Local anaesthetic drug are sequestrated in the
lungs, thereby preventing a large proportion of the
injected dose from reaching the coronary and
cerebral circulations.
Metabolism:

In general , ester drug are broken down so

rapidly by plasma cholinestersae that systemic
toxicity is unusual.
So the rate of disappearance of drug is
dependent more upon liver blood flow. This has
practical relevance to the use of lidocain as an
antiarrhythmic in cardiogenic shock , when liver
blood flow is diminished.
Protein binding:

Local anaesthetics are bound to plasma

proteins to varying degrees. It is assumed sometimes
that drugs with the greatest degrees of protein
binding are less toxic because only a small fraction of
the total amount in plasma is free to diffuse into the
tissue and produce toxic effects.
Prevention of toxicity:

The most important factor in the prevention of

toxicity is the avoidance of accidental intravascular
injection. Careful aspiration tests are vital and
should be cheeked each time the needle is moved.
An alternative is to repeat the aspiration test
after each 5-10 ml of solution and to inject slowly
about 5ml /min.
The pt should be watched for early signs of
toxicity so that the injection may be stopped before
there are major sequelae.
Treatment of toxicity:

The airway is maintained and oxygen

administration by face mask, using artificial
ventilation if apnoea occurs.
Convulsion may be controlled with
midazolam 2mg. Excessive dose should not be given
to control convulsion, because cardiorespiratory
depression may be exacerbated.
If the cardiovascular collapse occur despite
adequate oxygenation – it should treated with an
adrenergic drug – Epherdin.

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Deferential sensory and motor blockade:

Sensory and motor nerve fibers may differ in

their susceptibility to local anaesthetics, because of
differences in fiber diameter and myelination.
In terms of absolute sensitivity, large-
diameter fibers are more sensitive then small ones,
but they are usually more heavily myelinated and
the myelin sheath presents a significant barrier to
drug diffusion.
Therefore the small unmyelinated fiber of pain
and temperature receptor are usually blocked more
rapidly than the large, myelinated fibers that
innervated skeletal muscle.
 Deferential blockade of sensory and motor fibers
may be useful clinically in producing analgesia with
relatively little motor blockade – provision of
epidural analgesia for labour or the postoperative
period.

Stability and storage:

The general structure of anaesthetic agents are
aromatic group and an amine linked by either an
ester or an amid bond.
The ester drug have short and amid have long
shelf- life.
Clinical factors affecting drug profile:

Increasing the dose of a drug shortens its onset

time and increases the duration of block. Dose may
be increased by using either a higher concentration
or a large volume, a large volume of a dilute solution
is usually more effective.
The site of injection also affects onset time and
duration.
Onset is almost immediate after infiltration and
is progressively delayed with subarachnoid,
peripheral nerve and epidural block.
 Pregnancy and age are said to increase
segmental spread of epidural blocks. For many
blocks, young healthy, tall pt seems to require more
drug, as do obese, alcoholic pt.

Pharmacology of the dugs:

Cocaine-
Cocaine has no role in modern anaesthetics
practice. It is used in ear, nose and throat surgery for
its vasoconstrictor action.
Benzocain:
This is an excellent topical agent of low
toxicity. It dose not ionize and its use is limited to
topical application.
Its mode of action cannot be explained
according to the theory.
Benxocain diffuse into the cell membrane, but
not into the cytoplasm and either causes the
membrane potential as the same away like other
agents.
Procaine:
The incidence of allergic problems, its short
shelf – life and brief duration of action of procaine
have resulted in its infrequent clinical use at the
present time.
Chloroprocaine:

This is an ester, which is used widely. Its

profile is very similar to that of procaine- differ only
the addition of a chlorine. As a result it hydrolysed
four times more quickly by cholinesterase.
 It has a more rapid onset of action then any
other agent and also very low toxicity- which
permits the use of relatively large dose.
There has been some concern that
chloropocaine might be neurotoxic because of
several reports of paraplegia after accidental
injection.
Evidence suggests that it was the
preservative in the solution that caused the
problems – not the drug itself.
Tetracaine:

This drug is relatively toxic for an ester

because it is hydrolysed very slowly by
cholinesterase.
It is also very potent drug for subarachnoid
anaestyhesia.
It has a prolonged duration of action but also a
slow onset time.
It may be used intrathecally.
Lidocaine:

Lidocaine is still the current standard agent.

It has no unusual features and is also a
standard anti-arrthytmic.
Lidocaine is used commonly for infiltration in
concentration of 0.5- 1.0% and for peripheral nerve
blocks.
It may be used for iv regional anaesthesia.
Lidocaine 5% has been used for subarachnoid
anaesthesia- the degree of spread is unpredictable
and the duration of action is relatively short.
 There have been concerns regarding transient
neurological symptoms occurring after the use such
high concentrations.
In a concentration of 1-2%, lidocaine produce
epidural anaesthesia with a short onset time.
Lidocain 2-4% is used as a topical solution for
anaesthesia of the upper airway in fibreoptic
intubation.
Prilocaine:

This is an underrated agent.

No vasodilatation action, is either metabolized
or sequestrated to a greater degree by the lung and is
metabolizes more rapidly by the liver.
As a result it is slightly short acting, less toxic
and is the drug of choice when the risk of toxicity is
high.
Metabolism reduce hemoglobin- but this
complication is rare unless the dose exceeds 600mg.
Cyanosis appears when Hb% less then 1.5 gm/dL
Prilocarpin should not be used for epidural
block during labour.
Bupivacaine:

Bupivacaine is a potent local anaesthetic agent,

with a long duration of action. Its introduction
represented significant advance in anaesthesia.
Relative to potency – the acute CNS toxicity of
bupivacaine is less and its longer duration of action
reduce the need for repeated doses.
This drug have more toxic effect on the
myocardium then other local anaesthetic agents- so
intravenous administration of large doses of
bupivacain death may occur.
 Cardiovascular collapse may occur suddenly
without prior CNS symptoms.

Bupivacaine may be used for infiltration-

only small doses because of its toxicity.

It is used frequently for peripheral nerve

blockade and for subarachnoid an epidural
anaesthesia because of prolong duration of action.
Levobupivacaine:

Levobupivacaine is less toxic

With higher plasma concentrations required to
produce CNS symptoms, convulsions and cardiac
arrhythmias.
Levobupivacaine may used for local
infiltration, peripheral nerve block and epidural
anaesthesia.
Additives:

Many substance are added to local anaesthetaics

for pharmaceutical purposes and also as well as
clinical purposes.

Vasoconstrictors:
The addition of a vasoconstrictor to a
solution of local anaesthetic drug slows the rate of
absorption, reduce toxicity, prolongs duration and
may result in a more profound block.
 They are absolutely contraindicated for
injection close to end-arteries. And intravenous
regional anaesthesia because of the ischemia.
There is a high risk that the use of
vasoconstrictor may increase the risk of permanent
neurological deficit by nerve tissue ischemia.
Many anaesthetist feel that –
vasoconstrictors should not be used unless there is a
alternative method of prolong duration of action
with less toxicity in the specific clinical situation.
 Adrenaline (epinephrine) is the most potent
agent. It produce its own systemic toxicity and
should be used with particular care.

Even in healthy pt , concentrations greeter

then 1: 200000 should not be used and the
maximum dose should not exceed 0.5 mg.
Specific concentration according to the site:
Lidocaine:

Skin infiltration- 0.5%

IV regional anaesthesia-0.5%
Minor nerve block- 1.0%
Brachial plexus- 1.0-1.5%
Sciatic/ Femoral1.0-1.5%
Epidural- 1.5-2.0%
Sbarachnoid- 2.0-5.0%
Thanks to all