HAMID MIREMADI

GROUP :180B

SUBJECT : LOCAL ANAESTHETICS

 INTRODUCTION
 local anesthesia refers to loss of sensation in a limited
region of the body.
 Local and regional techniques can be used to provide
anaesthesia for many surgical procedures.
 They can also provide good-quality post-operative
analgesia, especially when using continuous epidural
infusions.
 A local anaesthetic may be the method of choice for
patients with severe cardiorespiratory disease, as the
risks of general anaesthesia and systemic narcotic
analgesics are avoided.
Local anaesthetic techniques have also
proved useful in combination with
general anaesthesia.
Local anesthetics (LA) are drugs
employed to produce a transient and
reversible loss of sensation in a
circumscribed area of the body by
interfering with nerve conduction (both
sensory and motor) and without loss of
consciousness
Useful drugs must be:
 Water soluble.
 Serializable by heat.
 Have a rapid onset of effect.
 Have a duration of action suitable to
the operation performed.
 Be non-toxic.
 Leave no local after effects.
 BASIC PHARMACOLOGY OF LOCAL ANESTHETICS
 Most local anesthetic agents consist of a lipophilic
group (eg, an aromatic ring) connected by an
intermediate chain via an ester or amide to an
ionizable group (e.g., a tertiary amine) Most local
anesthetic agents consist of a lipophilic group (eg, an
aromatic ring) connected by an intermediate chain
via an ester or amide to an ionizable group (e.g., a
tertiary amine).
 Because ester (e.g. cocaine, procaine, tetracaine
and benzocaine) links are more prone to hydrolysis
than amide links, esters usually have a shorter
duration of action.
Local anesthetics are weak bases and are usually
made available clinically as salts to increase
solubility and stability.

In the body, they exist either as the uncharged

base or as a cation.

The relative proportions of these two forms are

governed by their pKa and the pH of the body
fluids according to the Henderson-Hasselbalch
equation, which can be expressed as:
pKa = pH – log [base]/[conjugate acid]
Mode of action:
 LA prevent the nerve impulses from arising
and propagating by interfering with the rate
of rise of the depolarization phase of the
action potential.

 Also the threshold of excitation increases

and the impulse conduction slows , finally
the cell does not depolarize sufficiently to
fire and therefore propagating action
potential fails to occur.
LA accomplish this by reducing the
passage of Na+ through the voltage
gated Na+ channels.
Increase in extracellular Ca partially
antagonizes the action of LA, this is
probably because LA compete with Ca
ions for a site in the nerve membrane
that controls the passage of Na+
through these channels.
The fibers in the nerve trunks are affected
according to:
 1- Fiber diameter:
 The small fibers are first affected (autonomic, sensory)
and then the larger myelinated motor fibers.
 Type B(preganglionic autonomic) then type C
(dorsal root for pain) and then the small type A
delta fiber (pain and temperature) and then type A
beta (touch and pressure) and then type A alpha
(proprioception, motor).
 The time of onset of action is shorter for the smaller
fibers and the concentration of the drug required is
also less.
2- Myelination:
 Myelinated nerves tend to become
blocked before the unmyelinated nerve of
the same diameter , for this reason pre-
ganglionic B fibers may be blocked before
the unmyelinated C fibers involved in
pain transmission.
 For myelinated fibers at least two
successive nodes must be blocked by The
LA to halt impulse propagation.
3- Firing frequency (conduction velocity):
LA effect is more marked on fibers
of higher frequencies of
depolarization and longer periods
of depolarization especially pain
fibers.
Motor fibers fire at a slower rate
and have a shorter action potential
duration .
4- Fiber position:
 The location of the fiber in the
peripheral nerve bundle whether
sensory or motor is important.
 Fibers located circumferentially are
blocked first because they are the first
to be exposed to the drug therefore it is
not uncommon that motor nerves are
blocked before the sensory in large
mixed nerve.
Local anaesthetics depress small
unmyelinated fibers first and larger
myelinated fibers last.
The order of loss of function is
therefore as follows:
• pain;
• temperature;
• touch;
• motor function.
BUPIVACAINE
 Is a long-acting amide local anaesthetic commonly
used for epidural and spinal anaesthesia.
 Although it has a slow onset, peripheral nerve and
plexus blockade can have a duration of 5–12 hours.
 Epidural blockade is much.
 shorter, at about two hours, but is still longer than
for lidocaine.
 The relatively short duration of epidural block is
related to the high vascularity of the epidural space
and consequent rapid uptake of anaesthetic into the
bloodstream.
Bupivacaine is the agent of choice for
continuous epidural blockade in
obstetrics, as the rise in maternal (and
therefore fetal) plasma concentration
occurs less rapidly than with lidocaine.
The acute central nervous system
toxicity of bupivacaine is similar to that
of lidocaine, it is thought to be more
toxic to the myocardium.
LIDOCAINE
 It has a quick onset and medium duration of
action. In addition to injection, lidocaine
can be administered topically as a gel or
aerosol. It is used in all forms of local
anaesthesia.
 Absorption following topical application
can be rapid (e.g. from the larynx, bronchi
or urethra).
 Systemic allergy is uncommon.
 PRILOCAINE
 Prilocaine is similar to lidocaine, but its clearance is more
rapid, so it is less toxic.
 It is most useful when a large total amount of local
anaesthetic is needed or a high plasma concentration is
likely (e.g. injection into vascular areas, such as the
perineum), or for use in intravenous regional anaesthesia.

 EMLA is a ‘eutectic mixture of local anaesthetic’ and is a

combination of prilocaine and lidocaine in the form of a
cream. If applied topically for 30–60 minutes and covered
with an occlusive dressing, it provides reliable anaesthesia
for venipuncture (important, especially for children).
Excessive doses can lead to systemic
toxicity, dependent on plasma
concentration.

Prilocaine is metabolized by amidases in the

liver, kidney and lungs. The rapid
production of oxidation products may rarely
give rise to methaemoglobinaemia.
FIN