Local Anesthetics
Lab. 4
Local Anesthetics (LA)
• L.A. reversibly block impulse conduction
along nerve axons and other excitable
membrane.
• A local anesthetic is a drug that causes
reversible local anesthesia and a loss of
nociception. When it is used on specific
nerve pathways (nerve block), effects
such as analgesia (loss of pain sensation)
and paralysis (loss of muscle power) can
be achieved.
Mechanism of action of LA
• They act by blockade of sodium channels
so that:
1- The threshold for excitation increase
2- Impulse conduction slow
3- The rate of rise of the action potential
declines, and
4- The ability to generate an action potential
is abolished or canceled.
Mechanism of action of LA
• When the influx of sodium is interrupted,
an action potential cannot arise and signal
conduction is inhibited. LA drugs bind
more readily to sodium channels in
activated state, thus onset of neuronal
blockade is faster in neurons that are
rapidly firing. This is referred to as state
dependent blockade.
Effect of PH
• Local anesthetics are weak bases and are
usually formulated as the hydrochloride salt to
render them water-soluble. At the chemical's
pKa the protonated (ionized) and unprotonated
(unionized) forms of the molecule exist in an
equilibrium but only the unprotonated molecule
diffuses readily across cell membranes. Once
inside the cell the local anesthetic will be in
equilibrium, with the formation of the
protonated (ionized form), which does not
readily pass back out of the cell. This is referred
to as "ion-trapping".
Effect of PH (cont.)
• LA are weak bases and their activity
increases by increasing PH
• This because if large amount of a drug is
unpolar, it will facilitate its penetration
through the cell membrane
• Once the drug has penetrated the lipid
barrier and reach its site of action it
ionized and the ionized form is responsible
for LA activity
• Acidosis such as caused by inflammation
at a wound partly reduces the action of
local anesthetics. This is partly because
most of the anesthetic is ionized and
therefore unable to cross the cell
membrane to reach its cytoplasmic-facing
site of action on the sodium channel.
• Local anesthetics block conduction in the
following order: small myelinated axons
(e.g. those carrying nociceptive impulses),
non-myelinated axons, then large
myelinated axons. Thus, a differential
block can be achieved (i.e. pain sensation
is blocked more readily than other sensory
modalities).
Methods of Administration
• 1- Surface anesthesia: direct application
of the drug on the surface such as skin
and wounds.
• 2- Infiltration anesthesia: injection of
LA in subcutaneous tissue in order to
paralyze nerve endings at the site of
action.
• 3- Nerve block: LA is injected in the
vacinity of major nerve such as teeth
Methods of Administration
• 4- Epidural anesthesia: injection of LA
into the epidural space.
• 5- Sympathetic block: inject LA around
sympathetic nerves
• 6- Spinal anesthesia: injection of LA
into subarachnoid space in the lumber
region
Clinical use
• 1- Systemic use as antiarrhythemic agents
e.g. Lidocaine
• 2- Locally use to produce anesthesia
Clinical LA
• Clinical local anesthetics belong to one of two
•
•
classes:
1- aminoamide and 2- aminoester
Synthetic local anesthetics are structurally
related to cocaine. They differ from cocaine
mainly in that they do not produce hypertension
or local vasoconstriction, with the exception of
Ropivacaine and Mepivacaine that do produce
weak vasoconstriction.
Classification of LA
1-Esters
A- esters of P- amine benzoic acid e.g. Procaine
B- Esters of benzoic acid e.g. Cocaine
• Benzocaine
• Chloroprocaine
• Cyclomethycaine
• Dimethocaine/Larocaine
• Propoxycaine
• Procaine/Novocaine
• Proparacaine
• Tetracaine/Amethocaine
Classification of LA
2-
•
•
•
•
•
•
•
•
•
•
•
Amide e.g. Lidocaine
Articaine
Bupivacaine
Cinchocaine/Dibucaine
Etidocaine
Levobupivacaine
Lidocaine/Lignocaine
Mepivacaine
Piperocaine
Prilocaine
Ropivacaine
Trimecaine
Classification of LA
3- Combinations
• Lidocaine/prilocaine (EMLA)
4- Natural local anesthetics e.g. Saxitoxin and
Tetrodotoxin
• Naturally occurring local anesthetics not derived
from cocaine are usually neurotoxins, and have
the suffix -toxin in their names. Unlike cocaine
produced local anesthetics which are
intracellular in effect, saxitoxin & tetrodotoxin
bind to the extracellular side of sodium
channels.
Potency LA
• The potency of LA is vary from one to
another where the potency and duration
of action are increased with decreased
water solublility of the agent for example
• Procaine ˃˃˃˃ 1 more water soluble
• Lidocaine ˃˃˃˃ 4
• Tetracaine ˃˃˃˃ 16
Frog’s plexus method
• “Foot withdrawal reflex of frog”
• Principle:
• The skin of the frog is very sensitive to
diluted HCL and will reflex by withdrawing
its leg when immersed in HCL
Procedure
1- Decapitaion the frog (avoid pithing the spinal cord)
2- Make a transverse incision in the abdominal wall just
below the xiphoid cartilage and eviscerate the abdomen
carefully to form abdominal sac and expose the lumbar
plexus without damaging it
3- suspend the frog in a stand and test the withdrawal
reflex with 0.1 N HCL by immersing one foot in HCL and
avoid touching the bottom of the beaker.
4- remove the acid and wash immediately with tap water
N.B. the withdrawal reflex time should not exceed 10
seconds and the contact with HCL too.
5- Administer 1 ml of LA solution in the abdominal sac of the frog and
observe the zero time.
6- Test the withdrawal reflex at 3 minutes interval and wash with tap
water after each exposure to the acid, observe the time at which
the absence of withdrawal reflex occurs
Onst time: is the time from adding LA untill the acid fails to provoke
withdrawal of the foot
Recovery time: is the time in minutes from washing the LA till the
appearance of the withdrawal reflex in response to HCL.
7- Tabulate your results and determine which of LA is more rapid in its
action than the other.
The time interval
Procaine
Lignocaine
3
-
-
6
-
+
9
-
12
-
15
-
18
+
• Negative (-)= means the presence of the
withdrawal reflex (the drug has no
activity).
• Positive (+)= means the absence of the
withdrawal reflex (the drug has activity
and blocks sodium channels)
• Conclusion:
From the table we conclude that lignocaine
is more rapid in inducing local anesthesia
than procaine