LOCAL ANESTHETICS
Definition
History
Classification
Chemistry
Mechanism of action
Pharmacokinetics
Uses
Adverse effects
Interactions
Definition:
Local anesthetics are drugs which upon
topical application or local injection
cause reversible loss of sensory
perception, in a part supplied by the
nerve.
order of blockade of nerve function in
the following manner
Pain, temperature, touch, pressure and
finally skeletal muscle power
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Classes
Amide linked Ester linked
LA’s LA’s :
•Lignocaine •Cocaine
•Bupivacaine •Procaine
•Mepivacaine •Chloroprocai
•Dibucaine ne
•Prilocaine •Tetracaine
•Ropivacaine •Benzocaine
Chemistry
CLASSIFICATION:
INJECTABLES:
[Link] potency, short duration
Procaine, Chloroprocaine
2. Intermediate potency, duration
Lignocaine, Prilocaine
3. High potency, long duration
Tetracaine, Bupivacaine, Ropivacaine,
Dibucaine
SURFACE ANESTHETICS
Soluble Insoluble
• Cocaine Benzocaine
• Lignocaine Oxethazine
• Tetracaine
Mechanism of Action
Action Potential
Channel
Closes
50
Transmembrane potential
ation
Repolariza
0 Depolariz
(mV)
tion
Channel
Opens
-50
Resting Resting
Undershoot
-100
0 5 10 15
Milliseconds
Nerves
Small diameter nerves are more easily
blocked than large diameter nerves
For the same diameter, myelinated nerves
will be blocked before unmyelinated nerves.
Nerves that fire frequently are
preferentially blocked over nerves that fire
infrequently.
Nerve Sensitivity
1. Autonomic
2. Pain
3. Temperature
4. Touch
5. Proprioception
6. Skeletal muscle tone
In nerve bundles, fibers that are located
circumferentially are affected first by LA.
Effect of Vasoconstrictor:
Prolongs duration of action of LA’s by
decreasing their rate of removal from
the local site into the circulation
Enhances the intensity of nerve block
Reduces the systemic toxicity of LA s
Makes the injection more painful
Provides the bloodless field for
surgery
Pharmacokinetics
• Most ester-linked local anesthetics are
quickly hydrolyzed by enzymes in blood.
• Amide-linked local anesthetics can be
widely distributed via the circulation and
are hydrolyzed in the liver.
• Water-soluble metabolites are excreted in
the urine.
Hypersensitivity reactions – more
with ester type of LA
Procaine and Lignocaine undergo
significant first-pass metabolism-
after oral ingestion-not given
during arrhythmias
Procaine
Ester Linkage
N
O N
• Slow onset n short duration
• Vasodilator O
• Ineffective topically.
• Uses: Infiltration anesthesia, nerve block, spinal
block
• Rarely used nowadays
Procainamide is an amide derivative of procaine –used as class
Ia anti arrhythmics
Benzocaine
Ester Linkage
• Only used topically-very low aq. solubility, less toxic.
• Produces long lasting anesthesia without systemic toxicity.
• LOZENGES FOR STOMATITS, SORE THROAT
Tetracaine (TOPICAL)
O
N N
Ester Linkage
• More potent and more toxic due to slow metabolism
• Used both as surface and conduction block anesthetic
• Topical application to the eye ,nose and throat
Cocaine
N
O
O
Ester Linkage
• Causes vasoconstriction (as do ropivacaine, bupivacaine, and
levobupivacaine).
• Protoplasmic poison-so no longer used
Lidocaine
(Xylocaine/Lignocaine)
N
N
Amide Linkage
• Is a versatile LA
• Used both as surface and injectable LA
• Popular antiarrhythmic in ICU
• Available as transdermal patch-post herpetic
neuralgia
• Adverse effects: dizziness, parasthesia, euphoria
Bupivacaine
S Bupivacaine
• Potent, long acting.
• Used in obstetrics and post operative pain relief epidural infusion.
• 0.25-0.5% Bupivacaine produces adequate analgesia without motor paralysis.
Prilocaine
N
N
Eutectic mixture
•Anesthetize the intact skin after surface application
•Lidocaine + Prilocaine in equal proportion at 25 degree C
Uses and techniques of
Local Anesthetic
Topical- produced by topical
application of surface anesthetics to
mucus membrane.
Infiltration Anesthesia-Dilute solution
of LA is infiltrated under the skin in the
area of operation-blocks sensory nerve
endings only.
Eg. Incisions, Excisions, hydrocele
Conduction Block :LA is injected around the
nerve trunks .Area distal to the injection is
anesthetized and paralyzed.
a. Field block :Produced by injecting the LA
subcutaneously. Larger area is anesthetized with
lesser drug. Eg. Appendicectomy, surgeries of
forearms and legs
b. Nerve block: Produced by injection of LA
around anatomically localized nerve trunks.
Larger area is anesthetized. Eg. Brachial, femoral,
intercostal nerve blocks
Central nerve block Anesthesia
[Link] anesthesia: LA is injected into epidural
space and acts primarily on nerve roots.
Lignocaine and bupivacaine are popular drugs for
epidural anesthesia.
2. Spinal anesthesia: LA is injected in the subarachnoid
space between L2-L3 or [Link] site of action is
nerve roots in cauda equina. Lower abdomen and lower
limbs are paralyzed.
Intravenous regional Anesthesia: It consists
of injection of LA in a vein of a tourniquet
occluded limb. Drug diffuses retrograde from
peripheral vascular bed to nonvascular tissues
including nerve endings. It is used for upper
limb and orthopedic procedures.
PRILOCAINE IS DRUG OF CHOICE FOR
IVRA
CNS Toxicity
Tends to occur first (relative to CVS toxicity)
•Excitatory signs and symptoms occur first
followed by depressant signs
•Circum oral and tongue numbness
•Lightheadedness and tinnitus
•Visual disturbance
•Muscle twitching
•Convulsions
•Respiratory arrest
CVS Toxicity
• Bradycardia
• Hypotension
• Arrythmias
ectopic beats
ventricular fibrillation
Allergic reactions:
Ester linked LA s are metabolized by PABA derivatives which in turn are
responsible for allergic reactions. It can manifest as contact dermatitis,
rashes, asthma
Neuromuscular Junction:
In large doses, LA s block neuromuscular transmission and enhances dTc
effect
