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Dr. Naila Abrar
After this session you should be able to:
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define local anesthesia;
classify local anesthetics;
describe pharmacokinetic properties of
commonly used local anesthetics;
describe the mechanism of action;
comprehend the structure-activity
characteristics of local anesthetics; and
describe the toxicity of local anesthetics.
DEFINITION
Loss
of
sensory
blockade
of
neuronal
cell
perception
sodium
due
channels
membrane
in
restricted/localized area of the body.
in
a
CHARACTERISTICS

Topical application or local injection
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Peripheral nerves

Consciousness not altered
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No amnesia
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Vital functions not affected
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No change in physiological functions
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Recovery is spontaneous, predictable &
without residual changes
ACCORDING TO CHEMISTRY
ESTERS
 Cocaine
 Procaine
 Tetracaine
 Benzocaine
AMIDES
 Lignocaine
 Prilocaine
 Mepivacaine
 Bupivacaine
 Ropivacaine
ACCORDING TO DURATION OF ACTION
SHORT
 Procaine, Chlorprocaine
MEDIUM
 Cocaine, Lidocaine, Mepivacaine,
Prilocaine
LONG
 Tetracaine, Bupivacaine, Levobupivacaine,
Ropivacaine
ACCORDING TO THERAPEUTIC USES
SURFACE ANESTHESIA
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Cocaine, lignocaine, tetracaine, benzocaine
FEILD BLOCK & INFILTRATION ANESTHESIA
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Procaine, lignocaine, bupivacaine
NERVE BLOCK
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Procaine, lignocaine, bupivacaine, tetracaine,
ropivacaine
SPINAL ANESTHESIA
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Lignocaine, bupivacaine, tetracaine
EPIDURAL ANESTHESIA
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Lignocaine, bupivacaine
OPHTHALMOLOGICAL ANESTHESIA
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Proparacaine
ESTERS
Cocaine
Procaine
Tetracaine
Benzocaine
AMIDES
Lidocaine
Mepivacaine
Bupivacaine
Ropivacaine
Articaine
ABSORPTION
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Dosage
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Site of injection
Termination of action
Systemic effects
intercostal>caudal>epidural>brachial>sciatic
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Drug-tissue binding
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Local tissue blood flow
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Use of vasoconstrictors- epinephrine
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Physiochemical properties of the drug
USE OF VASOCONSTRICTORS
 EPINEPHRINE used
 Blood supply limited
 Absorption restricted
 More time of contact-more
pronounced effect
 Delayed healing & tissue necrosis
 a2 receptors- decrease release of
substance P- clonidine
DISTRIBUTION
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Amides widely distributed
Initial rapid distribution phase
Slower distribution phase
METABOLISM & EXCRETION
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Converted to more water soluble forms
• liver- amides
Prilocaine>lidocaine>mepivacaine>ropivacaine
plasma- esters (butyrylcholinesterase)
Toxicity of amide type increased in liver
disease
•
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MECHANISM OF ACTION
Reversible
Diffusion into
nerve fibre
(only in nonionizable
form)
Block
voltagegated
sodium
channels
Threshold for excitation increases
Impulse conduction slows
Rate of rise AP decreases
Ability to generate AP is abolished
Propagation blocked if Na current
blocked over a critical length
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Higher affinity for inactivated phase
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Voltage & time dependent
Less affinity for resting state
 More effect on high frequency firing
 Use dependent block
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Resting potential not significantly altered
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Biological toxins-batrachotoxin, aconitine,
scorpion venoms
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Bind to receptors within Na channel and
prevent inactivation
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Prolonged influx of Na & depolarization
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Marine toxins tetrodotoxins & saxitoxin
have effects similar to LA
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LIPID SOLUBILITY

pKa
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CARBON DIOXIDE
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HYDROPHOBIC NATURE
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TACHYPHYLAXIS
SUSCEPIBILITY OF NERVE FIBRES TO
LOCAL ANESTHETICS
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Firing frequency
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Size
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State of myelination
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Fibre diameter
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Fibre position
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Pain sensation>temperature>touch>deep
pressure> motor
TOXICITY
1.
SYSTEMIC EFFECTS
 Absorption from site of administration
2.
DIRECT NEUROTOXICITY
 Local effects when high concentrations
are administered in close proximity to
the spinal cord and other major nerve
trunks
TOXICITY
A.
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CNS
Circumoral & tongue numbness, metallic
taste
Nystagmus, muscle twitching, tonicclonic convulsions
Depression of cortical inhibitory
pathways-unopposed activity of
excitatory neuronal pathways
Generalized CNS depression
Death due to respiratory failure
TOXICITY
B.
NEUROTOXICITY
 More with chloroprocaine and
lidocaine
 Transient radicular irritation or
neuropathic pain
 Interference with axonal transport
and disruption of calcium
homeostasis
TOXICITY
C.
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CARDIOVASCULAR SYSTEM
Direct effects on cardiac & smooth muscle
membranes
•
•
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

Myocardial depression
Arteriolar dilation-hypotension
Indirect effects on ANS
Bupivacaine is more cardiotoxic than othersslow idioventricular rhythm & broad QRS
complexes
Cocaine blocks norepinephrine reuptakevasoconstriction & hypertension, cardiac
arrythmias
TOXICITY
D.
HEMATOLOGIC EFFECTS
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Prilocaine – metabolite O-toluidine
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An oxidizing agent converts Hb to
met Hb
TOXICITY
E.
ALLERGIC REACTONS
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Esters converted to p -aminobenzoic
acid (PABA) derivatives
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Sympathomimetic action
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Potent vasoconstrictor
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Cardiac stimulation
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Marked pyrexia with overdose
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Low aqueous solubility
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Topical local anesthetic – not absorbed
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Relief of pain & irritation
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Anesthesia of mucous membranes
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PABA derivatives – antagonize effect of
sulfonamides locally
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Most widely used
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Effective by all routes but oral BA low
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High 1st pass metabolism
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Fast onset, more intense & lasting effect
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Alternative for ester allergic pts
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Toxicity equal to procaine but more
sedative than others
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Not effective topically
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Slower onset, longer acting
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Unique property of sensory & motor
dissociation
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Popular for anesthesia during labor
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More cardiotoxic
SURFACE ANESTHESIA
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Ear, eye, nose, throat, abraded skin
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Only superficial layer
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Soluble LA – rapid systemic absorption
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Eutectic lidocaine/prilocaine – intact
skin
INFILTRATION ANESTHESIA
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Dilute solution infiltrated under
skin
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Immediate onset & DoA is short
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Minor operations: incisions,
excisions
FIELD BLOCK or NERVE BLOCK
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Injected around nerve trunk
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Area distal to injection is anesthetized
and paralyzed
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Lidocaine
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Bupivacaine for longer
BIER BLOCK
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INTRAVENOUS
REGIONAL BLOCK
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Short surgical
procedures
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Upper or lower
extremities
SPINAL ANESTHESIA
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Subarachnoid space L2-3 or L3-4 – cauda
equina
Abdominal or pelvic surgery
Effective analgesia & muscle relaxation
Complications:
respiratory
paralysis,
hypotension (sympathetic reflexes inhibited),
headache, cauda equina syndrome, infection,
neurotoxicity
EPIDURAL
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Injection into epidural space
at L2-3
Used in obstetrics, lower
abdomen & pelvic surgery
Unwanted effects similar to
spinal but less because
longitudinal
spread
is
reduced
Lidocaine,
bupivacaine,
ropivacaine