Local Anesthesia

DR.PRASHANT MALIK
DEPT. OF OMFS
 DEFINITION OF LA :

“It is defined as loss of sensation in a circumscribed area of the body caused by depression of excitation in
nerve endings or inhibition of the conduction process in peripheral nerves without loss of consciousnes.”
many methods are used to induce local anesthesia:
1. mechanical trauma (compression of tissues)
2. low temperature
3. anoxia
4. chemical irritants
5. neurolytic agents such as alcohol and phenol
6. chemical agents such as local anesthetics
 IDEAL REQUIREMENTS OF LA

 1. It should not be irritating to the tissue to which it is applied.

 2. It should not cause any permanent alteration of nerve structure.
 3. Its systemic toxicity should be low.
 4. It must be effective regardless of whether it is injected into the tissue or is applied topically to mucous
membranes.
 5. The time of onset of anesthesia should be as short as possible.
 6. The duration of action must be long enough to permit completion of the procedure yet not so long as to
require an extended recovery.
 Bennett other desirable properties of an ideal local anesthetic:
 1. It should have potency sufficient to give complete anesthesia without the use of
harmful concentrated solutions.
 2. It should be relatively free from producing allergic reactions.
 3. It should be stable in solution and should readily undergo biotransformation in the
body.
 4. It should be sterile or capable of being sterilized by heat without deterioration.
 The Neuron
The neuron, or nerve cell, is the structural unit of the nervous system.
It is able to transmit messages between the central nervous system (CNS) and all
parts of the body.

There are two basic types of neuron:

sensory (afferent) and motor (efferent).
The basic structure of these two neuronal types differs significantly

A=Multipolar motor neuron. B= Unipolar sensory neuron.

 Nerve membrane

• It consist two layers of lipid molecules (bilipid layer of phospholipids) and associated proteins, lipids, and
carbohydrates. The lipids are oriented with their hydrophilic (polar) ends facing the outer surface and their
hydrophobic (nonpolar) ends projecting to the middle of the membrane.
• It is selectively permeable to certain molecules via specialized pores or channels, and to transduce information
through protein receptors responsive to chemical or physical stimulation by neurotransmitters or hormones
(chemical) or light, vibration, or pressure (physical).
Channel proteins are thought to be continuous pores through the membrane, allowing some ions (Na+, K+,
Ca2+) to flow passively, whereas other channels are gated, permitting ion flow only when the gate is open.

Physiology of the Peripheral Nerves

 The function of a nerve is to carry messages from one part of the body to another. These messages, in
the form of electrical action potentials, are called impulses.

 Action potentials are transient depolarizations of the membrane that result from a brief increase in the
permeability of the membrane to sodium, and usually also from a delayed increase in its permeability to
potassium.

 Impulses are initiated by chemical, thermal, mechanical, or electrical stimuli.

 The impulse remains constant without losing strength as it passes along the nerve because the energy
used for its propagation is derived from energy that is released by the nerve fiber along its length and
not solely from the initial stimulus.
Electrophysiology of Nerve Conduction

 A nerve possesses a resting potential .

 This is a negative electrical potential of −70 mV that exists across the nerve membrane,
produced by differing concentrations of ions on either side of the membrane .
 The interior of the nerve is negative relative to the exterior.
 1. An initial phase of slow depolarization. The electrical potential within the nerve
becomes slightly less negative.
 When the falling electrical potential reaches a critical level, an extremely rapid phase of
depolarization results. This is termed threshold potential, or firing threshold.
This phase of rapid depolarization results in a reversal of the electrical potential across the nerve
membrane .
The interior of the nerve is now electrically positive in relation to the exterior.
An electrical potential of +40 mV exists inside the nerve cell.
After these steps of depolarization, repolarization occurs .
 The electrical potential gradually becomes more negative inside the nerve cell
relative to outside until the original resting potential of −70 mV is again
achieved.

 The entire process (steps 1 and 2) requires 1 millisecond:

depolarization (step 1) takes 0.3 milliseconds.
 repolarization (step 2) takes 0.7 milliseconds
 Electrochemistry of Nerve Conduction
 The preceding sequence of events depends on two important factors:
 1)concentrations of electrolytes in the axoplasm (interior of the nerve cell) and extracellular fluids,
 2) permeability of the nerve membrane to sodium and potassium ions.
 Resting State
 In its resting state, the nerve membrane is
a)slightly permeable to sodium ions (Na+)
b)freely permeable to potassium ions (K+)
c)freely permeable to chloride ions (Cl−)

 Potassium remains within the axoplasm, because the negative charge of the nerve membrane restrains the
positively charged ions by electrostatic attraction.
 Chloride remains outside the nerve because the opposing, nearly equal, electrostatic influence forces
outward migration. The net result is no diffusion of chloride through the membrane.
 Sodium migrates inwardly because both the concentration (greater outside) and the electrostatic gradient
(positive ion attracted by negative intracellular potential) favor such migration. Only the fact that the resting
nerve membrane is relatively impermeable to sodium prevents a massive influx of this ion.
 Membrane Excitation

 1) Depolarization
 Excitation of a nerve segment leads to an increase in permeability of the cell membrane to sodium
ions.
 This is accomplished by a transient widening of transmembrane ion channels sufficient to permit the
unhindered passage of hydrated sodium ions.
 The rapid influx of sodium ions to the interior of the nerve cell causes depolarization of the nerve
membrane from its resting level to its firing threshold of approximately −50 to −60 mV
 A decrease in negative transmembrane potential of 15 mV (e.g., from −70 to −55 mV) is necessary
to reach the firing threshold; a voltage difference of less than 15 mV will not initiate an impulse.
 Exposure of the nerve to a local anesthetic raises its firing threshold. Elevating the firing threshold
means that more sodium must pass through the membrane to decrease the negative transmembrane
potential to a level where depolarization occurs.
 When the firing threshold is reached, membrane permeability to sodium increases dramatically and
sodium ions rapidly enter the axoplasm. At the end of depolarization (the peak of the action
potential), the electrical potential of the nerve is actually reversed; an electrical potential of +40 mV
exists
 The entire depolarization process requires approximately 0.3 milliseconds.
 2) Repolarization
 The action potential is terminated when the membrane repolarizes.
 This is caused by the extinction (inactivation) of increased permeability to sodium. In
many cells, permeability to potassium also increases, resulting in the efflux of K+, and
leading to more rapid membrane repolarization and return to its resting potential.
 movement of sodium ions into the cell during depolarization and subsequent movement of
potassium ions out of the cell during repolarization are passive (not requiring the
expenditure of energy), because each ion moves along its concentration gradient (higher to
lower). After the return of the membrane potential to its original level (−70 mV),
 Immediately after a stimulus has initiated an action potential, a nerve is unable, for a time,
to respond to another stimulus regardless of its strength. This is termed the absolute
refractory period, and it lasts for about the duration of the main part of the action potential.
 The absolute refractory period is followed by a relative refractory period, during which a
new impulse can be initiated but only by a stronger than-normal stimulus. The relative
refractory period continues to decrease until the normal level of excitability returns, at
which point the nerve is said to be repolarized
 Impulse Propagation
 Site of Action of Local Anesthetics
 Nerve membrane is the site at which local anesthetics exert their pharmacologic actions.
 Many theories have been proposed over the years to explain the mechanism of action of local anesthetics.
Acetylcholine theory
 It states that acetylcholine is involved in nerve conduction, in addition to its role as a neurotransmitter at
nerve synapses.
 No evidence exists indicating that acetylcholine is involved in neural transmission along the body of the
neuron.
Calcium displacement theory
 It maintains that local anesthetic nerve block is produced by the displacement of calcium from some
membrane site that controls permeability to sodium.
 Evidence that varying the concentration of calcium ions bathing a nerve does not affect local anesthetic
potency has diminished the credibility of this theory.
The surface charge (repulsion) theory
 It proposes that local anesthetics act by binding to the nerve membrane and changing the electrical potential
at the membrane surface
 Membrane expansion theory
 It states that local anesthetic molecules diffuse to hydrophobic regions of excitable membranes, producing a
general disturbance of the bulk membrane structure, expanding some critical region(s) in the membrane, and
preventing an increase in permeability to sodium ion.

specific receptor theory

 the most favored today, proposes that local anesthetics act by binding to specific receptors on the sodium
channel .
 The action of the drug is direct, not mediated by some change in the general properties of the cell
membrane
Mechanism of action of local anesthetics.

Displacement of calcium ions from the sodium channel receptor site, which permits …

Binding of the local anesthetic molecule to this receptor site, which produces

Blockade of the sodium channel

Decrease in sodium conductance, which leads to .

Depression of the rate of electrical depolarization and .

Failure to achieve the threshold potential level, along with .

Lack of development of propagated action potentials,

Conduction blockade
 Active Forms of Local Anesthetics
 Most injectable local anesthetics are tertiary amines. Only a few (e.g.,
prilocaine, hexylcaine) are secondary amines.
 Structure of LA:
 All local anesthetics are amphipathic; that is, they possess both lipophilic and
hydrophilic characteristics, generally at opposite ends of the molecule.
 The lipophilic part is the largest of the molecule. Aromatic in structure, it is
derived from benzoic acid, aniline, or thiophene (articaine).
 The hydrophilic part is an amino derivative of ethyl alcohol or acetic acid.
 Local anesthetics without a hydrophilic part are not suited for injection but are
good topical anesthetics (e.g., benzocaine).
 The anesthetic structure is completed by an intermediate hydrocarbon chain
containing an ester or an amide linkage
 Local anesthetics are basic compounds that are poorly soluble in water and unstable on exposure to air.
 Their pKa values range from 7.5 to 10. In this form, they have little or no clinical value.
 However, because they are weakly basic, they combine readily with acids to form local anesthetic salts, in which
form they are quite soluble in water and comparatively stable.
 Acidification of tissue decreases local anesthetic effectiveness.
 Inadequate anesthesia frequently occurs when local anesthetics are injected into inflamed or infected areas.
 The inflammatory process produces acidic products.
 The pH of normal tissue is 7.4; the pH of an inflamed area is 5 to 6.
 Elevating the pH (alkalinization) of a local anesthetic solution speeds its onset of action, increases its clinical
effectiveness, and makes its injection more comfortable.
 Dissociation of Local Anesthetics :
 It exists simultaneously as uncharged molecules (RN), also called the base, and as positively charged molecules
(RNH+), called the cation.
 As the pH of the solution is acidic, hydrogen ions (H+) are also present.
 RNH+ ⇌ RN + H+
 In the presence of a high concentration of hydrogen ions (low pH), the equilibrium shifts to the left, and most of
the local anesthetic solution exists in cationic form:
 RNH+ >RN + H+
 As hydrogen ion concentration decreases (higher pH), the equilibrium shifts toward the free base form:
RNH+< RN + H+
 The relative proportion of ionic forms also depends on the pKa, or dissociation constant, of the specific local
anesthetic.
 The pKa is a measure of the affinity of a molecule for hydrogen ions (H+). When the pH of the solution has the
same value as the pKa of the local anesthetic, exactly 50% of the drug exists in the RNH+ form and 50% in the
RN form.
 The percentage of the drug existing in either form can be determined from the Henderson-Hasselbalch
equation .
 Henderson-Hasselbalch equation :
 log [acid] pH = pKa + log [acid]/[conjugate base] Henderson-Hasselbalch equation
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