2. Local anesthesia has been defined as a loss of
sensation in a circumscribed area of the body caused
by a depression of excitation in nerve endings or an
inhibition of the conduction process in peripheral
nerves.
METHODS OF INDUCING LOCAL ANESTHESIA
Mechanical trauma
Low temperature
Anoxia
Chemical irritants
Neurolytic agents
Chemical agents - LA
3. DESIRABLE PROPERTIES OF LOCAL ANESTHESIA
Non irritating
Completely reversible
Low systemic toxicity
Effective topically & if injected
Time of onset – short
Adequate duration of action
Should give complete anesthesia w/o use of
harmful conc. solutions
Should not produce allergic reactions
Should be stable & readily undergo
biotransformation
Should be sterile or capable of being sterilized
4. FUNDAMENTALS OF IMPULSE GENERATION &
TRANSMISSION
NERVE ANATOMY :
Neuron – structural unit of the nervous system.
Transmits messages b/w CNS & all parts of the
body.
Sensory and motor neuron
PARTS OF NEURON :
Dendritic zone
Axon
Cell body
AXOPLASM
AXOLEMMA
EXTRACELLULAR FLUID
7. ELECTROCHEMISTRY :
Depends on
Conc. Of electrolytes in the axoplasm & ECF
Permeability to Na+ & K+
RESTING STATE :
Slightly permeable to Na+
Freely permeable to K+ & Cl-
MEMBRANE EXCITATION :
Depolarization :
Excitation
Increased permeability to Na+
Transient widening – passage of Na+
Decrease of 15 mV necessary to reach firing threshold
- initiate impulse ( - 50 to -60 mV )
Na+ permeability increases.
Electrical potential reversed
8. DEPOLARIZATION :
Absolute refractory period - lasts for duration of axn
potential
Relative refractory period – new impulse initiated (
stronger stimuli )
REPOLARIZATION :
Action potential terminated
Inactivation / extinction of permeability of Na+
Permeability to K+ increases – efflux of K+
Rapid membrane repolarization ( - 70 mV )
AFTER REACHING RESTING STATE :
Excess Na+ in axoplasm
Excess K+ ECF
Energy provided by oxidative metabolism of ATP.
9. Where do local anesthetics work ?
Nerve membrane is the site at which local anesthesia exert their
pharmacological actions
THEORIESTO EXPLAINTHE MECHANISM OF AXN :
Acetyl choline theory
ACh – a neurotransmitter ,was involved in nerve
conduction at nerve synapse.
No evidence that Ach is involved in neural transmission
along the body of neuron.
Calcium displacement theory
Displacement of calcium from some membrane site that
controlled permeability to Na.
Varying the conc. of Ca does not affect the potency of LA
– hence credibility of this theory diminished
10. Surface charge (repulsion) theory
LA binds to nerve membrane & changes the electrical
potential at membrane surface.
Cationic drug molecules – LA molecules net positive
charge – EP positive
Increases threshold potential
Decreases excitability of nerve
Resting potential – unaltered & LA act within the
membrane.
Cannot explain activity of uncharged molecules
11. Membrane expansion theory
LA diffuse – hydrophobic regions – general disturbance of
membrane structure – prevents inc. in permeability to Na+
LA –highly lipid soluble – penetrates – lipid portion.
Change in configuration – decreased diameter of Na
channel
Inhibition of Na conduction & neural excitation
No direc evidence tat nerve conduction is entirely blocked
Specific receptor theory
Specific receptor site for LA exist in Na channel ( either
on externel or internal surface )
LA binds to these specific receptor
Permeability of Na decreases
Interruption in nerve conduction
12. Calcium – bound form within nerve membrane –
regulating role for movement of sodium
Release of bound calcium – primary factor – increased Na
permeability.
LA molecule act by competitive antagonism with calcium
Nerve membrane – polarized state
Ionic movements fail to develop
Membrane’s electrical potential – unchanged
Local currents do not develop.
Impulse arriving at blocked nerve segment – stopped
Unable to release energy for continued propagation
Nerve block produced by LA - NONDEPOLARIZING
NERVE BLOCK
How do local anesthetics work
13. Displacement of Ca+ from sodium channel receptor site
Binding of LA to this receptor site
Blockade of sodium channel
Decrease in sodium conductance
Depression of rate of electrical depolarization
Failure to achieve threshold potential
Lack of development of propagated axn potential
CONDUCTION BLOCKADE
14. SPECIAL NOTE
Why LA does not work in an area of
inflammation & infection ?
RNH+ RN + H+
At lower pH,concentration of H+ increases
At higher pH , concentration of H+ decreases
RNH+ > RN + H+
RNH+ < RN + H+
Proportion of ionic forms depend on pKa.
pKa = pH ,then 50 % - 50 %
% of drug calculated by Henderson- Hasselbalch eqn.
Log Base/Acid = pH - pKa
15. RNH+ RN + H+
RNH+RN
Na channel
INFECTION / INFLAMMATION :
pH = 6
Dec. pH ,RNH+ inc.
Inc. vascularity causes inc. absorption into blood
vessels.
Adeqate blockade not possible because only a small
amt of base form cross the nerve sheath and increased
absorption into dilated blood vessels.
16. DOSE CALCULATION
Maximum permissible dose of lignocaine = 4.4 mg/kg body wt
Maximum permissible dose of lignocaine = 7 mg/kg body wt
with adrenaline
Concentration of lignocaine = 2 % = 20 mg/ml
1 ml = 1/20 mg
Example : for 70 kg patient
Maximum permissible dose of lignocaine = 4.4 * 70 = 308 mg
= 15.4 ml
Maximum permissible dose of lignocaine = 7 * 70 = 490 mg
with adrenaline = 24.5ml
17. Maximum permissible dose of adrenaline = 0.2/0.0125
= 16 ml
Maximum permissible dose of adrenaline = 0.04 /0.0125
in cardiovascular patients = 3.2 ml
1 : 80,000 dilution of adrenaline = 1 gm of adrenaline
in 80,000 ml of
solvent
1000 mg/ml = 0.0125 mg/ml
80000
1 ml = 1/0.0125 mg
Maximum permissible dose of adrenaline = 0.2 mg/appt.
Maximum permissible dose of adrenaline = 0.04 mg/appt.
in cardiovascular patients
