Actions of Local Anaesthetics

By:-
Vaishnavi A. Bhosale
Local Actions
• No irritant local action
• It blocks
1. Sensory Nerve Endings
2. Neuromuscular Junction
3. Ganglionic Synapse
4. Receptor (non- selectively)
ACTION AT
• Motor nerve endings- Decreases AcH release
• Mixed nerve- Anaesthesia of skin and paralysis of the
voluntary muscle supplied by that nerve.
• In Mixed type of nerves,
Motor fibres are placed CIRCUMFERENTIALLY
than sensory fibres
Therefore Motor fibres are blocked first

• Sensory and motor fibres are inherently equally sensitive

but some exhibit unequal ability to block them.
• Action of LAs on nerves depend on

Diameter of
Type of fibre
fibre

• Blockage is as
 Myelinated > Non- Myelinated
 Smaller > Longer
 Autonomic > Somatic
• In general, fibres that are more susceptible to LA are
first to be blocked and last to recover
• Location of fibres- Diffusion through nerve sheath
• i.e. Outer fibres > Inner fibres
In Inflammation,
LAs fail to afford pain control in inflammed tissues. E.g. Infected tooth
Because
• In inflammation,
Lower pH

General fraction of
LA is ionized form
hinders diffusion
into the axolemma
Blood flow
increases and LA is
removed from the
site

Effect of Adr
injected with LA is
reduced at the
inflammed site
Systemic Actions:-
• Any LA when absorbed produces systemic effects depending on
concentration attained in plasma and tissues.
I. CNS
• All LA are capable of producing a sequence of stimulation
followed by depression
• Cocaine a powerful CNS stimulant causes the following in
sequence
• Euphoria Excitement Mental confusion
Restlessness Tremor Twitching of muscles
Convulsions Unconsciousness Respiratory
depression
• This all events are dose dependent and higher dose produces CNS
stimulation followed by depression
• Procaine and other synthetic LA are much less potent in this regard.
At safe clinical doses, they produce little apparent CNS effects.
Higher dose or accidental I.V. Injection produces CNS stimulation
followed by depression.

• The early neurological symptoms of overdose with lidocaine and

other clinically used LA are
 Circumoral numbness
 Abnormal sensation in the tongue
 Dizziness
 Blurred vision
 Tinnitus followed drowsiness, dysphoria and lethargy
• Still higher doses produce excitation, restlessness, agitation, muscle
twitching, seizures and finally unconsciousness
• The basic action of all LA is NEURONAL INHIBITION , the
apparent stimulation initially is due to inhibition of inhibitory
neurons.
• At high doses, all neurons are inhibited and flattening of waves in
the ECG is seen

• LA interfere with the excitation process in nerve membrane by one

of the following mechanism:
• Altering the basic RESTING potential of the nerve membrane
• Altering the THRESHOLD potential
• Decreasing the rate of DEPOLARIZATION
• Prolonging the rate of REPOLARIZATION
• The primary effects of LA occur DEPOLARIZATION PHASE OF
THE ACTION POTENTIAL
II. CVS
• LAs are CARDIAC DEPRESSANTS
• At high doses, they DECREASE automaticity, excitability,
contractility, conductivity, prolong ERP
• They have quinidine like anti- arrhythmic

III. BLOOD VESSELS

• LAs tend to decrease B.P. Due to sympathetic blockade but at
increased concentration there is direct relaxation of arteriolar
smooth muscle.
• Bupivacaine is more vasodilatory than lidocaine, while prilocaine
is the least vasodilatory
• Toxic doses of LA produce cardiovascular collapse
• Cocaine has sympathomimetic property increases
sympathomimetic tone causes local vasoconstriction, marked rise
in BP and tachycardia
Pharmacokinetics
• Because LAs act near their site of administration, pharmacokinetic
characteristics are not important
determinants of their efficacy, but markedly influence their systemic
effects and toxicity.
• Soluble surface anaesthetics (lidocaine, tetracaine) are rapidly
absorbed from mucous
• membranes
• Procaine does not significantly penetrate mucous membranes. Rate
of absorption depends on the blood flow to the area of application or
injection.
• The absorbed LA being lipophilic is widely distributed; rapidly
enters highly perfused brain, heart, liver, and kidney, followed by
muscle and other viscera.
• Procaine is negligibly bound to plasma proteins, but amide LAs are
bound to plasma α1 acid glycoprotein. LAs are rapidly but
temporarily bound to tissues, especially nerves, at the site of
injection.
• Absorption is related to the site of injection, dosage employed, use
of vasoconstrictors and physicochemical profile of specific agents.
• The metabolism of LAs varies according to their chemical
classification.
 Amino esters are metabolised by PSEUDOCHOLINESTERASES in
the plasma.
 Amino amides are primarily metabolized in the liver by microsomal
enzymes.
• LA are primarily excreted by the kidneys.
Adverse effects
1) CNS effects are light-headedness, dizziness, auditory and visual
disturbances, mental confusion, disorientation, shivering, twitching,
involuntary movements, finally convulsions and respiratory arrest.
This can be prevented and treated by diazepam.
(2) Cardiovascular toxicity of LAs is manifested as bradycardia,
hypotension, cardiac arrhythmias
and vascular collapse.
(3) Injection of LAs may be painful, but local tissue toxicity of LAs is
low. However, wound
• healing may be sometimes delayed. Addition of vasoconstrictors
enhances the local tissue
• damage; rarely necrosis results.
• (4) Hypersensitivity reactions like rashes, dermatitis, contact
sensitization, asthma and rarely anaphylaxis occur. These are more
common with ester-linked LAs, but rare with lidocaine or its
congeners.
• Often methyl paraben added as preservative in certain LA solutions
is responsible for allergic reactions
Interactions:
• Cholinesterase inhibitors like neostigmine and pyridostigmine can
lead to decrease in the metabolism of ester local anesthetics

• Propranolol (probably other β blockers also) may reduce

metabolism of lidocaine and other amide LAs by reducing hepatic
blood flow.

• Vasoconstriction (adrénaline) containing LA should be avoided for

patients with ischemic heart disease, cardiac arrhythmia,
thyrotoxicosis ,uncontrolled hypertension, and those receiving β
blockers (rise in BP can occur due to unopposed α action) or
tricyclic antidepressants (uptake blockade and potentiation of Adr).