Local anaesthetics are drugs that block nerve conduction when

applied locally to the nerve tissue in appropriate concentration.

Classification of local anaesthetics based on the route of

administration and duration of action

Used parenterally

Short acting as Procaine, Chloroprocaine

Intermediate acting as Lignocaine, Prilocaine

Long acting as Tetracaine, Bupivacine, Ropivacaine

Used topically: Cocaine, Lignocaine, Tetracaine, Benzocaine, Oxethazaine,

Dibucaine.

The techniques of local anaesthesia are easily mastered.

The equipment required is limited in amount.

The local anaesthesia is economical.

It is easily transportable.

The patency of the airway is not impaired

The anaesthetic can be administered by the operator.

Its use enable the patient to co-operate with the dentist to facilitate his

own treatment.

Usually preoperative preparation of the patient is not reqired.

The patient can leave the surgery unescorted and often return to wark

after a local anaesthetic has been used.

The advantages

The contraindication

The presence of acute infection at the site of operation.

The patient afflicted with certain rare haemorrhagic diseases such

as haemophilia, Christmas disease, or von Willebrand's disease.

Some patients acquire a sensitivity to certain local anaesthesia

lipid solubility helps in migration of active drug into the neuronal

fiber

water solubility is to get the drug to the site of action from the side

of administration.

Chemistry

a hydrophilic amino group lipophilic aromatic residue

Mechanism of action

Local anaesthetics prevent the generation and conduction of nerve impulse.

The primary mechanism of action is blockade of voltage-gated sodium channels.

Local anaesthetics diffuse through the cell membrane and bind to the voltage-

sensitive sodium channels from the inner side of the cell membrane.

They prevent the increase in permeability to Na+ and gradually raise the

threshold for excitation.

With increasing concentration, impulse conduction slows, rate of rise of action

potential decreases and finally the ability to generate an action potential is

abolished.

These result from binding of local anaesthesia to more and more sodium

channels. Thus they prevent the generation of an action potential and its

conduction.

Small nerve fibers are more susceptible as they present a greater surface area

per unit volume.

Thus smaller fibers , autonomic fibers are blocked first followed by sensory fibers

conducting pain, temperature sense, than touch, pressure, and vibration

sensations in the same order which called differential blockade.

Sensory and motor fibers are equally sensitive. Non-myelinated fibers are

blocked more readily than the myelinated because the axon can only be effected

by the anaesthetic agent at the nodes of Ranvier.

local anaesthetic agents

vasoconstrictor

reducing agents

preservative

fungicide

vehicle

Local anaesthetic agents

The requirement

Potency and reliability: When the agent is administered correctly and in

adequate dosage it consistently produces effective local anaesthesia.

Approximately 98% of injection using a 2% Lignocaine with 1:80000

adrenaline solution are followed by effective anaesthesia.

Reversibility of action: The action of any drugs used to obtain local anaesthesia

must be completely reversible within a predictable time.

Safety: All local anaesthetic agents must have a wide margin of safety from the

poisonous side effects which are collectively known as toxicity. This margin of

safety is called therapeutic ratio. Procaine has the highest therapeutic ratio,

followed in descending order by mepivacaine, prilocaine, and Lignocaine. The

toxic effect of these drugs is also increased by inadvertent intravascular injection.

Lack of irritation: No injury to or irritation of the tissue should result from the

injection of a local anaesthetic agent. For this reason local anaesthetic solutions

should be isotonic and have a pH compatible with that of the tissues.

Rapidity of onset: Ideally the injection of such an agent should be followed

immediately by the onset of local anaesthesia. It is very important to appreciate

the difference between the onset of changed sensation which heralds analgesia

and actual surgical anaesthesia with complete blockage of impulses, for example

a 2% Lignocaine, 1:80000 adrenaline solution is about 1 minute 20 seconds.

Duration of effect: The duration of anaesthesia is longer than is required for

dental procedures. The vasoconstrictor in a local anaesthetic solutions affects the

duration of anaesthesia. Lignocaine solutions produce the longest duration of

anaesthesia, followed in descending order by prilocaine, procaine, and

mepivacaine.

Sterility: The local anaesthetic agents must be possible to sterilize them without

affecting either their structure or properties.

Adequate shelf life: Unless the local anaesthetic agent is stable in solution and

compatible with the other constituents the shelf life of the preparation will be

reduced. Most solutions have a shelf life of 2-2.5 years.

Penetration of mucous membrane: Ideally the drug should have the property of

penetrating mucous membrane, so that topical anaesthesia is practicable and the

best example is lignocaine.

Vasoconstrictors

The advantages of addition of a small quantity of a vasoconstricting drug are:

It reduces toxic effects by retarding the absorption of the constituents.

By confining the anaesthetic agent to a localized area it increases the depth

and duration of anaesthesia.

It produce a relatively bloodless field of operation for surgical procedures.

The vasoconstrictors in general use are:-

Adrenaline (epinephrine): a synthetic alkaloid almost identical with

natural secretion of the adrenal medulla.

Noradrenaline (norepinephrine): a synthetic substance similar to the

pressor amine secreted in the human body by monoaminergic neurons in

the brain and at adeno-neural and myo-neural junctions of sympathetic

nervous system.

Felypressin (octapressin): a synthetically produced polypeptide similar to

that secreted from the humane posterior pituitary gland.

In general the lower the concentration of vasoconstrictor the less depth and

duration of anaesthesia.

Both the depth and duration of anaesthesia may be modified by the

amount of vasoconstrictor in the solution.

lignocaine solution containing adrenaline or noradrenaline in concentration

of 1:50000, 1:80000, or 1:100000

felpypressin a concentration of 0.03 I.U./ml.

Reducing agent

Vasoconstrictor are unstable in solution and may oxidize, especially on

prolonged exposure to sunlight.

This results in the solution Turning brown and this discoloration is an

indication that such a small quantity of sodium meta- bisulphate which

competes for the available oxygen, is include in the solution.

Preservative

Modern local anaesthetic solutions are very stable and often have a shelf-

life of two years or more. Their sterility is maintained by the inclusion of a

small amount of a preservatives, such as, cuprienotoxin which is included

in xylotox.

Fungicide

In several modern solutions a small quantity of thymol is added to serve as a

fungicide and fungal growth.

The vehicle

The anaesthetic agent and the additives referred to above are dissolved in

modified Ringer's solution. This isotonic vehicle minimizes discomfort during

injection.

Local anaesthesia are rapidly absorbed from the mucous membranes and abraded

skin.

Rate of absorption is depend on the vascularity of the area.

The vasoconstriction is decrease the absorption.

Toxicity depends on the balance between absorption and metabolism.

Binding to tissues decrease the concentration in systemic circulation and therapy

toxicity.

Pharmacokinetics

The ester type agents are dissociated by esterases in the blood and liver

and hydrolyzed to benzoic acids and alcohol. Some oxidation may also take

place in the liver and all breakdown products are excreted in the urine.

The metabolism of the amide type agents is more complex and somewhat

slower. It appears that hydrolysis takes place mainly in the presence of

catalysts in the liver. The products are then oxidized further and some

conjugation with glucuronic acid takes place. Finally, conjugated and un

conjugated products are excreted in the urine.

Metabolism and excretion

Mode of action

All Anaesthetic agents are formed by the combination of a week base

and a strong acid. They are readily hydrolysed in the alkalinity of the

human tissues (pH 7.4) to liberate the alkaloid base which is then free

to be taken up by the lipids in the nerve fiber.

Since the hydrochloride salt is the most common form in which the

local anaesthetic agents are used, this process may be represented by

the equation:-

B.HCl + NaHCO3pH 7.4 B. + NaCl + H2CO3

(anaesthetic Salt) (free base)

Pharmacological action

Systemic actions depending on the concentration attained in the plasma, any

local anaesthetics can produce systemic effects.

Local anaesthetics interfere with the function of all organs in which conduction

or transmission of impulses occur.

Action on CNS

Local anaesthetics stimulate CNS and produce:

Restlessness

Tremor

mental confusion

convulsion.

In toxic dose, it causes:

respiratory depression

coma

death.

Cocaine is a powerful stimulant while procaine and other agents produce

less CNS stimulant effect.

Action on CVS

Local anaesthetics are:

myocardial depressant

decrease heart rate

amplitude of myocardial contraction.

In high doses, they produce changes in the ECG and may precipitate

ventricular fibrillation.

Bupivacaine is more cardiotoxic and can produce ventricular tachycardia

or fibrillation.

Local anaesthetics also produce decrease in blood pressure which may

be due to sympathetic blockade.

Only cocaine has the property to rise the BP due to its sympathomimetic

property.

Therapeutic uses

Surface anaesthesia

Spinal anaesthesia

Infiltration anaesthesia

Nerve block

Intraligamentous anaesthesia

Intraosseous anaesthesia

For systemic use in the treatment of cardiac arrhythmias

Clinical action of specific agents

Lidocaine (Lignocaine)

Lidocaine is the 1st amide local anaesthetic and the most widely used.

It is fast and long-acting.

It is useful for all types of anaesthesia.

Maximum anaesthetic effect is seen in 2-5 minutes and lasts for 30-45

minutes.

Allergy to amide type local anaesthetics is virtually nonexistent. This is a

major advantage over ester type local anaesthetics.

Lidocaine is available as 4% topical solution, 2% jelly, 5% ointment, 2%

without a vasoconstrictor, 2% with epinephrine 1:50000 or 1:100000.

recently 2% with 1:200000 ha became available.

Procaine

Procaine is the first injectable local anaesthetic synthesized ester type.

The onset of action 6-10 minutes.

Effective dental concentration 2-4%.

Procaine topical anaesthetic action is not acceptable clinically.

Procain is an important drug in the immediate management of accidental

intraarterial injection of a drug.

Bupivacaine

Bupivacaine is widely used, however, it can cause more cardiotoxicity than

others.

Injection 0.25-0.5% with or without adrenaline.

Levobupivacaine is a derivative of bupivacaine that seems to be less

neurotoxic and less cardiotoxic effect.

.

Mepivacaine

Mepivacaine action is more rapid in onset and more prolonged than that of

Lignocaine.

Injection 1-3% or nerve block and epidural anaesthesia.

Cocaine

Cocaine is natural Erythroxylon coca which produces euphoria and is a drug

of dependence and abuse.

It is a surface anaesthetic.

It is protoplasmic poison and hence can not be injected.

Lidocaine 2% with epinephrine 1:80000

Lidocaine 2% with epinephrine 1:100000

Lidocaine 2%

Prilocaine 3% with felypressin 0.03 IU

Prilocaine 4%

Prilocaine 3% with epinephrine 1:300000

Articaine 4% epinephrine 1:100000

.