L.

A IN DENTISTRY I

BRIEF HISTORY OF ANAESTHESIA

General anaesthesia already existed before local anaesthesia became available. General
anaesthesia was introduced by the American dentist Horace Wells. In 1844, together with his
wife Elizabeth, he witnessed a demonstration at the circus, whereby a number of volunteers were
intoxicated with laughing gas. Wells took the experiment upon himself and asked a colleague to
extract one of his molars after he had inhaled some laughing gas. It was a success. Wells
independently organized some additional extraction sessions, after which the Massachusetts
General Hospital invited him for a demonstration. The demonstration was a failure as the patient
was insufficiently anaesthetized. The physician Morton, a previous assistant to Wells, absconded
with the idea of general anaesthesia, but used ether instead of laughing gas for a ‘painless sleep’.

Sigmund Freud in 1884 was one of the first to gain experience with local anaesthesia. Freud
experimented with the use of cocaine. Freud used cocaine in the treatment of some of his
patients, and then became addicted himself.

The German surgeon August Bier and senior doctor Hildebrandt, experimented on each other
using cocaine for spinal anaesthesia. It was a success. However, the severe side effects
experienced by both of them made them refrain from its use.

In 1899, the French surgeon Tuffer was unaware of Bier’s work but operated on a young lady
with a hip sarcoma under local anaesthesia, applying a cocaine solution to the spinal canal.

The first use of local anaesthesia in dentistry is attributed to the American Halsted, who
anaesthetized himself with a cocaine solution. Because of the high toxicity and addictive effects
of cocaine, a safer local anaesthetic was sought. This was eventually found in 1905 in the form
of procaine, an ester derivative of cocaine. Procaine became known under the brand name of
Novocain (‘the new cocaine’).
During the Second World War the Swedish scientist Nils Lofgren succeeded in making the
amide compound lidocaine.

1
Lidocaine remedy works faster and more effectively than cocaine and is not addictive. In 1947,
the American company Novocol marketed the cartridge syringe, glass cartridges with local
anaesthetic and disposable needles. With this, modern local anaesthesia was born.

Local anaesthetics interfere reversibly with the generation of the action potential and with
cellular impulse conduction by blocking the sodium channels in the nerve cell. This results in a
local insensibility to pain stimuli.

Classification
Local anaesthetics share several common characteristics in their molecular structure . A
lipophilic group can be identified which determines lipid solubility. Another part contains a
hydrophilic group that determines the degree of water solubility. Usually the lipophilic part
of the molecule is an aromatic structure that contains a benzene ring.The hydrophilic part
contains a secondary or a tertiary amine. Both parts, present at the opposite ends of the molecule,
are connected by an intermediate section. This intermediate section consists of an ester or an
amide group and a relatively short chain of four to five carbon atoms.

Based on Amide- and Ester-Linked

Amide-linked local anaesthetics
Lidocaine
Prilocaine
Bupivacaine
Dibucaine
Ropivacaine
Mepivacaine
Articaine

2
Ester-linked local anaesthetics
Cocaine
Procaine
Chloroprocaine
Tetracaine
Benzocain

Based on Duration of Action of LA

1. Injectable
1. Low potency and short duration
Procaine
Chloroprocaine
2. Intermediate potency and long duration
Lidocaine
Mepivacaine
Prilocaine
3. High potency and long duration
Tetracaine
Bupivacaine
Ropivacaine
Dibucaine
2. Topical anaesthetics
1. Soluble compounds
Cocaine,
Lidocaine
Tetracaine
2. Insoluble compounds
Benzocaine
Butylaminobenzoate
Oxethazaine

3
 Mechanism of Action
They reversibly decrease the rate of depolarization and repolarization of excitable membranes.
Sensory information passes along nerve fibers via electrical impulse, or action potential. When
nerve is at rest, the interior has a negative charge. An action potential is generated by the influx
of Na ions into the interior of the nerve, giving it a positive charge-Depolarization. The nerve
fiber is returned to its resting potential by efflux of k ions- repolarization. The action potential is
then generated along the axon by successive depolarization & repolarization of adjacent regions.
Specific receptor Theory:
In producing a conduction block, the primary action of local anaesthetics is to decrease the
permeability of the ion channels to sodium ions.
Displacement of calcium ions from the sodium channel receptor site, which permit binding of the
local anaesthetic molecule to this receptor site, which produces blockade of the sodium channel.
Local anaesthetic molecules may act by competitive antagonism with calcium for same site on
the nerve membrane. This leads to depression of the rate of electrical depolarization, and failure
to achieve the threshold potential level, along with a lack of development of propagated action
potentials, which is called conduction blockade.

Metabolism and excretion

Ester anaesthetics are metabolised in plasma by the enzyme pseudo cholinesterase, which
generates PABA analogues and amino alcohol. The PABA analogues are excreted in the
urine mainly unaltered; the amino alcohol is further metabolised in the liver. Approximately 2%
of ester anaesthetics are excreted unchanged by the kidneys. The PABA analogues are
responsible for the allergic reactions that frequently occur with the use of local anaesthetics of
the ester type.

Anaesthetics of the amide type are metabolised in the liver first by the cytochrome P 450 system.
This reaction is followed by conjugation resulting in highly water-soluble metabolites that are
excreted by the kidneys. Between 70 and 90% of the amide anaesthetic is metabolised, and 10–
30% is excreted by the kidneys unchanged. Patients with severe liver insufficiency degrade
amide-type local anaesthetics at a delayed rate, which increases the risk of a toxic effect

4
Articaine is exceptional because it contains an additional ester group that is metabolized by
esterases in blood and tissue.

Local anaesthetics differ considerably in onset time, duration of action and strength of the
analgesic effect. The strength of the local anaesthetic effect is directly related to the lipid
solubility of the local anaesthetic. Of the series bupivacaine–articaine–lidocaine–prilocaine–
mepivacaine, the first anaesthetic is the most lipid soluble and the last one the least. The same
order applies to the strength of the analgesic effect of these compounds.

Pharmacokinetics
Local anaesthetics are weak bases, unstable and poorly water soluble. With a single exception,
they are tertiary amines. Therefore, hydrochloric acid (HCl) is added to the local anaesthetic,
which converts the tertiary amine, expressed below as R3N, into a chloride salt:
R3N + HCl →R3NH+ + Cl−
This increases the stability and water solubility of a local anaesthetic:

From the site of administration, a local anaesthetic must cross several barriers to reach the actual
site of action. For this, the uncharged base form of the local anaesthetic is necessary (R3N). This
form is lipophilic (fat soluble), enabling it to pass through the cell membrane of neurons.
The fat solubility of a local anaesthetic is primarily determined by the charge of the molecule and
– to a lesser extent – by the length of the molecule skeleton: the longer the chain, the greater the
fat solubility. Once the uncharged lipophilic form is inside the cell, a new equilibrium with the
water-soluble charged form will be established. The intracellular pH is lower than outside, so the
equilibrium will shift towards R3NH+, the active cationic form of the anaesthetic. Consequently,
the proportion between both forms (R3N and R3NH+) plays an essential role in the function of
local anaesthetics.

5
 Composition of LA
In addition to hydrochloric acid, to make the base form of local anaesthetic water soluble, several
other ingredients are added to the solutions of the various local anaesthetic agent.
i. 2% Lidocaine hydrochloride—local anaesthetic
ii. 1:80,000–1:1,00,000adrenaline —vasoconstrictor.
iii. Sodium metabisulphite—reducing agent.
iv. Capryhydrocuprienotoxin—preservative.
v. Thymol—antifungal.
vi. Ringer’s solution—solvent.

Enzyme [Hyaluronidase] may be included in some cases enhance the spread of L.A within
tissues. Sodium hydroxide to adjust ph may be present. Nitrogen bubble-1-2mm in diameter
may be present to prevent oxygen from being trapped in the cartridge and potentially
destroying the Vasopressor.

LIGNOCAINE /Lidocaine
[ Xylocaine]
Is the most widely used local anaesthetic agent. It comes in injectable and topical forms
Onset time 2-4mins
Half-life ∼ 90mins
Effective dental concentration. 2%
Topical anesthetic action. Yes (in clinically acceptable concentrations [5%]).
Pregnancy classification. B.
Lactation: Safe
Maximum dose with adrenaline 7mg/kg
Plain 4mg/kg
pKa. 7.9.
pH of plain solution. Approximately 6.5.
pH of vasoconstrictor-containing solution. Approximately ∼3.5.

6
Vasoconstrictors
Without these compounds, the clinical use of local anaesthetics in dentistry would be hampered
by their limited duration of action, as most anaesthetics produce vasodilatation. Exceptions are
mepivacaine and prilocaine. All clinically effective injectable local anesthetics are vasodilators.
Procaine is the most potent vasodilator. Prilocaine and mepivacaine have minimal vasodilating
activity while cocaine causes vasoconstriction.
Vasoconstrictors reduce the blood flow at the site of injection, which reduces the spread and
resorption of the local anaesthetic, thereby enhancing the duration and intensity. In addition,
vasoconstriction delays the absorption, which decreases systemic toxicity. Vasoconstrictors
decrease bleeding at the site of administration. Addition of vasoconstrictors in the local
anesthetic solution is useful when increased bleeding is anticipated (e.g., during a surgical
procedure)

The vasoconstrictors commonly used in conjunction with injected local anesthetics are
chemically identical or similar to the sympathetic nervous system mediators epinephrine
and norepinephrine. The actions of the vasoconstrictors so resemble the response of adrenergic
nerves to stimulation that they are classified as sympathomimetic, or adrenergic,
drugs. Epinephrine, norepinephrine, and dopamine are the naturally occurring catecholamines of
the sympathetic nervous system. Isoproterenol and levonordefrin are synthetic catecholamines.

Adrenaline (epinephrine)
Adrenaline is an endogenous compound, released into the blood by the adrenal medulla, with a
half-life of only a few minutes. Vasoconstriction by adrenaline is achieved by stimulation of α1-
adrenergic receptors of the smooth muscles of the vessel wall. The maximum dose of adrenaline
for adults is 200 μg. A concentration of 1:1000 means that 1 g (1000 mg) of drug is contained in
1000 mL of solution. Therefore, a 1:1000 dilution contains 1000 mg in 1000 mL or 1.0 mg per
milliliter of solution (1000 μg/mL). The 1:200,000 dilution, which contains 5 μg/mL (or 0.005
mg/mL), has become widely used in both medicine and dentistry, and is currently found for
articaine, prilocaine, lidocaine.

7
Other vasoconstrictors used include norepinephrine, phenylephrine, levonordefrin, and
felypressin. Sodium bisulfite is commonly added to epinephrine solutions to delay the process of
deterioriation.

Norepinephrine (Levarterenol)

Norepinephrine (as the bitartrate) in dental cartridges is relatively stable in acid solutions,
deteriorating on exposure to light and air. Acetone–sodium bisulfite is added to the cartridge to
retard deterioration.It is available in both synthetic and natural forms. The natural form
constitutes approximately 20% of the catecholamine production of the adrenal medulla.
Norepinephrine, lacking significant β2 actions, produces intense peripheral vasoconstriction with
possible dramatic elevation of blood pressure, and is associated with a side effect ratio nine times
higher than that of epinephrine.

Felypressin(octapressin)
Is a synthetic vasoconstrictor, derived from vasopressin (antidiuretic hormone). The
vasoconstrictive activity of felypressin mainly originates from inducing constriction of the
venous part of the circulation. It’s duration of action is longer than that of adrenaline. For adults,
the maximum dose of felypressin is 5.4 μg. Felypressin has both antidiuretic and oxytocic
actions, the latter contraindicating its use in pregnant patients.

Preservatives
Methyl- and propylparaben are a bacteriostatic agents. (1 mg/ml). Because of their chemical
structure, closely related to PABA, they frequently induce allergic reactions. Therefore, these
preservatives are currently hardly ever added to local anaesthetic solutions.
Caprylhydrocuprienotoxin is now used in modern cartridges of L.A

Reducing agent
Another preservative is bisulphite (0.3–2.0 mg/ml). This antioxidant is necessary to prevent
oxidation of the vasoconstrictor potentially present, usually adrenaline. Cartridges containing a

8
vasoconstrictor also contain an antioxidant, most often sodium (meta)bisulfite. Sodium bisulfite
prevents oxidation of the vasoconstrictor by oxygen, which can be trapped in the cartridge during
manufacture or can diffuse through the semipermeable diaphragm after filling. Sodium bisulfite
reacts with oxygen faster than the oxygen is able to destroy the vasoconstrictor. When oxidized,
sodium bisulfite becomes sodium bisulfate, having an even lower pH. Some individuals may
develop an allergy to this antioxidant.

Fungicide:
Thymol; to prevent fungal growth. It turns cloudy when fungi grow in L.A

Instruments
Cartridges
The glass cartridges usually contain 1.7–1.8 ml of anaesthetic fluid, although in the UK also 2.2
ml cartridges are available. The cartridge is closed, on one side by a rubber or synthetic
diaphragm and on the other side by a rubber or synthetic stopper that may or may not be
prepared for aspiration. The outside of the cartridge is printed with the name, composition and
vasoconstrictor of the local anaesthetic. This information is printed on the glass or on a thin
plastic foil. The latter ensures that, if the glass breaks (with intraligamental anaesthesia), the
fragments are held together by the plastic foil and do not end up in the oral cavity. Cartridges are
delivered in sterile packing and on the cartridges the expiry date, the stock number and other
information are written. A cartridge that has just been unpacked does not need to be disinfected
before use.

Needles
The needle is the vehicle that permits local anesthetic solution to travel from the dental cartridge
into the tissues surrounding the needle tip. Virtually all needles used in dentistry are stainless
steel and disposable. All needles used for local anaesthesia in dentistry are disposable and meant
for single use only. All needles have the following components in common: the bevel, the shaft,
the hub, and the cartridge-penetrating end .

9
The bevel defines the point or tip of the needle. A variety of bevel types are available on dental
needles, including short, medium, long, multileveled, and scalpel
The shaft of the needle is one long piece of tubular metal running from the tip of the needle
through the hub, continuing to the piece that penetrates the cartridge. Two factors to be
considered about this component of the needle are the diameter of its lumen (i.e. the needle
gauge) and the length of the shaft from point to hub.
The hub is a plastic or metal piece through which the needle attaches to the syringe. The interior
surface of metal- hubbed needles is prethreaded, as are most but not all plastic-hubbed needles.
The cartridge-penetrating end of the dental needle extends through the needle adaptor and
perforates the diaphragm of the local anesthetic cartridge. Its blunt end rests within the cartridge.
When one is selecting needles for use in various injection techniques, two factors that must be
considered are gauge and length.

A long needle is approx. 36 mm, a short one approx. 25 mm and an extra-short needle is approx.
12 mm. These needles are suitable for regional block anaesthesia, infiltration anaesthesia and
intraligamental anaesthesia respectively. The length—measured from hub to tip .The diameter of
the lumen of the needle is measured in terms of gauge. The smaller the gauge number the larger
the needle’s diameter.Most needles used in dentistry have a gauge of 25–30. A number higher
than 30 (i.e. very thin) should not be used, because aspiration of blood is then no longer
possible.27 needle is the most common for dental use.
The needle is contained in a metal or plastic cover. Part of the needle sticks out at the bottom and
is meant to be inserted through the diaphragm into the anaesthetic fluid. The other part of the
needle is used to actually apply the injection. The needles are packed in sterile packing and have
two plastic caps that are removed from the needle by unscrewing and simultaneously bending
them slightly. After use the needle should be preferably completely disassembled and disposed
of in a sharps container. If such a container is not available, the cap should be replaced carefully
over the needle.

The syringe
The cartridge syringe can usually be sterilised and is therefore made of rust-proof steel. Some
cartridge syringes are made of plastic and thus disposable. There are two different types of

10
syringes: an insert type (breech loading) and a snap-in type (end loading). In the breech loading
the cartridge is inserted into the syringe from the side of the barrel of the syringe.

Both the insert-type and snap-in-type syringes have a spring mechanism that aids automatic
aspiration. By decreasing the pressure on the plunger, a few microlitres are sucked into the
syringe, so it is easy to see whether the point of the needle is intravascular.

To prepare the cartridge syringe, the following steps are taken. First, a cartridge is placed in the
syringe by pulling the plunger back slightly (insert type) or snapping it into the syringe (snap-in
type). Then the plunger with harpoon, corkscrew, cap or bulb is pressed into the back of
the rubber stopper to enable aspiration. After this, the mantle of the needle is screwed onto the
screw thread of the front of the syringe. By applying slight pressure, one can now verify whether
the syringe is ready to be used.

Properties of an Ideal Anaesthetic

It has reversible action.
It is nonirritating to the tissues and produces no secondary local reaction.
It has a low degree of systemic toxicity.
It has a rapid onset and is of sufficient duration to be advantageous.
It has potency sufficient to give complete anaesthesia without the use of harmful concentrated
solutions.
It has sufficient penetrating properties to be effective as a topical anaesthetic.
It is relatively free from producing allergic reaction.
It is stable in solution and undergoes biotransformation readily within the body.
It is either sterile or is capable of being sterilized by heat without deterioration.

No local anesthetic in use today satisfies all these criteria; however, all anesthetics do meet most
of them.

11
Factors Affecting Local Anaesthetic Action 1.8

FACTOR ACTION AFFECTED DESCRIPTION

pKa Onset Lower pKa results in more rapid onset of
action as more RN molecules are present to
diffuse through the nerve sheath

Lipid solubility Anaesthetic potency Increased lipid solubility results in increased

potency (e.g., procaine = 1; etidocaine = 140)

Protein binding Duration Increased protein binding allows anesthetic

cations (RNH+) to be more firmly attached to
proteins located at receptor sites; hence the
duration of action is increased

Vasodilator Anaesthetic potency Greater vasodilator activity results in increased

activity And duration blood flow to the region, resulting in rapid
removal of anaesthetic molecules from the
injection site;

12
Phentolamine mesylate is a local anesthesia reversal agent used to reverse soft
tissue anesthesia at the completion of a procedure
Phentolamine mesylate (OraVerse), a nonselective a-adrenergic blocking drug, for the reversal of
soft-tissue anaesthesia and the associated functional deficits resulting from an intraoral
submucosal injection of a local anaesthetic containing a vasoconstrictor.

The FDA has approved the use of Oraverse in patients 6 years of age or older,
weighing more than 15 kg (33 lb)

13