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Local Anesthetics

PROF:DR: MANZOOR AHMED UNAR

2015

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 Local Anesthetics ( L.A )
Local Anesthetics are agents those
effectively and reversibly blocks the impulse
conduction along the nerves and other
excitable membranes,
without a loss of patient’s consciousness.

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 Local Anesthetics (L.A)
Pain awareness (Nociception) can be
blocked by these drugs acting periphery.

Local anesthetics are often used as

analgesics, by
complete loss of sensory modalities.

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 History of Local Anesthetics
In 1860, Cocaine was isolated from Coca
leaves by Albert Niemann in Germany as
first local anesthetic.
In 1884, the very first clinical use of Cocaine
was introduced by Kollar as ophthalmology
anesthetic.
( 15 Sept: 1884 is “Birth of Local anesthetic )
In 1905, Procaine was synthesized by Einhorn.
In 1943, Lidocaine was synthesized by
Lofgren.( prototype local anesthetic)

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 Characters of Ideal Local Anesthetics

Less local irritation

Less tissue damage
Faster onset of action
Longer duration of action
Minimum systemic toxicity
No residual effect on nerve fiber

None of the currently available

Local Anesthetics is an ideal

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 Chemistry of Local Anesthetics
Local anesthetics are weak bases.
Most local anesthetics consist of three parts:
Lipophilic group ( eg aromatic ring )

Intermediate chain ( ester or amide )

Ionizable group ( eg tertiary amine )

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 Classification of Local Anesthetics

AMIDES
ESTERS
Lidocaine (medium)
Mepivacaine (medium)
Cocaine (medium) Articaine (fast & medium)
Procaine (short) Prilocaine (medium)

Tetracaine (Long) Etidocaine (Long)

Benzocaine (surface) Bupivacaine (Long)

Chloroprocaine Levobupivacaine (Long)

Ropivacaine (Long)

Amide L.A has two “i” in their names

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 Pharmacokinetics of Local Anesthetics
Administered by injection into dermis and soft
tissues around nerve.
Thus absorption and distribution are not
important in controlling the onset of effect.

Topical application (transmucosal, Transdermal)

requires drug diffusion for onset & offset of
effects.

Intracavitary ( intra-articular, intraperitoneal) has

more rapid onset & shorter duration of effect.

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 Pharmacokinetics of Local Anesthetics

Most L.A producing some vasodilatation

Ester L.A local are potent vasodilating drugs

Procaine possesses tremendous vasodilating

ability which are employed to halt
arterio-spasm (IA injection)

Cocaine is the only L.A that produces

vasoconstriction .

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 Pharmacokinetics of Local Anesthetics
Distribution of Local Anesthetics

Esters L.A: Due to short plasma half life

( ˂ one min:) distribution is not studied.
Amides L.A: Widely distributed after i/v.
Once reaches in the blood, L.A are distributed
to all tissues ( Brain, Head, Liver, Lungs,
kidneys, Spleen )
Skeletal muscle have high levels of L.A.
All L.A crosses Blood Brain Barrier & Placenta.
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 Pharmacokinetics of Local Anesthetics
Metabolism: of Esters L.A
Hydrolyzed in plasma by “Butyryl-choline-esterase”,
(a pseudo-cholinesterase) to inactive agents.

One of the by-product of metabolism is

Para-Amino Benzoic Acid (causes allergic reaction).

Metabolism: of Amides L.A

Metabolized in the liver (P450) to inactive agents.
Prilocaine fastest, while Levobupivacaine is slowest
metabolized.
True allergic reactions are rare ( Lidocaine )
Excretion: by kidney
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Mechanism of action of Local Anesthetics

Local anesthetics bind and block directly to the

intracellular voltage-gated sodium channels.
They block nerve conduction by reducing the
influx of sodium ions into the nerve cytoplasm,
there by inhibiting the depolarization of the
nerve.

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Mechanism of action of Local Anesthetics

Result in :
Slows impulse conduction
Increases threshold for excitation
Decreases action potential amplitude
Declines the rising rate of action potential
Abolish the ability

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 Mechanism of action of Local Anesthetics

Elevated extra cellular calcium

Partially antagonize the actions of L A, by
increasing the surface potential on the
membrane.

Elevated extra cellular potassium

Enhance the effects of L A, by
depolarizing the membrane potential and
favors the inactivated stage,
enhancing the effects of local anesthetics.
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 Factors Affect The Actions of L. A

(i) Lipid solubility

All local anesthetics are weak bases.
Smaller and more lipophilic the molecule,
the faster the rate of interaction
Potency is related with lipid solubility as well
as the agent retain sufficient water solubility.
Lidocaine, procaine, mepivacaine are more
water soluble than tetracaine, bupivacaine,
ropivacaine.

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 Factors Affect The Actions of L .A

(ii) Fiber Size & Function

L.A block the all nerves.

Smaller fibers blocked first.
Smaller diameter fibers blocked first.
Pain fibers blocked first.
Motor function blocked last.
Myelinated fibers blocked before unmyelinated
fibers.

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 Factors Affect The Actions of L .A

Order of sensory function block

1. Pain
2. Cold
3. Warmth
4. Touch
5. Deep pressure
6. Motor
“Recovery in reverse order”
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 Routes of Administration of L.A

Surface anesthetic / Topically

on cornea, nose, ear, throat
e.g. Lignocaine, Tetracaine, Benzocaine
Perineural Infiltration: ( Peripheral )
for suturing or stitching e.g. Lignocaine

Epidural or Subarachnoid space,

e.g. Lignocaine, Procaine
Intravenous regional (Bier block ):
in distal vein with tourniquet for foot, arm, lower extremity e.g.
Bupivacaine

.
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 Clinical Pharmacology of L.A

L.A provide reversible but complete

anesthesia, of well defined parts of the body.
Duration can be prolonged by adding
vasoconstrictor (epinephrine / phenylephrine)
On set of L.A accelerated by adding sodium
bicarbonate.
Repeated injection of L.A can results in
loss of effectiveness (tachyphylaxis).

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 Clinical Pharmacology of L.A

Block pain sensation in specific areas of the

body.
LA have weak neurotransmitter blocking effect.
Effect on cardiac cell membranes are of
major clinical significance (as antiarrhythmics)

Vasoconstrictor property of cocaine can be used

to decrease bleeding from mucosal damage.
Pregnancy appear to increase susceptibility to
local anesthetics toxicity.
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 Uses of Local Anesthetics

Neuropathic Pain,
In combination with Antidepressants,
In combination with Anticonvulsants,

I/V for reducing acute pain in Perioperative,

Cardiac arrhythmias,
Anesthesia for superficial short surgical
procedures.

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 Toxicity of Local Anesthetics

CNS: At low conc: Sedation, Light headedness,

Tongue numbness, Metallic test.
Visual and Auditory disturbance,
At high conc : Muscular twitching, Nystagmus,
Convulsion, CNS depression, Death.

ANS: Cocaine blocks reuptake of norepinephrine

results in vasoconstriction and hypertension.
Precipitate cardiac arrhythmias, Leads to
ischemia and Ulceration to Mucous membrane.

Peripheral N.S: Neurotoxicity

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 Toxicity of Local Anesthetics

CVS: L.A can block cardiac sodium channels,

thus depresses abnormal cardiac pacemaker
activity, excitability and conduction.

At very higher conc: block Ca2+ channel,

Hypotension (arteriolar dilation).

Bupivacaine is more cardiotoxic than other LA.

(cardiovascular collapse and death usually occur)

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 Toxicity of Local Anesthetics

Blood: Prilocaine, during regional anesthesia may

accumulate metabolite o-toluidine, that converts
hemoglobin to methemoglobin, so patient may
appear cyanotic.
Rx: Methylene blue , Ascorbic acid.

Localized Toxicity: Neural injury,

Transient Neurologic Symptoms (TNS),
Spinal and Epidural administration of LA,
transient pain can occur.

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 Toxicity of Local Anesthetics

Allergic reaction:
Esters L.A:
metabolized to Para-Amino Benzonic Acid,
which are responsible for allergic reaction.

Amides L.A: allergic reaction is rare.

Toxicity is more to occur in patient with
hepatic disease.

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