Pharmacology Of Local
Anesthetics
Presented By :
Monica Raafat Mikhail
Sherouk Salah Ibrahim
Constituents Of Local Anathetic Carpule
Local anasthetic agent
Vasoconstrictor
Reducing agent
Fungicide
Preservative
Vehicle
Note That !!
Virtually all drugs, regardless of the route through which
they are administered, must ultimately enter into the
circulatory system in sufficiently high concentrations before
they can begin to exert a clinical action.
Local anesthetics, however, when used for pain control,
cease to provide a clinical effect when they are absorbed
from the site of administration into the circulation. One
prime factor involved in the termination of action of
local anesthetics used for pain control is their redistribution
from the nerve fiber into the cardiovascular system
Classification Of Local Anesthetic Agents
According to occurance in According to duration of
nature : action :
1- Natural 1- Short acting :
ex. : cocaine ex. : Lidocaine – Articaine
2- Synthetic 2- Long acting :
ex. : Lidocaine ex. : Bupvicaine
According to chemical structure
Ester Group Amide Group
Composed of : Composed of :
• Aromatic group • Aromatic group
• Intermediate chain containing
• Intermediate chain containing
amide linkage
ester linkage
• Hydrophilic secondary or tertiary
• Hydrophilic secondary or tertiary
amino group
amino group
Esters Vs. Amides
Examples of Esters And Amides
Ester Group Amide Group
Cocaine Lidocaine
Piperocaine Mepivacaine
Procaine Pyrrocaine
Tetracaine Prilocaine
Chloroprocaine Articaine
Primacaine Dibucaine
Benzocaine Etidocaine
Note that :
Most of esters have one “I” while most of amides have double “I”
Hydroxy Group ??
They are group of local anesthetics that are almost
insoluble in water as they lack the hydrophilic
group
They are used as topical analgesics
Pharmacokinetics Of Local Anasthetics
Uptake
When injected into soft tissues, local anesthetics exert
pharmacologic action on blood vessels in the area .
All local anesthetics have a degree of vasoactivity , most
of which are vasodilators , also degree of vasodilation
differs from one drug to another
Ester local anasthetics are known to be potent
vasodilators
• Procaine is most potent vasodilator
among local anesthetics
• Tetracaine, chloroprocaine, and
propoxycaine also possess
vasodilating properties to varying
degrees but not to the degree of
procaine.
• Cocaine is the only local anesthetic
that consistently produces
vasoconstriction. The initial action
of cocaine is vasodilation followed
by an intense and prolonged
vasoconstriction.
• Mepivacaine is a weak vasodilator
Clinical effect of vasodilatation
Increase rate of
absorption of local Increase anesthetic plasma
anesthetics in blood concentration
stream
Decrease
Increase
duration and
potential for
quality of pain
toxic reaction
control
Distribution
once absorbed , they are distributed to all
tissues of the body such as brain , liver , kidney ,
heart , spleen
Plasma concentration of local anesthetic in a
certain target organ has a significant effect on
the potential toxicity of the drug
The blood level of the local anesthetic is
influenced by the following factors:
1. Rate at which the drug is absorbed
into the cardiovascular system
2. Rate of distribution of the drug
from the vascular compartment to
the tissues(more rapid in healthy
patients than in those who are
medically compromised)
3. Elimination of the drug through
metabolic or excretory pathways
The latter two factors serve to decrease
the blood level of the local anesthetic.
Metabolism
A significant difference between the two groups of
local anesthetic drugs , is the means by which the
body transform the active form of the drug into
inactive form
Metabolism of local anesthetics is important because
the overall toxicity of a drug depends on a balance
between its rate of absorption into the bloodstream at
the site of injection and its rate of removal from the
blood through tissue uptake and metabolism
Ester Local anesthetics
Hydrolyzed in the plasma by the enzyme pseudocholinesterase
The rate at which hydrolysis of different esters occurs varies considerably
Chloroprocaine, the most rapidly hydrolyzed, is the least toxic
tetracaine, hydrolyzed 16 times more slowly than
chloroprocaine, has the greatest potential toxicity
Procaine undergoes hydrolysis to para-aminobenzoic acid (PABA), which is
excreted unchanged in the urine, and to diethylamine alcohol, which
undergoes further biotransformation before excretion
Amide Local Anesthetics
The biotransformation of amide local anesthetics is more
complex than that of the esters
The primary site of biotransformation of amide local
anesthetics is the liver
the entire metabolic process occurs in the liver for lidocaine, mepivacaine,
etidocaine, and bupivacaine . Their rates of biotransformation is nearly
similar
Prilocaine undergoes primary metabolism in the liver, with
some also possibly occurring in the lung
Articaine, a hybrid molecule containing both ester and amide
components, undergoes metabolism in both the blood and the liver
To Sum Up
Excretion
The kidneys are the primary excretory organ for
both the local anesthetic and its metabolites
A percentage of a given dose of local anesthetic
is excreted unchanged in the urine. This
percentage varies according to the drug.
Esters Amides
appear only in very small usually are present in the
concentrations as the parent urine as the parent compound
compound in the urine because in a greater percentage than
they are hydrolyzed almost the esters, primarily because of
completely in the plasma. their more complex process of
biotransformation
Procaine appears in the urine
as PABA (90%) with 2%
unchanged
Patients with significant renal impairment may be unable
to eliminate the parent local anesthetic compound
or its major metabolites from the blood, resulting in
slightly elevated blood levels and therefore increased
potential for toxicity
How To Calculate Maximum Number Of
Carpules For A Patient ??
Let’s think about it :
For Lidocaine as an example
• If we know that maximum • So , for an adult female who is
recommended dose for 60 kg , the maximum
lidocaine is recommended dose will be :
7mg/kg 7 × 60 = 420 mg
• For one anesthetic carpule containing 2 %
lidocaine
Each carpule contains 1.8 ml
Each 1 ml contains 1000 mg
2% of 1 ml = 20 mg
So 2% lidocaine of 1.8 ml ( one carpule ) = 36 mg
So ;
How many carpules a Number of carpules =
Girl whose maximum max. dose ÷ dose in one carpule
dose is 420 mg can take ?
420 ÷ 36 = 11.6 carpules
