Download Local Anesthetic

Local Anesthetics
By
Dr. HUSSAM .H.SAHIB , M.Sc
Local Anesthetic:
A local anesthetic is produce loss of sensation to pain in a specific
region of the body without a loss of patient consciousness. Normally,
the process is completely reversible .
Local anesthetics desirable characteristics:
1.Rapid onset of action and duration of action should be sufficient to
allow time for the surgical procedure.
2.Low degree of systemic toxicity.
3.soluble in water and stable in solution
4.Effective on all parts of the nervous system, all types of nerve fibers
and muscle fibers. (When injected into tissue &when applied topically
to mucous membranes).
5.It should not be irritating to tissue to which it is applied
The LAs consists of three parts:
1.A hydrophilic amino group. 2. An intermediate chain (ester or amide).
3.A lipophilic aromatic group.
Mechanism of action:
Local anesthetics block nerve conduction of sensory impulses. Na+ ion
channels are blocked to prevent the transient increase in permeability of
the nerve membrane to Na+ that is required for an action potential.
When propagation of action potentials is prevented, sensation cannot be
transmitted from the source of stimulation to the brain.
Pharmacokinetics:
Absorption: When injected into soft tissue, most local anesthetics
produce dilation of vascular bed. Cocaine is the only local anesthetic
that produces vasoconstriction; initially it produces vasodilation which
is followed by prolonged vasoconstriction.
Vasodilation causes increase in the rate of absorption of the local
anesthetic into the blood, thus decreasing the duration of pain control.
NOTE: ALL LA Pass easily mucous membrane except Procaine which
effective ONLY by injection
Esters:
They are hydrolyzed in plasma by pseudo-cholinesterase. One of the byproducts of metabolism is paraaminobenzoic acid (PABA), the common
cause of allergic reactions seen with these agents. Therefore, some
people have allergic reactions to the ester class of local anesthetics.
Amides:
They are metabolized in the liver to inactive agents. True
allergic reactions are rare.
Lidocaine half life is 1.6 hr in normal person while
more than 6 hrs in sever liver diseases.
ACTION:
LA are weak bases and their activity increases by increasing PH, This
because if large amount of a drug is nonpolar, it will facilitate its
penetration through the cell membrane. Once the drug has penetrated the
lipid barrier and reaches its site of action it ionized and the ionized form
is responsible for LA activity.
Acidosis such as caused by inflammation at a wound partly reduces the
action of local anesthetics. This is partly because most of the anesthetic
is ionized and therefore unable to cross the cell membrane to reach its
cytoplasmic-facing site of action on the sodium channel.
Factors affecting on local anesthetic action:
1-Lipid solubility
Increasing the lipid solubility leads to faster nerve penetration, block
sodium channels, and speed up the onset of action.
More lipophilic agents are more potent as local anesthetics.
The more tightly local anesthetics bind to the protein, the longer the
duration of onset action.
2-pH influence
Decrease in pH shifts equilibrium toward the ionized form, delaying
the onset action.
Lower pH, solution more acidic, gives slower onset of action
3-Vasoconstrictors
Vasoconstrictors decrease the rate of vascular absorption which allows
more anesthetic to reach the nerve membrane and improves the depth of
anesthesia. consequences of including vasoconstrictor:
Prolongation of anesthetic action, decreased risk of toxicity and
decrease in bleeding from surgical manipulations
epinephrine appears to be the best vasoconstrictor.
4-Inflammation: tends to produce lower pH in tissues therefore:
are more ionized - don’t penetrate very well so decreased ability of LA
to produce effects.
All local anesthetic agents readily cross the blood-brain barrier,
they also readily cross the placenta.
Thank you
Any question?
P H R M A C O L O G Y - NOTE 8 - Local Anesthesia
LOCAL ANESHESIA
weak Potency & short Duration
moderate Potency & intermediate
Duration
Lidocaine (Xylocaine)
Procaine
high Potency & long Duration
Tetracaine
Chloroprocaine
Mepivacaine
LA
Esters
Amide
•produce local loss
of sensation
without loss of
consciousness
•Procaine
• Chloroprocaine
•Tetracaine
• Benzocaine
•Benoxinate
Prilocaine
Bupivacaine
Etidocaine
Ropivacaine
•Lidocaine
(Xylocaine)
•Mepivacaine
•Bupivacaine
•Etidocaine
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| ‫ءاعدال مكألسن‬
P H R M A C O L O G Y - NOTE 8 - Local Anesthesia
DRUG
PHARMACOKINETIC

Chloroprocaine
High Potency &
long duration
Moderate Potency
& Intermediate
duration
Weak Potency &
short duration
Procaine
Absorption
NOT desirable because:
It duration.
It systemic side effects.
Lidocaine
(Xylocaine)
Metabolism
Easter& seussit yb dezilobatem yltsaf ,
plasma esterase.
Into PABA (cause allergy).
Short duration.
Amides, slowly metabolized by liver
microsomal enzymes.
Longer duration.
Mepivacaine
Prilocaine
Tetracaine
Bupivacaine
Etidocaine
Administration
Local injection.
Local application ( solution, powder
or cream)
.
Benzocaine





Ropivacaine
Benoxinate
ACTION
USES
Mechanism of action
LA block nerve conduction (initiation
& propagation of AP) by:
 Binding to Na+ channels &
prevent Na+ permeability.
1)
Action
LA are lipid soluble / weak base.
At pH= 7.4,
o they are UNIONIZED molecule.
o They pass lipid membrane.
When reach the cytoplasm,
o They become (ionized +
unionized).
o The IONIZED molecules:
 Bind to Na+ channels.
 Block Na+ influx.
 Prevent AP.
2)
The action are susceptible for (small
diameter / unmylinated) fibers more
than (large diameter / mylinated)
fibers.
 It is ester LA.
3)
4)
5)
Surface anesthesia:
o on Skin (wound & ulcer)
o on MM (mouth or nose).
o in Ophthalmology (corneal A).
o powder, solution creams or ointment
are used.
Infiltration anesthesia.
o as in (wound suturing, cyst removal).
Individual nerve block anesthesia.
o as in Dental anesthesia.
Spinal Epidural anesthesia.
o as in surgery of (LL, abd, pelvis,
rectum).
Treatment of cardiac dysrhythmia.
1) Infiltration anesthesia.
o as in (wound suturing, cyst removal).
2) Individual nerve block anesthesia.
o as in Dental anesthesia.
3) Spinal Epidural anesthesia.
o as in surgery of (LL, abd, pelvis,
rectum).
4) Treatment of cardiac dysrhythmia.
In ophthalmology for corneal A because :
 NO mydriasis.
 NO corneal injury.
Surface anesthesia on Skin (wound & ulcer)
Used as powder or cream.
Because it is insoluble, it produces less
systemic toxicity.
IF
1
2
3
4
‫|ءاعدال مكألسن‬
Dosage
Site
Lipid solubility
Infection/
inflammation
High
BV
LS
pH
5
Type of solution
Alkali
6
+ vasoconstrictors
INFLUENCING FACTORS
Advantage
Fast onset / long duration
SIDE EFFECT
 Usually minimum,
because:
o Applied locally.
o Combinewd with
vasoconstrictors.
1)Hypotension.
2)Bradicardia.
3)CNS:
 Tinnitus.
 Lightheadness.
 Headache.
 Convulsion.
4)Allergy (in ester type).
 Side effects occur due to:
o High dose.
o Injected into BV.
 They are potent & have
long duration.

Disadvantage
 side effect
 side effect / Short duration
 effect
action / ionized /effect
 absorb /  side effect/
duration
Vasodilation
Less painful / fast onset /
 non-ionized /  action / effect
duration/ absorb /side effect
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