Local Anesthetics By Dr. HUSSAM .H.SAHIB , M.Sc.
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Transcript of Local Anesthetics By Dr. HUSSAM .H.SAHIB , M.Sc.
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
The LAs consists of three parts: 1.A hydrophilic amino group. 2. An
intermediate chain (ester or amide). 3.A lipophilic aromatic group.
Pharmacokinetics: 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 by-products 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 4-Inflammation: tends to produce lower pH in
tissues therefore:
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 -
dont 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? moderate Potency & intermediate
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 high Potency & long Duration Lidocaine
(Xylocaine) Tetracaine Procaine Chloroprocaine Mepivacaine
Bupivacaine produce local losswithout loss of consciousness LA of
sensation Prilocaine Etidocaine Procaine Chloroprocaine Esters
Benzocaine Tetracaine Ropivacaine Benoxinate Lidocaine (Xylocaine)
Bupivacaine Etidocaine Amide Mepivacaine 25 | P H R M A C O L O G Y
- NOTE 8 - Local Anesthesia
DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT Procaine
Administration Local injection. Local application ( solution,
powder or cream) Absorption NOT desirable because: It duration. It
systemic side effects. Metabolism Easter, fastly metabolized by
tissues & plasma esterase. Into PABA (cause allergy). Short
duration. Amides, slowly metabolized by liver microsomal enzymes.
Longer duration. . Mechanism of action LA block nerve conduction
(initiation & propagation of AP) by: Binding to Na+ channels
& prevent Na+ permeability. 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. The action are susceptible for
(smalldiameter / unmylinated) fibers morethan (large diameter /
mylinated)fibers. 1) Surface anesthesia: o on Skin (wound &
ulcer) o onMM (mouth or nose). o in Ophthalmology (corneal A). o
powder, solution creams or ointment are used. 2) Infiltration
anesthesia. o as in (wound suturing, cyst removal). 3) Individual
nerve block anesthesia. o as in Dental anesthesia. 4) Spinal
Epidural anesthesia. o as in surgery of (LL, abd, pelvis, rectum).
5) Treatment of cardiac dysrhythmia. Usually minimum,because: o
Applied locally. o Combinewd with 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. Weak Potency
& short duration Chloroprocaine vasoconstrictors. Lidocaine
(Xylocaine) Moderate Potency & Intermediate duration
Mepivacaine Prilocaine Tetracaine 1)Infiltration anesthesia.
2)Individual nerve block anesthesia. 3)Spinal Epidural anesthesia.
rectum). o as in (wound suturing, cyst removal). Bupivacaine o as
in Dental anesthesia. High Potency & long duration Etidocaine o
as in surgery of (LL, abd, pelvis, Ropivacaine 4) Treatment of
cardiac dysrhythmia. Benoxinate It is ester LA. In ophthalmology
for corneal A because : NO corneal injury. NO mydriasis. Benzocaine
Used as powder or cream. Because it is insoluble, it produces less
systemic toxicity. Surface anesthesia onSkin (wound & ulcer)
INFLUENCING FACTORS IF Advantage Disadvantage 1 Dosage High Fast
onset / long duration side effect 2 Site BV side effect / Short
duration 3 Lipid solubility LS effect 4 Infection/ inflammation pH
action / ionized /effect Vaso- dilation absorb / side effect/
duration 5 Type of solution Alkali Less painful / fast onset /
non-ionized / action / effect 6 + vasoconstrictors duration/ absorb
/side effect 26 |