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 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

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

Amide • Mepivacaine

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• produce local loss

without loss of

consciousness

• Tetracaine

• Lidocaine (Xylocaine)

• Bupivacaine • Etidocaine

LOCAL ANESHESIA

weak Potency & short Duration

moderate Potency & intermediate Duration

high Potency & long Duration

Lidocaine (Xylocaine)

Tetracaine

Procaine

Chloroprocaine

Mepivacaine

Bupivacaine

LA of sensation

Prilocaine

Etidocaine

• Procaine • Chloroprocaine

Esters • Benzocaine

Ropivacaine • Benoxinate

P H R M A C O L O G Y - NOTE 8 - Local Anesthesia

vasoconstrictors.

(Xylocaine)

o as in (wound suturing, cyst removal.)

o as in Dental anesthesia.

o as in surgery of (LL, abd, pelvis,

4) Treatment of cardiac dysrhythmia.

NO mydriasis.

duration

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DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Wea

k P

ote

ncy

&

sh

ort

du

rati

on

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 (small diameter / unmylinated) fibers more than (large diameter / mylinated) fibers.

1 ) 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. 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.

Chloroprocaine

Mo

der

ate

Po

ten

cy

& In

term

edia

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du

rati

on

Lidocaine

Mepivacaine

Prilocaine

Hig

h P

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cy

&

long

du

rati

on

Tetracaine 1 ) Infiltration anesthesia.

2 ) Individual nerve block anesthesia.

3 ) Spinal Epidural anesthesia .

rectum.)

Bupivacaine

Etidocaine

Ropivacaine

Benoxinate It is ester LA. In ophthalmology for corneal A because :

NO corneal injury.

Benzocaine Used as powder or cream.

Because it is insoluble, it produces less systemic toxicity.

Surface anesthesia on Skin (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/

5 Type of solution Alkali Less painful / fast onset / non-ionized / action / effect

6 + vasoconstrictors duration/ absorb /side effect