Good Morning…

LOCAL ANESTHESIA
 OBJECTIVES

• TO UNDERSTAND LOCAL ANESTHESIA IN DETAIL : ITS

CONTENTS
• CLASSIFACATION
• TYPES OF LA
 Contents

• Introduction…
• Definition…
• History…
• Neurophysiology….
• Classification of LA….
• Mechanism of Action…
• Pharmacology of LA
• Types of LA.
 INTRODUCTION

• Local anesthesia creates an absence of pain in

specific location of body without loss of
consciousness as opposed to General anesthesia.Local
anesthetics produce anesthesia by inhibiting
excitation of nerve endings or by blocking conduction
of peripheral nerves.
“ Some pains are physical, some pains
are mental, But the pain which is
both physical and mental is….
Dental.”
- Ogden Nash
 Ideal properties of local anesthetics

• Action must be reversible…

• Non irritating to the tissue & produce no secondary local
rkn..
• Low degree of systemic toxicity…
• Rapid onset & sufficient duration of action …
• Potency to provide complete anesthesia…
• Sufficient penetrating properties… Bennett’s addition..
• Relatively free from producing allergic rkn…
• Stable in soln & undergo transformation readily…
• Either be sterile or be capable of being sterilized…
DEFINITION
• It is defined as transient regional loss of sensation to a painful or
potentially painful stimulus resulting from a reversible interruption
of a peripheral conduction along a specific neural pathway to its
central integration & perception in the brain.
- Daniel Laskin
• Local Anesthesia has been defined as loss of sensation in a
circumscribed area of the body caused by a depression of excitation
in nerve endings or an inhibition of the conduction process in
peripheral nerves.
- Stanley F. Malamed
HISTORY
• Discovery of suitable drugs & syringes….
• 1852… Charles Gabriel Pravaz – invented a silver hollow
needle combined with glass syringe … 1.5 ml …
• Alexender Woods 1853 dvlped – Metallic syringe….
- Injected Morphine close to nerves….
• COCAINE : The First Local Anesthetic …
• Conquest of PERU by Francis Pizzaro in 1530….
• Khoka means plant ( in Peru language )…
• Austrian Carl Von Scherzer imported these leaves & gave it to
German Chemists Albert Neimann & Wilhelm Lossen who
isolated the main alkaloid of Coca Plant …. ( 1859-1860)…
• These Chemists termed it Cocaine…..
• 1856 – Sameul Percy – first to use coca leaves as anesthetic…
• SIGMUND FREUD was the first to propose the idea of using
Cocaine for its local anesthetic property….KOLLER...

• Toxicity of Cocaine:-

- 1880 Anrep studied effects of cocaine on resp & CVS and

demonstrated depressant action…
- 1928 AMA was found which said tht cocaine should not be
injected subcutaneously & cocaine disappeared from clinical
practice as an injectable drug….
- 1951 study published …. Reported 3 deaths in 30,000 pt
treated…..
- addition of Barbitone to ↑ the fatal dose…
• Euphoric effect of Cocaine :-

- William Heldsted credited to first use of Cocaine fr nerve

blockade…
- Sigmund Freud …Psychoanalysis...

• Need for the less toxic drug :-

- led the pharmacological companies to conc on newly

described plants … Javanese variety of coca plant…
tropocaine… (same degree of toxicity)…
- new products made by modifying tropacaine….
• 1898, Eihorn synthesized first Amino Amide LA…
Nirvaquine… irritant to local tissues…
• 1890, Eihorn prepared Benzocaine & Procaine…
• Chlorine substitution on the aromatic ring produced
Chloroprocaine… which had:-
- Rapid onset
- Short duration of action..
LIDOCAINE :
• Prepared in 1944.
• First amide LA to be used clinically by LOFGREN in 1948..
• Widely employed for its potency, rapid onset, Peripheral nr
block & both Epidural and Spinal anesthesia..
NEUROPHYSIOLOGY
• Concept behind MOA of LA….

- Prevention of generation & conduction of nr impulses..

( Chemical roadblock betwn source of impulse & brain)

• Neuron:
• Is the structural unit of nervous system..

• Parts ???

• Afferent (sensory) / Efferent (motor)…

Electrophysiology of nerve conduction
• MODE & SITE OF LA ACTION :

It is possible for a LA agent to interfere with the excitation

process in a nr ending in one or more way :

- Altering the basic resting potential of the nr membrane.

- Altering the threshold potential ( firing potential ).

- ↓ the rate of depolarization.

- Prolonging the rate of repolarization.

 Where do local anesthetic act ??

• Theories:

A) Acetylcholine theory...

B) Calcium Displacement Theory…

C) Surface charge theory / Repulsion theory…

D) Membrane Expansion theory…

E) Specific Receptor theory…

Membrane expansion theory
 Specific receptor theory

• Most favored theory..

• Proposes tht LA act by binding to specific receptors on the

sodium channels..

• LA is classified based on their ability to react with specific

receptors :
- Within the sodium channels… e.g. Amide LA..
- At the outer surface of Na channels…e.g. Tetradoxin…
- At either the activation or inactivation gate… e.g. Scorpion
venom…
Specific receptor theory
 How do LA work??

• Sequence of proposed mechanism is…

displacement of Ca ions from the Na channel receptor site
which permits
↓

Binding of the LA molecule to this receptor site which thus

produces
↓
Blockade of Na channel & a
↓
Decrease in sodium conductance which leads to
 Depression of the rate of electrical depolarization and a..
↓

Failure to achieve the threshold potential level, along with a…

↓

Lack of development of Propagated AP, which is called…

↓

CONDUCTION BLOCKADE
 Active forms of local anesthetics

• Tertiary amines….
• Secondary amine… e.g. Prilocaine..

Structure of Ester LA

Structure of amide LA
• Amphipathic nature of LA…

• Esters readily hydrolyze … Amides resistant to hydrolysis…

(greater % of amide excreted unchanged)

• Why HCl is added to LA ????...

• Acidification of the tissue reduces LA action…

( pH of normal tissue.. 7.8.. pH of inflamed tissue 5-6)

• pH of LA with epinephrine… 3.3 (acidified by manufacturers

to inhibit Oxdn) … burning sensation & slow induction…
• ↑ the pH ( Alkalization ) of LA :
- Speeds the onset..
- ↑ the clinical effectiveness…
- Makes injection more comfortable…

• LA bases are unstable…CO2 & NaHCO3 are added …

• Actions on the nerve membrane :

- diffusion thru the nerve sheath &
- Binding at the receptor site in the ion channels…

• Unchanged lipid base form (RN) of the anesthetic is

responsible for the diffusion thru nr membrane..
PHARMACOLOGY OF LA
 Composition of LA Solution

• Lignocaine Hcl --- (Anesthetic) 24.64 mg (2 %)

• Adrenaline --- (Vaso constrictor) 0.0125 mg (1:80,000)
• Sodium metabisulphite (Reducing Agent) 0.5 mg
• Methyl paraben --- (Preservative) 1 mg
Or
Cupryl hydrocuprinotoxin 1 mg
• Thymol --- (Fungicide)

• Distilled Water / Ringer lactate --- (Vehicle) 100 ml

 REDUCING AGENT
• The vasoconstrictors in the LA are unstable in the solution
form & may oxidise on prolong exposure to the sun.
• To overcome this problem 0.5mg /ml of sodium
metabisulfite is added as a reducing agent
• It competes for the available oxygen in the vial.
 PRESERVATIVE

• Preservative are added to maintain the stability of the solution

• Methyl paraben 1 mg /ml is added to the LA solutions in order
to give it a shelf life of 2 yrs or so.
 FUNGICIDE

• To be on the safer side a small quantity of Thymol is added to

the LA solution
 SALTS

• Inorder to make the LA solution isotonic with the body pH,

salts are added to it.
• 5-6 mg of sodium chloride is added to each ml of solution to
make it isotonic.
 VEHICLE

• The anesthetic agent & other constituent of vial are dissolved in

distilled water which is used as a vehicle for making the
solution .
• 2% of xylocaine means 20 mg /ml
So if LA with adrenaline is injected in a 80kg man
80kg X 7mg/kg(dose of LA with adr.)
=560mg
560/20 =28ml can be injected.
Classification of LA
• According to chemical composition

• Ester linked
– Cocaine, Procaine, Chloroprocaine, Tetracaine, Benzocaine.
• Amide linked
– Lignocaine, Prilocaine, Bupivacaine, Ropivacaine, Dibucaine,
Quinilone Derivative
– Centbucridine.
• According to route of administration

Injectable / Surface or topical

• According to Duration of action

- Short duration :
Procaine, Chloroprocaine

- Intermediate duration :
Lignocaine, Prilocaine

- Long Duration :
Bupivacaine.

• According to type
- Natural / Semi synthetic
• According to site of action
CLASS SITE EXAMPLE

A Extero Receptors. Biotoxins

B Intero Receptors. Lidocaine

C Receptor independent Benzocaine

D Combination. Most L.A.

• Pharmacokinetics :

• Absorption :

– Local anesthetics are absorbed from the site of inj.

– Some local anesthetics may be absorbed in toxic amounts after topical use.

– Absorption after an injection depends on drug solubility in lipid and in water,

tissue vascularity and local anesthetic and vasoconstrictor effects on local
circulation.
Metabolism and excretion :

– Esters are hydrolyzed by plasma and liver esterase’s. Longer-acting esters are
often metabolized more slowly.

– Patients with altered pseudo-cholinesterase activity may be highly sensitive to

these drugs.

– Amides are metabolized in the liver. Patients with severe hepatic damage or
advanced congestive heart failure may be unusually sensitive to these drugs.

– Some amides are partially excreted unchanged in the urine.

• Systemic action of LA :
• CNS –
Low levels – no action
Toxic dose – tonic clonic convulsions
Blood- 0.5-4.0 mg/ml-no complication
4.5-7.0 mg/ml-pre seizure sign/
symptom
>7.5mg/ml-tonic clonic seizures.
Anti convulsive property –
As it causes depression of CNS.
Seizure threshold ↑
• CVS-

– Action on Heart
• Electrical excitability of myocardium .
• conduction rate
• Tone of contraction.
clinically effective level-1.8-5mg/ml –anti arrhythmic
used in premature ventricular contractures , arrhythmias.
Action on vasculature
- normal value : no change.
- over dose- hypotension (myocardial
contractility)
Lethal dose- cardio vascular collapse
( myocardial contractility, massive peripheral vasodilatation )

Action on Respiratory system

– Normal levels- no over dose- bronchial muscles relaxation .

– Over dose – Respiratory arrest due to CNS depression.
 Clinical significance

• Least toxic LA- 2 chlorprocaine.

• Most toxic LA- tetracaine

• If allergic to LA –diphenhydramine- anti histamine +

mild anesthetic

• For children - 2 chlorprocaine

Lignocaine :

Classified under – Amide

– 2-diethylamino 2,6 acetoxylidide HCl

– 1943 – Nils Lofgrens- intro 1948(dentistry)

– Metabolised- Liver by microsomal fixed function oxidases to monoethyl

glycerine and xylidide

– Excretion -<10% unchanged, >80%-metab

– Vasodilaton ->Procaine, <Mepivacaine

– Recommended dose – 7mg/kg not>500mg with VC
4.4mg/kg not>300mg

– For children with VC 3.2 mg/kg

– It is non allergic available in three

formulations Ligno2% with out Vc

Ligno2% with VC 1:80,000
Ligno2% with VC 1:100,000

– Adverse reactions- CNS stimulation then Depression ,Overdose causes

unconsciousness and respiratory arrest.
– Bupivacaine –Classified under amide
– 1-butyl 2,6 pipecoloxylidide
– Toxicity <4 times – Lignocaine, Mepivacaine
– Metabolism –Liver by Amidases
– Excretion by kidney (16% unchanged)
– Vasodilatation- relatively significant
– Pka-8.1,ph(plain)- 4.5-6, ph(vc)- 3-4.5
Onset of action –6-10 min,Anesthetic half life-2.7hrs,Dose 1.3mg/kg ,Maximum
dose-not >40mg,Absolute maximum dose-not> 90mg
– Available as 0.5% soln 1:2,00,000 (vc)
– Indication- pulpal anesthesia->90- min.
Full mouth reconstruction.
Extensive perio surgery.
management of post op pain.
– Duration –Pulpal- 90- 180 min
Soft tissue-4-12 hrs
– Contra indication- burning sensation at site of injection, in children-anticipating
self trauma .
– Articaine- classified- Amide
– 2 Carboxymethoxy 4 methylthiophene hcl
– Metabolized- Liver
– Excretion – Kidney 10% - unchanged.
– Anesthetic half life-1.2-2 hrs,
– Maximum dose – 1mg/kg , Absolute maximum dose –500mg
– first LA Agent with thiophene ring,little potential to diffuse through soft tissue.
– Adverse reaction-methymoglobinemia-Rx by using methylene blue 1mg/kg.
▪ Natural La agent COCAINE
▪ Safest LA given in children 2CHLOROPROCAINE
▪ Most toxic of all LA agents PROPOXYCAINE
▪ LA with longest duration of action ETIDOCAINE
▪ BUPIVACAINE
▪ TETRACAINE
▪ LA with shortest duration of action 2CHLOROPROCAINE
▪ LA widely used in dentistry LIDOCAINE
▪ La which is safe in which vasoconstrictor
▪ Not required MEPIVACAINE
PHARMACOLOGY OF VASOCONSTRICTORS
• LA injection leads to :
- An ↑ rate of absorption of LA into the CVS, which in turn
removes it from the inj site..
- Higher plasma levels of the LA, with an attendant ↑ in the risk
of LA toxicity..
- ↓ in depth of anesthesia & ↓ duration of action …
- ↑ bleeding at the site of treatment..
• Vasoconstrictors are the drugs tht constricts BV & controls
tissue perfusion…
• Actions of Vasoconstrictors :
- constricts BV,↓ blood flow to site of admn..
- Abs of LA into CVS is slowed …
- LA blood levels ↓, minimizing toxicity…
- ↑ duration of action..
 - ↓ bleeding from the site of admn..

• Chemically identical to the Sympathetic nervous system

mediators… Epinephrine & Norepinephrine..

• Classification based on chemical nature

Catecholeamines / NorCatecholeamines

• Classification based on mode of action

Direct Acting / Indirect Acting / Mixed Acting
 EPINEPHRINE FELYPRESSIN
Proprietary Adrenaline Octopressin
name
Mode of α1& β receptors Direct stimulation of
action vasculature
Systemic Systolic & Diastolic No direct effect on
• CVS pressure Myocardium
Heart rate Non-arrythmagenic
Oxygen consumption High doses – impaired
Stroke volume coronary flow
2) CNS CNS stimulation Adrenergic nerve – no
effect
3) RS Bronchodilator
4) Vasculature α1 – Vasoconstriction –
vasoconstriction coronary blood vessels
β 2 – vasodilation
5)Metabolism oxygen Anti-diuretic action
consumption Oxytocin like action –
blood sugar level uterus
6) Clinical Allergy, hemostasis As vaso-constrictor in
application L.A

7) Max 0.2 mg – healthy 0.04mg

dose 0.04mg – CVS impaired
8) Side CVS & CNS symptoms
effect
Cerebral hemorrhage
EPINEPHRINE :
Adrenaline
- action : α1& β receptors
- Effect on CVS :
Systolic & Diastolic pressure
Heart rate
Oxygen consumption
Stroke volume
- CNS -stimulation
- RS - Bronchodilator
- Blood vessels α1 – vasoconstriction
β 2 – vasodilation
- dosage :0.2 mg – healthy ,0.04mg – CVS impaired

- Adverse effects : CVS & CNS symptoms

- Clinical application : Allergy, hemostasis

FELYPRESSIN :
Octopressin
- Direct stimulation of vasculature
- No direct effect on Myocardium
- Non-arrythmogenic
- High doses – impaired coronary flow
- Oxytocin like action – uterus
- Maximum dosage : 0.04mg
• 2% of xylocaine means 20 mg /ml
So if LA with adrenaline is injected in a 80kg man
80kg X 7mg/kg(dose of LA with adr.)
=560mg
560/20 =28ml can be injected.
 Take Home Message

• Procedure to be done will decide the tyoe of

anesthesia to be used
 Questions

• Define local aneathesia

• Classify LA
• Write a note on Bupivacaine
• Lignocaine
• Contents of LA
• What do u mean by 2%lignocaine