DefinitionMechanism of ActionClassificationCompositionLocal Anesthesic AgentsVasocontrictors

Definition

Local Anesthesia is defined as a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve ending or an inhibition of the conduction process in the pheripheral nerves.

Important feature is that is does not cause loss of consciousness.

Only those methods or agents that induce a transient & completely reversible state of anesthesia have application in clinical practice.

Mechanism Of ActionTheories of mechanism of action of local anesthesiaAcetylcholine TheoryCalcium Displacement TheorySurface Charge TheoryMembrane Expansion TheorySpecific Receptor Theory

Membrane Expansion Theory

Local Anesthetics are highly lipid soluble & easily penetrate lipid portion of cell membrane

Thus causing expansion of nerve membrane & resulting in the decrease of the diameter of the sodium channels

Thereby inhibiting the influx of sodium & nerve impulse generation

Specific Receptor Theory

Local Anesthetics act by binding to specific receptor binding site present on the sodium channels

Specific receptor site are present on either the external or internal surface of the sodium channels

Local Anesthetics are classified according to biological site & mode of action

1.Agents acting at receptor site on external surface of nerve membrane – biotoxins eg tetrodotoxin

2.Agents acting at receptor site on internal surface of nerve membrane - quaternary ammonium analogues of lidocaine

3.Agents acting by a receptor-independent physico-chemical mechanism – benzocaine,

4.Agents acting by combination of receptor & receptor - independent mechanism -articaine, lidocaine, mepivacaine, prilocaine

Sequence of eventDiplacement of calcium ions from the sodium channel receptor site, which permitsBinding of the local anesthetic molecule to this receptor site, which permitsBlockade of sodium channel, & a Decrease in sodium conductance, which leads toDepression of the rate of electrical depolarization, & aFailure to achieve threshold potential level, along with aLack of development of propagated action potentials, which called Conduction blockade

Action of a local anesthetic is affected by 2 factorsDiffusion of the drug through the nerve sheath Binding at the receptor site

Local anesthetics are available as salts dissolved in sterile water or saline.

In this solution it exists simultaneously as uncharged molecule called base RN & positively charged cation RNH+

The uncharged lipid soluble free base form RN is responsible for diffusion through nerve sheath

The cationic form RNH+ is responsible for binding at the receptor site

The relative proportion of the solution varies according to the pH of the surrounding tissue

In presence of low pH, ie high concentration of hydrogen ions, most of the solution exists in cationic form RNH+

In presence of high pH, ie low concentration of hydrogen ions, most of the solution exists in free base form RN

The relative proportion of ionic form also depends on dissociation constant or pKa of the solution

When pH of the solution has same value as the pKa of local anesthetic, the agent exist in 50% RN & 50% RNH+ form

Composition of Local Anesthetic SolutionLocal Anesthetic agent- 2% LidocaineVasoconstrictor- Epinephrine 1:80,000 to 1:200,000Reducing Agent- Sodium MetabisulphitePreservative- Methyl ParabenSolvent- Distilled Water

Classification of Anesthetic agentsEster GroupAmide GroupQuinoline Group

Ester GroupBenzoic Acid Esters Cocaine Butacaine Piperocaine Tetracaine BenzocainePara-aminobenzoic Acid Esters Procaine Propoxycaine Chloroprocaine

Amide Group Bupivacaine Etidocaine Lidocaine Mepivacaine Prilocaine

Quinoline Centbucridine

LidocaineAmide groupPotency is 2 & toxicity is 2pKa is 7.9 ph 6.5pH with vasoconstrictor 5 to 5.5Vasodilating Concentration available- 2% Dental Concentration 5% Topical Agent 10% SprayMaximum Recommended Dose with vasoconstrictor 7 mg/kg without vasoconstrictor 4.4 mg/kg

Onset of action 2-3 minutesHalflife 1.6 hourMetabolised in liver by microsomal fixed function oxidases

ProcaineEster groupPotency 1 & toxicity 1pKa 9.1 pH 5 to 6.5pH with vasoconstrictor 3.5 to 5.5Most profound vasodilatationConcentration available 2% to 4%Onset of action 6 to 10 minutesHalflife 0.1 hourMetabolised in plasma by plasma pseudo-cholinesterase

MepivacaineAmide groupPotency 2 toxicity 1.5 to 2pKa 7.6 pH 4.5pH with vasoconstrictor 3 to 3.5VasodilationConcentration- 3% without vasoconstrictor 2% with vasoconstrictorOnset of action 1.5 to 2 minutesHalflife 1.9 hoursMaximum Recommended Dose- 6.6mg/kg

BupivacaineAmide groupPotency 4 time lidocaine toxicity 4 times less than lidocainepKa 8.1 pH 4.5 to 6pH of vasoconstrictor 3 to 4.5Vasodilation more than lidocaine but less than procaineConcentration 0.5%Maximum Recommended Dose 1.3 mg\kgOnset of action 6 to 10 minutesHalflife 2.7 hoursMetaboilsm in liver by amidases

CocaineEster groupThe only local anesthetic with vasoconstriction propertyExclusively used topicallyConcentration 2% to 10% but for mucous membrane should not exceed 4%Onset of action 1minuteHalflife 2 hoursMetabolised in liver

Eutectic Mixture of Local AnestheticsEMLA cream is emulsion with oil phase composed of lidocaine 2.5% & prilocaine 2.5%(1:1)It was designed as a topical anesthetic able to provide surface anesthesia of intact skin Used primarily before painful procedureEMLA has become popular during circumcision,leg ulcer debridement & gynecological procedureIt is appiled 1 hour before procedureEMLA is contraindicated for use in patient with congenital or idiopathic methemoglobinemia, infants under 12 years receiving methemoglobin-inducing agents or patients with sensitivity with amide group

VasoconstrictorVasoconstrictors are important addition to local anesthetic solution due to following reasons

To decrease the perfusion

To decrease absorption of local anesthetic

Minimise the risk of toxicity

Increase the duration of action

Decrease the bleeding

Vasoconstrictor used commonly are chemically identical to sympathetic nervous system mediatorsThey are classified as sympathomimetic or adrenergic

ClassificationDepending on chemical structureDepending on mode of action

NoncatecholaminesAmphetamineMethamphetamineEphedrineMephenteraminePhenylephrine

Chemical structureCatecholaminesEpinephrineNorepinephrineDopamineLevonordefrin

Mode of ActionBased on mode of action they are classified as Direct-acting drugs Indirect-acting drugs Mixed-acting drugs

Direct-acting drugsThey act through adrenergic receptors present in various tissues of the bodyReceptors are alpha & betaAlpha is further divided into alpha1 & alpha2Beta further divided into beta1 & beta2Eg. Epinephrine,Norepinephrine,Dopamine,Levonordefrin,Phenylephrine,Methoxamine

Indirectly-acting drugsThese drugs act indirectly by causing the release of the catecholamine norepinephrine from storage sites in adrenergic nerve terminalsEg. Tyramine, Amphetamine, Methamphetamine, Hydroxyamphetamine

Mixed-acting drugsMetaraminolEphedrine

EpinephrineEpinephrine is acid salt highly soluble in waterIt is available as a synthetic & also obtained from adrenal medullaIt acts directly on both alpha & beta receptors

Systemic ActionsOn myocardium increases force of contraction & rate of contractionIncreased heart rate & cardiac outputOn coronary arteries causes dilation thus increases coronary blood flowSystolic blood pressure increases & diastolic pressure decreases in small doses

In large doses diatolic pressure is increasedOn blood vessels supplying skin,mucous membranes & kidneys produces vasoconstrictionOn blood vessels supplying smooth muscles cause vasodilation on small doses & vasoconstriction on large dosesIt is potent bronchodilator

In DentistryIt is most potent & widely used vasocontrictor in dentistryIt is available in following dilution 1:50,000,1:80,000,1:100,000,1:200,000,1:300,000

NorepinephrineIt is available in both synthetic & natural formsThe natural forms constitutes 20% of catecholamine productionMode of action is direct exclusively through alpha receptorsSystemic ActionsOn myocardium produces positive inotropic actionIncreases coronary blood flow by causing dilation of coronary blood vesselsProduces decrease in heart rate by reflex action of carotid & aortic baroreceptorsBoth systolic & diastolic blood pressure is increasedCauses vasoconstriction of cutaneous blood vesselsCauses alpha induced constriction of lung arterioles, which reduces airway resistance to small degree

In DentistryIt is no longer available as vasoconstrictor agent in dentistryIt was used with procaine in 1:300,000 dilution

Contraindications for VasoconstrictorAbsolute Contraindication Uncontrolled Hypertension Severe Cardiovascular diseases such as Acute Myocardial Infarction within 6 months, Angina, Refractory Cardiac DysrhythmiasHyperthyroid state

Relative ContraindicationsPatients on MAO inhibitorsPatients on Tricyclic AntidepressentsArteriosclerosisDiabetes Mellitus

Reference

Handbook of LoacalAnesthesia by Stanley F. MalamedMonheim’s Local Anesthesia & Pain Control in Dental Practice