Chapter 9: Local Anesthetics Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All...

Chapter 9:Chapter 9:

Local AnestheticsLocal Anesthetics

Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

22Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.

Chapter 9 OutlineChapter 9 Outline HistoryHistory

Ideal local anestheticIdeal local anesthetic ChemistryChemistry Mechanism of actionMechanism of action PharmacokineticsPharmacokinetics Pharmacologic effectsPharmacologic effects Adverse reactionsAdverse reactions Compositions of local anesthetic solutionsCompositions of local anesthetic solutions Local anesthetic agentsLocal anesthetic agents VasoconstrictorsVasoconstrictors Choice of local anestheticChoice of local anesthetic Topical anestheticsTopical anesthetics Doses of local anesthetic and vasoconstrictorDoses of local anesthetic and vasoconstrictor


Local AnestheticsLocal Anesthetics

Haveles (p. 112)Haveles (p. 112) No drugs are used more often in the dental No drugs are used more often in the dental

office than local anesthetic agentsoffice than local anesthetic agents Use can become routine, but these agents have a Use can become routine, but these agents have a

potential for systemic effects in addition to desired potential for systemic effects in addition to desired local effectslocal effects


HistoryHistory

Haveles (p. 112) (Figs. 9-1, 9-2)Haveles (p. 112) (Figs. 9-1, 9-2) ““Painless” dentistry through use of a local Painless” dentistry through use of a local

anesthetic is a relatively recent developmentanesthetic is a relatively recent development Indigenous South American people chewed leaves Indigenous South American people chewed leaves

that made them feel betterthat made them feel better Tasting it produced not only a loss of taste, but Tasting it produced not only a loss of taste, but

also of the sensation of painalso of the sensation of pain

cont’d…cont’d…


HistoryHistory

Koller noticed that cocaine in the eye Koller noticed that cocaine in the eye produced complete anesthesiaproduced complete anesthesia

Sigmund Freud was also experimenting with Sigmund Freud was also experimenting with cocaine and its effects on the central nervous cocaine and its effects on the central nervous system (CNS)system (CNS) CNS stimulation, toxicity, and the potential for CNS stimulation, toxicity, and the potential for

abuse were quickly recognized as major problems abuse were quickly recognized as major problems with the widespread use of cocaine as a local with the widespread use of cocaine as a local anestheticanesthetic



HistoryHistory

Einhorn synthesized procaine in 1905; many Einhorn synthesized procaine in 1905; many years later, its use became common in years later, its use became common in dentistrydentistry

The amide lidocaine (Xylocaine) was The amide lidocaine (Xylocaine) was released in 1952released in 1952

mepivacaine (Carbocaine) was released in mepivacaine (Carbocaine) was released in 19601960

More recently, bupivacaine (Marcaine) has More recently, bupivacaine (Marcaine) has been made available for dental usebeen made available for dental use


Ideal Local AnestheticIdeal Local Anesthetic

Haveles (pp. 112-113)Haveles (pp. 112-113) Many local anesthetic agents are not clinically Many local anesthetic agents are not clinically

acceptableacceptable The ideal local anesthetic should possess certain The ideal local anesthetic should possess certain

propertiesproperties No local anesthetic in use today meets all of those No local anesthetic in use today meets all of those

requirements, although many acceptable agents requirements, although many acceptable agents are availableare available


Properties of the Ideal Local Properties of the Ideal Local AnestheticAnesthetic

Haveles (p. 113) (Box 9-1)Haveles (p. 113) (Box 9-1) Potent local anesthesiaPotent local anesthesia Reversible local anesthesiaReversible local anesthesia Absence of local reactionsAbsence of local reactions Absence of allergic reactionsAbsence of allergic reactions Rapid onsetRapid onset Satisfactory durationSatisfactory duration Adequate tissue penetrationAdequate tissue penetration Low costLow cost Stability in solution Stability in solution Sterilization by autoclaveSterilization by autoclave Ease of metabolism and excretionEase of metabolism and excretion


ChemistryChemistry

Haveles (pp. 113-114) (Table 9-1)Haveles (pp. 113-114) (Table 9-1) Local anesthetic agents are divided chemically Local anesthetic agents are divided chemically

into two major groups—amides and estersinto two major groups—amides and esters A few agents fall outside these two groupsA few agents fall outside these two groups

The importance of this division is associated The importance of this division is associated with potential allergic reactionswith potential allergic reactions Cross-hypersensitivity between amides and esters Cross-hypersensitivity between amides and esters

is unlikely is unlikely



ChemistryChemistry

The structure of local anesthetic is composed The structure of local anesthetic is composed of the following three partsof the following three parts Aromatic nucleus (R)Aromatic nucleus (R) Linkage (either an ester or amide, followed by an Linkage (either an ester or amide, followed by an

aliphatic chain, R)aliphatic chain, R) Amino groupAmino group

The aromatic nucleus (R) is lipophilic and the The aromatic nucleus (R) is lipophilic and the amino group is hydrophilicamino group is hydrophilic

Esters are largely metabolized in the plasma Esters are largely metabolized in the plasma and amides in the liverand amides in the liver


Mechanism of ActionMechanism of Action Haveles (pp. 113-115) (Fig. 9-3; Box 9-2)Haveles (pp. 113-115) (Fig. 9-3; Box 9-2)

Action on nerve fibersAction on nerve fibers A resting nerve fiber has a large number of positive ions on A resting nerve fiber has a large number of positive ions on

the outside and a large number of negative ions on the the outside and a large number of negative ions on the insideinside

The nerve action potential results in the opening of The nerve action potential results in the opening of sodium channels and in inward flux of sodiumsodium channels and in inward flux of sodium This results in a change from the –90-mV potential to a This results in a change from the –90-mV potential to a

+40-mV potential+40-mV potential The outward flow of potassium ions repolarizes the The outward flow of potassium ions repolarizes the

membrane and closes the sodium channelsmembrane and closes the sodium channelscont’d…cont’d…


Mechanism of ActionMechanism of Action

Haveles (p. 114)Haveles (p. 114) Action on nerve fibersAction on nerve fibers

Local anesthetics attach themselves to specific Local anesthetics attach themselves to specific receptors in the nerve membranereceptors in the nerve membrane

After combining with the receptor, local After combining with the receptor, local anesthetics block conduction of nerve impulses by anesthetics block conduction of nerve impulses by decreasing the permeability of the nerve cell decreasing the permeability of the nerve cell membrane to sodium ionsmembrane to sodium ions




Decreasing permeability to sodium ions Decreasing permeability to sodium ions Decreases the rate of depolarization of the nerve Decreases the rate of depolarization of the nerve

membranemembrane Increases the threshold for excitabilityIncreases the threshold for excitability Prevents propagation of the action potentialPrevents propagation of the action potential

Local anesthetics may reduce permeability by Local anesthetics may reduce permeability by competing with calcium for the membrane competing with calcium for the membrane binding sites and by preventing the onset of binding sites and by preventing the onset of nerve conductionnerve conduction




Haveles (pp. 114-115) (Fig. 9-4)Haveles (pp. 114-115) (Fig. 9-4) Ionization factorsIonization factors

Local anesthetic agents are weak bases occurring Local anesthetic agents are weak bases occurring equilibrated between equilibrated between • Fat-soluble (lipophilic) free baseFat-soluble (lipophilic) free base

• Water-soluble (hydrophilic) hydrochloride saltWater-soluble (hydrophilic) hydrochloride salt

The proportion in each form is determined byThe proportion in each form is determined by• The acid dissociation constant (pKa) of the local The acid dissociation constant (pKa) of the local

anestheticanesthetic

• The pH of the environmentThe pH of the environment




In the acidic pH of the dental cartridge (4.5), In the acidic pH of the dental cartridge (4.5), the proportion of the drug in the ionized form the proportion of the drug in the ionized form increases, increasing solubilityincreases, increasing solubility Once injected into tissues (pH 7.4), the amount of Once injected into tissues (pH 7.4), the amount of

local anesthetic in the free-base form increaseslocal anesthetic in the free-base form increases This provides for greater tissue (lipid) penetrationThis provides for greater tissue (lipid) penetration




In an acidic environment such as infection or In an acidic environment such as infection or inflammation (pH lower), the amount of free inflammation (pH lower), the amount of free base is reduced (more in ionized form)base is reduced (more in ionized form) This is one reason dental anesthesia with a local This is one reason dental anesthesia with a local

anesthetic is more difficult when infection is presentanesthetic is more difficult when infection is present Other reasons include dilution by fluid, Other reasons include dilution by fluid,

inflammation, and vasodilation in the areainflammation, and vasodilation in the area The free base form is needed to penetrate the The free base form is needed to penetrate the

nerve membranenerve membrane The cationic form exerts blocking action by binding The cationic form exerts blocking action by binding

to the specific receptor siteto the specific receptor site


PharmacokineticsPharmacokinetics

Haveles (p. 112)Haveles (p. 112) Absorption depends on its routeAbsorption depends on its route

When injected into tissues the rate depends on the When injected into tissues the rate depends on the vascularity of the tissuesvascularity of the tissues• This is a function of the degree of inflammation present, This is a function of the degree of inflammation present,

the vasodilating properties of the local anesthetic agent, the vasodilating properties of the local anesthetic agent, the presence of heat, or use of massagethe presence of heat, or use of massage




Haveles (p. 112)Haveles (p. 112) AbsorptionAbsorption

Reducing the systemic absorption of a Reducing the systemic absorption of a local anesthetic is important when it is local anesthetic is important when it is used in dentistryused in dentistry• With reduced absorption, the chance of With reduced absorption, the chance of

systemic toxicity is reducedsystemic toxicity is reduced




A vasoconstrictor is added to the local A vasoconstrictor is added to the local anesthetic to reduce absorptionanesthetic to reduce absorption

The vasoconstrictorThe vasoconstrictor Reduces the blood supply to the areaReduces the blood supply to the area Limits systemic absorptionLimits systemic absorption Reduces systemic toxicityReduces systemic toxicity




Haveles (p. 112)Haveles (p. 112) AbsorptionAbsorption

With topical application, especially on mucous With topical application, especially on mucous membranes or if the surface is denuded, membranes or if the surface is denuded, absorption can approximate that produced by absorption can approximate that produced by intravenous injectionintravenous injection

It is also determined by the proportion of the agent It is also determined by the proportion of the agent present in the free-base form (nonionized)present in the free-base form (nonionized)




Haveles (p. 115)Haveles (p. 115) DistributionDistribution

After absorption, local anesthetics are distributed After absorption, local anesthetics are distributed throughout the bodythroughout the body• Highly vascular organs have higher concentrations of Highly vascular organs have higher concentrations of

anestheticsanesthetics

Local anesthetics cross the placenta and blood-Local anesthetics cross the placenta and blood-brain barrierbrain barrier• Lipid solubility affects the potency of the agentLipid solubility affects the potency of the agent

• Bupivacaine 0.5% is about 10 times more lipid soluble Bupivacaine 0.5% is about 10 times more lipid soluble than lidocaine used as a 2% solutionthan lidocaine used as a 2% solution




Haveles (p. 115)Haveles (p. 115) MetabolismMetabolism

Local anesthetic agents are metabolized Local anesthetic agents are metabolized differently, depending on whether they are amides differently, depending on whether they are amides or estersor esters• Esters are hydrolyzed by plasma pseudocholinesterases Esters are hydrolyzed by plasma pseudocholinesterases

and liver esterasesand liver esterases

• Procaine is hydrolyzed to para-aminobenzoic acid Procaine is hydrolyzed to para-aminobenzoic acid (PABA), a metabolite that may be responsible for its (PABA), a metabolite that may be responsible for its allergic reactionallergic reaction




Haveles (p. 115)Haveles (p. 115) MetabolismMetabolism

Amide local anesthetics are metabolized primarily by Amide local anesthetics are metabolized primarily by the liverthe liver• In severe liver disease or with alcoholism, amides may In severe liver disease or with alcoholism, amides may

accumulate and produce systemic toxicityaccumulate and produce systemic toxicity

A small amount of prilocaine is metabolized to A small amount of prilocaine is metabolized to orthotoluidine, which can produce orthotoluidine, which can produce methemoglobinemia if given in very large dosesmethemoglobinemia if given in very large doses

Cimetidine can interfere with metabolism of amides Cimetidine can interfere with metabolism of amides by reducing hepatic blood flowby reducing hepatic blood flow




Haveles (p. 115)Haveles (p. 115) ExcretionExcretion

Metabolites and some unchanged drug of both Metabolites and some unchanged drug of both esters and amides are excreted by the kidneysesters and amides are excreted by the kidneys

Both parent drug and metabolites can accumulate Both parent drug and metabolites can accumulate with end-stage renal diseasewith end-stage renal disease


Pharmacologic EffectsPharmacologic Effects

Haveles (pp. 115-116)Haveles (pp. 115-116) Peripheral nerve conduction (blocker)Peripheral nerve conduction (blocker)

The main clinical effect of local anesthetic is The main clinical effect of local anesthetic is reversible blockage of peripheral nerve conductionreversible blockage of peripheral nerve conduction• These agents inhibit movement of the nerve impulse along These agents inhibit movement of the nerve impulse along

the fibers, at sensory endings, at myoneural junctions, and the fibers, at sensory endings, at myoneural junctions, and at synapsesat synapses

They do not penetrate the myelin sheath, but they They do not penetrate the myelin sheath, but they affect myelinated fibers only at the nodes of Ranvieraffect myelinated fibers only at the nodes of Ranvier

Local anesthetics affect small, unmyelinated fibers Local anesthetics affect small, unmyelinated fibers first and large; heavily myelinated fibers lastfirst and large; heavily myelinated fibers last


Common Order of Nerve Common Order of Nerve Function LossFunction Loss

Haveles (p. 116) (Box 9-3)Haveles (p. 116) (Box 9-3) AutonomicAutonomic ColdCold WarmthWarmth PainPain TouchTouch PressurePressure VibrationVibration ProprioceptionProprioception MotorMotor


Pharmacologic EffectsPharmacologic Effects

Haveles (pp. 115-116)Haveles (pp. 115-116) AntiarrhythmicAntiarrhythmic

Local anesthetics have a direct effect on cardiac Local anesthetics have a direct effect on cardiac muscle by blocking cardiac sodium channels and muscle by blocking cardiac sodium channels and depressing abnormal cardiac pacemaker activity, depressing abnormal cardiac pacemaker activity, excitability, and conductionexcitability, and conduction• They also depress strength of cardiac contraction and They also depress strength of cardiac contraction and

produce arteriolar dilation, leading to hypotensionproduce arteriolar dilation, leading to hypotension

These properties make than useful in treatment of These properties make than useful in treatment of arrhythmiasarrhythmias


Adverse ReactionsAdverse Reactions

Haveles (p. 116) (Table 9-2)Haveles (p. 116) (Table 9-2) ToxicityToxicity

Adverse reactions and toxicity are directly related Adverse reactions and toxicity are directly related to the plasma level of the drugto the plasma level of the drug• Their potential for danger must be minimalTheir potential for danger must be minimal

• Deaths from local anesthetics are difficult to document, Deaths from local anesthetics are difficult to document, dental-related mortality is even rarerdental-related mortality is even rarer




Factors influencing toxicity includeFactors influencing toxicity include Drug: inherent toxicity and amount of vasodilationDrug: inherent toxicity and amount of vasodilation Concentration Concentration Route of administrationRoute of administration Rate of injectionRate of injection VascularityVascularity Patient’s weightPatient’s weight Rate of metabolism and excretionRate of metabolism and excretion




Haveles (p. 116)Haveles (p. 116) ToxicityToxicity

CNS effectsCNS effects CNS stimulation may occur before CNS CNS stimulation may occur before CNS

depressiondepression• CNS stimulation caused by depression of inhibitory fibers CNS stimulation caused by depression of inhibitory fibers

results in restlessness, tremors, and convulsionsresults in restlessness, tremors, and convulsions

• CNS depression caused by depression of both inhibitory CNS depression caused by depression of both inhibitory and facilitative fibers results in respiratory and and facilitative fibers results in respiratory and cardiovascular depression, and coma followscardiovascular depression, and coma follows




Haveles (pp. 116-117)Haveles (pp. 116-117) ToxicityToxicity

Cardiovascular effectsCardiovascular effects• Local anesthetic agents can produce myocardial Local anesthetic agents can produce myocardial

depression and cardiac arrest with peripheral vasodilationdepression and cardiac arrest with peripheral vasodilation

• Usual concentrations that are achieved with administration Usual concentrations that are achieved with administration of dental anesthesia would not be expected to result in of dental anesthesia would not be expected to result in any of these adverse reactionsany of these adverse reactions

• It is postulated that the effect of these agents on heart It is postulated that the effect of these agents on heart conduction may produce a fatal arrhythmiaconduction may produce a fatal arrhythmia




Haveles (pp. 116-117)Haveles (pp. 116-117) Local effectsLocal effects

Most commonly the result of physical injury Most commonly the result of physical injury caused by injection technique or administration of caused by injection technique or administration of an excessive volume too quickly to be accepted by an excessive volume too quickly to be accepted by the tissuesthe tissues

Occasionally a hematoma may be producedOccasionally a hematoma may be produced




Haveles (p. 117)Haveles (p. 117) Malignant hyperthermiaMalignant hyperthermia

An inherited disease that is transmitted as an An inherited disease that is transmitted as an autosomal-dominant gene with reduced penetration autosomal-dominant gene with reduced penetration and variable expressionand variable expression

Symptoms include an acute rise in calcium, which Symptoms include an acute rise in calcium, which produces muscular rigidity, metabolic acidosis, and produces muscular rigidity, metabolic acidosis, and extremely high feverextremely high fever• Mortality is above 50%Mortality is above 50%

Treatment includes supportive measures and the Treatment includes supportive measures and the administration of dantroleneadministration of dantrolene




In the past, it was thought that amide local In the past, it was thought that amide local anesthetics might precipitate malignant anesthetics might precipitate malignant hyperthermia, but they are currently no longer hyperthermia, but they are currently no longer implicatedimplicated Patients with a family history of malignant Patients with a family history of malignant

hyperthermia can be given amide local anesthetic hyperthermia can be given amide local anesthetic agentsagents




Haveles (p. 117)Haveles (p. 117) Pregnancy and nursing considerationsPregnancy and nursing considerations

Elective dental treatment should be rendered Elective dental treatment should be rendered before a patient becomes pregnantbefore a patient becomes pregnant

Most sources suggest that lidocaine may be Most sources suggest that lidocaine may be administered to a pregnant woman if dental administered to a pregnant woman if dental treatment is neededtreatment is needed




Pregnancy and nursing considerationsPregnancy and nursing considerations Fetal bradycardia has been reported when larger Fetal bradycardia has been reported when larger

doses are administered to the mother near termdoses are administered to the mother near term• Lidocaine and prilocaine are U.S. Food and Drug Lidocaine and prilocaine are U.S. Food and Drug

Administration (FDA) pregnancy category BAdministration (FDA) pregnancy category B

• Mepivacaine, articaine, and bupivacaine are FDA Mepivacaine, articaine, and bupivacaine are FDA pregnancy category Cpregnancy category C




Haveles (p. 117)Haveles (p. 117) AllergyAllergy

Allergic reactions that result from local anesthetics Allergic reactions that result from local anesthetics have been reportedhave been reported• They range from rash to anaphylactic shockThey range from rash to anaphylactic shock

An allergy history should be elicited from each An allergy history should be elicited from each patient before a local anesthetic agent is chosenpatient before a local anesthetic agent is chosen

Esters have a much greater allergic potential; Esters have a much greater allergic potential; some question has surfaced about whether some question has surfaced about whether amides can produce allergic reactions at allamides can produce allergic reactions at all





Patients giving a history of allergies to all local Patients giving a history of allergies to all local anesthetic agents may be “tested” by giving them anesthetic agents may be “tested” by giving them an amide by injectionan amide by injection

Use of skin testing is unreliable; it can give both Use of skin testing is unreliable; it can give both false-positive and false-negative resultsfalse-positive and false-negative results





Another approach is to use the antihistamine Another approach is to use the antihistamine diphenhydramine (Benadryl) as a local anestheticdiphenhydramine (Benadryl) as a local anesthetic

Antihistamines, because of their similarity in Antihistamines, because of their similarity in structure to local anesthetics, have some local structure to local anesthetics, have some local anesthetic actionanesthetic action

diphenhydramine (Benadryl) in a concentration of diphenhydramine (Benadryl) in a concentration of 1% plus 1:100,000 epinephrine is recommended to 1% plus 1:100,000 epinephrine is recommended to be given by injection to produce a blockbe given by injection to produce a block• No prepared product is available; this combination must be No prepared product is available; this combination must be

prepared from its constituentsprepared from its constituentscont’d…cont’d…



AllergyAllergy Local anesthetics with vasoconstrictors also Local anesthetics with vasoconstrictors also

contain a sulfite that serves as an antioxidantcontain a sulfite that serves as an antioxidant• In sulfite-sensitive patients, the sulfites may produce a In sulfite-sensitive patients, the sulfites may produce a

hypersensitivity reaction that exhibits itself as an acute hypersensitivity reaction that exhibits itself as an acute asthmatic attackasthmatic attack

• The reaction is the same as the “salad bar” syndrome, a The reaction is the same as the “salad bar” syndrome, a hypersensitivity reaction to sulfiteshypersensitivity reaction to sulfites


Composition of Local Anesthetic Composition of Local Anesthetic SolutionsSolutions

Haveles (pp. 117-118)Haveles (pp. 117-118) Local anesthetic usually contains several other Local anesthetic usually contains several other

ingredients such as the followingingredients such as the following Vasoconstrictor: to retard absorption, reduce Vasoconstrictor: to retard absorption, reduce

systemic toxicity, and prolong duration of actionsystemic toxicity, and prolong duration of action Antioxidant: to retard oxidation of epinephrineAntioxidant: to retard oxidation of epinephrine Sodium hydroxide: to adjust the pH between 6 and 7Sodium hydroxide: to adjust the pH between 6 and 7 Methylparaben and propylparaben: preservatives Methylparaben and propylparaben: preservatives

added to multidose parenteral solutionsadded to multidose parenteral solutions• No dental cartridge contains methylparabenNo dental cartridge contains methylparaben


Local Anesthetic AgentsLocal Anesthetic Agents

Haveles (p. 118)Haveles (p. 118) AmidesAmides

Many local anesthetic agents are available with Many local anesthetic agents are available with similar pharmacologic and clinical effects and similar pharmacologic and clinical effects and systemic toxicitysystemic toxicity• Dental issues associated with local anesthetics are listed Dental issues associated with local anesthetics are listed

in Box 9-4in Box 9-4

• Table 9-3 lists the local anesthetics available in dental Table 9-3 lists the local anesthetics available in dental cartridgescartridges




Haveles (p. 118)Haveles (p. 118) AmidesAmides

The only class of anesthetics used parenterallyThe only class of anesthetics used parenterally• Esters are occasionally used topicallyEsters are occasionally used topically

• The relative lack of allergenicity of the amides is The relative lack of allergenicity of the amides is probably responsible for thisprobably responsible for this




Haveles (pp. 118-120)Haveles (pp. 118-120) Amides: lidocaineAmides: lidocaine

Introduced in 1948, it became an anesthetic Introduced in 1948, it became an anesthetic standard to which other local anesthetics were standard to which other local anesthetics were comparedcompared

Rapid onset related to its tendency to spread well Rapid onset related to its tendency to spread well through the tissuesthrough the tissues

Lidocaine 2% with vasoconstrictor provides profound Lidocaine 2% with vasoconstrictor provides profound anesthesia of medium durationanesthesia of medium duration• The local anesthetic solution most commonly used in The local anesthetic solution most commonly used in

dental officesdental officescont’d…cont’d…



Haveles (p. 118) (Fig. 9-5)Haveles (p. 118) (Fig. 9-5) Amides: lidocaineAmides: lidocaine

No cross-allergenicity among the amide lidocaine, No cross-allergenicity among the amide lidocaine, other available amides, or esters has been other available amides, or esters has been documenteddocumented

In toxic reactions, one is likely to observe CNS In toxic reactions, one is likely to observe CNS depression initially rather than the CNS stimulation depression initially rather than the CNS stimulation characteristic of other local anestheticscharacteristic of other local anesthetics

Adverse reactions include hypotension, positional Adverse reactions include hypotension, positional headache, and shiveringheadache, and shivering




Haveles (p. 119)Haveles (p. 119) Amides: lidocaineAmides: lidocaine

In dentistry, lidocaine 2% with 1:100,000 In dentistry, lidocaine 2% with 1:100,000 epinephrine is used for infiltration and block epinephrine is used for infiltration and block anesthesiaanesthesia• Lidocaine is used for topical anesthesia as a 5% ointment, Lidocaine is used for topical anesthesia as a 5% ointment,

a 10% spray, and a 2% viscous solutiona 10% spray, and a 2% viscous solution

Lidocaine with epinephrine 1:100,000 provides a Lidocaine with epinephrine 1:100,000 provides a 1.0- to 1.5-hour duration of pulpal anesthesia1.0- to 1.5-hour duration of pulpal anesthesia• Soft-tissue anesthesia is maintained for 3 to 4 hoursSoft-tissue anesthesia is maintained for 3 to 4 hours




Haveles (p. 119)Haveles (p. 119) Amides: lidocaineAmides: lidocaine

A new dose form of lidocaine is a patch applied to A new dose form of lidocaine is a patch applied to mucosal membranes for local anesthesiamucosal membranes for local anesthesia

Its maximal effect occurs after about 10 minutes, Its maximal effect occurs after about 10 minutes, which is probably too long to waitwhich is probably too long to wait




Haveles (p. 119)Haveles (p. 119) Amides: mepivacaineAmides: mepivacaine

Introduced in 1960, its rate of onset, duration, Introduced in 1960, its rate of onset, duration, potency, and toxicity are similar to those of lidocainepotency, and toxicity are similar to those of lidocaine

Mepivacaine is not effective topically; however, it is Mepivacaine is not effective topically; however, it is used for infiltration, block, spinal, epidural, and used for infiltration, block, spinal, epidural, and caudal anesthesiacaudal anesthesia

The usual dose form in dentistry is a 2% solution The usual dose form in dentistry is a 2% solution with addition of 1:20,000 levonordephrin (Neo-with addition of 1:20,000 levonordephrin (Neo-Cobefrin) as a vasoconstrictorCobefrin) as a vasoconstrictor




Haveles (p. 119)Haveles (p. 119) Amides: mepivacaineAmides: mepivacaine

Because mepivacaine produces less vasodilation Because mepivacaine produces less vasodilation than lidocaine, it can be used as a 3% solution than lidocaine, it can be used as a 3% solution without a vasoconstrictor without a vasoconstrictor

Can be used for short procedures when a Can be used for short procedures when a vasoconstrictor is contraindicatedvasoconstrictor is contraindicated




Haveles (p. 119)Haveles (p. 119) Amides: prilocaineAmides: prilocaine

Prilocaine is related chemically and Prilocaine is related chemically and pharmacologically to both lidocaine and mepivacainepharmacologically to both lidocaine and mepivacaine

Chemically, lidocaine and mepivacaine are xylidine Chemically, lidocaine and mepivacaine are xylidine derivatives, whereas prilocaine is a toluidine derivatives, whereas prilocaine is a toluidine derivativederivative

Prilocaine appears to be less potent and less toxic Prilocaine appears to be less potent and less toxic than lidocaine and has a slightly longer duration of than lidocaine and has a slightly longer duration of actionaction





Although toxicity of prilocaine is 60% that occurring Although toxicity of prilocaine is 60% that occurring with lidocaine, several cases of methemoglobinemia with lidocaine, several cases of methemoglobinemia have been reported after its usehave been reported after its use

Prilocaine is metabolized to orthotoluidine and in Prilocaine is metabolized to orthotoluidine and in large doses can induce some methemoglobinemialarge doses can induce some methemoglobinemia

Prilocaine should not be administered to patients Prilocaine should not be administered to patients with any condition in which problems of oxygenation with any condition in which problems of oxygenation may be especially criticalmay be especially critical





Drugs that affect the hemoglobin, such as Drugs that affect the hemoglobin, such as acetaminophen, may exacerbate the adverse acetaminophen, may exacerbate the adverse reactionreaction

Prilocaine is used for infiltration, block, epidural, Prilocaine is used for infiltration, block, epidural, and caudal anesthesiaand caudal anesthesia

It is available in dental cartridges as a 4% It is available in dental cartridges as a 4% concentration both with and without 1:200,000 concentration both with and without 1:200,000 epinephrineepinephrine



Local Anesthetic AgentsLocal Anesthetic Agents Haveles (p. 119)Haveles (p. 119)

Amides: prilocaineAmides: prilocaine Prilocaine’s niche in dentistry involves situations in which Prilocaine’s niche in dentistry involves situations in which

the desired duration of action is somewhat longer than the desired duration of action is somewhat longer than that obtained with mepivacaine both without and with that obtained with mepivacaine both without and with vasoconstrictorvasoconstrictor

Prilocaine plain has a duration of action slightly longer Prilocaine plain has a duration of action slightly longer than mepivacaine plain, and prilocaine with epinephrine than mepivacaine plain, and prilocaine with epinephrine has a duration of action slightly longer than lidocaine has a duration of action slightly longer than lidocaine with epinephrinewith epinephrine

The other potential advantage of prilocaine is that the The other potential advantage of prilocaine is that the concentration of epinephrine (1:200,000) is lower than in concentration of epinephrine (1:200,000) is lower than in other local anesthetic amide combinationsother local anesthetic amide combinations




Haveles (p. 119)Haveles (p. 119) Amides: bupivacaineAmides: bupivacaine

Bupivacaine is related to lidocaine and mepivacaineBupivacaine is related to lidocaine and mepivacaine More potent but less toxic than the other amidesMore potent but less toxic than the other amides The major advantage is its greatly prolonged The major advantage is its greatly prolonged

duration of actionduration of action Indicated in lengthy dental procedures when pulpal Indicated in lengthy dental procedures when pulpal

anesthesia of greater than 1.5 hours is needed or anesthesia of greater than 1.5 hours is needed or when postoperative pain is expectedwhen postoperative pain is expected




Haveles (p. 119)Haveles (p. 119) Amides: bupivacaineAmides: bupivacaine

Available in dental cartridges as a 0.5% solution Available in dental cartridges as a 0.5% solution with 1:200,000 epinephrinewith 1:200,000 epinephrine

Should not be used in patients prone to self-Should not be used in patients prone to self-mutilationmutilation

Bupivacaine has been used for infiltration, block, Bupivacaine has been used for infiltration, block, and peridural anesthesiaand peridural anesthesia




Haveles (p. 119)Haveles (p. 119) Amides: articaineAmides: articaine

Articaine was approved for use in the United States in Articaine was approved for use in the United States in 20002000• Its delay in the United States was a result of the addition of Its delay in the United States was a result of the addition of

methylparaben to both multidose vials and single-dose methylparaben to both multidose vials and single-dose cartridgescartridges

Articaine is derived from thiopheneArticaine is derived from thiophene• This allows for greater lipid solubility and ability to cross lipid This allows for greater lipid solubility and ability to cross lipid

barriers such as nerve membranesbarriers such as nerve membranes

• This mechanism may account for its enhanced action This mechanism may account for its enhanced action compared with other local anestheticscompared with other local anesthetics





Articaine also differs from other amide local Articaine also differs from other amide local anesthetics because it has an extra ester linkageanesthetics because it has an extra ester linkage• This extra linkage causes articaine to be hydrolyzed by This extra linkage causes articaine to be hydrolyzed by

plasma esteraseplasma esterase

• Only 5% to 10% of articaine is metabolized by the liver; Only 5% to 10% of articaine is metabolized by the liver; the other 90% to 95% is metabolized in the bloodthe other 90% to 95% is metabolized in the blood





Articaine is excreted by the kidneysArticaine is excreted by the kidneys The average patient can tolerate twice as much The average patient can tolerate twice as much

lidocaine as compared with articaine before the lidocaine as compared with articaine before the maximal dose is reachedmaximal dose is reached

Articaine, similar to prilocaine, may cause Articaine, similar to prilocaine, may cause methemoglobinemia in very high dosesmethemoglobinemia in very high doses

Articaine rarely causes paresthesia after a mandibular Articaine rarely causes paresthesia after a mandibular block when the 4% solution is usedblock when the 4% solution is used





Articaine is used for local, infiltrative, and Articaine is used for local, infiltrative, and conductive anesthesiaconductive anesthesia

Available as a 4% concentration with 1:100,000 Available as a 4% concentration with 1:100,000 epinephrine in a 1.7 ml cartridge unlike the more epinephrine in a 1.7 ml cartridge unlike the more common 1.8 ml dental cartridgecommon 1.8 ml dental cartridge




Haveles (p. 120)Haveles (p. 120) EstersEsters

No esters are currently available in a dental No esters are currently available in a dental cartridgecartridge

Esters, such as benzocaine, are commonly used Esters, such as benzocaine, are commonly used topicallytopically




Haveles (p. 120)Haveles (p. 120) Esters: procaineEsters: procaine

Procaine is a PABA esterProcaine is a PABA ester Procaine is used as an antiarrhythmic agent and is Procaine is used as an antiarrhythmic agent and is

combined with penicillin to form procaine penicillin Gcombined with penicillin to form procaine penicillin G Procaine is not used in dentistry today because of Procaine is not used in dentistry today because of

the high rate of allergic reactionthe high rate of allergic reaction The allergic reaction is usually a result of PABA and The allergic reaction is usually a result of PABA and

not procainenot procaine




Haveles (p. 120)Haveles (p. 120) Esters: propoxycaineEsters: propoxycaine

Propoxycaine, another ester of PABA, is not Propoxycaine, another ester of PABA, is not available in a dental cartridgeavailable in a dental cartridge




Haveles (p. 120)Haveles (p. 120) Esters: tetracaineEsters: tetracaine

Tetracaine, an ester of PABA, has a slow onset Tetracaine, an ester of PABA, has a slow onset and long duration, and is generally estimated to and long duration, and is generally estimated to have at least 10 times the potency and toxicity of have at least 10 times the potency and toxicity of procaineprocaine

Great care must be exercised if used for topical Great care must be exercised if used for topical anesthesiaanesthesia

Tetracaine is available in various sprays, Tetracaine is available in various sprays, solutions, and ointments for topical applicationsolutions, and ointments for topical application


Other Local AnestheticsOther Local Anesthetics

Haveles (p. 120)Haveles (p. 120) DyclonineDyclonine

Dyclonine is a topical local anesthetic that is Dyclonine is a topical local anesthetic that is neither an ester nor an amideneither an ester nor an amide

Its side effects involving the cardiovascular system Its side effects involving the cardiovascular system and CNS are similar to those of the other local and CNS are similar to those of the other local anestheticsanesthetics

The onset of local anesthesia is 2 to 10 minutes, The onset of local anesthesia is 2 to 10 minutes, and its duration is 30 to 60 minutesand its duration is 30 to 60 minutes



Other Local AnestheticsOther Local Anesthetics

Haveles (p. 120)Haveles (p. 120) BenzonatateBenzonatate

Benzonatate is a tetracaine congener indicated in Benzonatate is a tetracaine congener indicated in the management of nonproductive coughthe management of nonproductive cough

A topical anesthetic that acts on the respiratory A topical anesthetic that acts on the respiratory stretch receptors, which produces its antitussive stretch receptors, which produces its antitussive propertiesproperties


VasoconstrictorsVasoconstrictors Haveles (p. 120) (Box 9-5)Haveles (p. 120) (Box 9-5)

OverviewOverview Vasoconstricting agents are included in local anesthetic Vasoconstricting agents are included in local anesthetic

solutions for many reasonssolutions for many reasons• Vasoconstrictors are members of the autonomic nervous system Vasoconstrictors are members of the autonomic nervous system

drugs call the adrenergic agonists or sympathomimeticsdrugs call the adrenergic agonists or sympathomimetics

• When a local anesthetic solution does not contain a When a local anesthetic solution does not contain a vasoconstrictor, the anesthetic drug is more quickly removed vasoconstrictor, the anesthetic drug is more quickly removed from the injection site and distributed into systemic circulation from the injection site and distributed into systemic circulation than if the solution contained a vasoconstrictorthan if the solution contained a vasoconstrictor

• Any anesthetic given without a vasoconstrictor is more likely to Any anesthetic given without a vasoconstrictor is more likely to be toxic than those given without a vasoconstrictorbe toxic than those given without a vasoconstrictor



VasoconstrictorsVasoconstrictors Haveles (p. 121) (Figs. 9-6, 9-7)Haveles (p. 121) (Figs. 9-6, 9-7)

OverviewOverview The decision about whether epinephrine should be used The decision about whether epinephrine should be used

in a patient is made by weighing the risks and benefitsin a patient is made by weighing the risks and benefits A sufficient concentration must be used to keep the local A sufficient concentration must be used to keep the local

anesthetic localized at its site of action and provide anesthetic localized at its site of action and provide adequate depth, duration, and low systemic toxicity of the adequate depth, duration, and low systemic toxicity of the anestheticanesthetic

1:100,000 and 1:200,000 produce about the same 1:100,000 and 1:200,000 produce about the same amount of vasoconstriction and the same distribution of amount of vasoconstriction and the same distribution of the local anestheticsthe local anesthetics



VasoconstrictorsVasoconstrictors Haveles (p. 121) (Fig. 9-7)Haveles (p. 121) (Fig. 9-7)

OverviewOverview Research shows that a patient can produce endogenous Research shows that a patient can produce endogenous

epinephrine far in excess of that administered in dentistry in epinephrine far in excess of that administered in dentistry in the presence of inadequate anesthesia, which sometimes the presence of inadequate anesthesia, which sometimes occurs when vasoconstrictors are avoidedoccurs when vasoconstrictors are avoided

Patients with uncontrolled high blood pressure, Patients with uncontrolled high blood pressure, hyperthyroidism, angina pectoris, and cardiac arrhythmias hyperthyroidism, angina pectoris, and cardiac arrhythmias and those who have had a myocardial infarction or and those who have had a myocardial infarction or cerebrovascular accident in the past 6 months should make cerebrovascular accident in the past 6 months should make an appointment for elective dental treatment after their an appointment for elective dental treatment after their medical condition is under controlmedical condition is under control



VasoconstrictorsVasoconstrictors Haveles (p. 122) (Table 9-4)Haveles (p. 122) (Table 9-4)

OverviewOverview Patients with cardiovascular disease who are able to Patients with cardiovascular disease who are able to

withstand elective dental treatment can receive withstand elective dental treatment can receive epinephrine-containing local anesthetic agentsepinephrine-containing local anesthetic agents

Anesthetic should be administered in the lowest Anesthetic should be administered in the lowest possible dose by means of the best technique, possible dose by means of the best technique, including aspiration and a very slow injection rate to including aspiration and a very slow injection rate to minimize systemic absorptionminimize systemic absorption

The maximal safe dose of epinephrine for the healthy The maximal safe dose of epinephrine for the healthy patient is 0.2 mg and for the cardiac patient is 0.04 mgpatient is 0.2 mg and for the cardiac patient is 0.04 mg



VasoconstrictorsVasoconstrictors

Haveles (p. 122)Haveles (p. 122) Drug interactionsDrug interactions

The two epinephrine drug interactions that are The two epinephrine drug interactions that are most likely to be clinically significantmost likely to be clinically significant

Tricyclic antidepressantsTricyclic antidepressants• Administration of epinephrine may produce an Administration of epinephrine may produce an

exaggerated increase in pressor responseexaggerated increase in pressor response

Nonselective Nonselective ββ-blockers-blockers• Hypertension and reflex bradycardia may be exhibitedHypertension and reflex bradycardia may be exhibited



VasoconstrictorsVasoconstrictors Haveles (p. 122)Haveles (p. 122)

Drug interactionsDrug interactions The two drug interactions commonly mentioned but not The two drug interactions commonly mentioned but not

usually clinically significant areusually clinically significant are Monoamine oxidase inhibitors (MAOIs)Monoamine oxidase inhibitors (MAOIs)

Epinephrine can be given to patients taking MAOIs, Epinephrine can be given to patients taking MAOIs, because epinephrine is eliminated primarily by reuptake because epinephrine is eliminated primarily by reuptake and secondarily by catechol-O-methyltransferase and secondarily by catechol-O-methyltransferase (COMT) rather than by monoamine oxidase (MAO)(COMT) rather than by monoamine oxidase (MAO)

Indirect acting sympathomimetic agents should be Indirect acting sympathomimetic agents should be avoided in patients taking MAOIsavoided in patients taking MAOIs

PhenothiazinesPhenothiazines Phenothiazines are Phenothiazines are αα-blockers, and when an -blockers, and when an αα- and - and ββ--

agonist is given, the beta effects predominateagonist is given, the beta effects predominate


Choice of Local AnestheticChoice of Local Anesthetic Haveles (pp. 122-124) (Figs. 9-8, 9-9; Box 9-6; Table 9-6)Haveles (pp. 122-124) (Figs. 9-8, 9-9; Box 9-6; Table 9-6)

Local anesthetic should be chosen depending on Local anesthetic should be chosen depending on the duration of local anesthesia desired and the the duration of local anesthesia desired and the side effects that must be avoidedside effects that must be avoided pKa is related to duration of actionpKa is related to duration of action

• With lower pKa, the local anesthetic is distributed more in the With lower pKa, the local anesthetic is distributed more in the base form and so is better absorbedbase form and so is better absorbed

Duration of action is primarily related to its protein-binding Duration of action is primarily related to its protein-binding capacitycapacity• Duration is unrelated to the local anesthetic’s half-lifeDuration is unrelated to the local anesthetic’s half-life

Lipid solubility determines the potency of a local Lipid solubility determines the potency of a local anesthetic agentanesthetic agent



Choice of Local AnestheticChoice of Local Anesthetic

Haveles (pp. 123, 125) (Table 9-7)Haveles (pp. 123, 125) (Table 9-7) The vasodilating property can affect both the The vasodilating property can affect both the

potency and duration of actionpotency and duration of action The dental practitioner should become familiar The dental practitioner should become familiar

with a short-, an intermediate-, and a long-acting with a short-, an intermediate-, and a long-acting agentagent

The duration of the procedure and any patient-The duration of the procedure and any patient-specific information will determine the anesthetic specific information will determine the anesthetic of choiceof choice


Topical AnestheticsTopical Anesthetics

Haveles (p. 123) (Table 9-8)Haveles (p. 123) (Table 9-8) Benzocaine, an ester, is the most commonly Benzocaine, an ester, is the most commonly

used topical anestheticused topical anesthetic Lidocaine, an amide, is the second most commonly Lidocaine, an amide, is the second most commonly

used used Comparison should take into account their onset, Comparison should take into account their onset,

duration of action, and allergenic potentialduration of action, and allergenic potential The patient should be instructed to avoid eating for 1 The patient should be instructed to avoid eating for 1

hour after application to oral mucosa so that the gag hour after application to oral mucosa so that the gag reflex can become fully functionalreflex can become fully functional




Haveles (pp. 123-124)Haveles (pp. 123-124) Amides: lidocaineAmides: lidocaine

Lidocaine is available as the base or hydrochloride Lidocaine is available as the base or hydrochloride saltsalt• The base is preferred when large areas of the mucosal The base is preferred when large areas of the mucosal

surface are ulcerated, abraded, denuded, or erythematoussurface are ulcerated, abraded, denuded, or erythematous Base is available as a jelly and an oral topical solutionBase is available as a jelly and an oral topical solution

• The hydrochloride salt is water soluble and penetrates the The hydrochloride salt is water soluble and penetrates the tissue bettertissue better

Hydrochloride is available as an ointment, an oral topical, and Hydrochloride is available as an ointment, an oral topical, and an oral aerosolan oral aerosol




Haveles (p. 124)Haveles (p. 124) Amides: lidocaine and prilocaine (injection-free local Amides: lidocaine and prilocaine (injection-free local

anesthesia)anesthesia) The combination of lidocaine and prilocaine gel (Oraqix) The combination of lidocaine and prilocaine gel (Oraqix)

applied into the periodontal pocket offers pain relief during applied into the periodontal pocket offers pain relief during scaling and root planing proceduresscaling and root planing procedures

Lidocaine provides rapid anesthesia, and prilocaine has a Lidocaine provides rapid anesthesia, and prilocaine has a slower onset of actionslower onset of action

The more common side effects include pain, soreness, The more common side effects include pain, soreness, irritation, edema or redness at the area of application, and irritation, edema or redness at the area of application, and taste changestaste changes




Haveles (p. 124)Haveles (p. 124) Esters: benzocaineEsters: benzocaine

Benzocaine, an ester of PABA, cannot be Benzocaine, an ester of PABA, cannot be converted to a water-soluble form for injectionconverted to a water-soluble form for injection

Poorly absorbed and lacks significant systemic Poorly absorbed and lacks significant systemic toxicitytoxicity

Benzocaine is used in many dental offices, Benzocaine is used in many dental offices, although a hypersensitivity reaction is possiblealthough a hypersensitivity reaction is possible




Haveles (pp. 124-125)Haveles (pp. 124-125) Esters: cocaineEsters: cocaine

Cocaine is a naturally occurring ester of benzoic Cocaine is a naturally occurring ester of benzoic acid that is potent and extremely toxicacid that is potent and extremely toxic

Although cocaine has ideal pharmacokinetics, the Although cocaine has ideal pharmacokinetics, the systemic absorption and subsequent CNS systemic absorption and subsequent CNS stimulation and its great potential for abuse make stimulation and its great potential for abuse make the use of cocaine as a local anesthetic untenablethe use of cocaine as a local anesthetic untenable




Haveles (p. 125) (Box 9-7)Haveles (p. 125) (Box 9-7) Precautions in topical anestheticsPrecautions in topical anesthetics

Some local anesthetics are absorbed rapidly when Some local anesthetics are absorbed rapidly when applied topically to mucous membranesapplied topically to mucous membranes

To avoid toxic reactions from surface anesthesia, To avoid toxic reactions from surface anesthesia, the dental health care provider should consider the dental health care provider should consider many factorsmany factors


Doses of Local Anesthetic and Doses of Local Anesthetic and VasoconstrictorVasoconstrictor

Haveles (pp. 125-126)Haveles (pp. 125-126) The amounts of local anesthetic and The amounts of local anesthetic and

vasoconstrictor contained in a certain volume of vasoconstrictor contained in a certain volume of solution can be calculated from the solution can be calculated from the concentration of that solutionconcentration of that solution The dental health care provider should be able to The dental health care provider should be able to

determine the number of milligrams of both local determine the number of milligrams of both local anesthetic and vasoconstrictor given in any clinical anesthetic and vasoconstrictor given in any clinical situationsituation

The maximal safe dose for each component should The maximal safe dose for each component should not be exceedednot be exceeded



Doses of Local Anesthetic and Doses of Local Anesthetic and VasoconstrictorVasoconstrictor

Haveles (p. 126)Haveles (p. 126) Each dose should be recorded in the patient’s Each dose should be recorded in the patient’s

chart as soon as possible after the injectionchart as soon as possible after the injection Information recorded should include the strength Information recorded should include the strength

of both ingredients and the volume of solution of both ingredients and the volume of solution used or the number of milligrams of each givenused or the number of milligrams of each given

Chapter 9: Local Anesthetics Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All...

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Transcript of Chapter 9: Local Anesthetics Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All...