Local AnestheticsLocal Anesthetics

Dr. HalaDr. Hala

What are local anesthetics?What are local anesthetics?

Local anesthetic: produce loss of Local anesthetic: produce loss of sensation to pain in a specific area of sensation to pain in a specific area of the body without the loss of the body without the loss of consciousnessconsciousness

Local anesthetics - Local anesthetics - MechanismMechanism

Local anesthetics - Local anesthetics - MechanismMechanism

Limit influx of sodium, thereby limiting Limit influx of sodium, thereby limiting propagation of the action potential.propagation of the action potential.

Cocaine AddictionCocaine Addiction

More physicians began to do research of cocaine in the More physicians began to do research of cocaine in the clinic trials.clinic trials.

The physician Sigmund Freud used the stimulant effect The physician Sigmund Freud used the stimulant effect of cocaine to treat the morphine addiction in patientsof cocaine to treat the morphine addiction in patients

An ophthalmologist Carl Koller realized the importance An ophthalmologist Carl Koller realized the importance of the alkaloid’s anesthetic effect on mucous of the alkaloid’s anesthetic effect on mucous membranesmembranes

In 1884, he used the first local anesthetic on a patient In 1884, he used the first local anesthetic on a patient with glaucomawith glaucoma

Freud, Halsted, and Koller became addicted to the Freud, Halsted, and Koller became addicted to the drug through self-experimentationdrug through self-experimentation

Procaine replaced Procaine replaced Novocaine Novocaine cocainecocaine ProblemsProblems

procaine is the first procaine is the first derivative of cocaine, also derivative of cocaine, also known as the first known as the first synthetic local anesthetic synthetic local anesthetic drugdrug

Trade name is Novocaine®Trade name is Novocaine®

Took too long to set (i.e. to Took too long to set (i.e. to produce the desired produce the desired anesthetic result)anesthetic result)

Wore off too quickly, not Wore off too quickly, not nearly as potent as cocainenearly as potent as cocaine

Classified as an ester; esters Classified as an ester; esters have high potential to cause have high potential to cause allergic reactionsallergic reactions

Caused high conc. of Caused high conc. of adrenaline resulted in adrenaline resulted in increasing heart rate, make increasing heart rate, make people feel nervouspeople feel nervous

Most dentists preferred not to Most dentists preferred not to used any local anesthetic at used any local anesthetic at all that time; they used all that time; they used nitrous oxide gas.nitrous oxide gas.

LidocaineLidocaine

In 1940, the first modern local In 1940, the first modern local anesthetic agent was lidocaine, trade anesthetic agent was lidocaine, trade name Xylocaine®name Xylocaine®

It developed as a derivative of xylidineIt developed as a derivative of xylidine Lidocaine relieves pain during the Lidocaine relieves pain during the

dental surgeriesdental surgeries Belongs to the amide class, cause little Belongs to the amide class, cause little

allergenic reaction; it’s hypoallergenicallergenic reaction; it’s hypoallergenic Sets on quickly and produces a Sets on quickly and produces a

desired anesthesia effect for several desired anesthesia effect for several hourshours

It’s accepted broadly as the local It’s accepted broadly as the local anesthetic in United States todayanesthetic in United States today

Differences of Esters and AmidesDifferences of Esters and Amides

All local anesthetics are weak bases. Chemical structure of local All local anesthetics are weak bases. Chemical structure of local anesthetics have an amine group on one end connect to an anesthetics have an amine group on one end connect to an aromatic ring on the other and an amine group on the right side. aromatic ring on the other and an amine group on the right side. The amine end is hydrophilic (soluble in water), and the aromatic The amine end is hydrophilic (soluble in water), and the aromatic end is lipophilic (soluble in lipids)end is lipophilic (soluble in lipids)

Two classes of local anesthetics are amino amides and amino Two classes of local anesthetics are amino amides and amino esters.esters.

Amides:Amides: Esters:Esters:

--Amide link b/t intermediate--Amide link b/t intermediate --Ester link b/t intermediate chain --Ester link b/t intermediate chain and chain and aromatic ringand chain and aromatic ring aromatic ring aromatic ring

--Metabolized in liver and very--Metabolized in liver and very --Metabolized in plasma through --Metabolized in plasma through soluble in the solutionsoluble in the solution pseudocholinesterases and not pseudocholinesterases and not

stable in the solutionstable in the solution

--Cause allergic reactions--Cause allergic reactions

Local anesthetics - Classes Local anesthetics - Classes (Rule of “i’s”)(Rule of “i’s”)

EstersEsters

CocaineCocaine

ChloroprocaineChloroprocaine

ProcaineProcaine

TetracaineTetracaine

Am”i”desAm”i”des

BupBupiivacainevacaine

LLiidocainedocaine

RopRopiivacainevacaine

EtEtiidocainedocaine

MepMepiivacainevacaine

Structures of Amides and EstersStructures of Amides and Esters The amine end is hydrophilic (soluble in water), anesthetic The amine end is hydrophilic (soluble in water), anesthetic

molecule dissolve in water in which it is delivered from the molecule dissolve in water in which it is delivered from the dentist’s syringe into the patient’s tissue. It’s also responsible for dentist’s syringe into the patient’s tissue. It’s also responsible for the solution to remain on either side of the nerve membrane. the solution to remain on either side of the nerve membrane.

The aromatic end is lipophilic (soluble in lipids). Because nerve The aromatic end is lipophilic (soluble in lipids). Because nerve cell is made of lipid bilayer it is possible for anesthetic molecule to cell is made of lipid bilayer it is possible for anesthetic molecule to penetrate through the nerve membrane. penetrate through the nerve membrane.

The trick the anesthetic molecule must play is getting from one The trick the anesthetic molecule must play is getting from one side of the membrane to the other.side of the membrane to the other.

MechanismMechanism The mechanism of local anesthetics connects with the ion channels, The mechanism of local anesthetics connects with the ion channels,

nerve, and depolarization.nerve, and depolarization. Local anesthetics block the conduction in peripheral nerves that Local anesthetics block the conduction in peripheral nerves that

inhibited the nerve to excited and created anesthesia.inhibited the nerve to excited and created anesthesia. The anesthetic is a reversible reaction. It binds and activates the The anesthetic is a reversible reaction. It binds and activates the

sodium channels.sodium channels. The sodium influx through these channels and depolarizes the nerve The sodium influx through these channels and depolarizes the nerve

cell membranes. It also created high impulses along the way.cell membranes. It also created high impulses along the way. As a result, the nerve loses depolarization and the capacity to create As a result, the nerve loses depolarization and the capacity to create

the impulse, the patient loses sensation in the area supplied by the the impulse, the patient loses sensation in the area supplied by the nerve.nerve.

Local anesthetics - FormulationLocal anesthetics - Formulation

Biologically active substances are Biologically active substances are frequently administered as very dilute frequently administered as very dilute solutions which can be expressed as solutions which can be expressed as parts of active drug per 100 parts of parts of active drug per 100 parts of

solution (grams percent)solution (grams percent)

Ex.: 2% solution =Ex.: 2% solution =

__2 grams2 grams__ = ___ = _2000 mg2000 mg_ = ___ = __20 20 mgmg__ __

100 cc’s 100 cc’s 1 cc100 cc’s 100 cc’s 1 cc

Local anesthetics - FormulationLocal anesthetics - Formulation

Biologically active substances are Biologically active substances are frequently administered as very dilute frequently administered as very dilute solutions which can be expressed as solutions which can be expressed as parts of active drug per 100 parts of parts of active drug per 100 parts of

solution (grams percent)solution (grams percent)

Ex.: 2% solution =Ex.: 2% solution =

__2 grams2 grams__ = ___ = _2000 mg2000 mg_ = ___ = __20 20 mgmg__ __

100 cc’s 100 cc’s 1 cc100 cc’s 100 cc’s 1 cc

Factors Affect the Reaction of Local Factors Affect the Reaction of Local AnestheticsAnesthetics

Lipid solubilityLipid solubility All local anesthetics have weak bases. Increasing the lipid All local anesthetics have weak bases. Increasing the lipid

solubility leads to faster nerve penetration, block sodium solubility leads to faster nerve penetration, block sodium channels, and speed up the onset of action.channels, and speed up the onset of action.

The more tightly local anesthetics bind to the protein, the The more tightly local anesthetics bind to the protein, the longer the duration of onset action.longer the duration of onset action.

Local anesthetics have two forms, ionized and nonionized. Local anesthetics have two forms, ionized and nonionized. The nonionized form can cross the nerve membranes and The nonionized form can cross the nerve membranes and block the sodium channels. block the sodium channels.

So, the more nonionized presented, the faster the onset So, the more nonionized presented, the faster the onset action.action.

pH influencepH influence Usually at range 7.6 – 8.9Usually at range 7.6 – 8.9 Decrease in pH shifts equilibrium toward the ionized form, Decrease in pH shifts equilibrium toward the ionized form,

delaying the onset action.delaying the onset action. Lower pH, solution more acidic, gives slower onset of actionLower pH, solution more acidic, gives slower onset of action

Factors Affect the Reaction of Local Factors Affect the Reaction of Local Anesthetics (cont.)Anesthetics (cont.)

VasodilationVasodilation Vasoconstrictor is a substance used to keep the anesthetic Vasoconstrictor is a substance used to keep the anesthetic

solution in place at a longer period and prolongs the action solution in place at a longer period and prolongs the action of the drugof the drug

vasoconstrictor delays the absorption which slows down the vasoconstrictor delays the absorption which slows down the absorption into the bloodstream absorption into the bloodstream

Lower vasodilator activity of a local anesthetic leads to a Lower vasodilator activity of a local anesthetic leads to a slower absorption and longer duration of actionslower absorption and longer duration of action

Vasoconstrictor used the naturally hormone called Vasoconstrictor used the naturally hormone called epinephrine (adrenaline). Epinephrine decreases epinephrine (adrenaline). Epinephrine decreases vasodilator.vasodilator.

Side effects of epinephrineSide effects of epinephrine Epinephrine circulates the heart, causes the heart beat Epinephrine circulates the heart, causes the heart beat

stronger and faster, and makes people feel nervous.stronger and faster, and makes people feel nervous.

ToxicityToxicity Toxicity is the peak circulation levels of local anestheticsToxicity is the peak circulation levels of local anesthetics Levels of local anesthetic concentration administered to Levels of local anesthetic concentration administered to

patients are varied according to age, weight, and health.patients are varied according to age, weight, and health. Maximum dose for an individual is usually between 70mg to Maximum dose for an individual is usually between 70mg to

500mg500mg The amount of dose also varied based on the type of solution The amount of dose also varied based on the type of solution

used and the presence of vasoconstrictorused and the presence of vasoconstrictorExample:Example:---For adult whose weight is 150lbs and up, maximum dose ---For adult whose weight is 150lbs and up, maximum dose

Articaine and lidocaine is about 500mgArticaine and lidocaine is about 500mg---For children, the dosage reduced to about 1/3 to ½ depending ---For children, the dosage reduced to about 1/3 to ½ depending

on their weight.on their weight.The doses are not considered lethal.The doses are not considered lethal.

Some common toxic effects:Some common toxic effects: --light headedness--light headedness ---shivering or twitching---shivering or twitching ----

seizuresseizures--hypotension (low blood pressure)--hypotension (low blood pressure) --numbness--numbness

Local Anesthetics - AllergyLocal Anesthetics - Allergy

True allergy is very rareTrue allergy is very rare Most reactions are from ester class - ester Most reactions are from ester class - ester

hydrolysis (normal metabolism) leads to hydrolysis (normal metabolism) leads to formation of PABA - like compoundsformation of PABA - like compounds

Patient reports of “allergy” are frequently Patient reports of “allergy” are frequently due to previous intravascular injectionsdue to previous intravascular injections

Local Anesthetics - ToxicityLocal Anesthetics - Toxicity

Tissue toxicity - RareTissue toxicity - Rare Can occur if Can occur if

administered in high administered in high enough enough concentrations concentrations (greater than those (greater than those used clinically)used clinically)

Usually related to Usually related to preservatives added preservatives added to solutionto solution

Systemic toxicity - RareSystemic toxicity - Rare Related to blood level Related to blood level

of drug secondary to of drug secondary to absorption from site of absorption from site of injection.injection.

Range from Range from lightheadedness, lightheadedness, tinnitus to seizures tinnitus to seizures and and CNS/cardiovascular CNS/cardiovascular collapsecollapse

Factors of circulation levelsFactors of circulation levels Factors of circulation levels are the rates of Factors of circulation levels are the rates of

absorption, distribution, and metabolism.absorption, distribution, and metabolism. Absorption depends on the speed of administration Absorption depends on the speed of administration

and levels of the doses.and levels of the doses. Distribution allows absorption to occur in three Distribution allows absorption to occur in three

phases. First, the drug occurs at highly vascular phases. First, the drug occurs at highly vascular tissues in the lungs and kidneys. Then it appears tissues in the lungs and kidneys. Then it appears less in vascular muscle and fat. Then the drug is less in vascular muscle and fat. Then the drug is metabolized.metabolized.

Metabolism involves in the chemical structure Metabolism involves in the chemical structure based on two classes, amide and ester as based on two classes, amide and ester as discussed earlier.discussed earlier.

Decreasing the potential toxicity resulted in rapid Decreasing the potential toxicity resulted in rapid metabolism.metabolism.

ConclusionConclusionAnestheticAnesthetic pKapKa Onset Onset Duration Duration

(with (with EpinephrineEpinephrine) in minutes) in minutes

Max Dose Max Dose (with (with EpinephrineEpinephrine))

ProcaineProcaine 9.19.1 SlowSlow 45 - 9045 - 90 8mg/kg – 8mg/kg – 10mg/kg10mg/kg

LidocaineLidocaine 7.97.9 RapidRapid 120 - 240120 - 240 4.5mg/kg – 4.5mg/kg – 7mg/kg7mg/kg

BupivacaineBupivacaine 8.18.1 SlowSlow 4 hours – 8 4 hours – 8 hourshours

2.5mg/kg – 2.5mg/kg – 3mg/kg3mg/kg

PrilocainePrilocaine 7.97.9 MediumMedium 90 - 36090 - 360 5mg/kg – 5mg/kg – 7.5mg/kg7.5mg/kg

ArticaineArticaine 7.87.8 RapidRapid 140 - 270140 - 270 4.0mg/kg – 4.0mg/kg – 7mg/kg7mg/kg

Local anesthetics - DurationLocal anesthetics - Duration

Determined by rate of elimination Determined by rate of elimination of agent from site injectedof agent from site injected

Factors include lipid solubility, dose Factors include lipid solubility, dose given, blood flow at site, addition of given, blood flow at site, addition of vasoconstrictors (does not reliably vasoconstrictors (does not reliably prolong all agents)prolong all agents)

Some techniques allow multiple Some techniques allow multiple injections over time to increase injections over time to increase duration, e.g. epidural catheterduration, e.g. epidural catheter

Local anesthetics - Local anesthetics - vasoconstrictorsvasoconstrictors

Ratios

Epinephrine is added to local anesthetics in extremely dilute concentrations, best expressed as a ratio of grams of drug:total cc’s of solution. Expressed numerically, a 1:1000 preparation of

epinephrine would be

1 gram epi

1000 cc’s solution

1000 mg epi

1000cc’s solution =

1 mg epi

1 cc =

Local anesthetics - Local anesthetics - vasoconstrictorsvasoconstrictors

Therefore, a 1 : 200,000 solution of epinephrine would be

1 gram epi

200,000 cc’s solution

=1000 mg epi

200,000 cc’s solution

or

5 mcg epi

1 cc solution

Local anesthetics - Local anesthetics - vasoconstrictorsvasoconstrictors

Vasoconstrictors should not be used in Vasoconstrictors should not be used in the following locationsthe following locations

FingersFingers ToesToes NoseNose Ear lobesEar lobes PenisPenis

REGIONAL ANESTHESIAREGIONAL ANESTHESIA

Regional anesthesia - Regional anesthesia - DefinitionDefinition

Rendering a specific area of the Rendering a specific area of the body, e.g. foot, arm, lower body, e.g. foot, arm, lower extremities, insensate to extremities, insensate to

stimulus of surgery or other stimulus of surgery or other instrumentationinstrumentation

Regional anesthesia - UsesRegional anesthesia - Uses

Provide anesthesia for a surgical Provide anesthesia for a surgical procedure procedure

Provide analgesia post-operatively or Provide analgesia post-operatively or during labor and deliveryduring labor and delivery

Diagnosis or therapy for patients Diagnosis or therapy for patients with chronic pain syndromeswith chronic pain syndromes

Regional anesthesia - typesRegional anesthesia - types

TopicalTopical Local/FieldLocal/Field Intravenous block (“Bier” block)Intravenous block (“Bier” block) Peripheral (named) nerve, e.g. Peripheral (named) nerve, e.g.

radial n.radial n. Plexus - brachial, lumbarPlexus - brachial, lumbar Central neuraxial - epidural, spinalCentral neuraxial - epidural, spinal

Topical AnesthesiaTopical Anesthesia Application of local anesthetic to mucous Application of local anesthetic to mucous

membrane - cornea, nasal/oral mucosamembrane - cornea, nasal/oral mucosa Uses : Uses :

awake oral, nasal intubation, superficial awake oral, nasal intubation, superficial surgical proceduresurgical procedure

Advantages :Advantages : technically easytechnically easy minimal equipmentminimal equipment

Disadvantages :Disadvantages : potential for large doses leading to toxicity potential for large doses leading to toxicity

Local/Field AnesthesiaLocal/Field Anesthesia Application of local subcutaneously to Application of local subcutaneously to

anesthetize distal nerve endingsanesthetize distal nerve endings Uses:Uses:

Suturing, minor superficial surgery, line Suturing, minor superficial surgery, line placement, more extensive surgery with placement, more extensive surgery with sedationsedation

Advantages:Advantages: minimal equipment, technically easy, rapid minimal equipment, technically easy, rapid

onsetonset Disadvantages:Disadvantages:

potential for toxicity if large field potential for toxicity if large field

IV Block - “Bier” blockIV Block - “Bier” block

Injection of local anesthetic intravenously for Injection of local anesthetic intravenously for anesthesia of an extremityanesthesia of an extremity

UsesUses any surgical procedure on an extremityany surgical procedure on an extremity

Advantages:Advantages: technically simple, minimal equipment, rapid technically simple, minimal equipment, rapid

onsetonset Disadvantages:Disadvantages:

duration limited by tolerance of tourniquet pain, duration limited by tolerance of tourniquet pain, toxicitytoxicity

PeripheralPeripheral nerve block nerve block Injecting local anesthetic near the Injecting local anesthetic near the

course of a named nervecourse of a named nerve Uses:Uses:

Surgical procedures in the distribution of Surgical procedures in the distribution of the blocked nervethe blocked nerve

Advantages: Advantages: relatively small dose of local anesthetic to relatively small dose of local anesthetic to

cover large area; rapid onsetcover large area; rapid onset Disadvantages:Disadvantages:

technical complexity, neuropathytechnical complexity, neuropathy

Plexus BlockadePlexus Blockade Injection of local anesthetic adjacent to a Injection of local anesthetic adjacent to a

plexus, e.g cervical, brachial or lumbar plexusplexus, e.g cervical, brachial or lumbar plexus Uses :Uses :

surgical anesthesia or post-operative analgesia in surgical anesthesia or post-operative analgesia in the distribution of the plexusthe distribution of the plexus

Advantages:Advantages: large area of anesthesia with relatively large dose large area of anesthesia with relatively large dose

of agentof agent Disadvantages:Disadvantages:

technically complex, potential for toxicity and technically complex, potential for toxicity and neuropathy.neuropathy.

Central neuraxial blockade - Central neuraxial blockade - “Spinal”“Spinal”

Injection of local anesthetic into CSFInjection of local anesthetic into CSF Uses:Uses:

profound anesthesia of lower abdomen and profound anesthesia of lower abdomen and extremitiesextremities

Advantages:Advantages: technically easy (LP technique), high success technically easy (LP technique), high success

rate, rapid onsetrate, rapid onset Disadvantages:Disadvantages:

““high spinal”, hypotension due to sympathetic high spinal”, hypotension due to sympathetic block, post dural puncture headache.block, post dural puncture headache.

Central Neuraxial Blockade - Central Neuraxial Blockade - “epidural”“epidural”

Injection of local anesthetic in to the epidural Injection of local anesthetic in to the epidural space at any level of the spinal columnspace at any level of the spinal column

Uses:Uses: Anesthesia/analgesia of the thorax, Anesthesia/analgesia of the thorax,

abdomen, lower extremitiesabdomen, lower extremities Advantages:Advantages:

Controlled onset of blockade, long duration when Controlled onset of blockade, long duration when catheter is placed, post-operative analgesia.catheter is placed, post-operative analgesia.

Disadvantages:Disadvantages: Technically complex, toxicity, “spinal headache”Technically complex, toxicity, “spinal headache”