local anesthetics
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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 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”
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