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Physiology of local anasthesiaPhysiology of local anasthesia
Dr.Mohamed Rhael AliDr.Mohamed Rhael Ali
2016-20172016-2017
Nerve physiology
Nerve anatomyNerve anatomy
• Periphral nerve composed from hundreds to thousands ofPeriphral nerve composed from hundreds to thousands of
axonsaxons
• Each axon coverd by sheath called endoneuriumEach axon coverd by sheath called endoneurium
• Each group of axons bind togather in a special sheath calledEach group of axons bind togather in a special sheath called
perineurium , these group of axons (bundle) called fasciculiperineurium , these group of axons (bundle) called fasciculi
which consider the main barrior to diffusion of localwhich consider the main barrior to diffusion of local
anasthesia in to the nerve .anasthesia in to the nerve .
• The whole bundles covered by loose connective tissue calledThe whole bundles covered by loose connective tissue called
epineuriumepineurium
• Local anasthesia able to diffuse through this tissues becauseLocal anasthesia able to diffuse through this tissues because
of its loose consistency .of its loose consistency .
• nutrient blood vessels and lymphatics transverse thenutrient blood vessels and lymphatics transverse the
epineurium and these vessels absorb local ansthesia andepineurium and these vessels absorb local ansthesia and
thus removing them from the nervethus removing them from the nerve
Physiology of local anasthesia
Physiology of local anasthesia
Physiology of local anasthesia
Nerve membraneNerve membrane
Two layers of lipid molecules with associated proteinTwo layers of lipid molecules with associated protein
and carbohydrates moleculesand carbohydrates molecules
Physiology of local anasthesia
Properties of nerve membraneProperties of nerve membrane
• impermeable to water soluble moleculesimpermeable to water soluble molecules
• selectively permeable to certain molecules viaselectively permeable to certain molecules via
specialized channelsspecialized channels
• Transduce information by protein receptors inTransduce information by protein receptors in
response to chemical or physical stimuliresponse to chemical or physical stimuli
Nerve membarne selectively permeable soNerve membarne selectively permeable so
There is a diffrence between ions concentrationThere is a diffrence between ions concentration
around itaround it
High concentration of k+ inside while highHigh concentration of k+ inside while high
concentration of Na+ outside the nerve membraneconcentration of Na+ outside the nerve membrane
Physiology of local anasthesia
Resting stateResting state
• In resting state nerve membrane have –ve restingIn resting state nerve membrane have –ve resting
potential (-70 mv)potential (-70 mv)
• Coming from different concentration of ionsComing from different concentration of ions
around the membranearound the membrane
DepolarizationDepolarization
• Rabid influx of Na+ ions to the inside of nerveRabid influx of Na+ ions to the inside of nerve
• Must reach firing threshould which areMust reach firing threshould which are
approximately ( -50 to -60 mv)approximately ( -50 to -60 mv)
RepolarizationRepolarization
• Movement of K+ to outside which lead to return ofMovement of K+ to outside which lead to return of
nerve membrane to its resting potential ( - 70 mv )nerve membrane to its resting potential ( - 70 mv )
• Movement of ions in depolarization are passiveMovement of ions in depolarization are passive
process ( not required energy )process ( not required energy )
• While movement of ions in depolarization areWhile movement of ions in depolarization are
active processactive process
ImpulseImpulse
• Function of nerve is to carry messages fromFunction of nerve is to carry messages from
one part of the body anotherone part of the body another
• These messages called impulseThese messages called impulse
• impulse initiated by chemical , thermal,impulse initiated by chemical , thermal,
mechanical or electrical stimulimechanical or electrical stimuli
Physiology of local anasthesia
Physiology of local anasthesia
Mechanism of action of localMechanism of action of local
anasthesiaanasthesia
• Local anastheesia act by prevention of bothLocal anastheesia act by prevention of both
generation and conduction of nerve impulsegeneration and conduction of nerve impulse
• Nerve membrane consider the site at whichNerve membrane consider the site at which
local anasthetic agents exert theirlocal anasthetic agents exert their
pharmacological actionspharmacological actions
Theories for working ofTheories for working of
local anasthesialocal anasthesia
Membrane expansion theoryMembrane expansion theory
• This theory explain that local anasthetic moleculesThis theory explain that local anasthetic molecules
diffuse through the nerve membrane and causingdiffuse through the nerve membrane and causing
general disturbance in the bulk of of membranegeneral disturbance in the bulk of of membrane
structure which lead to blockage of the membranestructure which lead to blockage of the membrane
permeability to Na+ and so inhibit both conductionpermeability to Na+ and so inhibit both conduction
and nerve excitationand nerve excitation
Physiology of local anasthesia
Specific receptor theorySpecific receptor theory
• This theory propose that local anastheticsThis theory propose that local anasthetics
bind to specific receptors in sodium channelbind to specific receptors in sodium channel
leading to direct decrease in permeability toleading to direct decrease in permeability to
Na ionsNa ions
• This theory is the most acceptable theoryThis theory is the most acceptable theory
Physiology of local anasthesia
Induction of local anasthesiaInduction of local anasthesia
In the tissue LA move according to itsIn the tissue LA move according to its
concentrationconcentration
DiffusionDiffusion
•LA reach faster to mantle bundle(prephralLA reach faster to mantle bundle(prephral
bundle ) than core bundle (central bundle)bundle ) than core bundle (central bundle)
• Core bundle need need more volume andCore bundle need need more volume and
longer time to get anasthesia due to barrierslonger time to get anasthesia due to barriers
and also absorbtion of LA by bloodand also absorbtion of LA by blood
cappilaries within the nerve fibercappilaries within the nerve fiber
Factors affecting localFactors affecting local
anasthetic actionsanasthetic actions
PH valuePH value
Action of local anasthesia decrease in acidicAction of local anasthesia decrease in acidic
media as in inflamed areamedia as in inflamed area
Lipid solubilityLipid solubility
Lipid soluble LA penetrate the nerve membraneLipid soluble LA penetrate the nerve membrane
more easymore easy
increase theincrease the potencypotency of itof it
Protein bindingProtein binding
It affect on theIt affect on the durationduration of local anasthesiaof local anasthesia
Increase protein binding capacityIncrease protein binding capacity
Increase its durationIncrease its duration
Nonnervous tissue diffusubilityNonnervous tissue diffusubility
• Affect on theAffect on the onsetonset of action (starting point)of action (starting point)
Increase infusibility of LA to the nerveIncrease infusibility of LA to the nerve
membranemembrane
Decrease time of onsetDecrease time of onset
Vasodilator activityVasodilator activity
Increase vasodilator activityIncrease vasodilator activity
DecreaseDecrease potencypotency andand durationduration
Factors affecting duration of anasthesiaFactors affecting duration of anasthesia
• Protein binding capacityProtein binding capacity
• Vascularity of the injected siteVascularity of the injected site
• Presence or absence of vasoactive substancePresence or absence of vasoactive substance
Classification of local anasthesiaClassification of local anasthesia
• According to chemical linkage LA classify in to :According to chemical linkage LA classify in to :
• Ester groupEster group
• Amide groupAmide group
• All LA molecules have both hydrophilic andAll LA molecules have both hydrophilic and
lipophilic characteristics at the opposing end oflipophilic characteristics at the opposing end of
molecules but the lipophilic part represent themolecules but the lipophilic part represent the
largest part of moleculelargest part of molecule
Notes :
• LA without hydrophilic part are not suitable forLA without hydrophilic part are not suitable for
injection .injection .
• Ester linked LA are readly hydrolized in aqueousEster linked LA are readly hydrolized in aqueous
solution while amide liked types are relativelysolution while amide liked types are relatively
resistant to hydrolysisresistant to hydrolysis
• great percentage of amide groups excretedgreat percentage of amide groups excreted
unchanged in the urine than ester groupunchanged in the urine than ester group
• All LA readily cross the blood brain barrier andAll LA readily cross the blood brain barrier and
placentaplacenta
Ester type local anastheticsEster type local anasthetics
1.Procaine 2.chloroprocaine 3. propxycaine1.Procaine 2.chloroprocaine 3. propxycaine
4. butacaine 5. cocaine 6. benzocaine4. butacaine 5. cocaine 6. benzocaine
7.hexylcaine 8.piperocaine7.hexylcaine 8.piperocaine
Amide type local anasthetcs:Amide type local anasthetcs:
1.Lidocaine 2. prilocaine 3. articaine 4.bupivacaine1.Lidocaine 2. prilocaine 3. articaine 4.bupivacaine
5.Dibucaine 6. etidocaine 7. mepivacain5.Dibucaine 6. etidocaine 7. mepivacain
• To know which is this anasthetic are ester orTo know which is this anasthetic are ester or
amide groupamide group
All ester group have oneAll ester group have one ( i )( i ) exceptexcept piperocainepiperocaine
like procaine ,butacaine ,propoxycaine , ……like procaine ,butacaine ,propoxycaine , ……
While amide group have doubleWhile amide group have double ( ii )( ii ) like lidocaine ,like lidocaine ,
bupivacaine ,articaine , ……bupivacaine ,articaine , ……
Pharmacokinetic of local anasthesiaPharmacokinetic of local anasthesia
DistributionDistribution
• After injection LA absorbed by blood vessels andAfter injection LA absorbed by blood vessels and
distribute to all body tissuedistribute to all body tissue
Factors that influence the blood level of LA are :Factors that influence the blood level of LA are :
1.Rate at which the drug is absorbed into the1.Rate at which the drug is absorbed into the
cardiovascular sysytem.cardiovascular sysytem.
2. Rate of distribution of the drug from the vascular2. Rate of distribution of the drug from the vascular
compartment to the tissuescompartment to the tissues
3. Elimination of the drug through the metabolic or3. Elimination of the drug through the metabolic or
excretory pathwaysexcretory pathways
MetabolismMetabolism
• Ester groups hydrolized in the plasma by theEster groups hydrolized in the plasma by the
enzyme pseudocholinesteraseenzyme pseudocholinesterase
• Procaine hydrolysed to para-aminobenzoicProcaine hydrolysed to para-aminobenzoic
acid ,this byproduct excreted unchanged inacid ,this byproduct excreted unchanged in
the urine and most of allergic reactionsthe urine and most of allergic reactions
occure due to this byproduct ( para-occure due to this byproduct ( para-
aminobenzoic acid) and not to the originalaminobenzoic acid) and not to the original
local anasthetic (procaine)local anasthetic (procaine)
Some people have atypical form ofSome people have atypical form of
pseudocholinesterase so they have inability topseudocholinesterase so they have inability to
hydrolyse ester local anasthetics and sohydrolyse ester local anasthetics and so
develop toxicity due to higher blood level ofdevelop toxicity due to higher blood level of
these agentthese agent
Amide LAAmide LA
• Metabolism more compex than ester groupMetabolism more compex than ester group
• occur in liveroccur in liver
• Byproduct of some these agents may showByproduct of some these agents may show
clinical activityclinical activity
• e.g lidocaine not cause sedation but some pfe.g lidocaine not cause sedation but some pf
its byproduct component may cause sedationits byproduct component may cause sedation
ExcretionExcretion
• The Kidney is the primary site for theThe Kidney is the primary site for the
excretion of both local anasthetic and itsexcretion of both local anasthetic and its
byproductbyproduct
• Patients with renal failure have proplem inPatients with renal failure have proplem in
excretion of local anasthetic and itsexcretion of local anasthetic and its
byproductbyproduct
• So it represent a relative contraindication toSo it represent a relative contraindication to
the administration of local anastheticthe administration of local anasthetic
constituents of local anasthesiaconstituents of local anasthesia
1. local anasthetic agent1. local anasthetic agent
2. vasoconstrictor agent2. vasoconstrictor agent
3. reducing agent3. reducing agent
reducing agent asreducing agent as sodium bisulphatesodium bisulphate used to stabilizeused to stabilize
vasoconstrictor agentvasoconstrictor agent
4. Preservative :4. Preservative : used to maintain the sterility of LA ,but it mayused to maintain the sterility of LA ,but it may
be the responsible for allergic reactions in some patiantbe the responsible for allergic reactions in some patiant
5. Fungicide5. Fungicide ; to prevent fungi growth which may lead to; to prevent fungi growth which may lead to
cloudness of solutioncloudness of solution
6.Vehicle :6.Vehicle : all prevouse components dissolved in modifiedall prevouse components dissolved in modified
ringers solution which decrease the discomfort during injectionringers solution which decrease the discomfort during injection
Role of vasoconstrictors in localRole of vasoconstrictors in local
anasthesiaanasthesia
• decrease rate of absorptiondecrease rate of absorption
• Decrease plasm level of LA and so decreaseDecrease plasm level of LA and so decrease
its toxicityits toxicity
• Increase duration of local anasthesiaIncrease duration of local anasthesia
• Decrease bleeding at the site of injectionDecrease bleeding at the site of injection
Dilution of the vasoconstructorsDilution of the vasoconstructors
• Dilution refered to ratio ( e.g 1 / 1000) (gramDilution refered to ratio ( e.g 1 / 1000) (gram
/ml) which mean 1gram of vasoconstrictor in/ml) which mean 1gram of vasoconstrictor in
1000 ml of solution1000 ml of solution
• Availability in dentistryAvailability in dentistry
• 1:50000
• 1:80000
• 1:100000
• 1:200000
Specific types of vasoconstrictorSpecific types of vasoconstrictor
1. adrenaline1. adrenaline
• source :source : either synthetic or obtained fromeither synthetic or obtained from
adrenal medulla of animalsadrenal medulla of animals
• Mode of action ;Mode of action ; act directly on both A and Bact directly on both A and B
adrenergic receptorsadrenergic receptors
• Heart ;Heart ; increase HR , O2 consumption, Bloodincrease HR , O2 consumption, Blood
pressurepressure
• Blood vesselsBlood vessels .. Vasoconstriction.. Vasoconstriction
• Respiratory systemRespiratory system … bronchodilator… bronchodilator
• CNSCNS … not potent CNS stimulant at therapeutic… not potent CNS stimulant at therapeutic
dosesdoses
Maximum dosesMaximum doses
•For pain controlFor pain control
•Normal patients …Normal patients … 0.2 mg0.2 mg per appointmentper appointment
5 cartridges if percentage of dilution 1:500005 cartridges if percentage of dilution 1:50000
11 cartridge if percentage of dilution 1:10000011 cartridge if percentage of dilution 1:100000
22 cartridges if percentage of dilution 1:20000022 cartridges if percentage of dilution 1:200000
. In patients with cardiovascular disease. In patients with cardiovascular disease
• Safe dose …Safe dose … 0.04 mg0.04 mg per appointmentper appointment
• 1 cartidges if percentage of dilution 1:500001 cartidges if percentage of dilution 1:50000
• 2 cartridges if percentage of dilution 1:1000002 cartridges if percentage of dilution 1:100000
• 4 cartidges if percentage of dilution 1:2000004 cartidges if percentage of dilution 1:200000
• For hemostatis :For hemostatis : 1:50000 more effective but1:50000 more effective but
1:100000 solution better to use to avoid1:100000 solution better to use to avoid
vascularity compromisationvascularity compromisation
noreadrenalinenoreadrenaline
• Its similar to adrenaline but it show moreIts similar to adrenaline but it show more
vascular periphral resistance , heart ratevascular periphral resistance , heart rate
decrease ,and no effect on bronchial smoothdecrease ,and no effect on bronchial smooth
musclesmuscles
• Availabilty in dentistryAvailabilty in dentistry
• 1: 30000 dilution1: 30000 dilution
Maximum dosesMaximum doses
•NoradrenalineNoradrenaline four timesfour times more potent thanmore potent than
adrenaline so its used for pain control only andadrenaline so its used for pain control only and
not as a heamostatenot as a heamostate
• for normal patientfor normal patient 0.034 mg0.034 mg per appointmentper appointment
•For patient with cardiovascular diseases :For patient with cardiovascular diseases : 0.140.14
mgmg per appointmentper appointment
LevonordefrinLevonordefrin
• Synthetic vasoconstrictorSynthetic vasoconstrictor
• Show less cardiac and CNS stimulation thanShow less cardiac and CNS stimulation than
epinephrineepinephrine
• Availability in dentistryAvailability in dentistry
used with mepivacaine or with propoxycaineused with mepivacaine or with propoxycaine
procaine in 1:20000 dilutionprocaine in 1:20000 dilution
Maximum doses : for all patients maximum doseMaximum doses : for all patients maximum dose
1mg per appointment1mg per appointment
FelypressinFelypressin
• Synthetic analogue of vasopressinSynthetic analogue of vasopressin
(antidiuretic hormone)(antidiuretic hormone)
• Mode of action: direct stimulant of vascularMode of action: direct stimulant of vascular
smooth musclessmooth muscles
• Act mainly on venous vesselsAct mainly on venous vessels
• No effect on heart or CNSNo effect on heart or CNS
• It has both antidiuretic and oxytocic actionsIt has both antidiuretic and oxytocic actions
so its contraindicated in pregnant womens.so its contraindicated in pregnant womens.
Thank You forThank You for

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Physiology of local anasthesia

  • 1. Physiology of local anasthesiaPhysiology of local anasthesia Dr.Mohamed Rhael AliDr.Mohamed Rhael Ali 2016-20172016-2017
  • 3. Nerve anatomyNerve anatomy • Periphral nerve composed from hundreds to thousands ofPeriphral nerve composed from hundreds to thousands of axonsaxons • Each axon coverd by sheath called endoneuriumEach axon coverd by sheath called endoneurium • Each group of axons bind togather in a special sheath calledEach group of axons bind togather in a special sheath called perineurium , these group of axons (bundle) called fasciculiperineurium , these group of axons (bundle) called fasciculi which consider the main barrior to diffusion of localwhich consider the main barrior to diffusion of local anasthesia in to the nerve .anasthesia in to the nerve . • The whole bundles covered by loose connective tissue calledThe whole bundles covered by loose connective tissue called epineuriumepineurium • Local anasthesia able to diffuse through this tissues becauseLocal anasthesia able to diffuse through this tissues because of its loose consistency .of its loose consistency . • nutrient blood vessels and lymphatics transverse thenutrient blood vessels and lymphatics transverse the epineurium and these vessels absorb local ansthesia andepineurium and these vessels absorb local ansthesia and thus removing them from the nervethus removing them from the nerve
  • 7. Nerve membraneNerve membrane Two layers of lipid molecules with associated proteinTwo layers of lipid molecules with associated protein and carbohydrates moleculesand carbohydrates molecules
  • 9. Properties of nerve membraneProperties of nerve membrane • impermeable to water soluble moleculesimpermeable to water soluble molecules • selectively permeable to certain molecules viaselectively permeable to certain molecules via specialized channelsspecialized channels • Transduce information by protein receptors inTransduce information by protein receptors in response to chemical or physical stimuliresponse to chemical or physical stimuli
  • 10. Nerve membarne selectively permeable soNerve membarne selectively permeable so There is a diffrence between ions concentrationThere is a diffrence between ions concentration around itaround it High concentration of k+ inside while highHigh concentration of k+ inside while high concentration of Na+ outside the nerve membraneconcentration of Na+ outside the nerve membrane
  • 12. Resting stateResting state • In resting state nerve membrane have –ve restingIn resting state nerve membrane have –ve resting potential (-70 mv)potential (-70 mv) • Coming from different concentration of ionsComing from different concentration of ions around the membranearound the membrane
  • 13. DepolarizationDepolarization • Rabid influx of Na+ ions to the inside of nerveRabid influx of Na+ ions to the inside of nerve • Must reach firing threshould which areMust reach firing threshould which are approximately ( -50 to -60 mv)approximately ( -50 to -60 mv)
  • 14. RepolarizationRepolarization • Movement of K+ to outside which lead to return ofMovement of K+ to outside which lead to return of nerve membrane to its resting potential ( - 70 mv )nerve membrane to its resting potential ( - 70 mv ) • Movement of ions in depolarization are passiveMovement of ions in depolarization are passive process ( not required energy )process ( not required energy ) • While movement of ions in depolarization areWhile movement of ions in depolarization are active processactive process
  • 15. ImpulseImpulse • Function of nerve is to carry messages fromFunction of nerve is to carry messages from one part of the body anotherone part of the body another • These messages called impulseThese messages called impulse • impulse initiated by chemical , thermal,impulse initiated by chemical , thermal, mechanical or electrical stimulimechanical or electrical stimuli
  • 18. Mechanism of action of localMechanism of action of local anasthesiaanasthesia • Local anastheesia act by prevention of bothLocal anastheesia act by prevention of both generation and conduction of nerve impulsegeneration and conduction of nerve impulse • Nerve membrane consider the site at whichNerve membrane consider the site at which local anasthetic agents exert theirlocal anasthetic agents exert their pharmacological actionspharmacological actions
  • 19. Theories for working ofTheories for working of local anasthesialocal anasthesia
  • 20. Membrane expansion theoryMembrane expansion theory • This theory explain that local anasthetic moleculesThis theory explain that local anasthetic molecules diffuse through the nerve membrane and causingdiffuse through the nerve membrane and causing general disturbance in the bulk of of membranegeneral disturbance in the bulk of of membrane structure which lead to blockage of the membranestructure which lead to blockage of the membrane permeability to Na+ and so inhibit both conductionpermeability to Na+ and so inhibit both conduction and nerve excitationand nerve excitation
  • 22. Specific receptor theorySpecific receptor theory • This theory propose that local anastheticsThis theory propose that local anasthetics bind to specific receptors in sodium channelbind to specific receptors in sodium channel leading to direct decrease in permeability toleading to direct decrease in permeability to Na ionsNa ions • This theory is the most acceptable theoryThis theory is the most acceptable theory
  • 24. Induction of local anasthesiaInduction of local anasthesia In the tissue LA move according to itsIn the tissue LA move according to its concentrationconcentration DiffusionDiffusion •LA reach faster to mantle bundle(prephralLA reach faster to mantle bundle(prephral bundle ) than core bundle (central bundle)bundle ) than core bundle (central bundle)
  • 25. • Core bundle need need more volume andCore bundle need need more volume and longer time to get anasthesia due to barrierslonger time to get anasthesia due to barriers and also absorbtion of LA by bloodand also absorbtion of LA by blood cappilaries within the nerve fibercappilaries within the nerve fiber
  • 26. Factors affecting localFactors affecting local anasthetic actionsanasthetic actions
  • 27. PH valuePH value Action of local anasthesia decrease in acidicAction of local anasthesia decrease in acidic media as in inflamed areamedia as in inflamed area
  • 28. Lipid solubilityLipid solubility Lipid soluble LA penetrate the nerve membraneLipid soluble LA penetrate the nerve membrane more easymore easy increase theincrease the potencypotency of itof it
  • 29. Protein bindingProtein binding It affect on theIt affect on the durationduration of local anasthesiaof local anasthesia Increase protein binding capacityIncrease protein binding capacity Increase its durationIncrease its duration
  • 30. Nonnervous tissue diffusubilityNonnervous tissue diffusubility • Affect on theAffect on the onsetonset of action (starting point)of action (starting point) Increase infusibility of LA to the nerveIncrease infusibility of LA to the nerve membranemembrane Decrease time of onsetDecrease time of onset
  • 31. Vasodilator activityVasodilator activity Increase vasodilator activityIncrease vasodilator activity DecreaseDecrease potencypotency andand durationduration
  • 32. Factors affecting duration of anasthesiaFactors affecting duration of anasthesia • Protein binding capacityProtein binding capacity • Vascularity of the injected siteVascularity of the injected site • Presence or absence of vasoactive substancePresence or absence of vasoactive substance
  • 33. Classification of local anasthesiaClassification of local anasthesia • According to chemical linkage LA classify in to :According to chemical linkage LA classify in to : • Ester groupEster group • Amide groupAmide group • All LA molecules have both hydrophilic andAll LA molecules have both hydrophilic and lipophilic characteristics at the opposing end oflipophilic characteristics at the opposing end of molecules but the lipophilic part represent themolecules but the lipophilic part represent the largest part of moleculelargest part of molecule
  • 34. Notes : • LA without hydrophilic part are not suitable forLA without hydrophilic part are not suitable for injection .injection . • Ester linked LA are readly hydrolized in aqueousEster linked LA are readly hydrolized in aqueous solution while amide liked types are relativelysolution while amide liked types are relatively resistant to hydrolysisresistant to hydrolysis • great percentage of amide groups excretedgreat percentage of amide groups excreted unchanged in the urine than ester groupunchanged in the urine than ester group • All LA readily cross the blood brain barrier andAll LA readily cross the blood brain barrier and placentaplacenta
  • 35. Ester type local anastheticsEster type local anasthetics 1.Procaine 2.chloroprocaine 3. propxycaine1.Procaine 2.chloroprocaine 3. propxycaine 4. butacaine 5. cocaine 6. benzocaine4. butacaine 5. cocaine 6. benzocaine 7.hexylcaine 8.piperocaine7.hexylcaine 8.piperocaine Amide type local anasthetcs:Amide type local anasthetcs: 1.Lidocaine 2. prilocaine 3. articaine 4.bupivacaine1.Lidocaine 2. prilocaine 3. articaine 4.bupivacaine 5.Dibucaine 6. etidocaine 7. mepivacain5.Dibucaine 6. etidocaine 7. mepivacain
  • 36. • To know which is this anasthetic are ester orTo know which is this anasthetic are ester or amide groupamide group All ester group have oneAll ester group have one ( i )( i ) exceptexcept piperocainepiperocaine like procaine ,butacaine ,propoxycaine , ……like procaine ,butacaine ,propoxycaine , …… While amide group have doubleWhile amide group have double ( ii )( ii ) like lidocaine ,like lidocaine , bupivacaine ,articaine , ……bupivacaine ,articaine , ……
  • 37. Pharmacokinetic of local anasthesiaPharmacokinetic of local anasthesia
  • 38. DistributionDistribution • After injection LA absorbed by blood vessels andAfter injection LA absorbed by blood vessels and distribute to all body tissuedistribute to all body tissue Factors that influence the blood level of LA are :Factors that influence the blood level of LA are : 1.Rate at which the drug is absorbed into the1.Rate at which the drug is absorbed into the cardiovascular sysytem.cardiovascular sysytem. 2. Rate of distribution of the drug from the vascular2. Rate of distribution of the drug from the vascular compartment to the tissuescompartment to the tissues 3. Elimination of the drug through the metabolic or3. Elimination of the drug through the metabolic or excretory pathwaysexcretory pathways
  • 39. MetabolismMetabolism • Ester groups hydrolized in the plasma by theEster groups hydrolized in the plasma by the enzyme pseudocholinesteraseenzyme pseudocholinesterase • Procaine hydrolysed to para-aminobenzoicProcaine hydrolysed to para-aminobenzoic acid ,this byproduct excreted unchanged inacid ,this byproduct excreted unchanged in the urine and most of allergic reactionsthe urine and most of allergic reactions occure due to this byproduct ( para-occure due to this byproduct ( para- aminobenzoic acid) and not to the originalaminobenzoic acid) and not to the original local anasthetic (procaine)local anasthetic (procaine)
  • 40. Some people have atypical form ofSome people have atypical form of pseudocholinesterase so they have inability topseudocholinesterase so they have inability to hydrolyse ester local anasthetics and sohydrolyse ester local anasthetics and so develop toxicity due to higher blood level ofdevelop toxicity due to higher blood level of these agentthese agent
  • 41. Amide LAAmide LA • Metabolism more compex than ester groupMetabolism more compex than ester group • occur in liveroccur in liver • Byproduct of some these agents may showByproduct of some these agents may show clinical activityclinical activity • e.g lidocaine not cause sedation but some pfe.g lidocaine not cause sedation but some pf its byproduct component may cause sedationits byproduct component may cause sedation
  • 42. ExcretionExcretion • The Kidney is the primary site for theThe Kidney is the primary site for the excretion of both local anasthetic and itsexcretion of both local anasthetic and its byproductbyproduct • Patients with renal failure have proplem inPatients with renal failure have proplem in excretion of local anasthetic and itsexcretion of local anasthetic and its byproductbyproduct • So it represent a relative contraindication toSo it represent a relative contraindication to the administration of local anastheticthe administration of local anasthetic
  • 43. constituents of local anasthesiaconstituents of local anasthesia 1. local anasthetic agent1. local anasthetic agent 2. vasoconstrictor agent2. vasoconstrictor agent 3. reducing agent3. reducing agent reducing agent asreducing agent as sodium bisulphatesodium bisulphate used to stabilizeused to stabilize vasoconstrictor agentvasoconstrictor agent 4. Preservative :4. Preservative : used to maintain the sterility of LA ,but it mayused to maintain the sterility of LA ,but it may be the responsible for allergic reactions in some patiantbe the responsible for allergic reactions in some patiant 5. Fungicide5. Fungicide ; to prevent fungi growth which may lead to; to prevent fungi growth which may lead to cloudness of solutioncloudness of solution 6.Vehicle :6.Vehicle : all prevouse components dissolved in modifiedall prevouse components dissolved in modified ringers solution which decrease the discomfort during injectionringers solution which decrease the discomfort during injection
  • 44. Role of vasoconstrictors in localRole of vasoconstrictors in local anasthesiaanasthesia • decrease rate of absorptiondecrease rate of absorption • Decrease plasm level of LA and so decreaseDecrease plasm level of LA and so decrease its toxicityits toxicity • Increase duration of local anasthesiaIncrease duration of local anasthesia • Decrease bleeding at the site of injectionDecrease bleeding at the site of injection
  • 45. Dilution of the vasoconstructorsDilution of the vasoconstructors • Dilution refered to ratio ( e.g 1 / 1000) (gramDilution refered to ratio ( e.g 1 / 1000) (gram /ml) which mean 1gram of vasoconstrictor in/ml) which mean 1gram of vasoconstrictor in 1000 ml of solution1000 ml of solution • Availability in dentistryAvailability in dentistry • 1:50000 • 1:80000 • 1:100000 • 1:200000
  • 46. Specific types of vasoconstrictorSpecific types of vasoconstrictor
  • 47. 1. adrenaline1. adrenaline • source :source : either synthetic or obtained fromeither synthetic or obtained from adrenal medulla of animalsadrenal medulla of animals • Mode of action ;Mode of action ; act directly on both A and Bact directly on both A and B adrenergic receptorsadrenergic receptors • Heart ;Heart ; increase HR , O2 consumption, Bloodincrease HR , O2 consumption, Blood pressurepressure • Blood vesselsBlood vessels .. Vasoconstriction.. Vasoconstriction • Respiratory systemRespiratory system … bronchodilator… bronchodilator • CNSCNS … not potent CNS stimulant at therapeutic… not potent CNS stimulant at therapeutic dosesdoses
  • 48. Maximum dosesMaximum doses •For pain controlFor pain control •Normal patients …Normal patients … 0.2 mg0.2 mg per appointmentper appointment 5 cartridges if percentage of dilution 1:500005 cartridges if percentage of dilution 1:50000 11 cartridge if percentage of dilution 1:10000011 cartridge if percentage of dilution 1:100000 22 cartridges if percentage of dilution 1:20000022 cartridges if percentage of dilution 1:200000
  • 49. . In patients with cardiovascular disease. In patients with cardiovascular disease • Safe dose …Safe dose … 0.04 mg0.04 mg per appointmentper appointment • 1 cartidges if percentage of dilution 1:500001 cartidges if percentage of dilution 1:50000 • 2 cartridges if percentage of dilution 1:1000002 cartridges if percentage of dilution 1:100000 • 4 cartidges if percentage of dilution 1:2000004 cartidges if percentage of dilution 1:200000
  • 50. • For hemostatis :For hemostatis : 1:50000 more effective but1:50000 more effective but 1:100000 solution better to use to avoid1:100000 solution better to use to avoid vascularity compromisationvascularity compromisation
  • 51. noreadrenalinenoreadrenaline • Its similar to adrenaline but it show moreIts similar to adrenaline but it show more vascular periphral resistance , heart ratevascular periphral resistance , heart rate decrease ,and no effect on bronchial smoothdecrease ,and no effect on bronchial smooth musclesmuscles • Availabilty in dentistryAvailabilty in dentistry • 1: 30000 dilution1: 30000 dilution
  • 52. Maximum dosesMaximum doses •NoradrenalineNoradrenaline four timesfour times more potent thanmore potent than adrenaline so its used for pain control only andadrenaline so its used for pain control only and not as a heamostatenot as a heamostate • for normal patientfor normal patient 0.034 mg0.034 mg per appointmentper appointment •For patient with cardiovascular diseases :For patient with cardiovascular diseases : 0.140.14 mgmg per appointmentper appointment
  • 53. LevonordefrinLevonordefrin • Synthetic vasoconstrictorSynthetic vasoconstrictor • Show less cardiac and CNS stimulation thanShow less cardiac and CNS stimulation than epinephrineepinephrine • Availability in dentistryAvailability in dentistry used with mepivacaine or with propoxycaineused with mepivacaine or with propoxycaine procaine in 1:20000 dilutionprocaine in 1:20000 dilution Maximum doses : for all patients maximum doseMaximum doses : for all patients maximum dose 1mg per appointment1mg per appointment
  • 54. FelypressinFelypressin • Synthetic analogue of vasopressinSynthetic analogue of vasopressin (antidiuretic hormone)(antidiuretic hormone) • Mode of action: direct stimulant of vascularMode of action: direct stimulant of vascular smooth musclessmooth muscles • Act mainly on venous vesselsAct mainly on venous vessels • No effect on heart or CNSNo effect on heart or CNS • It has both antidiuretic and oxytocic actionsIt has both antidiuretic and oxytocic actions so its contraindicated in pregnant womens.so its contraindicated in pregnant womens.