Physiology of local Physiology of local anasthesiaanasthesia

Dr.Mohamed Rhael AliDr.Mohamed Rhael Ali2016-20172016-2017

Nerve physiology

Nerve anatomyNerve anatomy• Periphral nerve composed from hundreds to thousands of axonsPeriphral nerve composed from hundreds to thousands of axons• Each axon coverd by sheath called endoneurium Each axon coverd by sheath called endoneurium • Each group of axons bind togather in a special sheath called perineurium Each group of axons bind togather in a special sheath called perineurium

, these group of axons (bundle) called fasciculi which consider the main , these group of axons (bundle) called fasciculi which consider the main barrior to diffusion of local anasthesia in to the nerve .barrior to diffusion of local anasthesia in to the nerve .

• The whole bundles covered by loose connective tissue called epineurium The whole bundles covered by loose connective tissue called epineurium • Local anasthesia able to diffuse through this tissues because of its loose Local anasthesia able to diffuse through this tissues because of its loose

consistency .consistency .• nutrient blood vessels and lymphatics transverse the epineurium and nutrient blood vessels and lymphatics transverse the epineurium and

these vessels absorb local ansthesia and thus removing them from the these vessels absorb local ansthesia and thus removing them from the nervenerve

Nerve membrane Nerve membrane Two layers of lipid molecules with associated protein Two layers of lipid molecules with associated protein

and carbohydrates molecules and carbohydrates molecules

Properties of nerve membrane Properties of nerve membrane

• impermeable to water soluble moleculesimpermeable to water soluble molecules• selectively permeable to certain molecules via selectively permeable to certain molecules via

specialized channels specialized channels • Transduce information by protein receptors in Transduce information by protein receptors in

response to chemical or physical stimuliresponse to chemical or physical stimuli

Nerve membarne selectively permeable so Nerve membarne selectively permeable so There is a diffrence between ions concentration There is a diffrence between ions concentration

around it around it

High concentration of k+ inside while high High concentration of k+ inside while high concentration of Na+ outside the nerve membraneconcentration of Na+ outside the nerve membrane

Resting stateResting state• In resting state nerve membrane have –ve resting In resting state nerve membrane have –ve resting

potential (-70 mv) potential (-70 mv) • Coming from different concentration of ions Coming from different concentration of ions

around the membrane around 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 are Must 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 of Movement 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 passive Movement of ions in depolarization are passive process ( not required energy ) process ( not required energy )

• While movement of ions in depolarization are While movement of ions in depolarization are active processactive process

ImpulseImpulse

• Function of nerve is to carry messages from Function of nerve is to carry messages from one part of the body anotherone part of the body another

• These messages called impulse These messages called impulse

• impulse initiated by chemical , thermal, impulse initiated by chemical , thermal, mechanical or electrical stimulimechanical or electrical stimuli

Mechanism of action of local Mechanism of action of local anasthesiaanasthesia

• Local anastheesia act by prevention of both Local anastheesia act by prevention of both generation and conduction of nerve impulsegeneration and conduction of nerve impulse

• Nerve membrane consider the site at which Nerve membrane consider the site at which local anasthetic agents exert their local anasthetic agents exert their pharmacological actions pharmacological actions

Theories for Theories for working of local working of local

anasthesia anasthesia

Membrane expansion theoryMembrane expansion theory

• This theory explain that local anasthetic molecules This theory explain that local anasthetic molecules diffuse through the nerve membrane and causing diffuse through the nerve membrane and causing general disturbance in the bulk of of membrane general disturbance in the bulk of of membrane structure which lead to blockage of the membrane structure which lead to blockage of the membrane permeability to Na+ and so inhibit both conduction permeability to Na+ and so inhibit both conduction and nerve excitationand nerve excitation

Specific receptor theorySpecific receptor theory

• This theory propose that local anasthetics This theory propose that local anasthetics bind to specific receptors in sodium channel bind to specific receptors in sodium channel leading to direct decrease in permeability to leading to direct decrease in permeability to Na ions Na ions

• This theory is the most acceptable theoryThis theory is the most acceptable theory

Induction of local anasthesiaInduction of local anasthesia

In the tissue LA move according to its In the tissue LA move according to its concentrationconcentration

Diffusion Diffusion

•LA reach faster to mantle bundle(prephral LA reach faster to mantle bundle(prephral bundle ) than core bundle (central bundle)bundle ) than core bundle (central bundle)

• Core bundle need need more volume and Core bundle need need more volume and longer time to get anasthesia due to barriers longer time to get anasthesia due to barriers and also absorbtion of LA by blood and also absorbtion of LA by blood cappilaries within the nerve fibercappilaries within the nerve fiber

Factors affecting local Factors affecting local anasthetic actionsanasthetic actions

PH valuePH valueAction of local anasthesia decrease in acidic Action of local anasthesia decrease in acidic

media as in inflamed areamedia as in inflamed area

Lipid solubilityLipid solubility

Lipid soluble LA penetrate the nerve membrane Lipid soluble LA penetrate the nerve membrane more easymore easy

increase the increase the potencypotency of it of it

Protein bindingProtein binding

It affect on the It affect on the durationduration of local anasthesia of local anasthesia Increase protein binding capacityIncrease protein binding capacity

Increase its durationIncrease its duration

Nonnervous tissue diffusubilityNonnervous tissue diffusubility

• Affect on the Affect on the onsetonset of action (starting point) of action (starting point)

Increase infusibility of LA to the nerve Increase infusibility of LA to the nerve membrane membrane

Decrease time of onset Decrease time of onset

Vasodilator activityVasodilator activity

Increase vasodilator activityIncrease vasodilator activity

Decrease Decrease potencypotency and and durationduration

Factors affecting duration of anasthesiaFactors affecting duration of anasthesia

• Protein binding capacityProtein binding capacity

• Vascularity of the injected site Vascularity 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 and All LA molecules have both hydrophilic and lipophilic characteristics at the opposing end of lipophilic characteristics at the opposing end of molecules but the lipophilic part represent the molecules but the lipophilic part represent the largest part of moleculelargest part of molecule

Notes :• LA without hydrophilic part are not suitable for LA without hydrophilic part are not suitable for

injection .injection .

• Ester linked LA are readly hydrolized in aqueous Ester linked LA are readly hydrolized in aqueous solution while amide liked types are relatively solution while amide liked types are relatively resistant to hydrolysisresistant to hydrolysis

• great percentage of amide groups excreted great 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 and All 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.bupivacaine5.Dibucaine 6. etidocaine 7. mepivacain5.Dibucaine 6. etidocaine 7. mepivacain

• To know which is this anasthetic are ester or To know which is this anasthetic are ester or amide groupamide group

All ester group have one All ester group have one ( i ) ( i ) except except piperocaine piperocaine like procaine ,butacaine ,propoxycaine , ……like procaine ,butacaine ,propoxycaine , ……

While amide group have double While amide group have double ( ii ) ( ii ) like lidocaine , like lidocaine , bupivacaine ,articaine , …… bupivacaine ,articaine , ……

Pharmacokinetic of local Pharmacokinetic of local anasthesia anasthesia

DistributionDistribution• After injection LA absorbed by blood vessels and After injection LA absorbed by blood vessels and

distribute to all body tissuedistribute to all body tissueFactors 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 the 1.Rate at which the drug is absorbed into the

cardiovascular sysytem.cardiovascular sysytem.2. Rate of distribution of the drug from the vascular 2. Rate of distribution of the drug from the vascular

compartment to the tissuescompartment to the tissues3. Elimination of the drug through the metabolic or 3. Elimination of the drug through the metabolic or

excretory pathwaysexcretory pathways

MetabolismMetabolism

• Ester groups hydrolized in the plasma by the Ester groups hydrolized in the plasma by the enzyme pseudocholinesterase enzyme pseudocholinesterase

• Procaine hydrolysed to para-aminobenzoic Procaine hydrolysed to para-aminobenzoic acid ,this byproduct excreted unchanged in acid ,this byproduct excreted unchanged in the urine and most of allergic reactions the urine and most of allergic reactions occure due to this byproduct ( para-occure due to this byproduct ( para-aminobenzoic acid) and not to the original aminobenzoic acid) and not to the original local anasthetic (procaine)local anasthetic (procaine)

Some people have atypical form of Some people have atypical form of pseudocholinesterase so they have inability to pseudocholinesterase so they have inability to

hydrolyse ester local anasthetics and so hydrolyse ester local anasthetics and so develop toxicity due to higher blood level of develop toxicity due to higher blood level of

these agent these 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 show Byproduct of some these agents may show

clinical activity clinical activity • e.g lidocaine not cause sedation but some pf e.g lidocaine not cause sedation but some pf

its byproduct component may cause sedation its byproduct component may cause sedation

ExcretionExcretion• The Kidney is the primary site for the The Kidney is the primary site for the

excretion of both local anasthetic and its excretion of both local anasthetic and its byproductbyproduct

• Patients with renal failure have proplem in Patients with renal failure have proplem in excretion of local anasthetic and its excretion of local anasthetic and its byproductbyproduct

• So it represent a relative contraindication to So it represent a relative contraindication to the administration of local anastheticthe administration of local anasthetic

constituents of local anasthesia constituents of local anasthesia 1. local anasthetic agent1. local anasthetic agent2. vasoconstrictor agent2. vasoconstrictor agent

3. reducing agent 3. reducing agent reducing agent as reducing agent as sodium bisulphate sodium bisulphate used to stabilize used to stabilize

vasoconstrictor agent vasoconstrictor agent 4. Preservative : 4. Preservative : used to maintain the sterility of LA ,but it may used 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 patiant5. Fungicide 5. Fungicide ; to prevent fungi growth which may lead to ; to prevent fungi growth which may lead to

cloudness of solutioncloudness of solution6.Vehicle : 6.Vehicle : all prevouse components dissolved in modified all prevouse components dissolved in modified

ringers solution which decrease the discomfort during injectionringers solution which decrease the discomfort during injection

Role of vasoconstrictors in local Role of vasoconstrictors in local anasthesia anasthesia

• decrease rate of absorption decrease rate of absorption • Decrease plasm level of LA and so decrease Decrease plasm level of LA and so decrease

its toxicity its toxicity • Increase duration of local anasthesia Increase 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) (gram Dilution 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 dentistry Availability 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 from either synthetic or obtained from

adrenal medulla of animalsadrenal medulla of animals• Mode of action ; Mode of action ; act directly on both A and B act directly on both A and B

adrenergic receptorsadrenergic receptors• Heart ; Heart ; increase HR , O2 consumption, Blood increase HR , O2 consumption, Blood

pressurepressure• Blood vessels Blood vessels .. Vasoconstriction.. Vasoconstriction• Respiratory system Respiratory system … bronchodilator… bronchodilator• CNSCNS … not potent CNS stimulant at therapeutic … not potent CNS stimulant at therapeutic

dosesdoses

Maximum dosesMaximum doses

•For pain control For pain control •Normal patients … Normal patients … 0.2 mg 0.2 mg per appointment per 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 mg 0.04 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 but 1:50000 more effective but 1:100000 solution better to use to avoid 1:100000 solution better to use to avoid vascularity compromisation vascularity compromisation

noreadrenalinenoreadrenaline

• Its similar to adrenaline but it show more Its similar to adrenaline but it show more vascular periphral resistance , heart rate vascular periphral resistance , heart rate decrease ,and no effect on bronchial smooth decrease ,and no effect on bronchial smooth musclesmuscles

• Availabilty in dentistry Availabilty in dentistry • 1: 30000 dilution1: 30000 dilution

Maximum doses Maximum doses •Noradrenaline Noradrenaline four times four times more potent than more potent than adrenaline so its used for pain control only and adrenaline so its used for pain control only and not as a heamostatenot as a heamostate• for normal patient for normal patient 0.034 mg 0.034 mg per appointmentper appointment•For patient with cardiovascular diseases : For patient with cardiovascular diseases : 0.14 0.14 mg mg per appointment per appointment

LevonordefrinLevonordefrin• Synthetic vasoconstrictor Synthetic vasoconstrictor • Show less cardiac and CNS stimulation than Show less cardiac and CNS stimulation than

epinephrine epinephrine

• Availability in dentistry Availability in dentistry used with mepivacaine or with propoxycaine used with mepivacaine or with propoxycaine

procaine in 1:20000 dilutionprocaine in 1:20000 dilution

Maximum doses : for all patients maximum dose Maximum doses : for all patients maximum dose 1mg per appointment 1mg per appointment

FelypressinFelypressin

• Synthetic analogue of vasopressin Synthetic analogue of vasopressin (antidiuretic hormone)(antidiuretic hormone)

• Mode of action: direct stimulant of vascular Mode of action: direct stimulant of vascular smooth muscles smooth muscles

• Act mainly on venous vesselsAct mainly on venous vessels• No effect on heart or CNS No effect on heart or CNS • It has both antidiuretic and oxytocic actions It has both antidiuretic and oxytocic actions

so its contraindicated in pregnant womens. so its contraindicated in pregnant womens.

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