Physiology of local anasthesia - cden.tu.edu.iq
Transcript of Physiology of local anasthesia - cden.tu.edu.iq
Physiology of local anasthesia
Dr.Mohamed Rhael Ali
2016-2017
Nerve physiology
Nerve anatomy
• Periphral nerve composed from hundreds to thousands of axons
• Each axon coverd by sheath called endoneurium
• Each group of axons bind togather in a special sheath called perineurium , these group of axons (bundle) called fasciculi which consider the main barrior to diffusion of local anasthesia in to the nerve .
• The whole bundles covered by loose connective tissue called epineurium
• Local anasthesia able to diffuse through this tissues because of its loose consistency .
• nutrient blood vessels and lymphatics transverse the epineurium and these vessels absorb local ansthesia and thus removing them from the nerve
Nerve membrane
Two layers of lipid molecules with associated protein and carbohydrates molecules
Properties of nerve membrane
• impermeable to water soluble molecules
• selectively permeable to certain molecules via specialized channels
• Transduce information by protein receptors in response to chemical or physical stimuli
Nerve membarne selectively permeable so
There is a diffrence between ions concentration around it
High concentration of k+ inside while high concentration of Na+ outside the nerve membrane
Resting state
• In resting state nerve membrane have –ve resting potential (-70 mv)
• Coming from different concentration of ions around the membrane
Depolarization
• Rabid influx of Na+ ions to the inside of nerve
• Must reach firing threshould which are approximately ( -50 to -60 mv)
Repolarization
• Movement of K+ to outside which lead to return of nerve membrane to its resting potential ( - 70 mv )
• Movement of ions in depolarization are passive process ( not required energy )
• While movement of ions in depolarization are active process
Impulse
• Function of nerve is to carry messages from one part of the body another
• These messages called impulse
• impulse initiated by chemical , thermal, mechanical or electrical stimuli
Mechanism of action of local anasthesia
• Local anastheesia act by prevention of both generation and conduction of nerve impulse
• Nerve membrane consider the site at which local anasthetic agents exert their pharmacological actions
Theories for working of local
anasthesia
Membrane expansion theory
• This theory explain that local anasthetic molecules diffuse through the nerve membrane and causing general disturbance in the bulk of of membrane structure which lead to blockage of the membrane permeability to Na+ and so inhibit both conduction and nerve excitation
Specific receptor theory
• This theory propose that local anasthetics bind to specific receptors in sodium channel leading to direct decrease in permeability to Na ions
• This theory is the most acceptable theory
Induction of local anasthesia
In the tissue LA move according to its concentration
Diffusion
• LA reach faster to mantle bundle(prephral bundle ) than core bundle (central bundle)
• Core bundle need need more volume and longer time to get anasthesia due to barriers and also absorbtion of LA by blood cappilaries within the nerve fiber
Factors affecting local anasthetic
actions
PH value Action of local anasthesia decrease in acidic
media as in inflamed area
Lipid solubility
Lipid soluble LA penetrate the nerve membrane more easy
increase the potency of it
Protein binding
It affect on the duration of local anasthesia
Increase protein binding capacity
Increase its duration
Nonnervous tissue diffusubility
• Affect on the onset of action (starting point)
Increase infusibility of LA to the nerve membrane
Decrease time of onset
Vasodilator activity
Increase vasodilator activity
Decrease potency and duration
Factors affecting duration of anasthesia
• Protein binding capacity
• Vascularity of the injected site
• Presence or absence of vasoactive substance
Classification of local anasthesia
• According to chemical linkage LA classify in to :
• Ester group
• Amide group
• All LA molecules have both hydrophilic and lipophilic characteristics at the opposing end of molecules but the lipophilic part represent the largest part of molecule
Notes :
• LA without hydrophilic part are not suitable for injection .
• Ester linked LA are readly hydrolized in aqueous solution while amide liked types are relatively resistant to hydrolysis
• great percentage of amide groups excreted unchanged in the urine than ester group
• All LA readily cross the blood brain barrier and placenta
Ester type local anasthetics
1.Procaine 2.chloroprocaine 3. propxycaine
4. butacaine 5. cocaine 6. benzocaine
7.hexylcaine 8.piperocaine
Amide type local anasthetcs:
1.Lidocaine 2. prilocaine 3. articaine 4.bupivacaine
5.Dibucaine 6. etidocaine 7. mepivacain
• To know which is this anasthetic are ester or amide group
All ester group have one ( i ) except piperocaine like procaine ,butacaine ,propoxycaine , ……
While amide group have double ( ii ) like lidocaine , bupivacaine ,articaine , ……
Pharmacokinetic of local anasthesia
Distribution
• After injection LA absorbed by blood vessels and distribute to all body tissue
Factors that influence the blood level of LA are :
1.Rate at which the drug is absorbed into the cardiovascular sysytem.
2. Rate of distribution of the drug from the vascular compartment to the tissues
3. Elimination of the drug through the metabolic or excretory pathways
Metabolism
• Ester groups hydrolized in the plasma by the enzyme pseudocholinesterase
• Procaine hydrolysed to para-aminobenzoic acid ,this byproduct excreted unchanged in the urine and most of allergic reactions occure due to this byproduct ( para-aminobenzoic acid) and not to the original local anasthetic (procaine)
Some people have atypical form of pseudocholinesterase so they have inability to
hydrolyse ester local anasthetics and so develop toxicity due to higher blood level of
these agent
Amide LA
• Metabolism more compex than ester group
• occur in liver
• Byproduct of some these agents may show clinical activity
• e.g lidocaine not cause sedation but some pf its byproduct component may cause sedation
Excretion
• The Kidney is the primary site for the excretion of both local anasthetic and its byproduct
• Patients with renal failure have proplem in excretion of local anasthetic and its byproduct
• So it represent a relative contraindication to the administration of local anasthetic
constituents of local anasthesia
1. local anasthetic agent
2. vasoconstrictor agent
3. reducing agent
reducing agent as sodium bisulphate used to stabilize vasoconstrictor agent
4. Preservative : used to maintain the sterility of LA ,but it may be the responsible for allergic reactions in some patiant
5. Fungicide ; to prevent fungi growth which may lead to cloudness of solution
6.Vehicle : all prevouse components dissolved in modified ringers solution which decrease the discomfort during injection
Role of vasoconstrictors in local anasthesia
• decrease rate of absorption
• Decrease plasm level of LA and so decrease its toxicity
• Increase duration of local anasthesia
• Decrease bleeding at the site of injection
Dilution of the vasoconstructors
• Dilution refered to ratio ( e.g 1 / 1000) (gram /ml) which mean 1gram of vasoconstrictor in 1000 ml of solution
• Availability in dentistry • 1:50000
• 1:80000
• 1:100000
• 1:200000
Specific types of vasoconstrictor
1. adrenaline
• source : either synthetic or obtained from adrenal medulla of animals
• Mode of action ; act directly on both A and B adrenergic receptors
• Heart ; increase HR , O2 consumption, Blood pressure
• Blood vessels .. Vasoconstriction • Respiratory system … bronchodilator • CNS … not potent CNS stimulant at therapeutic
doses
Maximum doses
• For pain control
• Normal patients … 0.2 mg per appointment
5 cartridges if percentage of dilution 1:50000
11 cartridge if percentage of dilution 1:100000
22 cartridges if percentage of dilution 1:200000
. In patients with cardiovascular disease
• Safe dose … 0.04 mg per appointment
• 1 cartidges if percentage of dilution 1:50000
• 2 cartridges if percentage of dilution 1:100000
• 4 cartidges if percentage of dilution 1:200000
• For hemostatis : 1:50000 more effective but 1:100000 solution better to use to avoid vascularity compromization
noreadrenaline
• Its similar to adrenaline but it show more vascular periphral resistance , heart rate decrease ,and no effect on bronchial smooth muscles
• Availabilty in dentistry
• 1: 30000 dilution
Maximum doses • Noradrenaline four times more potent than
adrenaline so its used for pain control only and not as a heamostate
• for normal patient 0.034 mg per appointment
• For patient with cardiovascular diseases : 0.14 mg per appointment
Levonordefrin
• Synthetic vasoconstrictor • Show less cardiac and CNS stimulation than
epinephrine
• Availability in dentistry used with mepivacaine or with propoxycaine procaine in 1:20000 dilution Maximum doses : for all patients maximum dose 1mg per appointment
Felypressin
• Synthetic analogue of vasopressin (antidiuretic hormone)
• Mode of action: direct stimulant of vascular smooth muscles
• Act mainly on venous vessels
• No effect on heart or CNS
• It has both antidiuretic and oxytocic actions so its contraindicated in pregnant womens.
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