local anaesthesia undergrad
TRANSCRIPT
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Local Anaesthesia and
VasoconstrictorsDr. Hassan Abdin
Division of Oral & MaxillofacialSurgery
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Local anaesthesia
Anaesthesia is the loss of consciousnessand all form of sensation.
Local Anaesthesia is the local loss of pain,temperature, touch, pressure and all othersensation.
In dentistry, Only loss of pain sensation is
desirable. Local Analgesia.
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Local anaesthesia
Methods: Reducing temperature.
Is used only to produce surface anaesthesia e.g. ethylchloride spray.
Physicaldamage to nerve trunk e.g. nervesectioning. Unsafe for therapeutic uses, only in Trigeminal Neuralgia.
Chemicaldamage to nerve trunk e.g. neurolyticagents. Silver nitrate, Phenol - Unsafe for therapeutic use.
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Local anaesthesia
Methods:Cont Anoxia or hypoxiaresulting in lack of oxygen
to nerve.
Unsafe as well.
Stimulation of large nerve fibres, blocking theperception of smaller diameter fibres.
includes Acupuncture and TENS (TranscutaneousElectronic Nerve Stimulation)
Drugsthat block transmission at sensorynerve endings or along nerve fibres.
There action is fully reversible and withoutpermanent damage to the tissues.
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Local anaesthesia
Properties of Ideal local Anaesthetic:
Possess a specific and reversible action.
They stabilize all excitable membrane including motorneurones
CNS is extremely sensitive to its action.
Non-irritant with no permanent damage totissues.
No Systemic toxicity
High therapeutic ratio.
Rapid onset and long duration
Active Topically or by injection
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Local anaesthesia
Chemistry:
They are weak bases, insoluble in water
converted into soluble salts by adding Hcl for clinical use.
They are composed of three parts: Aromatic(lipophilic) residue with acidic group R1.
Intermediatealiphatic chain, which is either ester or amidelink R2.
Terminal amino(hydrophilic) group R3and R4.
R3R1CO R2 N
R4
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Classi f icat ion:
Classified according to their chemical structures
and the determining factor is the intermediate
chain, into two groups:
Ester Amide
They differ in two important respect: Their ability to induce hypersensitivity reaction.
Their pharmacokinetics - fate and metabolism.
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Physiochemical properties:
These are very important for localanaesthetic activity.
Ionization: They are weak base and exist partly in an
unionized and partly in an ionized form.
The proportion depend on:
the pKa
or dissociation constant
The pH of the surrounding medium.
Both ionizing and unionizing are important inproducing local anaesthesia.
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Physiochemical properties: (cont.)
pKa is the pH at which the ionized and
unionized form of an agent are present in
equal amounts. The lower the pKa , the more the unionized
form, the greater the lipid solubility.
The higher the pKa , the more the ionizedform and the slower the lipid solubility
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Physiochemical properties: (cont.)
Cont:
Unionized form is able to cross the bi-lipidnerve membrane.
The ionized form then blocks conduction.
Some of the unionized inside the cell will
become ionized depending upon the pKaand the intracellular pH (lower thanextracellular)
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Physiochemical properties: (cont.)
Cont:
In general the amide type have lower pKa,and greater proportion of the drug ispresent in the lipid-soluble (unionized)form at the physiological pH
This produces faster onset of action.
Lignocaine 12 minutes Procaine 25 minutes.
The lower the pKathe faster the onset.
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Physiochemical properties: (cont.)
Partition coefficient:
This measures the relative solubility of anagent in fat and water.
High numerical value means:
High lipid-soluble
less water-soluble.
More fat solubility, means rapid crossing ofthe lipid barrier of the nerve sheath.
The greater partition coefficient, The faster the onset
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Physiochemical properties: (cont.)
Protein binding: Local anaesthetic agents bind with:
1-acid glycoprotein, which possess high affinitybut low capacity.
Albumin, with low affinity but high capacity The binding is simple, reversible and tend to
increase in proportion to the side chain.
Lignocaine is 64% bound, Bupivacaine is 96% The duration of action is related to the degree
of binding.
Lignocaine 15 45 minutes, Bupivacaine 6hours
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Physiochemical properties: (cont.)
Vasodilatory ability:
Most Local anaesthetics possess avasodilatory action on blood vessels except
Cocaine. It influence the duration of action of the
agent.
Prilocaine is 50% bound to proteins but has a
longer duration than Lignocaine (64%) sinceit possess no strong vasodilatory effect.
Affect the duration of action of the agent
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Physiochemical properties: (cont.)
Summary
Rapid Onset:
Low pKavaluemore unionizedAmides
Higher Partition coefficientmore lipid soluble
Long duration of action:
High protein binding.
Low vasodilating property.
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Physiochemical properties: (cont.)
Agent pKa %basepH 7.4
P-C P-B t0.5
(m)
Max dosemg/kg
Lignocaine 7.9 25 3 64 90 4.4
Prilocaine 7.9 25 1 50 90 6.0Mepivacaine 7.6 33 1 77 120 4.4
Bupivacaine 8.1 17 28 96 160 1.3
Etidocaine 7.9 25 141 94 160 8.0
Procaine 9.0 2 0.6 6 6 6.0
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Pharmacodynamics:
Pharmaco log ical act ions:
Reversible block of conduction in nerve.
Direct relaxation of smooth muscle & inhibitionof neuro-muscular transmission in skeletalmuscle producing vasodilatation.
Intra-arterial procaine reverse arteriospasmduring I.V. Sedation
Class I antidysrhythmic-like action on theheart.
Stimulation and/or depression of the CNS.
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Pharmacodynamics:
Mechanism of Act ion : (cont.)
The site of action is the nerve cellmembrane
Theories:
The membrane expansion theory.
The specific binding theory.
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Pharmacodynamics:
Mechanism of Act ion : (cont.)
Membrane expansion theory:
A non-specific mechanism similar to the actionof general anaesthetic agents.
Relies upon the lipophilic moiety of localanaesthetic agent.
The molecules of the agent are incorporated
into the lipid cell membrane.
The resultant swelling produces physical obstruction ofthe sodium channels, preventing nerve depolarization.
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Pharmacodynamics:
Mechanism of Act ion : (cont.)
Specific receptor theory:
Local anaesthetic drug binds to specific receptor within
the sodium channel producing physical obstruction to
entry of sodium ions.
The act of binding produces a conformational changes
within the channel.
It bind to a closed gate and maintain it in the closed
position.
It is, then, essential that the nerve fires, and the gateassumes the closed position. (Use-dependant
phenomenon
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Fate & Metabo l ism :
Absorption:
Many factors influence entry of local anaestheticinto the circulation:
Vasodilating ability of the drug.
Volume and concentration.
Vascularity of the tissues.
The route of administration.
The presence of vasoconstrictor.
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Ester-type drugs
Cocaine: The first and most potent local anaesthetic
agent, rarely used because of the problems of
misuse. It is unique in it is ability to produce intense
vasoconstriction. Half life 30 minutes.
Dosage: Used as topical 410% solution Maximum dose is 1.5 mg/kg100mg max.
Used intranasally during apical surgery.
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Ester-type drugs
Procaine:
The only indication for its use in dentistry is inpatients with proven allergy to the amide group.
Used intra-arterially, as part of the recognizedregimen, to treat the arteriospasm which mightoccur during intravenous sedation.
It has an excellent vasodilatory properties.
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Ester-type drugs
Procaine (cont)
Onset & duration of Action: Has a very shot duration (5 minutes) and a long onset
time of 10 minutes
Dosages: The maximum dose is 6 mg/kg, 400 mg max.
Used as 2% with 1:80 000 epinephrine to increaseefficacy.
Metabolism: Rapidly by plasma esterase.
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Ester-type drugs
Benzocaine:
Used mainly as topical, due to its poor watersolubility, and because of its low toxicity, it is
used in concentration up to 20%.
Hydrolyzed rapidly by plasma esterase to
p-aminobenzoic acid accounting for its lowtoxicity.
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Fate & Metabolism:
Metabolism of Ester drugs: Metabolized in plasma by
peudocholinesterase enzyme, and some inthe liver.
People, who lack the enzyme, are at risk ofan overdose by the ester type localanaesthetic
Para-aminobenzoic acid (PABA) is the major
metabolite of ester with no anaestheticeffect.
It is the agent responsible for ester allergies.
Rapid metabolism procaine half-life is 2 minutes
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Amide-type drugs:
Lignocaine (Lidocaine):
Synthesized in 1943 and used in dentistrysince 1948 and is also known as Xylocaine
It highly lipophilic (partition coefficient 3) ,rapidly absorbed.
Metabolized only in the liver and its
metabolites are less toxic with no action. Has half-life (t0.5) of 90 minutes
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Amide-typedrugs
Lignocaine (con t)
Dosage:
4.4 mg/kg300 mg max Used as 2% plain or with 1:80 000 epinephrine
4 and 10% spray, 2% gel and 5% ointments. Onset & duration of action:
Rapid onset 23 minutes
Plain- short duration (10 minutes)
With epinephrine- intermediate duration (4560 minutes)
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Amide-type drugs
Prilocaine:
A very potent local anaesthetic and is less toxicthan Lignocaine.
It produces less vasodilatation than lignocaine
Rate of clearance is higher than other amide-types, suggesting extra-hepatic metabolism
with relatively low blood concentration. Its metabolite o-toluidine lead to methaemo-
globinaemia (more than 600 mg in adults)
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Amide-type drugs
Pri locaine:
Used either plain 4% or 3% combined with0.03IU/mL of Felypressin as vasoconstrictor.
Onset & Duration:
Slower onset4 minutes. Its duration of action is similar to Lignocaine.
Dosage; 6.0 mg/kgmax. 400 mg.
Combined with Lignocaine as a topicalanaesthetic agent to be used prior to vene-section and during dental sedation in children.
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Amide-type drugs
Mepivacaine:
Possess the least vasodilating effect.
Metabolized in the liver and has t0.5 of 120
minutes.
Its main indication is when local anaestheticwithout vasoconstrictor is needed. 3% plain is
more effective than lignocaine. Onset & duration:
Rapid onset but slightly shorter duration.
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Amide-type drugs
Bupivacaine: A long-acting local anaesthetic agent, with a t0.5of
160 minutes due grater binding capacity to plasmaprotein and tissue proteins
Metabolized in the liver. Used mainly in Oral surgical procedures for its long-
lasting pain control.
Longer onset and longer duration (Regional 68 hors)
Dosage: 1.3 mg/kgMax 90 mg
0.250.75% with or without adrenaline 1:200 000
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Amide-type drugs
Etidocaine:A long-acting agent similar to Bupivacaine but
with faster onset.
Metabolized in the liver. Dosage:
8 mg/kgMax 400 mg
1.5% with 1:200 000 epinephrine.
Lignocaine is the most common used agent bothtopically and by injection as 2% with or withoutadrenaline, with a maximum dose of 4.4 mg/kg.
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Fate & Metabolism:
Amide Drugs: metabolized in the liver, except Prilocaine
which undergo some biotransformation inthe kidney and lungs.
Some of the metabolites possess localanaesthetic and sedative properties.
Normal local anaesthetic dose in patient withimpaired liver function will result in relativeoverdosage.
Old age patient shows reduction in liver function
Reduce dose
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Vasoconstrictors
Originally added to reduce systemicuptake in an attempt to limit toxicity.
Prolong the duration
Produces profound anaesthesia. Reduce operative bleeding.
Two types: Sympathomimetic naturally occurring.
Synthetic polypeptides, Felypressin
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Vasoconstrictors
Epinephrine: (Adrenaline) Uses in dentistry:
Local anaesthetic solution.
Gingival retraction cords. In the ER as life-saving drug in anaphylaxis.
Mechanism of action: Interact with adrenergic receptors in the vessels
1 & 2 producing vasoconstriction in skin & MM
2 stimulation causing vasodilatation in skeletal muscles.
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Vasoconstrictors
Epinephr ine
Metabolism:
Appears very rapidly in the systemiccirculation !!!
Exogenously administered epinephrine ismetabolized extraneuronal and 1% isexcreted in the urine unchanged.
Dosage:
1:80,000 is the commonest dose used,12.5 g/ml
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Vasoconstrictors
Epinephr ine
Systemic effect:
Being a naturally occurring hormone, it exerta number of physiological responses on the
different systems. The heart:
Has direct and indirect action.
Direct action on 1receptors increases the rate and
force of contraction raising cardiac output. Indirect action, increase pulse and cardiac output,
lead to rise in systolic blood pressure, (not withdental dose)
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Vasoconstrictors
Epinephr ine
Blood vessels:
Contain 1,2and2 adrenoreceptors inthe vessels of the skin, mucous membrane
and skeletal muscles.
1receptors causes vasoconstriction since they
are susceptible to endogenous nor-epinephrine
and exogenous epinephrine. Reduce operativebleeding
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Vasoconstrictors
Epinephr ine
2receptors are only susceptible tocirculating epinephrine.
2 found in the skeletal muscles, andvery uncommon in the skin and mucousmembrane. 2stimulation result in
vasodilatation, lowering peripheralresistance and a fall in the diastolicblood pressure. (with dental dose)
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Vasoconstrictors
Epinephr ine
Haemostasis:
The vasoconstricting effect.
Adrenaline promote platelets aggregation in the earlystages.
Fibrinolytic activity compromise clot stability. Lungs:
Stimulation of 2receptors in the lung lead to bronchialmuscle relaxation, life-saving in bronchial (spasm)constriction during anaphylactic reaction.
Wound healing:
Reduced local tissue oxygen tension.
Epinephrine-induced fibrinolysis.
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Vasoconstrictors
Felypressin: It is an analogue of the naturally occurring Vasopressin.
Bind to vasopressin V1receptor in the vascular smoothmuscle producing vaso-constriction and reduce local blood
flow. Less potent than the catecholamines &poorer control of
bleeding during operative procedures.
Acts on the venous side rather than the arterial side.
Dose: 0.03 IU/ml (0.54 g/ml)