local anaesthesia undergrad

8/10/2019 Local Anaesthesia Undergrad

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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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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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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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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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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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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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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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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:


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:


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)

local anaesthesia undergrad

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