local ansthesia

Local anesthesia

Lecture 3

Composition of local anesthetic solution

Local anesthetic agent
Vasoconstrictor
Preservative
Reducing agent
Fungicidal agent
Sodium chloride and distilled water

Local anesthetic agent

Amide
Lidocaine
Mepivicaine
Prilocaine
Articaine
Bupivicaine
Etidocaine


Ester
Cocaine
Procaine
Propoxycaine
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Lidocaine

Most common agent
Discovered in 1948 ( first of amide group)
Regarded as the standard
Minimal allergisity
Have topical anesthetic activity
Vasodilating activity
PKa =7.9

Onset of action = 2-3 min

Duration = 60 min (pulpal) and 60-120 min (soft tissue)
Maximum recommended dose (MRD)= 4.4mg/kg =300 mg

Metabolism and safety

Lidocaine metabolized in liver and excreted in urine (10% unchanged completely)


On CNS large dose cause initial stimulation followed by depression ( anticonvulsant effect)

On CVS large dose cause myocardial depression ( used in ventricular tachycardia)

Maximum dose calculation
Available concentration =2% =2gm in each 100 ml /100
→→→→0.02gm/ml = 20 mg/ml
*1.8ml/dental cartridge =36 mg /dental cartridge
300 /36 = 8.3 dental cartridge (MRD)
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Mepivicaine

Same potency to lidocaine
Similar to lidocaine in metabolism and excretion
Same onset
slight extended duration (weak vasodilatation)
PKa =7.6

Less toxic than lidocaine

Used for child and geriatric patient when vasoconstrictor contraindicated
MRD =4.4 mg/Kg= 300mg
2% → 8.3 cartridge
3% → 5.5 cartridge
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Prilocaine (citanest)
Same potency to lidocaine
Less toxicity
Less vasoldilating activity
PKa =7.9
MRD =6mg/kg
3% → 7.5 cartridge
4% → 5 cartridge

Prilocaine (citanest)

Metabolism occur mostly in liver into orthotolidine which can cause methemoglobulinemia in susceptible individual (patient with hemolytic anemia) if used in large dose → poor oxygen carrying capacity resulting in cyanosis
Clinically patient may have cyanosis in the lip, mucous membrane and skin. Patient may also have respiratory distress in severe cases
Treatment by methyline blue 1% injection 1-2 mg/kg IV/5min

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Articaine
Slightly more potent than lidocaine
Similar toxicity, and vasodilating activity
Some literature present a cross allergisity with sulfate so it is best to be avoided in patient allergic to sulfonamide
MRD =7mg/kg
4% → 7 cartridge
Similar to prilocaine in producing methemoglbulinemia


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Bupivicaine

Four times more potent than lidocaine and 4 times less toxic
Slower onset (5-10 min) and extended duration lasting for 90-180 min
MRD =1.3mg/kg
0.5% → 10 cartridge
• Dental Indication
• Prolonged dental procedure
• Expected post operative pain
• Contraindication
• Child and mentally retarded patient
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Etidocaine

• Similar to bupivicaine except:
• More toxic than lidocaine
• MRD= 8mg /kg available in1.5% → 13 cartridge
• In general surgery both indicated in prolonged procedure when uses of vasoconstrictor is contraindicated systemically or locally
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Local anesthetic agent
Amide
Lidocaine
Mepivicaine
Prilocaine
Articaine
Bupivicaine
Etidocaine

Ester

Cocaine
Procaine
Propoxycaine
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Cocaine

Oldest anesthetic agent used since 18th century
It is the only agent having a vasoconstrictor activity( sympathomimatic activity) and can be used topically because it is rapidly absorbed through mucous membrane
It has liability for dependence which makes its uses very limited
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Procaine
Has 50% potency and toxicity than lidocaine
It has prominent vasodilating activity which reduce its duration
PKa =9.1 (slow onset)
MRD =1000mg
• Its hydrolyses occurs in plasma by enzyme pseudocholine esterase
• High incidence of allergisity
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Propoxycaine

More potent and more toxic than lidocaine
Has rapid onset and adequate duration
It is available in combination form with procaine to reduce toxicity
0.4% propoxycaine + 2% procaine =24mg/ml
MRD =400 mg
It is indicated only in patient allergic to amide form of local anesthesia
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Composition of local anesthetic solution

Local anesthetic agent
Vasoconstrictor
Preservative
Reducing agent
Fungicidal agent
Sodium chloride and distilled water


Vasoconstrictor
• Advantages of vasoconstrictor in combination with local anesthesia:
• Reduce blood flow thus reduce bleeding
• Reduce local anesthetic absorption and toxicity (reduce systemic effect)
• Increase duration and depth of anesthesia

Types of vasoconstrictor

• Adrenergic agonist agent
• Vasopressin

Adrenergic agonist agent (sympathomimetic agent) - catecholamine

• Mode of action:
• Direct (binding)
• Indirect (displacing)
• Mixed action

• Sympathetic receptors:

• 1 vasoconstriction
• 2 Reuptake
• 1 Cardiac stimulation
• 2 Vasodilatation


Affinity of adrenergic agents on receptors
• 2
• 1
• 2
• 1
• ++
• ++
• ++
• ++
• Adrenaline
• -
• -
• ++
• ++
• Nor - adrenaline
• +
• ++
• ++
• +
• Levonordephrine
• -
• -
• +
• +
• Phenylphrine


OH

CH

CH

1

NH
Epinephrine
Levonordefrin
Norepinephrine
CH
H
H
3
H
CH
H
3
1


2

HO
2

HO

Adrenaline

Synthetic or natural abstract from adrenal medulla . It is the most common and potent vasoconstrictor.
Concentration:
Expressed in ratio gm: ml / 1: 100000
Meaning 1 gm in 100000 ml

Concentration

1:100000 means:
=1 gm in 100000 ml
=1000 mg in 100000 ml
= 0.01 mg /ml
In single dental cartridge (1.8 ml)
= 0.018 mg =18 g (microgram)


Adrenaline availability (concentration)
1:1000 (alone) is used for control of bleeding?
contraindicated in arterial bleeding- Rebound bleeding
1:50000 for surgery where hemostasis is necessary
1:80000 and 1:100000 commonly used concentration
1:200000 low concentration used for medically compromised patient (vasoconstrictor contraindicated) and where hemostasis is of little importance

Maximum recommended dose (MRD)

• Potency
• Available concentration
• MRD (mg)
• 100
• 0.2
• Adrenaline
• 25
• 1:30000
• 0.34
• Nor - adrenaline
• 5
• 1:2500
• 4
• Phenylphrine
• 15
• 1:20000
• 1
• levonordephrine


Other adrenergic agonist vasoconstrictor
Nor-adrenaline and phenylphrine have prominent alpha activity comparing to beta activity which may result in severe vasoconstriction (increase blood pressure) and ischemia.
It is contraindicated in patients with cardiac problem.
It is contraindicated in terminal extremities

Metabolism of catecholamines

MAO

MAO

Receptor

a

Extraneuronal

tissues
Renal
excretion

[ COMT ]

[ COMT]


Adrenergic
nerve terminal

Injected

drug
COMT: Catechol-O-methyltransferase
MAO: monoamine oxidase

Side effects and overdose

CNS: Fear apprehension palpitation

CVS: Cardiac stimulant effects , increase blood pressure and rebound bleeding at prolonged dental procedure.
Causes of rebound bleeding:
Adrenaline selectivity on receptor:
Low concentration  effect
High concentration  effect

Limitation of adrenergic vasoconstrictor

Precautions/contraindications
Uncontrolled Cardiovascular disease
Uncontrolled thyrotoxic goiter
Drug interactions
Tricyclic antidepressants
General anesthetics
Adrenergic antagonists
COMT inhibitors
Not MAO inhibitors


Vasoconstrictors (epinephrine, Levonordefrin) with
Tricyclic antidepressants (imipramine, desipramine)

Hypertensive and/or cardiac reactions are more likely. Use epinephrine cautiously; avoid Levonordefrin.

Vasoconstrictors (epinephrine, Levonordefrin) with

Volatile anesthetics
(halothane)

Increased possibility of cardiac arrhythmias exists for some agents.

Vasoconstrictors (epinephrine, Levonordefrin) with
Nonselective beta blockers
(Propranolol, Nadolol)

Hypertensive and/or cardiac reactions are more likely. Use cautiously.

COMT inhibitors
(Tolcapone, Entacapone)

Hypertensive and/or cardiac reactions are more likely. Use cautiously.

Vasoconstrictors (Epinephrine, Levonordefrin) with

Consideration

MRD for cardiovascular disease patient = 0.04 mg of adrenaline = 2 dental cartridge of 2ml 1:100000 concentration adrenaline
Controversy still exists on using adrenaline in controlled cardiovascular diseased patient. Explain why?

Uses of small amount available in dental cartridge is better than exposing the patient to failure anesthesia which produce pain and bleeding that can stimulate fear and increase intrinsic adrenaline that may have more dangerous effect than extrinsic adrenaline

Vasopressin (Felypressin)

Synthetic analogue of posterior pituitary hormone (Octopressin)
Act on V1 receptor that is found on venous site of microcirculation
It posses mild hemostatic effect and used only when other vasoconstrictor contraindicated
Available concentration = 0.03 IU/ml in combination with prilocaine 2% or 3%
MRD= 0.27 IU
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Preservative

Maintains sterility of the solution
Caprylhydrocuprienotoxin used for this purpose
Methylparaben used in the past but nowadays not used ?
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Reducing agent (in vasoconstrictor containing solution)
Antioxidant (reducing agent) used to prevent oxidation of vasoconstrictor that may deteriorate on exposure to sunlight (brown discoloration)
Sodium metabisulfite used for this purpose
On exposure to oxygen it will diffuse through the rubber of the cartridge where sodium metabisulfite will be converted to sodium metabisulfate (oxidized)
Oxidized instead of vasoconstrictor
Why is an old solution more acidic? Painful ? Irritant?
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Fungicide

Thymol

Sodium chloride and distilled water

(ringers solution)
For isotonicity of injected solution to reduce edema and discomfort on injection