1. Local anesthesia
Lecture 3

2. Composition of local anesthetic solution
Local anesthetic agent
Vasoconstrictor
Preservative
Reducing agent
Fungicidal agent
Sodium chloride and distilled water

3. Local anesthetic agent
Amide
Lidocaine
Mepivicaine
Prilocaine
Articaine
Bupivicaine
Etidocaine
Ester
Cocaine
Procaine
Propoxycaine
Other agents:
TCAD
Tramadol
Diphenhydramine
meteclopromide
neosaxitoxin

4. 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 min (soft tissue)
Maximum recommended dose (MRD)= 4.4mg/kg =300 mg

5. Metabolism and safety
Lidocaine metabolized in liver and excreted in urine (10% unchanged completely)? Contraindicated in end stage liver disease
On CNS large dose cause initial stimulation followed by depression ( anticonvulsant effect)
On CVS large dose cause myocardial depression ( used in ventricular tachycardia)

6. Maximum dose calculation
Available concentration =2% =2gm in each 100 ml /100
→→→→0.02gm/ml = 20 mg/ml
*2 ml/dental cartridge =40 mg /dental cartridge
300 /40 = 7.5 dental cartridge (MRD)
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7. 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% → 7.5 cartridge
3% → 5 cartridge
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8. Prilocaine (citanest)
Same potency to lidocaine
Less toxicity
Less vasoldilating activity
PKa =7.9
MRD =6mg/kg
3% → ?? cartridge
4% → ??? cartridge

9. 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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10. 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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11. Child and mentally retarded patient
Bupivicaine
Four times more potent than lidocaine and 4 times less toxic
Slower onset (5-10 min) and extended duration lasting for 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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12. Similar to bupivicaine except: More toxic than lidocaine
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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13. Ropivicaine
A newer long acting local anethesia as an isomer of bupivicaine with minimum toxicity and more effectiveness

14. Local anesthetic agent
Amide
Lidocaine
Mepivicaine
Prilocaine
Articaine
Bupivicaine
Etidocaine
Ester
Cocaine
Procaine
Propoxycaine

15. Oldest anesthetic agent used since 18th century
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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16. 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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17. 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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18. H W MD calculation in prilocaine
Other agents having local anesthetic properties
WriteAbout
EMLA, carbonated local anesthesia

19. Composition of local anesthetic solution
Local anesthetic agent
Vasoconstrictor
Preservative
Reducing agent
Fungicidal agent
Sodium chloride and distilled water

20. Vasoconstrictor Reduce blood flow thus reduce bleeding
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

21. Types of vasoconstrictor
Adrenergic agonist agent
Vasopressin

22. Adrenergic agonist agent (sympathomimetic agent) - catecholamine
Mode of action:
Direct (binding)
Indirect (displacing)
Mixed action

23. Sympathetic receptors:
1 vasoconstriction
2 Reuptake
1 Cardiac stimulation
2 Vasodilatation

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

25. HO CH CH NH OH 1 2 HO 1 2 CH H H H CH H Epinephrine Levonordefrin3
Levonordefrin CH H 3
Norepinephrine H H

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

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

29. 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: commonly used concentration
1: low concentration used for medically compromised patient (vasoconstrictor contraindicated) and where hemostasis is of little importance

30. 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

31. 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

32. Metabolism of catecholamines
Adrenergic
Extraneuronal
Renal
nerve terminal
tissues
excretion
[ COMT]
MAO
MAO
[ COMT ]
Injected
drug a
Receptor
COMT: Catechol-O-methyltransferase
MAO: monoamine oxidase

33. 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

34. 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

35. Vasoconstrictors (epinephrine, Levonordefrin) with
Tricyclic antidepressants (imipramine, desipramine)
Hypertensive and/or cardiac reactions are more likely. Use epinephrine cautiously; avoid Levonordefrin.

36. Vasoconstrictors (epinephrine, Levonordefrin) with
Volatile anesthetics
(halothane)
Increased possibility of cardiac arrhythmias exists for some agents. 1 µg/kg safe dose for halothane with thiopental induction.

37. Vasoconstrictors (epinephrine, Levonordefrin) with
Nonselective beta blockers
(Propranolol, Nadolol)
Hypertensive and/or cardiac reactions are more likely. Use cautiously.

38. Vasoconstrictors (Epinephrine, Levonordefrin) with
COMT inhibitors
(Tolcapone, Entacapone)
Hypertensive and/or cardiac reactions are more likely. Use cautiously.

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

40. 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

41. 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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42. Maintains sterility of the solution
Preservative
Maintains sterility of the solution
Caprylhydrocuprienotoxin used for this purpose
Methylparaben used in the past but nowadays omitted ?
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43. 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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44. Sodium chloride and distilled water
Fungicide
Thymol
Sodium chloride and distilled water
(ringers solution)
For isotonicity of injected solution to reduce edema and discomfort on injection