2. In the name of Allah, Most Gracious, ‫ﺑ ﻢ ﷲ ﺮ ﻦ ﺮﺣ ﻢ‬
ِ ‫ِﺴْ ِ ا ِ اﻟ ﱠﺣْﻤ ِ اﻟ ﱠ ِﯿ‬
Most Merciful
And swell not thy cheek ‫وﻟ ﺗﺼﻌ ﺧ ﱠك‬
َ ‫ََﺎ ُ َ ﱢﺮْ َﺪ‬
(for pride) at men, nor ‫ﻟ ﻨ س وﻟ ﺗ ﺶ‬
ِ ْ‫ِﻠ ﱠﺎ ِ ََﺎ َﻤ‬
walk in insolence through ‫ﺄ ض ﻣﺮ ﺎ‬
ً‫ِﻲ اﻟَْرْ ِ َ َﺣ‬ ‫ﻓ‬
the earth; for Allah loveth
‫إن ﻠﻪ ﻟ ﻳﺤﺐ‬
‫ِ ﱠ اﻟ ﱠ َ َﺎ ُ ِ ﱡ‬
not any arrogant boaster
‫ﻛﻞ ﻣ ﺘ ل ﻓﺨ ر‬
ٍ ‫ُ ﱠ ُﺨْ َﺎ ٍ َ ُﻮ‬
Luqmân 18 [18 : ‫]ﻟﻘﻤﺎن‬

3. PHARMACOLOGY OF LOCAL
ANESTHESIA
Dr. Hesham El-Hawary
hesham@elhawarydentalclinic.com

4. Pharmacology of Local Anesthesia
CONSTITUENTS OF THE ANESTHETIC CARPULE

5. Anesthesia with V.C.
1. Local anesthetic agent
( L.A.)
2. Vasoconstrictor agent
( V.C.)
3. Preservative for V.C.
agent
(anti- oxidant)
4. Vehicle to make solution
isotonic
( 0.9%NaCl)

6. Anesthesia with V.C. Plain Anesthesia
(without V.C.)
1. Local anesthetic agent 1. Local anesthetic agent
( L.A.) ( L.A.)
2. Vasoconstrictor agent 2. Vehicle to make solution
( V.C.) isotonic
3. Preservative for V.C. ( 0.9%NaCl)
agent
(anti- oxidant)
4. Vehicle to make solution
isotonic
( 0.9%NaCl)

7. Keep in mind:
• The main agent in the carpule is the L.A. agent
• The other ingredients of the local anesthetic
carpule are added :
1. To potentiate the action of the L.A. agent
2. To prevent deterioration of the contents

8. Pharmacology of Local Anesthesia
THE LOCAL ANESTHETIC DRUG

9. Local anesthetic drugs
• Drugs temporary interrupt nerve conduction when
absorbed into it and have little or no irritating
effect when injected
• They are all synthetic compounds except the
cocaine

10. Properties of ideal anesthetic agent
1. Reversible action
2. Nonirritant
3. Produce no secondary local reaction (No allergic reaction)
4. No systemic toxicity
5. Rapid onset
6. Sufficient duration
7. Potent
8. Sufficient penetrating properties
9. Stable in solution and undergo biotransformation in body
10. Can be sterilized without deterioration
11. Not interfere with healing of local tissues
12. Have vasoconstrictor action or compatible with V.C.
13. Not expensive

11. Common properties of injectable LA
Agents
1. Form salts with strong acids which is water soluble
2. When injected in the body (alkali)
• Hydrolyzed by plasma proteins to free the alkaloid base which is lipid
soluble
• Undergo biotransformation
3. Affect the nerve conduction and have reversible action
4. Compatible with vasoconstrictors
5. Not or slightly irritant to the tissue in the concentration used
6. Capable of producing toxic effect when sufficient high
plasma concentration is reached

12. Mode of Action Of Local
Anesthetic Drugs
Mechanical or Reversible coagulation theory
Physiological theory
Acetyl choline and enzyme system theory
Electrical potential theory
Displacing calcium ions from receptor sites

13. Pharmacokinetics of local
anesthetics
Uptake
Potency
Duration
Biotransformation
Excretion

14. Uptake
• Most L.A. agents producing vasodilatation
• Procaine is the most potent vasodilator
• Cocaine is the only L.A. agents that produces
vasoconstriction
• Vasodilatation results in
– ↑ rate of absorption
– ↓ duration of action of anesthesia
– ↑ anesthetic blood level & risk for toxicity

15. Potency
• The majority of local anesthetics are tertiary
amines
• Few local anesthetics are secondary amines as
Procaine
• NH3 → NR3
• Local anesthetic agent is prepared in the carpule in
the form of hydrochloride salt of tertiary amine
( NR3 ̶ HCL)

16. • The free base (NR3) of the hydrochloride salt of
tertiary amine ( NR3 ̶ HCL) is liberated from its
salt (HCL) by interaction with alkaline medium,
alkaline PH, ( body fluids, NaHCO3 )
• (NR3 ̶ HCL) + NaHCO3 → NR3 + Na CL + H2 CO3

17. • In presence of tissue infection or inflammation
(Acidic PH)
The free base (NR3) of the hydrochloride salt of tertiary
amine ( NR3 ̶ HCL) fail to liberated from its salt
(HCL) & failure of anesthesia occurs
• (NR3 ̶ HCL) + Acidic PH → (NR3 ̶ HCL)

18. Duration
The following factors affect both duration & depth of
anesthetic action :
• Factors related to the anesthesia
– Lipid solubility
– Concentration and type of the drug
– Presence or absence of vaconstrictor or vasoconstriction effect
– Duration of exposure

19. • Factors related to the injection technique
– Technique ( infiltration vs. nerve block)
– Volume of the solution
– Accuracy of the technique
– Anatomical variation
• Factors related to the site of injection
– Alkalinity; Affect the ionization of the drug and the rate of liberation
of free base
– Vascularity of tissue
• Factors related to the individual to be injected
– Individual variation in response

20. Biotransformation
(metabolism)
• Ester group
– Metabolized in
• Plasma by plasma pseudo-cholinesterase enzyme
• Liver by the estrase enzyme
– Toxicity (high toxic blood level) occurs in patients with plasma
pseudo-cholinesterase enzyme deficiency ( 1 out of 2500)
• Amide group
– Metabolized in
– Liver by the liver microsomal enzymes
– Toxicity (high toxic blood level) occurs in patients with impaired
liver function (liver dysfunction)

21. Excretion
• Both groups of local anesthetics & their metabolites are
excreted by kidneys
• Patients with renal dysfunction may be unable to eliminate
local anesthetics & their metabolites from the blood with
increase risk of toxicity

22. Local Anesthetic Agents

23. Local
anesthetic
agents
Ester Group Amide Group

24. Esters
• Esters of benzoic acid
– Cocaine
– Butacaine
– Tetracaine
– Benzocaine
– Hexylcaine
• Esters of Para-aminobenzoic acid
– Procaine
– Chloroprocaine
– Ravocaine
– Propoxycaine
• Esters of Meta - amino benzoic acid
– Unacaine
– Primcaine
• Esters of Para - ethyox benzoic acid
– Intracaine

25. Amides
• Lidocaine
• Bupivacaine
• Articaine
• Mepivacaine
• Prilocaine
• Etidocaine
• Ropivacaine

26. Biotransformation of LA Drugs
• Ester group undergo biotransformation in
– Liver by the estrase enzyme
– Plasma by the cholinesterase enzyme
• Amide group undergo biotransformation in the liver

27. Contrast between ester & amide groups
Features Esters Amides
Chemical bond Ester bond Amide bond
Procaine Lidocaine
Common example
( Novocaine) ( Xylocaine)
Allergy Low Very low
Plasma
Liver
Metabolism in pseudo-
microsomal
cholinesterase
enzymes
enzyme

28. Keep in mind:
• Type: ester / amide
• Onset of action: rapid / slow
• Duration of action: Long / short
• Vasodilatation properties: VD – VC- Non
• Topical anesthetic properties: yes / no
• Metabolized in: plasma / liver
• Excreted by: kidney
• Allergy: allergic / non allergic
• Available forms: with / without VC

29. unacaine
tetracaine
buycaine
procaine
articaine
marcaine
mepivicaine
Lidocaine
Metabolism
Excretion
duration
Topical
Allergy
Onset
forms
Type
VD

30. Maximum doses of L.A. agents

31. L.A. agent Max. dose Normal dose
Lidocaine 300 mg 4.4 mg / kg
Mepivacaine 400 mg 6.6 mg / kg
Marcaine 90 mg 1.3 mg / kg
Articaine 400 mg 6 mg / kg
Prilocaine 500 mg 7 mg / kg

32. Dilution of L.A. agents

33. • The dilution of L.A. agent as 2 % means that there is
two grams (2000 mg) of the L.A. agent in 100 ml of
the solution
• 2 % means 2 g / 100 ml
• 2 % means 2000 mg / 100 ml
• 2000 mg – 100 ml
• ? mg - 1.8 ml
• ? = 1.8 x 2000 / 100 = 36 mg
• Therefore carpule of 1.8 ml contains 36 mg solution

34. The Vasoconstrictor

35. Advantages
It causes V.C. of B.V. that
1. Aid in producing local ischemia by vasocntricting the
blood vessels leading to:
1. Aids positively in producing anesthesia
2. Decreases bleeding caused by the surgical procedure
2. Decreases absorption rate of the anesthetic drug
leading to:
1. Increases duration of action of the L.A.
2. Decreases the volume of local anesthetic solution needed
3. Decreases the toxicity of the anesthetic drug
3. It stimulate the heart
Thus counteract the depressant effect of the local anesthetic agent
on the heart

36. Contra-Indications
1. Diabetics:
As V.C. counteract the action of insulin
i.e. ( increase blood glucose level)
2. Hypertensive pt:
As V.C. raises patient’s blood pressure
3. Cardiac pt.:
As V.C. stimulate the heart, produce tachycardia & increase H.R.
( this is doubtful because of the small amount used which is about
0.04 mg if 2 ml of 1:50 000 solution is used & this is about 1/5
permissible dose that can be given to cardiac pt without ill effect)

37. Contra-Indications Cont.
4. Pregnancy:
Because the V.C. causes uterine contraction & may causes abortion
5. Extraction of teeth with chronic peri-apical sepsis:
Because V.C. decrease blood flow to the tissues & may lead to dry
socket
5. Hyperthyroidism (toxic goiter):
Because V.C. specially adrenaline may cause thyroid crisis & sudden
death

38. Types of V.C.
1. Epinephrine ( adrenaline)
2. Nor- Epinephrine ( nor - adrenaline)
3. Neo- cobefrin (levonordefrin)
4. Phenylephrine (neosynephrine)
5. Felypressin (octapressin)

39. Dilution of V.C. Cont.
The dilution of V.C. 1: 1000 means
that there is one gram (1000 mg) of
the V.C. in 1000 ml ( 1 liter) of the
solution, or in other words 1.0 mg/ml
of the solution

40. • Examples
1: 50 000 means 0.02mg/ml
1 gm : 50 000 ml
1000 mg : 50 000 ml
(1000/50 000) mg : (50 000/50 000) ml
(1/50) mg : (1/1) ml
0.02 mg: 1 ml or 0.02mg/ml

41. • Examples
1: 20 000 means 0.05mg/ml
1 gm : 20 000 ml
1000 mg : 20 000 ml
(1000/20 000) mg : (20 000/20 000) ml
(1/20) mg : (1/1) ml
0.05 mg: 1 ml or 0.05mg/ml

42. A & B adrenergic receptors
• A receptors
– Vasodilatation of cardiac coronaries
– Peripheral vasoconstriction
• B1 receptors
– Increase cardiac output
– Increase heart rate
• B2 receptors
– Broncho-dilatation

43. Epinephrine Nor Levo Phenyl Felypressen
Epinephrine nordefrine ephrine
Action
CVS
RS
CNS
Potency
Toxicity
Stability
CI

44. Maximum Doses Of V.C.
V.C. Max. dose Concentration
epinephrine 0.2mg 20ml 1 : 100 000
nor epinephrine 0.34mg 10ml 1 : 100 000
levonordefrin 1.0mg 20ml 1 : 20 000
Phenylephrine 4.0mg 20ml 1 : 2 500
felypressin 0.27 IU 9ml 0.03 IU

45. Vehicle

46. • The vehicle to make the local anesthetic solution
isotonic
• The isotonicity of the local anesthetic solution is
important to produce the desired anesthetic
effect
• It may be:
– Saline solution ( 0.9 % Na CL)
– Ringer’s solution (0.5 % Na CL , 0.04 % Ca CL and
0.02 % K CL)

47. • If the injected anesthetic solution is hypotonic:
water will pass from the injected anesthetic
solution to inside the tissue cells until equilibrium
occurs between the intercellular & the
intracellular fluids & this results in:
1. Postoperative pain & delayed healing:
As water escapes from the injected solution
intercellularly:
• Increases the volume of intercellular fluid
• Rupture of the cells in the area occurs
2. Less profound anesthesia:
As viscosity of the injected solution increased due to
loss of water & thus the power of diffusion of the
injected solution in the area is reduced

48. • If the injected anesthetic solution is hypertonic:
water will escape from the intracellular fluids to
outside towards the injected anesthetic solution
until equilibrium occurs between the intercellular
& the intracellular fluids & this results in:
1. Postoperative pain & delayed healing:
As water escapes from the cells, the volume of
intercellular fluid decreases & shrinkage of the cells in the
area occurs
2. Less profound anesthesia:
As concentration of the injected solution decreased due
gain of water ( dilution of the injected solution in the area)

49. Preservative

50. • Na bisulphite (0.5mg/ml)
– It is added to local anesthetic carpule to prevent
oxidation of the V.C. agent
• Methylparaben ( 1mg/ml)
– It is added to local anesthetic carpule as preservative to
L.A. agent as Articaine
– It may cause allergic reactions
– Patients with para -group allergy (sulfa & procaine)
should not take local anesthetic carpule that contains
this preservative

51. Topical anesthetics

52. 1. Topical anesthetics that produce their effect by the
chemical action on the free nerve endings
( spray, gel, or ointment):
– Xylocaine (5-10%)
– Benzocaine (10-20%)
2. Topical anesthetics that produce their effect by the
means of the refrigerant action:
– Application of cold on the surface of mucous
membranes ( ice bags or crushed ice)
– Topical use of ethyl chloride

53. Thank You
Hesham El-Hawary
www.elhawarydentalclinic.com