Pharmacology and use of local anesthetics in dentistry.

1. LOCAL
ANAESTHETICS
DR.VRUSHALI MAHAMUNI-TARKASBAND
B.D.S.(M.D.S.CONS &ENDO) 07/05/2020

2. Table of contents-
Introduction
Definition
History
Classification
Properties of local anaesthetics
Composition
Indications
Contraindications
Basic physiology of nerve conduction.
Mechanism of action
Pharmacokinetics of local anaesthetics
Complications of local anaesthetics
Individual local anaesthetic agents
Recent advances
Conclusion.

3. Introduction-
Pain is one of the most commonly experienced symptoms in dentistry. It is often
spoken of as a protective mechanism since it is usually manifested when an
environmental change occurs that causes injury to responsive tissues.
Local anaesthetics when used for the management of pain differ from most other
drugs commonly used in Medicine and Dentistry in one very important manner.

4. Definition-
Local anesthesia is defined as a loss of sensation in a circumscribed area of the
body caused by a depression of excitation in nerve endings or inhibition of the
conduction process in peripheral nerve. -(Grune & Straton-1976)
Local anesthesia is also defined as a transient regional loss of sensation to a
painful or potentially painful stimuli resulting from a reversible interruption of
peripheral conduction along a specific neural pathway to its central integration
and perception in the brain.

5. PAIN:The International Association for the Study of Pain (IASP)
defines pain as “an unpleasant sensory and emotional experience
which we primarily associate with tissue damage or describe in
terms of such damage, or both.”
LOCAL ANESTHETICS: are chemicals that reversibly block the
action potentials in all excitable membranes.

6. History-

7. Classification-
According to the chemical structure-
1)Ester group
(a)Benzoic acid esters
◦ Cocaine
◦ Benzocaine
◦ Butacaine
◦ Hexycaine
◦ Piperocaine
◦ Tetracaine
(b)Para-amino benzoic acid esters
◦ Procaine
◦ Propoxycaine
◦ 2-chloroprocaine
2) Non Ester group -
(a) Amide group
 Bupivacaine
 Articaine
 Dibucaine
 Etidocaine
 Lidocaine
 Mepivacaine
 Prilocaine
(b) Quinoline derivative
Centbucridine

8. Based on biological site and mode of action.
1)Class A: Agents acting at receptor site on external surface of
nerve membrane.
Chemical substance: Bio toxins
Tetrodotoxin
2)Class B: Agents acting at receptor site on internal surface of
nerve membrane.
Chemical substance: Quaternary analogs of lidocaine
Scorpion Venom.
3)Class C: Agents acting by a receptor independent
mechanism
Chemical substance: Benzocaine.
4)Class D: Agents acting by combination of receptor and
receptor: Independent mechanism
Chemical substance: Lidocaine
,Mepivacaine,Prilocaine.

9. Based on duration of action -
1)Ultra short acting-
Less than 30 min
Eg: 2% Lidocaine without a vasoconstrictor.
2)Short acting
45 to 75min
Eg: 2% lidocaine with 1:100,000 epinephrine
3)Medium acting
90 – 150 minutes
Eg: 4% Prilocaine with 1:200,000 epinephrine
4)Long acting
180 minutes a longer
Eg: 0.5% Bupivacaine with 1:200,000
epinephrine

10. Based on mode of application
A)Topical- Soluble :Lidocaine.
Tetracaine.
Non soluble: Benzocaine.
B)Injectable-
Short duration-
Intermediate duration-
Long duration-

11. Properties-
Its action must be reversible
It must be non-irritating to the tissues and produce no secondary local reaction.
It should have low grade of toxicity.
It should have a rapid onset and be of sufficient duration to be advantageous.
It should have potency sufficient to give complete anaesthesia without the use of
harmful concentrated solution.

12. It should have sufficient penetrating properties to be effective as a topical
anaesthesia.
It should be relatively free from producing allergic reactions.
It should be stable in solution and undergo biotransformation readily within the
body.
It should be either sterile or capable of being sterilized by heat without
deterioration.

13. Composition-
The local anaesthetic solutions contains the following constituents.
Local anaesthetic agent.
Vasoconstrictor.
Reducing agents.
Preservative.
Fungicide.
Salt to make it isotonic.
Vehicle.


14. a) Local anaesthetic agent-
2% lignocaine hydrochloride.
Recommended dose of 2% lignocaine with adrenalin
A)Normal healthy patient
16 ml of a 1:80,000 dilution.(8 cartridges)
B)Patient with cardiovascular disease.
3.2 ml of a 1:80,000 dilution.(1.6 cartridges)

15. Role of vasoconstrictor drugs in local anesthetics
solution-
The LA drugs are vasodilators with the exception of cocaine. Therefore, these
drugs are combined with vasoconstrictor agents in order to avoid undesirable
effects of the anesthetic agents.
Advantages-
As the absorption is slow
The duration of action is prolonged.
The efficacy of LA solution is increased.
They reduce the toxicity of the drug by slow absorption.
A bloodless surgical area is achieved by its presence.

16. The Vasoconstrictors used are:
(1) Adrenaline
(2) Nor adrenaline
(3) Felypressin
Maximum Dose for Dental Appointment
◦ Normal healthy patient
0.2 mg. per appointment
◦ Significant cardiovascular impairment
0.04 mg per appointment
1:200000 or 1:300000 with lidocaine are preferred for pain control.
1:100000 epinephrine is used for extended pain control

17. a) Local anaesthetic agent-
2% lignocaine hydrochloride.
Agents Onset in min Duration in Hrs
1) Lidocaine 2% 2-4 1-2
2) Lidocaine with 1: 10000
epinephrine
2-4 3-4
3) Lidocaine with 1: 15000
epiephrine
2-4 3-4
4)Mepivacaine 3% 2-4 3-4
5) mepivacaine 2% with 1:20000
Levonordefrin
2-4 3-4
6) Prilocaine 4% 2-4 1.5-2
7) Prilocaine wih 1:20000
epinephrine
2-4 2-4
8) Etidocaine 1.5% with 1:20000
epinephrine
2-4 4-9
9) Bupivacaine 4% with 1:20000
epinephrine
5-8 4-9

18. c) Reducing agent-
A reducing agent in the form of Sodium Metabisulphite is
added. This competes with the available oxygen and gets oxidised
thereby preserving the vasoconstrictor.
d) Preservative-
In the form of Methyl paraben in added to prolong the
shelf life. If patient is allergic to this, the other alternation is
capryl hydro cuprinotoxin.

19. e) Fungicide-
In the form of thymol is used. This prevents clogging of solution due to development of fungi.
f) Salt-
In order to make the LA solution isotonic with the body ph, salts are added to it.
5-6 mg of sodium chloride.
g) Vehicle-
Ringers solution, used since it is isotonic and is less irritable to tissues when they are injected.
In general, it is used to produce insensibility of pain of the teeth and supporting structures.

20. DOSE CALCULATION-
2% Lignocaine with 1:80,000 Epinephrine.
2% Lidocaine means 2gm in 100ml of solution.
2000mg in 100ml of solution.
20mg in 1ml of solution.
1:80,000 Epinephrine in lidocaine means
1gm in 80,000ml of sol.
1000mg in 80,000ml of sol.
1mg in 80 ml of sol.
0.0125 mg in 1 ml of sol.

21. Indications-
Extraction of teeth.
Surgical removal of teeth
Alveoloplasty and alveolectomy
Incision and drainage of abscess
Cavity preparation especially in deeper painful cavities
Pulp procedures like pulpotomy and pulpectomy
Cyst enucleation a marsupialization
Treatment of trismus
Diagnostic test of various facials pains especially trigeminal neuralgia
As a treatment therapy of trigeminal neuralgia
In radiography when the patient is gagging due to placement of film in the mouth

22. Contraindications-
Fearful and apprehensive patients who refuse for injection.
Allergy to local anaesthesia
Acute infection – as there is fear of needle contamination and spread of
injection into various planes. Moreover, they are ineffective in acidic
medium.
Mentally retarded and un-cooperative children or very young children.
Hyperthyroidism – since it contains vasoconstrictor and can produce
thyroid crisis.
Liver disorders – as the drug is metabolised in the liver.

23. Renal disorders especially renal failure as the drug is excreted through the
kidney.
Patients with cardiac problems especially ischemia, infarction, coronary artery
blockade.
Patients with diabetes mellitus as the vasoconstrictor present in the solution
mobilizes the liver glycogen to increase the blood sugar levels
Major surgical procedure should not be undertaken under local anaesthesia as
they are time consuming procedures needing wider area of exposure and one
may the co-operation of the patient.

25. Basic physiology of nerve conduction-
Electric potential is negative (-70 to -90mV)

26. Firing threshold potential -appoximately -50to -60mV
Electric potential in depolarizing phase becomes +40 mV

27. Return of membrane potential to its original level (-70mV)

28. Mechanism of action-
It is possible for local anesthetics to interfere with the excitation process in a
nerve membrane in one or more of the following ways:
Altering the basic resting potential of the nerve membrane.
Altering the threshold potential.
Decreasing the rate of depolarization.
Prolonging the rate of repolarization.

29. THEORIES OF MECHANISM OF L.A…
Ca2+ DISPLACEMENT THEORY (Goldman-1966)
SURFACE CHARGE THEORY (Wei-1969)
ACETYLCHOLINE THEORY (Dett barn-1967)
MEMBRANE EXPANSION THEORY (Lee-1976)
SPECIFIC RECEPTOR THEORY (Strichartz-1987)

30. 1. Calcium displacement theory
According to this theory,Displacement of Ca++ ions from nerve
membrane plays an important role in nerve membrane permeability to Na+ ions
which is blocked by LA.
But, various concentration of Ca++ ions bathing a nerve does not affect LA
potency disproves the efficacy of this theory.

31. 2. Surface Charge (Repulsion) theory
According to this theory ,LA acts binding to the nerve
membrane and changing the electric potential across the nerve
membrane surface.
But, resting membrane potential of nerve membrane, remains
unultered by local anaesthetic agents(they do not become
hyperpolarized)

32. 3. The acetylcholine theory-
According to this theory- Acetylcholine (neurotrnsmitter) is involved in
nerve conduction.
However, there is no evidence that acetylcholine is invoved...

33. 4. Membrane Expansion Theory -

34. 5. Specific Receptor Theory
LA act by binding to specific receptors on the Na+ channel, Direct action
of LA rather than change in general properties of cell membrane is responsible
for its mechanism.
Four sites in Na+ channel at which drugs can alter nerve conduction –
1. Within the Na+ channel (30amine).
2. Outer surface of Na+ channel (Tetrodoxin & Saxitoxin)
3. Either activation or, inactivation gates (Scorpion venom).

36. How local anesthesia works ?-
Displacement of calcium ions from the sodium channel receptor site, which permits..
Binding of the local anesthetic molecule to this receptor site ,which produces..
Blockade of sodium channels and …
Decrease in sodium conductance ,which leads to ..
Depression of rate of electric depolarization, and
Failure to acheive threshold potential level along with ..
Lack of development ofaction potentials, which is called ..
Conduction blockade

37. Pharmacokinetics of local anesthesia-
Absorption-
Since all local anaesthetic agents except for cocaine are vasodilator,
they are rapidly absorbed into blood stream from the point of injection.
Factors affecting the absorption and nerve conduction-
i) Vasoconstrictor in solution- Less readily absorbed
ii) Tissue pH- low pH – interference with achieving adequate anesthesia.
iii) Site of injection- rapid absorption in highly vascular area
v) Type and size of nerve- myelinated nerves and thicker diameter nerves
requires higher conc.of LA solutions.

38. Bio transformation of the drug-
Distribution-
The higher concentration are reported from blood rich organs like liver,
kidney, heart, skeletal muscle and brain.

39. Metabolism-
Ester LA-
Plasma by the enzyme plasma
cholinesterase.
Amide LA-
In liver by microsomal enzymes.

40. Excretion-
 Kidneys are the primary
excretory organ.
 Renal impairment
causes accumulation of
drug and its metabolites
causing toxcity.

41. COMPLICATIONS OF LOCAL ANESTHESIA
Local complications
Needle breakage
Prolonged anesthesia or paraesthesia
Facial nerve paralysis
Trismus
Soft tissue injury
Haematoma
Pain on injection
Infection
Edema
Sloughing of tissues
Post anesthetic intraoral lesions

Systemic complications
 Allergy
More common with Ester local anesthetics
 Fever
 Angioedema
 Urticaria
 Dermatitis
 Depression of blood forming organs
 Photosensitivity
 Anaphylaxis
 Overdose reactions
More common with Amide local anesthetics

43. MINIMAL TO MODERATE OVERDOSE-
SIGNS
Talkativeness
Excitability
Apprehension
Slurred speech
Stutter( Muscular twitching / tremors )
Euphoria
Dysarthria
Nystagmus
SYMPTOMS:
Light-headed and dizzy
Restless
Nervous
Numbness
Nervousness
Sensation of twitching (before actual
twitching is observed)
Metallic taste
Visual disturbances
Auditory disturbances
Drowsy and disoriented
Losing consciousness
Sweating
Nausea/vomiting
Failure to follow commands
Elevated BP
Elevated heart rate
Elevated resp rate

44. MODERATE TO HIGH OVER DOSE
Generalized tonic-clonic seizure activity
followed by
Generalized CNS depression
Depressed BP, heart rate
Depressed respiratory rate.

45. Management
• Terminate the dental
treatment as soon as the
signs of toxicity first
appear.
• Provide basic life support

46. Individual local anaesthetic agents-
Procaine HCL-
• Is a 2-diethylaminoethyl 4-aminobenzoate HCL.
• The first synthetic injectable local anesthetic.
• Procaine produces the most vasodilatation of all clinically used LA.
• The maximum recommended dose-1000mg.

47. •Propoxycaine HCL-
• Is a 2-diethylaminoethyl 4-amino-2-
propoxybenzoate HCL.
• propoxycaine was combined with procaine to
provide a more rapid onset and longer lasting
anesthesia.

48. Lidocaine HCL-
Classification – Amide group
•Chemical formula – 2 Diethylamino-2,6 actetoxylidide HCl
•Synthesized in1943 and marketed in 1948
•Produce more rapid onset of action and longer duration of action.
•It represents the “gold standard”, the drug against which all new local anesthetics are compared.
•Max. recommended dose-
• adult- 7mg/kg , children- 4.4mg/kg.
•It available in three formulations-
2% without a vasoconstrictor.
2% with epinephrine 1:50,000.
2% with epinephrine 1:100,000.

49. Mepivacaine HCL-
•Prepared by A.F EKENSTAN.
•The mild vasodilating properties.
•3% mepivacaine plain – 20-40 min of pulpal anesthesia.
•2% mepivacaine with vasoconstrictor produce-
-Pulpal anesthesia 60min.
-Soft tissue anesthesia 3-5 hr.
• Signs and symptoms of overdose follow the CNS stimulation followed by
depression.

50. Prilocaine HCL-
Prepared by lofgren and tegner 1953.
•Clinical actions of plane prilocaine-
infiltration-10-15min (pulpal anesthesia)
90-120 c)
regional nerve block-
60min (pulpal anesthesia)
2-4 hr (soft tissue anesthesia)
•Cinical actions of prilocaine with 1:200,000 epinephrine
Pulpal anesthesia 60-90min.
Pulpal anesthesia 3-8 hr.

51. Articaine HCL-
• Prepared by H.Rusching et al.
• Originally known as carticaine.
• It posses thiophene ring.
• Articaine with 1:100,000 epinephrine provide-
pulpal anesthesia 60-75 min.
• Articaine with 1:200,000 epinephrine provide-
pulpal anesthesia 45-60 min.
• Effective conc. 4% with 1:100,000 or 1:200,000 epinehrine.
• Max. Recommended dose is 7mg/kg of body weight.

52. Bupivacaine HCL-
Prepared by – Ekensman in 1975.
There are two primary indications-
1)lengthy dental procedures.
2) management of postoperative pain.
Onset of action- 6-10 min.
Max. recommended dose is 1.3mg/kg of body weight.

53. Etidocaine HCL-
Onset of action 3 min.
Duration of action 90- 180 min.
Effective dental conc. 1.5%.
Recommended dose is 8mg/kg of body weight.

54. Cocaine HCL-
•Onset of action-1min.
•Duration of action-2hr.
•Only LA demonstrated to produce vasoconstriction.
•Mild overdose- euphoria, excitement,restlessness, tremor, tachycardia.
•Acute overdose- excitement, restlessness, confusion, nausea, vommiting.
•Available in conc. Ranging from 2% to 10%.

56. TOPICAL LOCAL
ANAESTHETIC AGENTS-
Benzocaine-
•Benzocaine is available as aerosol, gel, patch,
ointments or liquids. It works in much the same
way as lidocaine.
•Poor absorption into cardiovascular system
•Remains at the site of application longer,
providing a prolonged duration of action.

58. EMLA-
The cream is a 1: 1 oil/water emulsion
of a eutectic mixture of lidocaine (2.5%)
and prilocaine(2.5%) bases.
EMLA is available as cream & discs.
Disc is a white round cellular disc preloaded with EMLA packaged in
a protective laminate foil surrounded with adhesive tape.

59. LIDOCAINE-
• Is available in two forms for topical application-
- Lidocaine base.
-Lidocaine HCL.
•Max. recommended dose is 200mg.
•Availability-Aerosol 100mg/metered spray.
-Ointment 50mg/ml
-Patch 46.1mg/patch
-Solution 25, 50 mg/ml.

60. Tetracaine HCL–
•Is a long duration ester LA that can be injected or
applied topically.
•Highly soluble in water.
•Duration of action is 45 min.
•Max recommended dose is 20 mg.
•Availability: aerosol- 0.7mg/metered spray

61. RECENT ADVANCES-
CENTBUCRIDINE
 Quinoline derivative
 Potency is five to eight times that of lidocaine
 It does not effect CNS & CVS significantly
 Vacharajini et al conducted a study on 120 patients
comparing 0.5% centbucridine & 2% lignocaine
 He concluded that analgesic affect was well with
centbucridine.

62. HYALURONIDASE-
Breaks down intercellular substance.
Used as an additive to la because it permits soln to spread & penetrate the tissues.
Added to the anesthetic cartridge just before administering the LA.
It is available as lyophilized powder of stabilized soln
Causes rapid onset of anesthesia.
Allergic reactions have been reported.
Reduces the duration of action

63. ULTRA –LONG ACTING LOCAL
ANESTHETICS
Biotoxins:
◦ Tetradotoxin -
◦ saxitoxin -
Block Na channels of nerve membrane.
As potent as procaine.
Highly toxic & difficult to synthesize

64. pH ALTERATIONS-
◦ Alkalinization - ↑ RN:
◦ Sodium bicarbonate.
◦ Rapid onset of action.
◦ Carbonation :
◦ Helps in the rapid diffusion of local anesthetic through the nerve membranes.
◦ Decreases intracellular pH traps RNH+ in the cell.
◦ Anesthetic drug must be administered immediately after preparing the syringe.

65. CONCLUSION-
Local anaesthesia remains the back bone of pain control in dentistry.
Local anesthesia doses must be controlled.
Medical history, pharmacology of local anesthetics and basic
knowledge of anatomy are essential things to avoid the complications of
LA.
One must be prepared to handle the complications of local anesthesia
before hand.

66. REFERENCES:
oHandbook of local anesthesia ,Stanley F Malamed
oManual of local anesthesia in dentistry,AP Chitre
oCohen’s Pathways of Pulp, 10th edition

67. THANK YOU!!