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1. 1

2. Local anesthesia and local
anesthetic agents
Presented by :
Dr. Suman Mukherjee
1st Year MDS
V.S.D.C.H.
2

3. CONTENTS :
Introduction
History
Definition
Desirable properties of LA
Other methods to induce LA
Modes and Sites of Action
Where do LA work ?
How LA works ?
Classification
Composition
LA Agents
Action of each component
Armamentarium
Local Complications
Systemic Complications
Adverse Drug effect
Checklist to treat overdose
Contraindications for LA
References
Acknowledgement
3

4. Introduction …
• An anesthesia is
derived from the
word (an-without
Aisthetos-sensation
it was given by oliver
bendel in 1846.)
4

5. History…
• 500’s : Coca
leaves used by
Peruvians for
psychotropic
effect.
• 1850’s: German
chemist Albert
Neimann
successfully
isolated the
active principle
of coca leaf ; and
named it cocaine.
5

6. • 1884 : Carl Koller introduced cocaine
into medical practice.
• 1884 : LA was used in dentistry by
Halsted and Hall
• 1905 : Einhorn reported the synthesis
of ‘Procaine’. It’s anesthetic properties
were identified by ‘Biberfield’ and the
agent was introduced into clinical
practice by ‘Braun’.
• 1948 : Lofgren marketed ‘Lidocaine’
• The discovery of its anesthetic
properties was followed in 1949 by its
clinical use by T. Gordh.
6

7. Definition…..
• Local anesthesia has been defined as
“loss of sensation in a circumscribed area
of the body caused by a depression of
excitation in nerve endings or an
inhibition of the conduction process in
peripheral nerves.”
- (Grune and Straton - 1976)
7

8. • “Local anesthetic are the drugs have a
little or no irritating effects when
injected into the tissues and that will
temporarily interrupt conduction when
absorbed into the nerves.”
(Monheims)
8

9. • “Local anesthesia has been defined as direct
administration of anesthetic agent to tissue to
include the absence of sensation in small area
of body.”
(Mosby’s dictionary)
9

10. • Regional analgesia : loss of pain
sensation over a portion of anatomy
without loss of consciousness.
• Regional anesthesia : it applies not only
to loss of pain sensation over a specific
part of anatomy without the loss of
consciousness but also to the
interruption of all other sensations,
including temperature , pressure and
motor function.
10

11. DESIRABLE PROPERTIES :
It should not be irritating to the tissue to which it is applied.
It should not cause any permanent alternation of nerve structure.
Its systemic toxicity should be low.
It must be effective regardless of whether it is injected into the
tissue or is applied locally to the mucous membrane.
The time of onset should be as short as possible.
The duration of action must be long enough to permit completion of
the procedure yet not so long as to require an extended recovery.
Most LA discussed in this section meet the first 2 criteria’s : (1) non
irritating to tissues and (2) completely reversible.
11

12. BENNETT LISTED OTHER CRITERIAS …..
It should have potency sufficient to give complete anesthesia without
the use of harmful concentrated solutions.
It should be relatively free from producing allergic reactions.
It should be stable in solution and should readily undergo
biotransformation in the body.
It should be sterile or capable of being sterilized by heat without
deterioration.
Bennett CR : Monheim’s local anesthesia and pain control in dental practice, ed 5 , St Louis , 1974 , Mosby
12

13. Other Methods to induce Local Anesthesia :
Mechanical trauma (compression of tissue)
Low temperature
Anoxia
Chemical irritants
Neurolytic agents like phenol and alchohol.
Chemical agents such as LA.
13

14. Modes and site of action …..
It is possible for the LA to interfere with the excitation in one or more
of the following ways :
• Alternating the basic resting potential of nerve membrane.
• Alternating the threshold potential (firing level).
• Decreasing the rate of depolarization.
• Prolonging the rate of repolarization.
It has been established that primary effect of LA occurs during
depolarization phase of action potential.
de Jong RH, Wagman IH :Physiological mechanism of peripheral nerve block by local anesthetics, Anesthesiology 24:684-
727,1963 14

15. Where do LA work ? (theories) …..
`I believe in a long, prolonged, derangement of the senses in order to
obtain the unknown.' – Jim Morrison, The Doors
The nerve membrane is the site at which the local anesthesia exerts their
pharmacological actions.
Acetyl choline.
Calcium displacement.
Surface charge theory.
15

16. Acetylcholine theory :
• It stated that
acetylcholine was
involved in nerve
conduction, in addition
to its role as a
neurotransmitter at
nerve synapses.
Dettebarn WD : The acetylcholine system
in peripheral nerve, Ann N Y Acad Sci
144:483-503 , 1967
16

17. Calcium displacement theory :
• Once popular , maintained that local anesthetic nerve block was produced by
the displacement of calcium from some membrane site that controlled
permeability to sodium.
• Evidence that varying the concentration of calcium ions bathing a nerve
does not affect local anesthetic property has diminished the credibility of
this theory .
Goldman DE, Blaustein MP : Ions , drugs and the axon membrane , Ann N Y Acad Sci 137:967-981, 1966.
17

18. Surface charge repulsion theory :
• Proposed that LA acts by binding
to the nerve membrane and
changing the electrical potential
at the membrane surface.
• Cationic drug molecule were
aligned at the membrane – water
interface, and because some of
the LA molecules carried a net
(+)ve charge , they made the
electrical potential at the
membrane surface more positive,
thus decreasing the excitability
of the nerve by increasing the
threshold potential.
18

19. • Current evidence indicates that the Resting Potential of the nerve
membrane is unaltered by LA (they don’t become hyperpolarized), and
that conventional LA acts within membrane channels rather than at
membrane surface .
• Also the surface charge theory cannot explain the activity of
uncharged anesthetic molecules in blocking nerve impulses (e.g.,
benzocaine).
Goldman DE, Blaustein MP : Ions , drugs and the axon membrane , Ann N Y Acad Sci 137:967-981, 1966.
19

20. • Two other theories ,
membrane expansion
and specific receptor
are given credence
today.
• Of the two, the
specific receptor is
most widely held.
• Two other theories ,
membrane expansion
and specific receptor
are given credence
today.
• Of the two, the
specific receptor is
most widely held.
20

21. Membrane expansion :
• This theory States that the LA molecules diffuse to hydrophobic regions
of excitable membranes, producing a general disturbance of the bulk
membrane structure , expanding some critical region(s) in the membrane,
and preventing an increase permeability to sodium ions.
• LA that are highly lipid soluble can easily penetrate the lipid portion of the
cell membrane, producing a change in configuration of the lipo-protein
matrix of the nerve membrane.
• This results in a decreased diameter of sodium channels, which leads to
inhibition of both sodium conductance and neural excitance .
21

22. • This theory serves as a possible
explanation for LA activity for
drugs such as benzocaine , which
does not exist in cationic form yet
still exhibit potent topical
anesthetic activity.
• It has been demonstrated that
nerve membrane, in fact , do expand
and become more fluid when
exposed to LA .
• However , no direct evidence
suggests that nerve conduction is
entirely blocked by membrane per
se
Lee AG : Model for action of local anesthetics, Nature 262:545-
548,1976
Seeman P: The membrane actions of anesthetics ans
tranquilizers, Pharmacol Rev 24:583-655,1972
22

23. Specific receptor theory…
• The most favoured theory, proposed that LA acts by binding to specific
receptors on the sodium channel . The action of the drug is direct, not
mediated by some change in the general properties of the cell membrane.
• Both biochemical and electrophysiologic studies have indicated that a
specific receptor for LA exists in the sodium channel either on its
exterior surface or on the internal axoplasmic surface.
• Once the LA has gained access to the receptors , permeability to sodium
ions is decreased or eliminated, and nerve conduction is interrupted.
23

24. • Local anesthesics are classified by their ability to react with specific
receptor sites in the sodium channel. It appears that drugs can alter
nerve conduction in at least four sites within the sodium channel.
1. Within the sodium channel (tertiary amine LA)
2. At the outer surface of the sodium channel (tetrodotoxin, saxitoxin)
3. And 4. At the activation and inactivation gate (scorpion venom)
24

25. How local anesthesia work …
• Displacement of Ca++ from sodium channel receptor site
• Binding of LA molecule to this site
• Blockade of sodium channel
• Decrease in sodium conductance
• Depression of the rate of electrical depolarization.
• Failure to achieve threshold potential level
• lack of development of propagated action potential
• Conduction blockade.
nerve block produced by LA is called non-depolarizing nerve block
25

26. Clinical implication of pH and LA activity
• Most commercially prep. LA without vasoconstrictor have a pH of 5.5 – 7
• When injected the vast buffering capacity of tissue return injection of
pH site to 7.4
• LA with vasoconstrictor are acidified by manufacturers by addition of
sodium metabisulfite to retard the oxidation of vasoconstrictor ,
thereby prolonging the period of effectiveness of drug.
26

27. • The pH of solutions without epinephrine is about 6.5, epinephrine –
cont. solutions have a pH of about 3.5. clinically , this lower pH is more
likely to produce a burning sensation on injection , as well as a slightly
slower onset of anesthesia.
• Elevating the pH (alkalinization) of a local anesthesia solution speeds
its onset of action, increases its clinical effectiveness, and makes
injection more comfortable . However, the LA base , because its
unstable , precipitates out of alkanized solutions, making these
preparations ill-suited for clinical use.
27

28. Classification :
I. Based on bioavailability
• Natural – eg. cocaine.
• Synthetic nitrogenous compound – eg. procaine, benzocaine,
lignocaine & bupivacane
• Non Nitrogenous compounds – benzyl alcohol
• Miscellaneous – clove oil , phenol.
28

29. II. According to structure:
1.Esters :
• Benzoic acid esters:
• Benzocaine
• Cocaine
• Para-amino benzoic esters:
• Tetracaine
• Chlorprocaine
• Procaine
• Propoxycaine
2. Amides :
• Articaine
• Bupivacaine
• Etidocaine
• Lidocaine
• Mepivacaine
• Prilocaine
3. Quinolones : Centbucridine
29

30. III. According to duration of action :
1) Ultra Short acting anesthetic – less than 30 min
• Procaine without a vasoconstrictor
• 2 chloroprocaine without vasoconstrictor
• 2% lidocaine without a vasoconstrictor
2) Short acting local anesthetic – 45 to 75 min
• 2% lidocaine with 1:100000 epinephreine
• 2% mepivacaine with 1: 20000 lavonordefrin
• 4% prilocaine when used to nerve block
30

31. 3) Medium acting anesthetics 90 – 150min
• 4% prilocaine with 1:200000 epinephrive
• 2% lidocaine and 2% mepivacaine with a vasoconstrictor
• May produce pulpal anesthesia of this duration
4) Longer acting anesthestic – 180 min or longer
• 0.5% bupivacaine with 1: 200000 epinephrine
• 0.5% or 1.5% etidocaine with 1:200000 epinephrine
31

32. 32

33. IV. According to mechanism of action
• Class A : Agents acting at receptor site on external surface of nerve
membrane eg: Biotoxins (tetratoxins, saxitoxins)
• Class B : Agents acting at receptor sites on internal surface of nerve
membrane eg: quarternary NH4 analogues of lidocaine , scorpion venom
• Class C : Agents acting by receptor independent physio-chemical mechanism
eg: Benzocaine
• Class D :Agents acting in combination of receptor dependent-independent
mechanism. eg: Lidocaine, Mepivacaine, Prilocaine, articaine .
33

34. V. ACCORDING TO MODE OF ACTION:
TOPICAL INJECTABLE
34

35. VI. ACCORDING TO ORIGIN (Vinod Kapoor 2nd Edition)
• Natural :- Cocaine
• Synthetic nitrogenous compounds
• a) Amino esters of para amino benzoic acid :- Procaine
• b) Alkyl esters of Paba (Benzocaine)
• c) Amino esters of Meta amino Benzoic acid (MABA) Unacaine
• d) Amino –amides (xylocaine) (Bupivacaine)
• Systemic non nitrogenous compounds (Benzyl alcohol)
• Miscellaneous drugs (Clove oil/Phenon)
35

36. Composition of Local Anaesthesia (L.A.)
• Local Anaesthetic agent : Lignocaine HCl – 2 %
(20ml)
• Vasoconstrictor : Adrenaline bitarterate - 1 :
80, 000(0.012mg) or Epinephrine
• Reducing Agent : Sodium Metabisulphite – 0.5
mg
• Preservatives : Methylparaben – 0.1% (1 mg)
36

37. Fungicide : Thymol
Isotonic solution : Sodium Chloride – 6mg
• Vehicle : Ringer’s Solution
• Diluting Agent : Distilled Water
• To Adjust pH : Sodium Hydroxide
• Nitrogen Bubble : 1-2 mm in diameter and is
present to prevent Oxygen from being trapped
in the cartridge and potentially destroying the
vasopressor or vasoconstrictor.
37

38. LA Agents :
Ester type
 Procaine HCl
 Procaine HCl + Propoxycaine HCl
Amide type
 Lidocaine HCl
 Mepivacaine HCl
 Prilocaine HCl
 Articaine HCl
 Bupivacaine HCl
Topical agents
• Benzocaine , butamben , and
tetracaine HCl
• Cocaine HCl
• Dyclonine HCl
• EMLA
• Lidocaine
• Tetracaine HCl
38

39. Procaine HCl
• Ester
• prepared by : Alfred Einhorn ; 1904-05
• Potency = 1 (procaine =1)
• Toxicity = 1 (procaine = 1)
• Produces the greatest vasodilation of all currently used LA
• pH of plain solution : 5.0 to 6.5
• pH of vasoconstrictor containing solution : 3.5 – 5.5
• Onset of action : 6 to 10 mins
• Effective dental conc. : 0.1 hr / 06 mins
• Maximum dose used for peripheral nerve block is : 1g
39

40. Comments :
• No longer avl. in north America in dental cartridges.
• Its proprietary name , Novocain , is synonymous throughout the world
with dental local anesthesia.
• Produce the greatest vasodilation of all clinically used local anesthetics.
Thus a clean (e.g.bloodless) surgical field is difficult to maintain.
• It is imp. In the immediate management of inadvertent intra-arterial
injection of a drug; its vasodialating properties are used to aid in breaking
arteriospasm.
• Although not extremely common, allergy to esters are more common than
amides.
• Metabolized in blood by plasma cholinesterase, it doesnot exhibit
increased toxicity in patients with hepatic dysfunction.
40

41. Lidocaine HCl
• Amide
• Prepared by : Nils Lofgren , 1943
• FDA approved : 1948
• Potency : 2
• Toxicity : 2
• Metabolized in liver and excreted by kidney
• Vasodilating properties : considerably less than that of procaine, greater
than those of prilocaine and mepivacaine.
• Pka : 7.9
• pH of the plain solution : 6.5
• pH of the vasoconstrictor cont. solution : 3.5
41

42. • Onset of action : 3-5 mins
• Effective dental concentration : 2%
• Anesthetic half life : 1.6 hrs = 90 mins
• Used as topical anesthetic
• Pregnancy classification : B
• Safety level during lactating : S
• Maximum dose : FDA recommended : 3.2mg/lb (with) or 7.0 mg/lb
(without epinephrine) for adults and pediatric patients , not to exceed
an maximum dosage of 500mg
42

43. Mepivacaine HCl
• Amide
• Prepared by : A.F.Ekenstam , 1957 ; introduced into dentistry in 1960 as a
2 % solution containing the synthetic vasopressor levonordefrin, and in
1961 as a 3% solution without a vasoconstrictor .
• FDA approved : April 1960
• Potency = 2
• Toxicity = 1.5 – 2
• Metabolized in liver and excreted via kidneys.
• Produces only slight vasodialation
43

44. • Pka : 7.6
• pH of plain solution : 5.5 – 6
• pH of vasoconstrictor cont. solution : 4.0
• Onset of action : 4.0
• Effective dental concentration : 3% without vasocons.; 2 % with
vasocons.
• Half life : 1.9 hours
• Pregnancy classification : C
• Safety during lactation : S ?
• Not used in topical solutions
• Max . Recommended dose : 6.6mg/kg or 3.0 mg/lb of body weight ; not
to exceed 400 mg (absolute maximum)
44

45. Prilocaine HCl
• Prepared by : Lofgren and Tegner , 1953 ; reported in 1960
• FDA approved : 1965
• Potency : 2
• Toxicity : 1
• Metabolism : because it’s a secondary amine ; it is hydrolysed straight
forwardly by hepatic amidase into orthotoludine and N-propylalanine .
• Orthotoludine can induce formation of methemoglobin ; causing
methemoglobinemia if large loses are adm. It consistenly reduces
blood oxygen carrying capacity ; at times sufficient to cause
observable cyanosis. Limiting the dose to 600 mg (FDA
recommendation) reduces symptomatic cyanosis.
45

46. • It undergoes biotransformation rapidly and completely than lidocaine ;
this takes not only liver but also to a lesser degree in kidneys and
lungs . Plasma levels of prilocaine decreases more rapidly than lidocaine
. Thus it is considered to be less toxic systemically than comparably
potent LA amides.
• Excreted via kidneys
• pka: 7.9
• pH of plain solution : 6.0 to 6.5
• pH of vasoconstrictor cont. solution : 4
46

47. • Onset of action : 3-5 mins
• Effective dental concentration : 4 %
• Anesthetic half life : 1.6 hours
• Not used as topical anesthesia
• Pregnancy classification : B
• Safety during lactation : unknown
• Max . Recommended dose : 8.0 mg/kg pr 3.6mg/lb of body weight of
adults , to a maximum recommended dose of 600 mg
47

48. Articaine HCl
• Hybrid molecule ; containing both esters and amides
• Prepared by : H. Rusching et al, 1969
• FDA approved : April 2000
• Potency : 1.9
• Toxicity : 1
• Metabolized in both plasma and liver ; excreted via kidneys
• pka : 7.8
• pH of plain solution : 4 % avl. In germany ; not avl. In USA
• pH of vasoconstrictor containing solution : 3.5 – 4.0
• Onset : 1: 2,00,000 infiltration : 1-2 mins ; mand. block : 2-3 mins
1: 1,00,000 infiltration : 1-2 mins ; mand. Block : 2 – 21/2 mins
48

49. • Effective dental conc : 4 % with 1: 100,000 or 1: 2,00,000 epinephrine.
• Half life : 0.5 hours (= 27 mins)
• Pregnancy classification : C
• Safety during lactation : unknown
• Max. recommended dose : FDA max recommended dose is 7.0 mg/kg or
3.2 mg/ld of body weights of adults.
• No absolute maximum dosage
49

50. Bupivacaine HCl
• Prep by : A.F. Ekenstam , 1957
• FDA approved : Oct 1972
• Potency : 4
• Toxicity : <4
• pH of plain solution : 4.5 -6.0
• pH pf vasoconstrictor cont. solution : 3.0 – 4.5
• Half life : 2.7 hours
• Effective dental conc : 0.5 %
50

51. • Maximum dosage : 90 mg. in Canada , max dose is based on 2.0 mg/kg
or 0.9mg/lb
• Two primary indications for its utilization in dentistry are :
1) Lengthy dental procedures for which pulpal (deep) anesthesia in
excess of 90 mins is necessary eg implant surgery , mouth
reconstruction and periodontal procedures
2) Management of post operative pain (endodontic , periodontal,
postimplant ,
surgical ).
51

52. 52

53. Topical anesthesia :
53

54. Lidocaine
• Avl. In two forms for topical application :
• Lidocaine base :poorly soluble in water; 5 % conc. ; indicated for use in
ulcerated, abraded,or lacerated tissues
• Lidocaine HCl , water soluble prep.2 % conc. Penetrated tissue more
efficiently than the base form. However, systemic toxicity is greater than
base form.
• Recommended dose for topical use : 200 mg
• Avl. (base) : as aerosols, sprays,oinments , patch and solution in various
dosage
• Avl. : lidocaine HCl is avl as an oral topical solution in 20mg/ml (viscous) and
40 mg/ml (solution) .
54

55. EMLA (Eutectic mixture of LA )
• EMLA cream (composed of lidocaine 2.5 % and prilocaine 2.5%) in an
emulsion in which the oil phase is a eutectic mixture of lidocaine and
prilocaine in a ratio of 1:1
• Designed to provide surface anesthesia for intact skin , eg. Venipuncture
and needle insertions.
• Contraindicated for patients with congenital or idiopathic
methemoglobinemia or patient with known sensivity to amide type LA
• Its used to produce topical anesthesia in oral cavity ; although the drug
package initially stated : ”not recommended for use in mucous membrane”,
subsequent clinical trials have demonstrated satisfactory results
55

56. Other topical anesthetics:
• Dyclonine hydrochloride : ketone derivates ; used by patients who are
allergic to common anesthetics. 0.5 % solution is used in dentistry with
max. recommended dosage of 200mg (40ml of a 0.5% solution).
• Cocaine HCl: because of extreme abusive potential not used in
dentistry
• Tetracaine hydrochloride : 5-8 times more potent than cocaine. But
caution is urged because of great potential for systemic toxicity.
56

57. Action of other components :
Vasoconstrictors :
Vasoconstrictors are chemical agents or adjuncts added to a local
anaesthesia solution
• To oppose the vasodilation caused by these agents .
• To achieve hemostatis
the addition of vasoconstrictor to L.A. causes constriction of blood
vessels and thereby control tissue perfusion. The net effect caused by
addition of vasoconstrictor to LA agents are :
57

58. Vasoconstrictor function :
• It decreases the blood flow to the site of injection, because of vasoconstriction.
• It decreases the rate of absorption of local anesthetic agent into cardiovascular system.
• It lowers the plasma level of local anesthetic agent (Cannall et al, 1975) and Wildsmith et
al, 1977), thereby decreasing the risk of systemic toxicity of local anesthetic agent.
• Higher volumes of local anesthetic agent remain in and around the nerve for longer
periods; thereby increasing the duration of action of most local anesthetic agents (Brown,
1968).
• It decreases bleeding at the site of injection because of decreased perfusion. This is
useful when increased bleeding is expected during a surgical procedure (Carpenter et al,
1989; and Myers and Heckman, 1989).
Manual of Local Anesthesia in DENTISTRY Second Edition AP Chitre : pg : 104 58

59. Side effects :
• Unfortunately, the effects of vasoconstrictors are not always
beneficial.
• The cardiac excitatory action of epinephrine, which is desired in the
management of medical emergencies such as anaphylaxis, may be
detrimental to a patient with reduced cardiovascular system reserve.
• Angina or myocardial infarction could conceivably result if the
patient's cardiovascular system is unable to respond to the demands
caused by actions of the vasoconstrictor.
Vasoconstrictors in Local Anesthesia for Dentistry . Allen L. Sisk. Anesth Prog 39:187-193 1992
59

60. • Epinephrine may indirectly cause central nervous system excitation, as
well have effects on metabolism and bronchial and gastrointestinal
smooth muscle.
• Signs and symptoms of vasoconstrictor toxicity include hypertension,
tachycardia, tremors, headache, palpitations, and cardiac
dysrhythmias.
• Drug interactions : Significant drug interactions may occur between
vasoconstrictors injected with local anesthetic agents and either
tricyclic antidepressants or β blockers.
Vasoconstrictors in Local Anesthesia for Dentistry . Allen L. Sisk. Anesth Prog 39:187-193 1992
60

61. HEMOSTASIS :
• Vasoconstrictors are added to local anesthetic solutions to provide
hemostasis at surgical sites.
• A 1: 50,000 concentration of epinephrine is sometimes used for this
purpose, although many studies have shown that this is not the
concentration of epinephrine that provides optimal vasoconstriction
balanced with potential for cardiovascular system toxicity.
61

62. • For example, studies of epinephrine's effects on cutaneous blood flow have
indicated that no measurable difference exists between equal volumes of 1:
50,000, 1: 100,000, and 1: 200,000 solutions.
• Harrington and Carpenter, in a study using a laser Doppler device to follow
dynamic changes in skin perfusion after infiltration of 1% lidocaine with graded
concentrations of epinephrine, found that the lidocaine alone caused an
increase in local blood flow of two to three times baseline. Five min after
infiltration of 1% lidocaine plus epinephrine (1: 50,000, 1:100,000, 1:200,000 1:
400,000), the vasodilating effect of lidocaine was effectively counterbalanced
by each of these concentrations. Concentrations of 1: 800,000 and 1:
1,600,000 were not reliably effective at 5 and 10 min.
62

63. • Periodontal flap surgery may be an exception, however, in that the 1:
50,000 concentration might be superior to more dilute solutions of
epinephrine.
• According to a study by Buckley et al, blood loss with 2% lidocaine
plus 1: 100,000 epinephrine injected locally for hemostasis is more
than double that when 2% lidocaine with 1: 50,000 epinephrine is used.
63

64. Reduction in Neuronal Blood Flow :
• Vasoconstrictors affect the blood supply to the nerves in the area of
injection, in addition to their effects on non nervous tissues in the area.
• Myers and Heckman found that the blood supply to rat sciatic nerve was
reduced 78% when 2% lidocaine with 1: 100,000 was applied to tissues
surrounding the nerve. Application of 1% lidocaine without vasoconstrictor
reduced blood flow to the nerve by 19%. Myers and Heckman believed that
epinephrine may have a pathogenic role in those relatively rare reports of
neurologic deficit following local anesthetic procedures.
Vasoconstrictors in Local Anesthesia for Dentistry . Allen L. Sisk. Anesth Prog 39:187-193 1992
64

65. • Partridge in a study of the effects of lidocaine and epinephrine on rat sciatic
blood flow, demonstrated similar reductions in nerve blood flow to those reported
by Myers and Heckman. Partridge also reported a synergistic reduction in blood
flow when lidocaine and epinephrine were combined. Two percent lidocaine alone
decreased nerve blood flow by 18%; application of 5 ,4g/mL epinephrine alone
decreased blood flow by 20%. The combination of lidocaine and epinephrine
reduced nerve blood flow by 60%. Bupivacaine, which is a more potent vasodilator
than lidocaine, also reduced nerve blood flow. A 0.25% bupivacaine solution
decreased nerve blood flow by 35%, 0.5% bupivacaine by 25%, and 0.75%
bupivacaine by 15%.
Vasoconstrictors in Local Anesthesia for Dentistry . Allen L. Sisk. Anesth Prog 39:187-193 1992
65

66. Intraoperative Versus Delayed Bleeding :
• Potential problems associated with the use of a vasoconstrictor in
surgical procedures are rebound, or delayed, postoperative bleeding
and impaired wound healing.
• Sveen, in a study of the effects of adding vasoconstrictor to the local
anesthetic solution, found no postoperative hemorrhage in a control
group of patients who had oral surgical procedures performed with
local anesthetic without added vasoconstrictor.
66

67. • Meyer and Allen found reduced intraoperative bleeding and
increased postoperative bleeding when vasoconstrictor was used.
• Gores et al measured blood loss in patients having multiple dental
extractions and alveoplasty.
• An important factor in the use of vasoconstrictors to control
intraoperative bleeding is the technique and location of
administration of the agent. Infiltration of the vasoconstrictor
near or in the surgical site is required. Nerve block anesthesia at a
distant site will be less effective in control of bleeding from a
surgical wound.
67

68. Epinephrine :
• Mode of action : Acts directly on both α- and β- adrenergic receptors; β
effects predominate.
• Systemic action :
 Myocardium : positive inotrophic (inc. force of contraction) effect &
chronotrophic (increased rate of contraction)effect.
both HR and CO are increased.
 Pacemaker cells : increased incidence of arrhythmias.
 Coronary arteries : inc. dilation of Coronary Arteries leading to inc. blood flow
 BP : systolic inc. & diastolic dec. when small doses of epinep. are administrd.
with Large doses there is inc. in diastolic BP.
68

69.  CVS DYNAMICS :
o Inc systolic & diastolic pressure
o Increased CO
o Increased stroke volume
o Increased heart rate
o Increased strength of contraction
o Increased myocardial oxygen consumption.
69

70.  Vasculature :the primary action is on small arterioles and precapillary
sphincters.
 Blood vessels supplying skin, mucous memb, and kidneys primarily
contains α receptors .epinephrine produces vasoconstriction in these
vessels. Vessels supplying the skeletal muscles contains both α & β2
receptors, with β2 predominating..
 Small doses of epinephrine produces dilation of these vessels as a
result of β2 action. β2 receptors are more sensitive to epinephrine
than α receptors. Large doses produces vasoconstriction because α
receptors are stimulated.
70

71. Hemostasis
• Clinically epineph. Is used frequently as a vasoconstrictor for
hemostatis during surgical procedures. Injection of epinephrine
directly into surgical sites rapidly produces high tissue conc. ,
predominant α- receptor stimulation, and hemostatis.
• As epineph. tissue levels decrease over time, its primary action on
blood vessels revert to vasodilation because β2 actions predominate;
therefore it is common for some bleeding to be noted at about 6 hrs
after a surgical procedure.
• In studies, additional findings of increased post surgical pain and
delayed wound healing were noted in epineph. Receiving groups.
Sveen K : Effect of the addition of a vasoconstrictor to local anesthetic solution on operative and postoperative bleeding,
analgesia, wound healing,Int J Oral Surg 8:301-306,1979
71

72.  RS : potent dilator of bronchiole smoth muscle . Imp.drug for
management of bronchospasm. (asthma)
 CNS : In usual therapeutic dosages, its not potent. Its CNS
stimulating actions become prominent when an excessive dose id adm.
 METABOLISM: it inc. oxygen consumption in all tissues.
β action , it stimulates glycogenolysis in the liver and skeletal muscle,
elevating blood sugar levels at plasma epinephrine conc. Of 150 to 200
pg/ml.
the equivalent of four dental LA cartridges of 1 : 100,000 epineph.
Must be administered to elicit this response.
72

73. • Termination of action and elimination : the action of epineph. Is
terminated primarily by its uptake by adrenergic nerves. Epineph. That
escapes reuptake is rapidly inactivated in the blood by the enzymes
COMT (catechol-O-methyltransferase) and MAO (monoamine oxidase)
, both of which are present in the liver.
• Only small amount of epineph. (1%) Are excreted unchanged in urine.
73

74. Side effects :
• c/l manifestations of overdose related to CNS stimulation include inc.
fear and anxiety, tension , restlessness , throbbing headache , tremor,
weakness , dizziness , pallor , respiratory difficulty and palpitations.
• With more inc. levels, cardiac dysrhythmias , anginal episodes and
cerebral hemorrhage may be noted .
• Because of rapid inactivation, the stimulation phase of toxic reaction is
usually brief.
74

75. Norepinephrine (Levarterenol)
• Noradrenaline, Levophed , levarterenol
• In USA, no longer avl. In LA solutions.
• In Germany, norepineph. Is included with lidocaine and mepivacaine or
as the combination of norepineph. and epineph. With Lidocaine
(Germany) and tolycaine (Japan).
• The IFDAS (International Federation of Dental Anesthesiology
Society) suggest that norephineph. Be eliminated as a vasoconstrictor
in dental LA.
75

76. Levonordefrin
• Considered one-sixth as effective a
vasopressor as epinephrine ; therefore
used in high concentration. (1:20,000)
• Obtained with mepivacaine in a 1:20,000
dilution.
• In a conc. It is avl. It has same effect
on clinical activity as does epinephrine in
1:50,000 or 1: 1,00,000 conc.
76

77. Phenylephrine Hydrochloride
• It is a vasoconstrictor in LA, for management
of hypotension, as a nasal decongestant, and
in ophthalmic solutions to produce mydriasis.
• No longer avl. In dental cartidges. (was used
along 4% procaine in 1:2500 dilution).
• Considered one twentieth as potent as
epineph. Is an excellent vasoconstrictor with
few side effects.
77

78. Felypressin :
• can be safely administered to hyperthyroid patients and anyone receiving MAO
inhibitors or tricyclic antidepressants.
• It has both antidiuretic and oxytocic actions, the latter containdicating its use
in pregnant pts.
• It has wide margin of safety and the incidence of systemic reaction is minimal
• It is employed in dilution of 0.03 IU/mL with 3% prilocaine in Japan , Germany
and other countries . It’s not avl. As vasoconstrictor in LA in North America.
• Not recommended for use where hemostatis is necessary because of its
predominant action on venous rather than the arterial circulation.
78

79. Preservatives :
They increase the self life .
Methylparaben : Bacteristatic and fungistatic agent. It has been excluded
from cartridges in USA, from Jan 1, 1984 following reports of allergy. However
, it’s still being used in multidose vials in some countries including India .
Thymol : Antiseptic , fungistatic and Antihelmenthic.
Chlorbutol : Antibacterial and Antifungal . 5mg added in single cartridges of
LA
Manual of Local Anesthesia in DENTISTRY Second Edition AP Chitre
79

80. 80

81. Reducing agent :
• These acts as preservatives for
vasoconstrictors agents. Vasoconstrictors
are unstable in solutions and may oxidize,
especially on prolonged exposure to
sunlight. Sodium Metabisulphite which
competes for the available oxygen is added
in the concentration of 0.05 % and 0.01%.
81

82. vehicle :
• All the above solutions and local
anesthetic agents are dissolved in
a modified ringer solution. This
isotonic vehicle minimizes
discomfort during injection.
82

83. why is nitrogen bubble present in the cartridge ?
• 1-2 mm in diameter and is
present to prevent oxygen from
being trapped in the cartridge
and potentially destroying the
vasopressor and
vasoconstrictor, so this is the
function of nitrogen bubble in
cartridge.
83

84. •Armamentarium for LA:
84

85. Syringes :
1. non disposable syringes :
a . Breech-loading, metallic, cartridge-type, aspirating
b. Breech-loading , plastic , cartridge-type, aspirating
c. Breech-loading, metallic , cartridge type, self aspirating
d. Pressure syringe for PDL
e. Jet injection (needle-less syringe)
2. Disposable syringes
3. Safety Syringes
4. Computed controlled LA delivery systems.
85

86. Needle :
For injection delivery devices [e.g.,
syringes and pen needles (PNs)],
important contributors include needle
diameter (gauge), needle length,
needle smoothness, and
lubrication. Additionally, sharpness or
bluntness of a needle directly affects
pain.
86

87. 87

88. 88

89. Cartridge :
• Cylindrical glass tube
• Stopper (plunger,bung)
• Aluminium cap
• diaphragm
89

90. additional armamentarium :
• Topical antiseptic
• Topical anesthesic
• Application sticks
• Cotton guage (2×2)
• hemostat
90

91. Selection of LA
• The decision to inject local anesthetic agents to achieve profound
anesthesia is dependent upon many factors, particularly the depth and
duration of anesthesia required, and the possible need for hemostasis.
To maximize the safety of local anesthetic injections, it is necessary
to weigh the risks against the benefits for each patient, for each
anesthetic agent, for use of a vasoconstrictor, and for the delivery
technique for the selected agent.
91

92. Factors affecting LA action :
92

93. local complications :
• Needle breakage
• Prolonged anesthesia or paresthesia
• Facial nerve paralysis
• Trismus
• Soft tissue injury
• Hematoma
• Pain on injection
93

94. • Burning on injection
• Infection
• Edema
• Sloughing of tissues
• Postanesthetic intraoral lesions
94

95. Causes
of localized
symptoms
include:
1. Neurotoxicity due to allergic reaction,
2. Excessive fluid pressure in a confined
space,
3. Severing of nerve fibers or support
tissue with the needle/catheter,
4. Injection-site hematoma that puts
pressure on the nerve, or
5. Injection-site infection that produce
inflammatory pressure on the nerve and/or
necrosis.
95

96. Systemic
complications:
• General systemic adverse effects are due
to the pharmacological effects of the
anesthetic agents used. The conduction
of electric impulses follows a similar
mechanism in peripheral nerves, the
central nervous system, and the heart.
The effects of local anesthetics are
therefore not specific for the signal
conduction in peripheral nerves.
96

97. A) Neurological complication of local anesthesia:-
• Local anesthetics may cause adverse effects either by action on the
nerves and muscles or neurotoxicity following systemic absorption.
• Injection injury of neural structures may result from the procedure.
• Seizures are a frequent adverse effect of local anesthetics, and
principal of management are those applicable to drug- induced
seizures.
• Careful selection of the anesthetic agent and meticulous procedure
for local anesthesia are important preventive measures.
97

98. Clinical manifestations
• CNS excitation manifested by:
• Restlessness
• Tremors
• Light-headedness
• Syncope – Tinitus
• Nausea and vomiting
• Slurring of speech
• Irrational conversation
• Seizures that may be followed by CNS depression.
98

99. CNS depression manifested by:
• Drowsiness
• Respiratory arrest – Coma
99

100. Complications related to peripheral and cranial nerves: –
• Irritation of spinal nerve roots
• Complications of leakage of cerebrospinal fluid
• Cauda equine syndrome
• Paraplegia due to toxic or ischemic myelopathy
• Meningitis
• Epidural hematoma
100

101. Effect on muscles:
• myonecrosis following local injection into muscles
• Neurologic manifestations of systemic toxicity of local anesthetics:
Numbness of the tongue and perioral region
101

102. Cardiovascular
system
• The conductive system of the heart is
quite sensitive to the action of local are
anesthetic. Cardiovascular manifestation
are usually depressant and
are characterized by bradycardia,
hypotension, and cardiovascular collapse,
which may lead to cardiac arrest.
102

103. Allergic :
• Allergic reactions are characterized by
cutaneous lesions, urticaria, edema or
anaphylactoid reactions. Allergic reactions
may occur as a result of sensitivity either to
local anesthetic agents or to the
methylparaben used as a preservative in the
multiple does vials. Allergic reactions as a
result of sensitivity to lidocaine are
extremely rare and, if they occur, should be
managed by conventional means. The
detection of sensitivity by skin testing is of
doubtful value.
103

104. Hypersensitivity/allergy :
• Adverse reactions to local anesthetics (especially the esters) are not
uncommon, but true allergy is very rare Allergic reactions to the esters is
usually due to a sensitivity to their metabolite, para-aminobenzoic acid
(PABA), and does not result in cross-allergy to amides. Therefore, amides
can be used as alternatives in those patients. Nonallergic reactions may
resemble allergy in their manifestations. In some cases, skin tests and
provocative challenge may be necessary to establish a diagnosis of allergy.
There are also cases of allergy to paraben derivatives, which are often
added as preservatives to local anesthetic solutions.
104

105. OCCULAR COMPLICATIONS ASS.
WITH LOCAL ANESTHESIA
ADMINISTRATION IN
DENTISTRY
• Amourosis
• Mydriasis
• Ptosis
• Diplopia
105

106. Sympathetic ganglion anesthesia :
• Campbell and the conjunctive a case with a Horner-like syndrome with
ptosis, vascular dilatation of the conjunctiva miosis, horseness in
vocalization, and wide-spread rash over the ipsilateral upper body. In
their report, it was suggested that the local anesthetic administration
resulted in a stellate ganglion block, which may explain the patient’s
hoarseness of voice. Proposed Causes of Occular Complications with
maxillary injections
106

107. ADVERSE DRUG REACTIONS
Local anesthetic agents are relatively safe and free of side effects
provided they are administered in an appropriate dosage and in an
appropriate anatomical location. The ester group of drugs is more toxic
than the amide group. The adverse drug reactions include:
1) Allergic reactions,
2) Anaphylactic reactions,
3) Toxic reactions (overdose),
4) idiosyncratic reactions.
107

108. Checklist for Treatment of Local Anesthetic Systemic Toxicity
• The Pharmacologic Treatment of Local Anesthetic Systemic Toxicity
(LAST) is Different from Other Cardiac Arrest Scenarios
• Get Help
• Initial Focus
• Airway management: ventilate with 100% oxygen
• Seizure suppression: benzodiazepines are preferred; AVOID
propofol in patients having signs of cardiovascular instability
• Alert the nearest facility having cardiopulmonary bypass capability
108

109. • Management of Cardiac Arrhythmias
• Basic and Advanced Cardiac Life Support (ACLS) will require adjustment
of medications and perhaps prolonged effort
• AVOID vasopressin, calcium channel blockers, beta blockers, or local
anesthetic
• REDUCE individual epinephrine doses to <1 mcg/kg
• Lipid Emulsion (20%) Therapy (values in parenthesis are for 70kg patient)
• Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (~100mL)
• Continuous infusion 0.25 mL/kg/min (~18 mL/min; adjust by roller clamp)
• Repeat bolus once or twice for persistent cardiovascular collapse
• Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low
• Continue infusion for at least 10 minutes after attaining circulatory
stability
• Recommended upper limit: Approximately 10 mL/kg lipid emulsion over the
first 30 minutes
109

110. Contraindications for LA:
110

111. References …..
• Vasoconstrictors in Local Anesthesia for Dentistry . Allen L. Sisk,
Anesth Prog 39:187-193 1992
• Manual of Local Anesthesia in DENTISTRY Second Edition AP Chitre.
• Bennett CR : Monheim’s local anesthesia and pain control in dental
practice, ed 5 , St Louis , 1974 , Mosby
• de Jong RH, Wagman IH :Physiological mechanism of peripheral nerve
block by local anesthetics, Anesthesiology 24:684-727,1963
• Dettebarn WD : The acetylcholine system in peripheral nerve, Ann N Y
Acad Sci 144:483-503 , 1967
• Goldman DE, Blaustein MP : Ions , drugs and the axon membrane , Ann
N Y Acad Sci 137:967-981, 1966.
• Lee AG : Model for action of local anesthetics, Nature 262:545-
548,1976
111

112. • Seeman P: The membrane actions of anesthetics ans tranquilizers,
Pharmacol Rev 24:583-655,1972
• Sveen K : Effect of the addition of a vasoconstrictor to local
anesthetic solution on operative and postoperative bleeding, analgesia,
wound healing,Int J Oral Surg 8:301-306,1979
112

113. thank you
113