Classification Mechanism of action Duration of action Absorption and distribution Mode of action Theories of action of L.A Pharmacokinetics of local anaesthetics Routes of administration Metabolism or biotransformation Individual agents Vasoconstrictors Systemic effects Toxicity Advantages Disadvantages Maximum allowable dose Local anaesthetics in community trust services

1. Dr. Ankit Mohapatra,
DEPARTMENT OF PUBLIC HEALTH DENTISTRY
1

2. CONTENTS
• Definition
• Introduction
• Indications
• Classification
• Mechanism of action
• Duration of action
• Absorption and distribution
• Mode of action
• Theories of action of L.A
• Pharmacokinetics of local anaesthetics
• Routes of administration
2

3. • Metabolism or biotransformation
• Individual agents
• Vasoconstrictors
• Systemic effects
• Toxicity
1. Causes
2. Factors reducing toxicity
• Advantages
• Disadvantages
• Maximum allowable dose
• Local anaesthetics in community trust services
• Conclusion
• References 3

4. What is local anesthesia?
• Local anaesthesia has been defined as loss of sensation in a
circumscribed area of the body caused by depression of
excitation in nerve endings or inhibition of the conduction
process in peripheral nerves.
4

5. INTRODUCTION
• Ancient time – dental treatment was associated with pain
• Earliest pain relief – Coca shrub  mood elevator
– Incas
• Cocoa shrub – foot hills of Andes
• Introduced by  Europeans to South America
• Cocaine
5

6. • 1855 – Gaedicke extracted alkaloid Erythroxylin
• 1860 – Dr. Scherzer  cocaine from this alkaloid
• 1844 – Francis Rynd (Dublin) 
– Acetate of morphine + Creosote
– Skin incision  TGN(trigeminal neuralgia) treatment
– First time liquid used - intradermally
• 1884 – marks birth of LA
6

7. • Sigmund Freud & Carl Koller
– Cocaine for eye operation
• William Steward Halsted
– Cocaine for inferior dental nerve
• 1886 – Cocaine - dental anesthetic documented by William
Alfred Hunt et al
• 1901 – E Mayers 
– Vasoconstrictor + cocaine
7

8. • 1905
– 13 lives claimed – addiction
– A Einhorn & E Uhlfelder(Sweden)
• Synthesized  Procaine hydrochloride
• Procaine  sterilizable, non-additive, non-toxic
• 1943
– N Lofgren(Sweden)
• Synthesized  Anilide called Lignocaine
• Lignocaine – amide linked synthetic derivative
8

9. • 1946 – Lignocaine introduced  Dental practice
• 1948 – Lignocaine ; published in BDJ – Lofgren
• Sweden – Birth place of newer LA agents
– Bupivacaine
– Ropivacaine
9

10. INDICATIONS FOR
LOCAL ANESTHESIA
•Most frequent use: regional anesthesia.
•Analgesic , espescially post operative pain.
•Lidocaine (xylocaine) also reduces blood pressure response to direct
laryngoscopic tracheal intubation, an effect probably secondary to
generalized cardiovascular depression.
•Treatment of intractable cough.
10

11. Local Vs General Anaesthesia
General Local
Site of action CNS Peripheral nerves
Area Whole body Restricted areas
Consciousness Lost Unaltered
Preferential use Major surgery Minor surgery
Use in non-coperative
patients
Possible Not possible
Poor health patient Risky Safer
Care for vital functions Essential Not needed
11

12. CLASSIFICATION OF LOCAL
ANESTHESIA
12

13. CLASSIFICATION ACCORDING
TO ROUTE OF ADMINISTRATION
• Injectable :
– Low potency, short duration – Procaine and
Chlorprocaine
– Intermediate potency – Lidocaine (Lignocaine) and
Prilocaine
– High potency and long duration – Tetracaine,
Bupivacaine, Ropivacaine, Etidocaine, Mepivacaine and
Dibucaine (Cinchocaine)
13

14. • Surface :
– Soluble – Cocaine, Lidocaine, Tetracaine and Benoxinate
– Insoluble – Benzocaine, Butylaminobenzoate and
Oxethazine
• Miscellaneous :
– Clove oil, phenol, chlorpromazine and diphenhydramine
etc.
14

15. CLASSIFICATION ACCORDING TO
CHEMISTRY
1. Esters (of benzoic acid)
-Butacaine
-Cocaine
-Benzocaine
-Hexylcaine
-Piperocaine
-Tetracaine
15

16. 2. Esters (of paraaminobenzoic acid)
-Chloroprocaine
-Procaine
-Propoxycaine
16

17. 3. Amides
-Articaine
-Bupivacaine
-Dibocaine
-Etidocaine
-Lidocaine
-Mepivacaine
-Prilocaine 17

18. 4. Quinoline
-Centbucridine
5. Combinations
- Lidocaine/Prilocaine(emla)
18

19. 6. Natural local anesthetics
- Saxitoxin and Tetrodotoxin
-Naturally occurring local anesthetics not derived from cocaine are
usually neurotoxins, and have the suffix -toxin in their names.
-Unlike cocaine produced local anesthetics which are intracellular in
effect,
-Saxitoxin & Tetrodotoxin bind to the extracellular side of sodium
channels. 19

20. REMEMBER: All LAs are weak Bases!
20

21. C
LAs are Weak Bases
C O
O
R N
R
R
N
H
O
R N
R
R
Aromatic
portion
Amine
portion
Intermediate
chain
ESTER
AMIDELIPOPHILIC
(quality of
dissolving in
lipids)
HYDROPHILIC
(able to absorb
water)
21

22. MECHANISM - LAs
• As you know, entry of Na+
is essential for Action
potential
• Two things happen:
– Rate and rise of AP and
depolarization decreases
– slowing of
conduction.
– Finally, local
depolarization fails to
reach threshold potential
– conduction block.
22

23. Mechanism of LAs – contd.
• LAs interact with a receptor
within the voltage sensitive
Na+ channel and raise the
threshold of opening the
channel
• Na+ permeability decreased
and ultimately stopped in
response to stimulus or
impulse
• Impulse conduction is
interrupted when a critical
length of fiber is blocked (2-
3 nodes of Ranvier). 23

24. Mechanism of LA – contd.
- Higher concentration of Ca++ reduces inactivation of Na+
channel
- Blockade is not due to hyperpolarization (RMP is unaltered as
K+ channels are not blocked)
- Blockade is related to pKa (acid dissociation constant) of
particular drug:
- 7.6 to 7.8: e.g. lidocaine - fast acting drugs (more
undissociated form)
- 8.1 to 8.9 : Bupivacine – slow acting (more dissociated
form) 24

25. 25

26. Summary of Mechanism - LAs
• All local anesthetics are membrane stabilizing drugs
– slows down speed of AP - ultimately stop AP generation
• Reversibly decrease the rate of depolarization and
repolarization of excitable membranes
• Act by inhibiting sodium influx through sodium-specific ion
channels in the neuronal cell - voltage-gated sodium channels
• When the influx of sodium is interrupted - action potential
cannot rise and signal conduction is inhibited
26

27. • Local anesthetic s bind (located at inner surface) more readily
to sodium channels in activated state – and slows its reversion
to the resting state – refractory period is increased - “state
dependent blockade” - no action on resting nerve.
• Blockade develops rapidly on stimulation of nerves repeatedly
(Greater the stimulation higher is the blockade)
• Many other drugs also have membrane stabilizing properties,
all are not used as LA, e.g. propranolol
27

28. Fundamentals Of Impulse
Generation And Transmission
• Concept behind action of local anaesthesia- prevent
conduction and generation of nerve impulse, set up chemical
roadblock between the source of impulse and the brain.
• NEURON is the fundamental unit of nerve cell.
• It transmits messages between CNS and all parts of the body.
• It is of 2 types:-
– Sensory (afferent)
– Motor (efferent)
28

29. Sensory Neuron
• It transmits pain sensation with 3 major portions:-
– Peripheral process (dendritic zone) composed of an
arborisation of free nerve endings in the most distal segment of
sensory neuron.
– Axon- Thin cable like structure, has free nerve endings that
respond to stimulation produced in the tissues in which they lie
provoking an impulse transmitted via axon.
– Cell Body- located at a distance from axon, provide vital
metabolic support for the entire neuron.
29

30. Motor Neuron
• They transmit nerve impulses from the CNS to the periphery
• Their cell body is interposed between axon and dendrites.
• Axon branches with each branch ending as a bulbous axon
terminal (or button)
• Axon terminals synapse with muscle cells.
30

31. 31

32. Physiology Of Peripheral
Nerves
• The function of nerve is to carry messages from one part of the
body to another in the form of electrical action potential called
IMPULSES initiated by chemical, mechanical, thermal or
electrical stimuli.
• Action Potential- transient depolarization of membrane which
leads to brief increase in permeability of membrane with
delayed increase in permeability of potassium.
32

33. THE ELECTRICAL IMPULSE
33

34. Nerve impulses are conducted by a
wave of action potentials. When a
stimulus is great enough to reach the
threshold potential of -55mV, sodium
ions flow into the neurone. It does so
via sodium gates to produce
depolarisation.
When depolarised, the membrane
potential is reversed to +40 mV.
At the same time, there is passive
outwards diffusion of potassium ions
to bring about repolarisation and the
membrane potential is again reversed
to -70mV
** mV - milivolt 34

35. Electrophysiology Of Nerve
Conduction
• Nerve possesses a resting potential which is negative electrical
potential of -70mV because of differing in concentration of
ions on either side of membrane.
• Internal to the membrane is negative in respect to the outer
part.
35

36. STEP 1
• Stimulation excites the nerve cells.
• Initial phase of slow depolarization, the electrical potential in the
nerve becomes slightly less negative.
• Falling electrical potential reaches a critical level. Extremely rapid
phase of depolarisation result reaches to a threshold potential or
firing potential where reversal of electrical potential across nerve
membrane occurs.
• Internal to the membrane becomes positive in respect to the
outside (+40mV)
36

37. 37

38. STEP 2
• This is a phase of Repolarisation.
• Electrical potential gradually becomes more negative in
respect to the outside until -70mv is achieved.
• Step1- 0.3msec
• Step2- 0.7msec
38

39. Mechanism of action
- Inhibiting excitation of nerve endings or blocking conduction in
peripheral nerves. Binding to and inactivating sodium channels.
- Local Anaesthetics are alkaloid bases that are combined with
acids, usually hydrochloric, to form water soluble salts. All
anaesthetic salts are formed by a combination of weak base and a
strong acid. They are stable and soluble in water; water solubility
is necessary for their diffusion through interstitial fluids to the
nerve fibers.
39

40. -Sodium influx through these channels is necessary for the
depolarization of nerve cell membranes and subsequent propagation
of impulses along the course of the nerve.
-when a nerve loses depolarization and capacity to propagate an
impulse, the individual loses sensation in the area supplied by the
nerve
40

41. block nerve fiber conduction by acting on nerve membranes
inhibit sodium ion activity
blocks depolarization
blocks nerve conduction
41

42. • When the influx of sodium is interrupted, an action potential
cannot arise and signal conduction is inhibited. LA drugs bind
more readily to sodium channels in activated state, thus onset
of neuronal blockade is faster in neurons that are rapidly firing.
This is referred to as state dependent blockade.
42

43. 43

44. Effect of PH
• Local anesthetics are weak bases and are usually formulated as
the hydrochloride salt to render them water-soluble. At the
chemical's pKa the protonated (ionized) and unprotonated
(unionized) forms of the molecule exist in an equilibrium but
only the unprotonated molecule diffuses readily across cell
membranes. Once inside the cell the local anesthetic will be in
equilibrium, with the formation of the protonated (ionized
form), which does not readily pass back out of the cell. This is
referred to as "ion-trapping". 44

45. Effect of PH
• LA activity increases by increasing PH
• It is because large amount of a drug is unpolar, it will facilitate
its penetration through the cell membrane
• Once the drug has penetrated the lipid barrier and reach its site
of action it is ionized and the ionized form is responsible for
LA activity
45

46. • Acidosis caused by inflammation at a wound partly reduces
the action of local anesthetics. This is partly because most of
the anesthetic is ionized and therefore unable to cross the cell
membrane to reach its cytoplasmic-facing site of action on the
sodium channel.
46

47. Local anesthetics blocks
conduction in the following order:
NB- Pain sensation is blocked more readily than other sensory
modalities 47

48. • Small nerve fibres are more sensitive than large nerve fibres
• Myelinated fibres are blocked before non-myelinated fibres of the
same diameter.
• Thus the loss of nerve function proceeds as loss of pain,
temperature, touch, proprioception, and then skeletal muscle tone.
This is why people may still feel touch but not pain when using
local anaesthesia.
48

49. Physicochemical characteristics of a
local anaesthetic affect its function
• The aromatic ring structure and hydrocarbon chain length
determine the lipid solubility of the drug.
• The more lipid soluble drug penetrates the cell membrane more
easily to exert its effect.
• Thus bupivacaine – which is highly lipid soluble –Thats the
reason it is approximately four times more potent than lidocaine.
49

50. BINDING OF LOCAL
ANESTHETIC TO RECEPTOR
50

51. • The affinity of the receptor site within the sodium channel for the
LA is a function of the state of the channel
• drugs binds to open and inactivated channels, therefore for those
with higher activity/firing
• use dependence - rapidly firing fibers are usually blocked before
slowly firing fibers.
51

52. DURATION OF ACTION
• The duration of action of the drug is also related to the length
of the intermediate chain joining the aromatic and amine
groups.
• Protein binding , Procaine is only 6% protein bound and has a
very short duration of action, whereas bupivacaine is 95%
protein bound. bupivacaine have a longer duration of action .
52

53. ABSORPTION AND DISTRIBUTION
• Some of the drug will be absorbed into the systemic circulation:
how much will depend on the vascularity of the area to which the
drug has been applied.
• The distribution of the drug is influenced by the degree of tissue
and plasma protein binding of the drug. the more protein bound the
agent, the longer the duration of action as free drug is more slowly
made available for metabolism.
53

54. MODE OF ACTION
• Altering the basic RMP of nerve
• Altering the threshold potential
• Decreasing the rate of depolarization
• Prolonging rate of repolarization
54

55. THEORIES OF ACTION OF L.A
• ACTEYLCHOLINE THEORY:
– Involved in nerve conduction in addition to its role as a
neurotransmitter at nerve synapses
• No such evidence
• CALCIUM DISPLACEMENT THEORY:
– L.A causes nerve block by displacement of Ca from some
membrane site that controls entry of Na
• Varying conc. Of Ca in nerve – not seen
55

56. • SURFACE CHARGE THEORY:
– Action by binding to nerve membrane and changing its
electric potential.
LA act on nerve channel rather than surface –It cannot
explained how uncharged LA molecule causes nerve
blockage.
56

57. • Non SPECIFIC MEMBRANE EXPANSION THEORY-
– LA are lipid soluble – enters nerve membrane and changes
configuration of membrane. There by reduced space for
sodium to enter and thus cause inhibition.
• Explains how non ionised drug causes- blockade, nerve
membrane do expand and become more fluid when
exposed to LA .
• No evidence to tell that the whole blockade is due to
this phenomenon. 57

58. SPECIFIC RECEPTOR THEORY:
The hydrophilic charged amino terminal binds to specific
receptors of the sodium gates to block the passage of sodium ions
58

59. 59

60. 60

61. PHARMACOKINETICS OF
LOCAL ANAESTHETICS
61

62. UPTAKE :
• When injected into soft tissues, it exerts
pharmacologic action on blood vessels in the
area.
• All LA possess a degree of vasoactivity,
Most LA produces vasodilation but
degree of vasodilation may vary &
May produce vasoconstriction.
62

63. • This effects may be concentration dependent.
• PROCAINE : The most potent vasodilator
• COCAINE : Only LA which produces
vasoconstriction consistently
-Initial action : Vasodilation
followed by,
an intense & prolonged vasoconstriction
63

64. HOW?
By inhibiting uptake of catecholamines into tissue
binding sites ( especially norepinephrine )
64

65. ROUTES FOR
ADMINISTRATION OF LA :
1) ORAL ROUTE
2) TOPICAL ROUTE
3) INJECTION
65

66. 1) ORAL ROUTE
• All LA are absorbed poorly except cocaine
• Reason : High first pass metabolism
66

67. • Absorbed at different rates after application to
mucous membranes.
• Whenever no layer of skin is present, topically
applied LA can produce an anaesthetic effect.
• Application to intact skin : no anaesthetic action
2) TOPICAL ROUTE :
67

68. Topical/Surface anesthesia
For Application to mucous membranes:
Nose- Mouth- Esophagus
Tracheobronchial tree- Genitourinary
tract.
Commonly used drugs:
• Cocaine (4%-10%).
• > 50% of rhinolaryngologic cases (USA).
• Unique pharmacological property: produces localized
vasoconstriction as well as anesthesia.
• Localized vasoconstriction:
– less bleeding.
– improved surgical field visualization. 68

69. 69

70. Cocaine substitution:
• lidocaine (Xylocaine) -
oxymetazoline (Afrin)
combinations.
• tetracaine (pontocaine)-
oxymetazoline (Afrin)
combinations.
• Tetracaine (pontocaine) (1%-
2%).
• Lidocaine (Xylocaine) (2%-4%). 70

71. Ineffective agents:
Procaine (Novocain) & chloroprocaine (Nesacaine): poor
mucous membrane penetration.
71

72.  Nebulized lidocaine (Xylocaine)-- surface anesthesia
• Upper & lower respiratory tract prior to bronchoscopy or
fiber-optic Laryngoscope.
• Treatment for intractable cough.
• Normal subjects: No effect on airflow resistance (they
produce some bronchodilation).
• Patients with asthma: nebulized lidocaine (Xylocaine) may
increase airflow resistance (bronchoconstriction)-- concern
if bronchoscopy is intended for this patient group.
72

73. 73

74. Skin Surface Application
Barrier: keratinized skin layer
– Higher local anesthetic concentrations required:
o 5% lidocaine (Xylocaine)-prilocaine (Citanest) cream {2.5%
lidocaine (Xylocaine) & 2.5% prilocaine (Citanest)}
no local irritation.
even absorption.
no systemic toxicity.
74

75. Combination of local anesthetic:
Definition: eutectic mixture of local anesthetics (EMLA) .
General definition: eutectic--said of a mixture which has the lowest
melting point which it is possible to obtain by the combination of
the given components.
Melting point of combined drug is lower then either lidocaine
(Xylocaine) or prilocaine (Citanest) alone.
75

76. Clinical uses of EMLA applications-- pain relief for:
– Venipuncture
– Lumbar puncture
– Arterial cannulation
76

77. 3) INJECTION :
• Commonly used route for administration of LA
• Uptake of LA after parentral administration
depends on :
I. Vascularity of the injection site
II. Vasoactivity of the drug
77

78. Local Infiltration
• Definition: Extravascular placement of the local anesthetic in
the region to be anesthetized.
– Example: subcutaneous local anesthetic injection in
support of intravascular cannula placement.
• Preferred local anesthetics for local infiltration:
– Most common: lidocaine (Xylocaine).
– Other choices: 0.25% Ropivacaine (Naropin) or
Bupivacaine (Marcaine) (effective for pain management at
inguinal operative location),
78

79. Duration of action:
– Duration extended by 2x using 1:200,000 epinephrine.
– Caution: Epinephrine-containing local anesthetic solution
should not be injected intracutaneously (intradermal) or into
tissues supplied by "end-arteries" such as ears, nose, fingers
because vasoconstriction may be sufficiently severe to produce
tissue ischemia and gangrene.
79

80. DISTRIBUTION :
• Once it enters the blood, then distributed to all
tissues
• Brain, head, liver, lungs, kidneys & spleen have
high levels of local anaesthetics
WHY?
Due to their high level of perfusion
• Skeletal muscle has the highest level because it
has the largest mass of tissue in the body 80

81. THE BLOOD LEVEL OF LOCAL
ANAESTHETICS IS INFLUENCED
BY
 Rate at which the drug is absorbed into the
CVS
 Rate of distribution from the vascular compartment to the
tissues
 Elimination of the drug through metabolic or excretory
pathways
81

82. ELIMINATION HALF LIFE :
• The rate at which a local anaesthetic is removed from the
blood, the time necessary for 50% reduction in the blood level.
All LAs can cross the blood brain barrier & placenta.
82

83. METABOLISM OR
BIOTRANSFORMATION
83

84. 1) PABA ( Paraaminobenzoic acid)
metabolism :
- Hydrolyzed in plasma by enzyme pseudo
cholinesterase
- Rate of hydrolysis is related to the degree of toxicity
- SLOW HYDROLYZATION= INCREASE IN TOXICITY
84

85. 2 ) AMIDE LOCAL
ANAESTHETICS :
• Primary site of metabolism : Liver
• Prilocaine is metabolized in the liver & lung
• Rate of metabolism is greatly affected by ,
1. Liver function
2. Hepatic perfusion
Articaine has a shorter half life than other amides because a
portion of its metabolism occurs in the blood by plasma
cholinesterase.
85

86.  Metabolism by-products of amide local anaesthetics can
possess clinical activity if allowed to accumulate in blood.
All local anaesthetics have the ability to cause sedation.
86

87. EXCRETION :
• Major excretory organ : Kidneys
• ESTERS : Almost completely hydrolyzed in
plasma,
Thus, appear in small concentrations in the
urine.
 In patients undergoing dialysis :
They are unable to excrete the unchanged portion of the esters
or amides thus increasing toxicity.
87

88. • PROCAINE : Appear in urine as 90% PABA & 2%
unchanged.
• COCAINE : Appear in urine as 10% unchanged.
88

89. COMPOSITION
• Local anaesthetic agent : Lidocaine HCL 2% (20 mg/ml
• Vasoconstrictor: Adrenaline 1:80,000 (0.012 mg)
• Reducing Agent: Sodium Metabisulphite 0.5 mg - This act's as
a preservative for the vasoconstrictor.
• Preservative: Methylparaben 0.1% (1mg)
• Isotonic Solution: Sodium Chloride 6 mg
89

90. • Fungicide: Thymol
• Vehicle: Ringer’s Solution - Minimises discomfort during
injection
• Diluting Agent: Distilled water
• To adjust pH: Sodium Hydroxide
• Nitrogen Bubble: 1-2mm in diameter and is present to prevent
Oxygen from being trapped in
90

91. INDIVIDUAL AGENTS
91

92. Lignocaine
Classified under – Amide
• 2-diethylamino 2,6 acetoxylidide hcl
• Metabolised- Liver by microsomal fixed function oxidases
to monoethyl glycerine and xylidide
• Excretion -<10% unchanged, >80%-metabolised
• Vasodilaton ->Procaine, <Mepivacaine
92

93. NH.CO.CH2.N
CH3
CH3
C2H5
C2H5
LIGNOCAINE
93

94. • Pka –7.9 , ph(plain)-6.5,ph(with Vc)5 –5.5,Onset of action
2-3 min,Anesthetic half life 1.6hrs,topical anesthetic -yes
• Recommended dose – 7mg/kg not>500mg with VC
• 4.4mg/kg not>300mg
• For children with VC 3.2 mg/kg
94

95. • It is non allergic available in three formulations
• Ligno2% with out Vc
• Ligno2% with VC 1:80,000
• Ligno2% with VC 1:100,000
• Adverse reactions- CNS stimulation then
Depression,Overdose causes unconsciousness and
respiratory arrest.
95

96. Bupivacaine
Classified under amide
• 1-butyl 2,6 pipecoloxylidide
• Toxicity <4 times – Lignocaine, Mepivacaine
• Metabolism –Liver by Amidases
• Excretion by kidney (16% unchanged)
• Vasodilation- relatively significant
96

97. • Pka-8.1,ph(plain)- 4.5-6, ph(vc)- 3-4.5
• Onset of action –6-10 min, Anesthetic half life-2.7hrs,Dose
1.3mg/kg ,Maximum dose-not >40mg,Absolute maximum
dose-not> 90mg
97

98. N
NH.CO
C4H9
CH3
CH3
BUPIVACAINE
98

99. • Available as 0.5% soln 1:2,00,000 (vc)
• Indicaton- pulpal anesthesia.
• Full mouth recontruction.
• Extensive perio surgery.
• management of post op pain.
• Duration –Pulpal- 90- 180 min
• Soft tissue-4-12 hrs
• Contra indication- burning sensation at site of injecton, in
children-anticipating self trauma .
99

100. Procaine
• Classified under –Esters
• 2Diethylamino ethyl 4aminobenzoate hcl
• Metabolised-in Plasma by plasma pseudocholine esterases
• Excretion >2%unchanged, 90% -PABA,8% diethyl aminoethanol
in urine.
• Pka-9.1,High degree of vasodilation, 2% procaine 15-30min soft
tissue LA
100

101. • No pulpal anesthesia ,
• > incidence of allergy,
• Drug of choice for intra arterial injection and accidents.
101

102. Mepivacine
• Classified -amide type
• 1 methyl 2,6 pipecoloxylidide hcl
• Metabolism-microsomal fixed funcn oxidasea in liver.
• Maximum dose 4.4 mg/kg , absolute max dose-300mg.
• Excretion-1-10% unchanged urine.
• Pka-7.6,anesthetic half life-90min,
• Mild vasodilator, 3% mepivacaine used in patients with vc
contraindicaton. Low reported cases-allergy. Over dose CNS
stimulation followed by depression. 102

103. Articaine
Classified- amide
– 2 carboxymethoxy 4 methylthiophene hcl
– Metabolised- liver
– Excretion – kidney 10% - unchanged.
– Pka 7.8, anesthetic half life-1.2-2 hrs,
– Maximum dose – 1mg/kg , absolute maximum dose –
500mg
103

104. • First LA agent with thiophene ring,little potential to diffuse
through soft tissue.
• Adverse reaction-methymoglobinemia-rx by using
methylene blue 1mg/kg.
104

105. Etidocaine
Classified –amide
– Metabolism –liver
– Excretion –urine- kidney
– Pka 7.7 ,anesthetic half life-56 min.
– Maximum dose 8mg /kg, absolute max dose 400 mg
– Employed mainly in epidural or caudal regional block.
105

106. VASOCONSTRICTORS
• Vasoconstrictors are the drugs that constricts the blood vessels and
thereby control tissue perfusion.
• They are added to local anaesthesia to oppose the vasodilatory
action of local anesthetic agent.
106

107. What happens if you don’t use a
vasoconstrictor?
*Plain local anesthetics are vasodilators by nature.
1) Blood vessels in the area dilate
2) Increase absorption of the local anesthetic into the
cardiovascular system (redistribution)
3) Higher plasma levels  increased risk of toxicity
4) Decreased depth and duration of anesthesia  diffusion
from site
5) Increased bleeding due to increased blood perfusion to the area.
107

108. 6) Patient is simply not as numb
7) More anesthetic goes into the circulation
108

109. Why We Need
Vasoconstrictors?
109

110. Vasoconstrictors resemble adrenergic drugs and are called
sympathomimetic, or adrenergic drugs
1) Constrict blood vessels  decrease blood flow to the
surgical site
2) Cardiovascular absorption is slowed  lower anesthetic
blood levels
110

111. 3) Local anesthetic blood levels are lowered  lower risk of
toxicity
4) Local anesthetic remains around the nerve for longer periods
 increased duration of anesthesia
5) Decreases bleeding
111

112. Vasoconstrictors should not be used in the following locations
• Fingers
• Toes
• Nose
• Ear lobes
112

113. CLASSIFICATION
113

114. Catecholamines Non catecholamines
Epinephrine Amphetamine
Norepinephrine Methamphetamine
Levonordefrin Ephedrine
Isoproterenol Mephentermine
Dopamine Hydroxyamphetamine
Metaraminol
Methoxamine
Phenylephrine
114

115. SYSTEMIC EFFECTS OF
LOCAL ANAESTHETICS
115

116. CNS
• In one word : DEPRESSION
• At high levels, LA will produce tonic-clonic
convulsions
• Procaine, Lidocaine etc produce ANTI-
CONVULSANT properties.
116

117. • This drugs are used for management of grand
mal & petit mal seizures
• The depressant action of LA raise the seizure
threshold by decreasing the excitability of
cortical neurons in epileptic patients
117

118. PRECONVULSIVE SIGNS &
SYMPTOMS
• Numbness of the tongue & circumoral regions
• If excitation or sedation occurs in the first 5 or 10 minutes
after administration of LA, it should consider as a warning that
convulsive activity could be possible.
• Shivering, slurred speech, muscular twitching, visual/auditory
disturbances, dizziness, drowsiness, disorientation & tremor.
118

119. CONVULSIVE PHASE
• Duration of seizures is related to blood level of
LA & inversely related to arterial pCO2 levels.
• Seizures last less than or equal to one minute.
• In seizure, 1) cerebral blood flow & 2) cerebral metabolism
increase
119

120. INCREASED CEREBRAL
BLOOD FLOW
INCREASE IN VOLUME OF
BLOOD FLOW BEING
DELIEVERED TO BRAIN
LONGER SEIZURE
1 ) CEREBRAL BLOOD FLOW :
120

121. INCREASED CEREBRAL
METABOLISM
ACIDOSIS
PROLONGS THE SEIZURE
2 ) CEREBRAL METABOLISM :
121

122. RESPIRATORY SYSTEM
• DUAL EFFECTS :
1. Non-overdose levels : Direct relaxant action on bronchial
smooth muscle
122

123. 2. Overdose levels :
GENERALIZED CNS
DEPRESSION
RESPIRATORYARREST
DEATH
123

124. CVS
• Direct action on myocardium & peripheral
vasculature.
• Increased LA blood levels result in
decreased myocardial depolarization
• Decrease in myocardial excitation, decrease in conduction rate
& decrease in the force of contraction
• Produces hypotension ( direct relaxation effect
on vascular smooth muscle )
124

125. LOCAL TISSUE TOXICITY
• Skeletal muscle will heal within 2 weeks of being injected
with local anaesthetic.
• Longer acting LA produces more damage to skeletal muscle
than shorter acting LA.
125

126. TOXICITY OF LOCAL ANAESTHESIA
1- Causes
2- Factors reducing toxicity.
126

127. CAUSES
• Accidental rapid intravenous injection.
• Rapid absorption, such as from a very vascular site ie mucous
membranes.
• Overdose .
127

128. FACTORS REDUCING TOXICITY
• Decide on the concentration of the local anaesthetic that is required
for the block to be performed. Calculation of the total volume of drug
should be done.
• Use the least toxic drug available.
• Use lower doses in frail patients or at the extremes of ages.
• Always inject the drug slowly (around 1ml /minute) and aspirate
regularly looking for blood to indicate an accidental intravenous
injection
128

129. • If Injection of a test dose of 2-3ml of local anaesthetic containing
adrenaline is accidentally given intravenously it will often (but not
always) cause significant tachycardia.
• Add adrenaline (epinephrine) to reduce the speed of absorption. The
addition of adrenaline will reduce the maximum blood concentration by
about 50%. Usually adrenaline is added in a concentration of
1:200,000, with a maximum dose of 200 micrograms.
129

130. • Make sure that the patient is monitored closely by the
anaesthetist or a trained nurse during the administration of the
local anaesthetic and following the surgery.
130

131. ADVANTAGES OF LOCAL ANAESTHESIA
• During local anesthesia the patient remains conscious
• Maintains his own airway.
• Excellent muscle relaxant effect.
• requires less skilled nursing care as compared to other anesthesia like
general anesthesia.
• Non inflammable.
131

132. • Less pulmonary complications
• Aspiration of gastric contents unlikely.
• Less nausea and vomiting.
• Contracted bowel so helpful in abdominal and pelvic surgery.
• Postoperative analgesia.
• There is reduction surgical stress.
• Earlier discharge for outpatients.
132

133. • Suitable for patients who recently ingested food or fluids.
• Local anesthesia is useful for ambulatory patients having minor
procedures.
• Ideal for procedures in which it is desirable to have the patient awake
and cooperative.
• Less bleeding.
• Expenses are less.
133

134. DISADVANTAGES OF LOCAL ANAESTHESIA
• There are individual variations in response to local anesthetic drugs.
• Rapid absorption of the drug into the bloodstream can cause severe,
potentially fatal reactions.
• Apprehension may be increased by the patient's ability to see and hear.
Some patients prefer to be unconscious and unaware.
134

135. • Direct damage of nerve.
• Post-dural headache from CSF leak.
• Hypotension and bradycardia through blockade of the sympathetic
nervous system.
• Not suitable for extremes of ages.
• Multiple needle pricks may be needed.
135

136. MAXIMUM ALLOWABLE DOSE
136

137. 137

138. 138

139. LOCAL ANAESTHETICS IN
COMMUNITY TRUST SERVICES
• Dentists can legally write prescriptions for medication and
administer LAs within their scope of practice and at
community outreach programmes.
139

140. The following local anaesthetics are prescribed for use within
the community dental services for local injection in dental
procedures:
• Articaine 4% with Adrenaline [epinephrine] (1 in 100,000)
Cartridges
• Mepivacaine 3% Cartridges
• Lidocaine 2% with Adrenaline [epinephrine] (1 in 80, 000)
Cartridges
• Prilocaine 3% with Octapressin Cartridges
140

141. CONCLUSION
141
• Local anesthesia has been the cornerstone of modern day pain-
free dental practice.
• However, the practitioners limitations in updating about newer
drug formulations available and newer techniques to
administer the drugs has, still not made the goal of pain-free
dentistry a reality.

142. • The availability and cost factors are not excuses not to adapt
newer proven methods, when the benefits outweigh the
shortcomings.
• There is a need in the current evidence-based era of dental
practice for us to constantly update, evaluate and incorporate
newer drugs and techniques into daily practice to provide our
patients the best of care at all times.
142

143. • A clinician s ability to administer an effective, safe and
atraumatic local anesthesia injection to a child (or adult) is a
major factor in creating a patient with a life long acceptance of
dental treatment. Rather than avoiding local administration for
fear of traumatizing the pediatric patient, the clinician should
strive to learn and use the latest modalities of local pain
control to create a pleasant and comfortable dental experience
for the patient.
Steven Schwartz, DDS. Continuing Dental Education . OHIO, USA: Local Anesthesia in
Pediatric Dentistry. 05 June 2016. http://www.dentalcare.com/en-US/dental-
education/continuing-
education/ce325/ce325.aspx?ModuleName=coursecontent&PartID=10&SectionID=-1
143

144. REFERENCES
• K.D. TRIPATHI text book of pharmacology.
• Pharmacology an introductory text: Mary Kaye Asperheim,
6th edn.
• Text book of pharmacology, 1st edn, H.L. Sharma. .
• Text book of Peridontology: Carranza.
• Malamed, Stanley F. Handbook of local anesthesia. 5TH
edition. Elsevier Health Sciences, 2014.
• Handbook of Local
Anesthesia.Br.J.Anaesth. (2013) 110 (4):666-667.
• Local Anesthesia of the Oral Cavity: Jastak JT .W.B.
Saunders Co.; 1995. 1st ed.
144

145. 145