PHARMACOLOGY OF LOCAL ANESTHESIA

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. PHARMACOLOGY OF LOCAL ANESTHESIA 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 V asoconstrictors Systemic effects Toxicity Causes 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 - A rticaine -Bupivacaine - D ibocaine - E tidocaine - L idocaine - M epivacaine - P rilocaine 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 NH O R N R R Aromatic portion Amine portion Intermediate chain ESTER AMIDE LIPOPHILIC (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

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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

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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

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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

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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: DIFFERENTIAL BLOCK 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

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60. SPECIFIC RECEPTOR THEORY — BY F AR THE MOST ACCEPTED THEORY . 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

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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

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74. Skin Surface Application Barrier: keratinized skin layer Higher local anesthetic concentrations required :  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 , Liver function 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.CH 2 .N CH 3 CH 3 C 2 H 5 C 2 H 5 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 C 4 H 9 CH 3 CH 3 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. 1 ) CEREBRAL BLOOD FLOW : 120

121. 2 ) CEREBRAL METABOLISM : 121

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

123. 2. Overdose levels : 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

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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 , 6 th edn . Text book of pharmacology, 1 st edn , H.L. Sharma. . Text book of Peridontology : Carranza. Malamed , Stanley F.  Handbook of local anesthesia . 5 TH 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

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