Local Anesthetics Local Anesthetics pharmacologypharmacologyDr.V.RAMKUMARDr.V.RAMKUMAR

CONSULTANT DENTAL&FACIOMAXILLARY SURGEONCONSULTANT DENTAL&FACIOMAXILLARY SURGEON

REG:4118 TAMINADU-INDIA(ASIA)REG:4118 TAMINADU-INDIA(ASIA)

Local Anesthetics (LA)Local Anesthetics (LA)

• L.A. reversibly block impulse conduction L.A. reversibly block impulse conduction along nerve axons and other excitable along nerve axons and other excitable membrane.membrane.

• A A local anestheticlocal anesthetic is a is a drug that causes that causes reversible reversible local anesthesia and a loss of and a loss of nociception. When it is used on specific . When it is used on specific nerve pathways (nerve pathways (nerve block), effects such ), effects such as as analgesia (loss of (loss of pain sensation) and sensation) and paralysis (loss of (loss of muscle power) can be power) can be achieved.achieved.

Mechanism of action of LAMechanism of action of LA

• They act by blockade of sodium They act by blockade of sodium channels so that:channels so that:

1- The threshold for excitation increase1- The threshold for excitation increase

2- Impulse conduction slow2- Impulse conduction slow

3- The rate of rise of the action potential 3- The rate of rise of the action potential declines, anddeclines, and

4- The ability to generate an action 4- The ability to generate an action potential is abolished or canceled.potential is abolished or canceled.

Mechanism of action of LAMechanism of action of LA

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

Effect of PHEffect of PH

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

Effect of PH (cont.)Effect of PH (cont.)

• LA are weak bases and their activity LA are weak bases and their activity increases by increasing PHincreases by increasing PH

• This because if large amount of a drug This because if large amount of a drug is unpolar, it will facilitate its is unpolar, it will facilitate its penetration through the cell membranepenetration through the cell membrane

• Once the drug has penetrated the lipid Once the drug has penetrated the lipid barrier and reach its site of action it barrier and reach its site of action it ionized and the ionized form is ionized and the ionized form is responsible for LA activityresponsible for LA activity

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

• Local anesthetics block conduction in Local anesthetics block conduction in the following order: small myelinated the following order: small myelinated axons (e.g. those carrying nociceptive axons (e.g. those carrying nociceptive impulses), non-myelinated axons, then impulses), non-myelinated axons, then large myelinated axons. Thus, a large myelinated axons. Thus, a differential block can be achieved (i.e. differential block can be achieved (i.e. pain sensation is blocked more readily pain sensation is blocked more readily than other sensory modalities).than other sensory modalities).

Methods of AdministrationMethods of Administration

• 1- 1- Surface anesthesiaSurface anesthesia: direct : direct application of the drug on the surface application of the drug on the surface such as skin and wounds.such as skin and wounds.

• 2- 2- Infiltration anesthesiaInfiltration anesthesia: injection : injection of LA in subcutaneous tissue in order of LA in subcutaneous tissue in order to paralyze nerve endings at the site to paralyze nerve endings at the site of action.of action.

• 3- 3- Nerve blockNerve block: LA is injected in the : LA is injected in the vacinity of major nerve such as teethvacinity of major nerve such as teeth

Methods of AdministrationMethods of Administration

• 4- 4- Epidural anesthesiaEpidural anesthesia: injection of : injection of LA into the epidural space.LA into the epidural space.

• 5- 5- Sympathetic blockSympathetic block: inject LA : inject LA around sympathetic nervesaround sympathetic nerves

• 6- 6- Spinal anesthesiaSpinal anesthesia: injection of : injection of LA into subarachnoid space in the LA into subarachnoid space in the lumber regionlumber region

Clinical useClinical use

• 1- Systemic use as antiarrhythemic 1- Systemic use as antiarrhythemic agents e.g. Lidocaineagents e.g. Lidocaine

• 2- Locally use to produce anesthesia2- Locally use to produce anesthesia

Clinical LAClinical LA

• Clinical local anesthetics belong to one of Clinical local anesthetics belong to one of two classes:two classes:

• 1- 1- aminoamideaminoamide and 2- and 2- aminoesteraminoester

• Synthetic local anesthetics are structurally Synthetic local anesthetics are structurally related to related to cocaine. They differ from . They differ from cocaine mainly in that they do not produce cocaine mainly in that they do not produce hypertension or local or local vasoconstriction, , with the exception of with the exception of Ropivacaine and and Mepivacaine that do produce weak that do produce weak vasoconstriction.vasoconstriction.

Classification of LAClassification of LA

1-Esters1-EstersA- esters of P- amine benzoic acid e.g. A- esters of P- amine benzoic acid e.g. ProcaineB- Esters of benzoic acid e.g. B- Esters of benzoic acid e.g. Cocaine• Benzocaine• Chloroprocaine• Cyclomethycaine• Dimethocaine//Larocaine• Propoxycaine• Procaine//Novocaine• Proparacaine• Tetracaine//Amethocaine

Classification of LAClassification of LA

2- 2- AmideAmide e.g. Lidocaine e.g. Lidocaine• Articaine• Bupivacaine• Cinchocaine//Dibucaine• Etidocaine• Levobupivacaine• Lidocaine//Lignocaine• Mepivacaine• Piperocaine• Prilocaine• Ropivacaine• Trimecaine

Classification of LAClassification of LA

3- Combinations3- Combinations• Lidocaine/prilocaine (EMLA)Lidocaine/prilocaine (EMLA)4- Natural local anesthetics e.g. 4- Natural local anesthetics e.g.

Saxitoxin and TetrodotoxinSaxitoxin and Tetrodotoxin• Naturally occurring local anesthetics not Naturally occurring local anesthetics not

derived from cocaine are usually derived from cocaine are usually neurotoxins, and have the suffix -toxin in neurotoxins, and have the suffix -toxin in their names. Unlike cocaine produced local their names. Unlike cocaine produced local anesthetics which are intracellular in anesthetics which are intracellular in effect, saxitoxin & tetrodotoxin bind to the effect, saxitoxin & tetrodotoxin bind to the extracellular side of sodium channels.extracellular side of sodium channels.

Potency LAPotency LA

• The potency of LA is vary from one to The potency of LA is vary from one to another where the potency and another where the potency and duration of action are increased with duration of action are increased with decreased water solublility of the decreased water solublility of the agent for exampleagent for example

• Procaine ˃˃˃˃ 1 more water solubleProcaine ˃˃˃˃ 1 more water soluble

• Lidocaine ˃˃˃˃ 4Lidocaine ˃˃˃˃ 4

• Tetracaine ˃˃˃˃ 16 Tetracaine ˃˃˃˃ 16

FrogFrog’’s plexus methods plexus method

• ““Foot withdrawal reflex of frogFoot withdrawal reflex of frog””

• PrinciplePrinciple::

• The skin of the frog is very sensitive The skin of the frog is very sensitive to diluted HCL and will reflex by to diluted HCL and will reflex by withdrawing its leg when immersed withdrawing its leg when immersed in HCLin HCL

ProcedureProcedure

1- Decapitaion the frog (avoid pithing the spinal cord)1- Decapitaion the frog (avoid pithing the spinal cord)

2- Make a transverse incision in the abdominal wall just 2- Make a transverse incision in the abdominal wall just below the xiphoid cartilage and eviscerate the below the xiphoid cartilage and eviscerate the abdomen carefully to form abdominal sac and expose abdomen carefully to form abdominal sac and expose the lumbar plexus without damaging itthe lumbar plexus without damaging it

3- suspend the frog in a stand and test the withdrawal 3- suspend the frog in a stand and test the withdrawal reflex with 0.1 N HCL by immersing one foot in HCL reflex with 0.1 N HCL by immersing one foot in HCL and avoid touching the bottom of the beaker.and avoid touching the bottom of the beaker.

4- remove the acid and wash immediately with tap water4- remove the acid and wash immediately with tap water

N.B. the withdrawal reflex time should not exceed 10 N.B. the withdrawal reflex time should not exceed 10 seconds and the contact with HCL too.seconds and the contact with HCL too.

5- Administer 1 ml of LA solution in the abdominal sac of the 5- Administer 1 ml of LA solution in the abdominal sac of the frog and observe the zero time.frog and observe the zero time.

6- Test the withdrawal reflex at 3 minutes interval and wash 6- Test the withdrawal reflex at 3 minutes interval and wash with tap water after each exposure to the acid, observe the with tap water after each exposure to the acid, observe the time at which the absence of withdrawal reflex occurstime at which the absence of withdrawal reflex occurs

Onst time:Onst time: is the time from adding LA untill the acid fails to is the time from adding LA untill the acid fails to provoke withdrawal of the footprovoke withdrawal of the foot

Recovery time:Recovery time: is the time in minutes from washing the LA is the time in minutes from washing the LA till the appearance of the withdrawal reflex in response to till the appearance of the withdrawal reflex in response to HCL.HCL.

7- Tabulate your results and determine which of LA is more 7- Tabulate your results and determine which of LA is more rapid in its action than the other.rapid in its action than the other.

The time The time intervalinterval

ProcaineProcaineLignocaineLignocaine

33----

66--++

99--

1212--

1515--

1818++

• Negative (-)= means the presence of the Negative (-)= means the presence of the withdrawal reflex (the drug has no withdrawal reflex (the drug has no activity).activity).

• Positive (+)= means the absence of the Positive (+)= means the absence of the withdrawal reflex (the drug has activity withdrawal reflex (the drug has activity and blocks sodium channels)and blocks sodium channels)

• Conclusion: Conclusion: From the table we conclude that lignocaine From the table we conclude that lignocaine

is more rapid in inducing local anesthesia is more rapid in inducing local anesthesia than procaine than procaine