Localanasthesia-160111185354.pdf

DR.VINAY JAIN PG 1ST YEAR

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DEFINITION Local Anaesthesia is defined as a transient reversible 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.(stanley f. malamed) 1/11/2016

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CLASSIFICATION OF LOCAL ANAESTHESIA 1. Esters (of benzoic acid) -Butacaine -Cocaine -Benzocaine -Hexylcaine -Piperocaine -Tetracaine

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Esters (of paraaminobenzoic acid) -Chloroprocaine -Procaine -Propoxycaine

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2. Amides -Articaine -Bupivacaine -Dibucaine -Etidocaine -Lidocaine -Mepivacaine -Prilocaine

3. Quinoline

4. Combinations Lidocaine/Prilocaine(EMLA)

Centbucridine 1/11/2016

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CLASSIFICATION ACCORDING TO DURATION OF ACTION SHORT DURATION (pulpal anesthesia approximately 30 minutes) Lidocaine HCl 2%

Mepivacaine HCl 3% Prilocaine HCl 4% (by infiltration) INTERMEDIATE DURATION (pulpal anesthesia approximately 60 minutes) Articaine HCl 4% + epinephrine 1:100,000 Lidocaine HCl 2% + epinephrine 1:50,000 and 1:100,000 Mepivacaine HCl 2% + levonordefrin 1:20,000 Mepivacaine HCl 2% + epinephrine 1:100,000 Prilocaine HCl 4% (via nerve block only) LONG DURATION (pulpal anesthesia approximately 90+ minutes) Bupivacaine HCl 0.5% + epinephrine 1:200,000 1/11/2016

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General Structure  A lipophilic group…usually a benzene ring  A Hydrophilic group…usually a tertiary amine  These are connected by an intermediate chain that

includes an ester or amide linkage

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Ester  Ester linkage is more easy

broken  Less stable in solution

Amide  Not broken easy  More stable in solution  Stored for long time

 Cannot be stored for long time  Metabolism of most esters

results in the production of para

 Amides, very rarely cause

allergic phenomena

aminobenzoate (PABA) which is associated with allergic reaction.

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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) 1/11/2016

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Sensory Neuron  It transmits pain sensation with 3 major portions: Peripheral process (dendritic zone) composed of free nerve endings .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. 1/11/2016

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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.

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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

that result from a brief increase in permeability of the membrane to sodium, and usually also from a delayed increase in permeability of potassium.

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ELECTRICAL IMPULSE

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Electrophysiology Of Nerve Conduction  Nerve possesses a resting potential (step 1) which is

negative electrical potential of -70mV because of differing in concentration of ions on either side of membrane.

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 RESTING POTENTIAL Internal to the nerve

membrane is negative in respect to the outer part.

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STEP 1  Stimulation excites the nerve cells.  A. Initial phase of slow depolarization, the electrical

potential in the nerve becomes slightly less negative.  B. When the falling electrical potential reaches a critical level,extremely rapid phase of depolarisation results. This term threshold potential or firing threshold.

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C. This phase of rapid depolarization result in a reversal of the

electrical potential across the nerve membrane . Internal to the membrane becomes positive in respect to the outside (+40mV).

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STEP 2  This is a phase of Repolarisation.  Electrical potential gradually becomes more negative

in respect to the outside until -70mv is achieved.

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Electrochemistry of Nerve Conduction  Resting State. In its resting state the nerve

membrane is  • Slightly permeable to sodium ions (Na+)  • Freely permeable to potassium ions (K+)  • Freely permeable to chloride ions (Cl−)  Potassium remains within the axoplasm  Chloride remains outside the nerve membrane

 Sodium ions remains outside.

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 Membrane Excitation  Depolarization--Excitation of a nerve segment leads to

an increase in permeability of the cell membrane to sodium ions.  The rapid influx of sodium ions to the interior of the nerve cell causes depolarization of the nerve membrane from its resting level to its firing threshold of approximately−50 to −60 mV.  A decrease in negative transmembrane potential of 15 mV (e.g., from −70 to −55 mV) is necessary to reach the firing threshold. 1/11/2016

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 Exposure of the nerve to a local anesthetic raises its

firing threshold. Elevating the firing threshold means that more sodium must pass through the membrane to decrease the negative transmembrane potential to a level where depolarization occurs. Repolarization--The action potential is terminated when the membrane repolarizes. This is caused by the extinction (“inactivation”) of increased permeability to sodium. 1/11/2016

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Mechanism of action of local anesthetics 1. Non-specific membrane expansion theory 2. Specific receptor theory

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Non-specific membrane expansion theory:

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The lipophilic part of the local anaesthetic attaches to the cell membrane to cause swelling. This then reduces the size of the sodium channel to obstruct the flow of sodium ions.  This results in a decreased diameter of sodium channels, which leads to an inhibition of both sodium conductance and neural excitation.  There is no direct evidence that nerve conduction is entirely blocked by membrane expansion.

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Specific receptor theory:

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The hydrophilic charged amino terminal binds to specific receptors of the sodium gates to block the passage of sodium ions.  Both biochemical and electrophysiological studies have indicated that a specific receptor site for local anesthetic agents exists in the sodium channel either on its external surface or on the internal axoplasmic surface.

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Local anesthetics are classified by ability to react with specific receptor sites in the sodium channel 1. Within the sodium channel (tertiary amine local anesthetics) 2. At the outer surface of the sodium channel (tetrodotoxin, saxitoxin) 3–4. At either the activation or the inactivation gates (scorpion venom)

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•Drugs in Class C exist only in the uncharged form (RN) • Class D drugs exist in both charged and uncharged forms. •Approximately 90% of the blocking effects of Class D drugs are caused by the cationic form of the drug; only 10% of blocking action is produced by the base.

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PHARMACOLOGY OF LOCAL ANESTHESIA

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KINETICS OF LOCAL ANESTHETIC ONSET AND DURATION OF ACTION  Diffusion. The rate of diffusion is governed by several

factors, the most significant of which is the concentration gradient. The greater the initial concentration of the local anesthetic, the faster is the diffusion of its molecules and the more rapid its onset of action.  Blocking Process. After deposition of the local anesthetics close to the nerve as possible, the solution diffuses in all directions according to prevailing concentration gradients. 1/11/2016

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 Induction Time->> Induction time is defined as the

period from deposition of the anesthetic solution to complete conduction blockade. Several factors control the induction time  Under the operator’s control are-> the concentration of the drug and the pH of the local anesthetic solution.  Factors not under the operator’s control are-> the diffusion constant of the anesthetic drug and the anatomical diffusion barriers of the nerve.

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Effect of PH On LA  Local anesthetics are available as salts (usually the hydrochloride)

for clinical use. The local anesthetic salt, both water soluble and stable, is dissolved in either sterile water or saline. In this solution

it exists simultaneously as uncharged molecules (RN),also called the base, and positively charged molecules (RNH+),called the cation.

RNH+ ↔ RN + H+  Ionic form in the solution varies with the pH of the solution or surrounding tissues. 1/11/2016

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 In the presence of a high concentration of hydrogen ions

(low pH), the equilibrium shifts to the left and most of the anesthetic solution exists in cationic form:

RNH+ > RN + H+  Hydrogen ion concentration decreases (higher pH),the

equilibrium shifts toward the free base form: RNH+ < RN + H+ 1/11/2016

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 The relative proportion of ionic forms also depends on the pKa, or

dissociation constant, of the specific local anesthetic. The pKa is a measure of a molecule’s affinity for hydrogen ions (H+). When the pH of the solution has the same value as the pKa of the local anesthetic, exactly 50% of the drug exists in the RNH+ form and 50% in the RN form Henderson-Hasselbalch equation.

BASE Log

==pH–pKa

ACID      

Benzocaine 3.5 Lidocaine 7.7 Prilocaine 7.7 Articaine 7.8 Etidocaine 7.9 Procaine 9.1 1/11/2016

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 A local anesthetic with a high pKa value has very few

molecules available in the RN form at a tissue pH of 7.4.  The onset of anesthetic action of this drug is slow because too few base molecules are available to diffuse through the nerve membrane  The rate of onset of anesthetic action is related to the pKa of the local anesthetic .  A local anesthetic with a lower pKa (<7.5) has a very large number of lipophilic free base molecules that are able to diffuse through the nerve sheath;

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Physical Properties and Clinical Actions 1)The effect of the dissociation constant (pKa):  The anesthetic are important in neural blockade, drugs with a lower pKa possess a more rapid onset of action than those with a higher pKa. 2)Lipid solubility->Increased lipid solubility permits the anesthetic to penetrate the nerve membrane (which itself is 90% lipid) more easily. This is reflected biologically in the increased potency of the anesthetic. Local anesthetics with greater lipid solubility produce more effective conduction blockade at lower concentrations than the less lipid soluble local anesthetics. 1/11/2016

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3) The degree of protein binding of the local anesthetic molecule is responsible for the duration of anesthetic activity.  In the sodium channel itself, the RNH+ ions bind at the receptor site. Proteins constitute approximately 10% of the nerve membrane, and local anesthetics (e.g., etidocaine, ropivacaine, and bupivacaine) possessing a greater degree of protein binding than others (e.g., procaine) appear to attach more securely to the protein receptor sites and to possess a longer duration of clinical activity.

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4)Vasoactivity affects both the anesthetic potency and the duration of anesthesia provided by a drug.  Injection of local anesthetics, such as procaine, with greater vasodilating properties increases perfusion of the local site with blood.

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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, wherease bupivacaine is 95% protein bound. bupivacaine have a longer duration of action .

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MAXIMUM DOSES OF LOCAL ANESTHETICS The doses of local anesthetic drugs are presented in terms of milligrams of drug per unit of body weight.

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Each ml of local anesthesia 1:2,00,000 contains:Lignocaine hydrochloride 21.3mg Adrenaline Methylparaben Sodium meta bisulfite

0.0125mg 1.00mg 0.5mg

In 30ml of local anesthesia, the quantity of lignocaine is approx. 640 mg. According to manufacturer, MRD of lidocaine with vasoconstrictor is 6.6 mg/kg. In a person of weight 60kg MRD is 396 mg . 396/21.3=18.5 ml of LA can be given as a MRD in a person of 60 kg .

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Absorption and Distribution  Absorption of local anesthetics is affected by following

factors:1)dosage 2)site of injection 3) drug –tissue – binding 4) presence of vasoconstricting drug  The distribution of the drug is influenced by the degree of tissue and plasma binding protein 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.

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Metabolism Ester Local Anesthetics. Ester local anesthetics are hydrolyzed in

the plasma by the enzyme pseudocholinesterase.  The rate of hydrolysis has an impact on the potential toxicity of a

local anesthetic.  Chloroprocaine, the most rapidly hydrolyzed, is the least toxic,

whereas tetracaine, hydrolyzed 16 times more slowly than chloroprocaine, has the greatest potential toxicity.  Procaine undergoes hydrolysis to paraaminobenzoic acid (PABA),

which is excreted unchanged in the urine 1/11/2016

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Amide Local Anesthetics- The biotransformation of amide local anesthetics is more complex than that of the esters. The primary site of biotransformation of amide drugs is the liver.  The entire metabolic process occurs in the liver for lidocaine,

mepivacaine, articaine,etidocaine, and bupivacaine.  Prilocaine undergoes primary metabolism in the liver, with

some also possibly occurring in the lung.

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Excretion  The kidneys are the primary excretory organ for both the local

anesthetic and its metabolites.  Esters appear in only very small concentrations as the parent

compound in the urine. This is because they are hydrolyzed almost completely in the plasma.  Amides usually are present in the urine as the parent compound in

a greater percentage than the esters, primarily because of their more complex process of biotransformation. 1/11/2016

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Adverse Effects  CNS: excitation followed by depression (drowsiness to

unconsciousness and death due to respiratory depression.  Cardiovascular System: bradycardia, heart block,

vasodilation (hypotension)  Allergic reactions: allergic dermatitis to anaphylaxis (rare,

but occur most often by ester-type drugs). Very uncommon  Esters more likely because of p-aminobenzoic acid (allergen)  Methylparaben preservative present in amides is also a known allergen 1/11/2016

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Clinical Consideration

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Properties of ideal LA  Reversible action.  It should be Non-irritant to the tissue  It should not cause any permanent alteration of nerve       

structure. No allergic reaction. Its systemic toxicity should be low. It should be rapid onset of action. Sufficient duration of action. Stable in solutions. Not expensive It should have potency sufficient to give complete anesthesia without the use of harmful concentrated solution.

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Sequence of clinical anesthesia •Sympathetic block (vasodilatation)(Type B fiber) •Loss of pain and temperature sensation(Type C and type A delta) •Loss of Proprioception(Type A gamma) •Loss of touch and pressure sensation(Type A beta) •Loss of motor function(Type A alpha)

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SIGNS AND SYMPTOMS OF LOCAL ANAESTHETIC TOXICITY: 1-CNS toxicity :  Early or mild toxicity: light-headedness, tinnitus,

circumoral numbness, abnormal taste, confusion and drowsiness.  Severe toxicity: tonic-clonic convulsion leading to

progressive loss of consciousness, coma,.respiratory depression, and respiratory arrest. 1/11/2016

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2-CVS toxicity:  Early or mild toxicity: tachycardia and rise in blood pressure. This will usually only occur if there is adrenaline in the local anaesthetic. If no adrenaline is added then

bradycardia with hypotension will occur.  Severe toxicity: Usually about 4 - 7 times the convulsant

dose needs to be injected before cardiovascular collapse occurs. Collapse is due to the depressant effect of the local anaesthetic acting directly on the myocardium. 1/11/2016

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ALLERGIC REACTIONS TO LOCAL ANESTHETICS  Hypersensitivity reactions to local anesthetics are

quite rare and generally account for less than 1% of all reported adverse drug reactions.

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Testing for anesthetic allergy using skin test  T.R.U.E. Test (thin –layer rapid use epicutanous patch   

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test) This is a patch test applied 23 allergens to the skin contained 12 polyester patches. The mixture of anesthetics is called the caine mix, in this Benzocaine, Tetracaine hydrochloride, Dibucaine hydrochloride,

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1.Peel open the package and remove the test panel (Figure 1).

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Sign and symptoms of allergic reaction  Generalized body rash or skin redness  Itching ,urticaria  Bronco spasm

 Swelling of the throat  Asthma  Abdominal cramping

 Irregular heart beat  Hypotension  Swelling of the face and lips 1/11/2016

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ADVANTAGES OF LOCAL ANAESTHESIA  During local anesthesia the patient remains conscious  Maintains his own airway.  Excellent muscle relaxant effect.  It requires less skilled nursing care as compared to other

anesthesia like general anesthesia.  Non inflammable. 1/11/2016

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 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. 1/11/2016

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 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. 1/11/2016

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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. 1/11/2016

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 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. 1/11/2016

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Contraindications for local anesthesia - Heart block, second or third degree (without pacemaker) - Severe sinoatrial block (without pacemaker). - Serious adverse drug reaction to lidocaine or amide local anaesthetics. - Concurrent treatment with quinidine, disopyramide, procainamide (class 1 antiarrhythmic agents). - Hypotension not due to arrhythmia. - Bradycardia.

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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.

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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 1/11/2016

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Why You Need Vasoconstrictors 1) Constrict blood vessels  decrease blood flow to the surgical site 2) Cardiovascular absorption is slowed  lower anesthetic blood levels 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

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Vasoconstrictors should not be used in the following locations  Fingers  Toes  Nose  Ear lobes

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Contraindications to Using Vasoconstrictors 1) Blood pressure > 200/115 mm Hg 2) Severe cardiovascular disease 3) Acute myocardial infarction in the last 6 months 4) Anginal episodes at rest. 5) Cardiac dysrhythmias that are refractory to drug treatment

6) Patient is in a hyperthyroid state 7) Levonordefrin and Norepinephrine are absolutely contraindicated in patients taking tricyclic antidepressants 1/11/2016

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Drug Interactions  Chloroprocaine epidurally may interfere with the analgesic     

effects of intrathecal morphine. Opioids and a2 agonists potentiate LA’s. Propranolol and cimetidine decrease hepatic blood flow and decrease lidocaine clearance. Pseudocholinesterase inhibitors decrease Ester LA metabolism. Dibucaine (amide LA) inhibits pseudocholinesterase. LA potentiate nondepolarizing muscle relaxant blockade.

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Other agents with LA properties     

Meperidine TCAs (amitriptyline) Volatile anesthetics Ketamine Tetrodotoxin (blocks Na channels from the outside of the cell membrane) Animal studies suggest that when used in low doses with vasoconstrictors it will significantly prolong duration of action of LA.

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Thanks for your attentions

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Steps in Administration of Local Anesthesia 1. Patient should be in supine position. This is preferred because it favors good blood supply and pressure to brain. 2. Syringe aspiration: Before injecting the solution into the body, first a little aspiration in the syringe is done to avoid chances of injecting solution in the blood vessels and consequently preventing toxic effect of local anesthesia. 3. The local anesthetic solution should not be injected into the inflamed and infected tissues to prevent possible spread of infection. In inflamed areas, the local anesthetic solution does not work properly due to acidic medium of inflamed tissues. 4. In every patient, disposable needle and syringe should be used. 5. Before loading syringe the temperature of the solution should be brought to body temperature to make injecting a painless procedure. 6. Before loading the solution in the syringe, it should be confirmed that anesthetic solution is fresh and not expired. 7. Before injecting the local anesthesia, the site of injection should be cleaned free of debris and saliva by a sterile cotton pellet. 8. Topical surface anesthetic solution or jelly may be applied before injecting the needle for painless penetration of needle. 9. Needle should be inserted at the junction of alveolar mucosa and vestibular mucosa and the angle of needle should not be parallel to the long axis of the tooth . Injection parallel to long axis causes more pain (Fig. 15.1). 10. Anesthetic solution is injected slowly not more than 1 ml per minute and in small increments to provide enough time for tissue diffusion of the solution. Needle should be continuously inserted inside till the periosteum or bone is felt by way of slight increase in resistance of the needle movement The needle is slightly withdrawn and here the remaining solution is injected. 11: Two minutes after injection the effect of anesthesia is checked before starting operative procedure. 12. Patient should be carefully watched during and after local anesthesia for about half an hour for delayed 1/11/2016 13. After use. the needle and syringe should be discarded in a container. 75 reactions

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The primary afferent nerve fibres have been divided into seven different groups depending on their function. Aa - Somatic motor and proprioception Ab - Touch and pressure - circumvent the dorsal horn by giving off collaterals that ascend in the posterior columns Ag - Proprioception, motor to muscle spindles Ad - Pain, cold T o and touch - synapse in Rexed's lamina I of the dorsal horn. B - Autonomic preganglionic C dorsal root - Pain, T o , mechanoreception and reflex responses - synapse in Rexed's lamina II (the substantia gelatinosa) of the dorsal horn. C sympathetic - Postganglionic sympathetics Preferential blockade of a nerve requires a minimal length of fibre exposed to an adequate concentration (Cm) of local anaesthetic. The blocking of three sequential nodes of Ranvier is always sufficient. As thick fibers have an increased distance between nodes of Ranvier this explains the onset of fiber blockade B - Autonomic preganglionic - vasodilatation with associated decrease in BP. C - Pain and T o - loss of thermal appreciation Ad - Pain and T o Ag - Proprioception - loss of awareness of limbs Ab - Touch and pressure Aa - Motor

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