Local Anesthetic Agent

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Local anaestheticagents

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The Pharmacology of Local Anaesthetic Agents (LA)

Local anaesthetic agents can be defined as drugs,which are used clinically to produce reversible loss of

sensation in a circumscribed area of the body.

Classification :The molecule of the clinically

useful LA agents consists of

1. A tertiary amine attached to an

2. Aromatic ring by an

3. Intermediate chain.5/2/2013 2


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There are important practical differences between these

2 groups of LA agents

Esters are relatively unstable in solution Amidesare relatively stable in solution

Esters are rapidly hydrolysed in the body by plasmacholinesterase (and other esterases)

Amides are slowly metabolised by hepatic amidases and

Esters: One of the main breakdown products is para-aminobenzoate (PABA) which is associated with allergic phenomenaand hypersensitivity reactions

Amides: hypersensitivity reactions to amide local anaestheticsare extremely rare

In current clinical practice esters have largely been superseded bythe amides.

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Mode of action-Membrane structure

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Mode of action

After injection, the tertiary amine base is liberated

by the relatively alkaline pH of tissue fluids: These effects are due to blockade of sodium

channels, thereby impairing sodium ion flux,across the membrane.

B.HCl + HCO3 B + H2CO3 + Cl- In clinical practice, local anaesthesia may beinfluenced by the local availability of free base(B), as only the unionised portion can diffusethrough the neuronal membrane. Thus, local

anaesthetics are relatively inactive when injectedinto tissues with an acid pH (e.g. pyogenicabscess), which is presumably due to reducedrelease of free base.

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Preparations of LA LA agents are usually acid (pH range 4.0-5.5)

and contain1. reducing agent (e.g. sodium metabisulphite)

to enhance the stability of added

vasoconstrictors2. preservative and a fungicide

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What does 1% Lidocain mean?The dilute preparations are presented as percentage (%)solutions

of LA.

A solution expressed as 1% contains 1g substance in each

100mls1 g in 100 ml = 1000mg in 100 ml 10 mg in 1 mlThe number of mg/ml can easily be calculated by

multiplying the percentage strength by10. Therefore a 0.25% solution of lidocaine contains2.5mg/ml of solution (10 * 0.25=2.5 mg /ml)

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vasoconstrictors

Most LA produce some degree ofvasodilation, andthey may be rapidly absorbed after local injection.

vasoconstrictors decrease the systemic toxicity andincrease the safety margin of local anaesthetics by

reducing their rate of absorption vasoconstrictors are frequently added to LA to

enhance their potency and prolong their duration ofaction

Adrenaline is the most commonly usedvasoconstrictorin concentrations ranging from 1 in80,000 to 1 in 300,000

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How can I prepare Adrenaline 1:200000?

Adrenaline dilution 1:200000 means

1 g in 200000 ml = 1000 mg in 200000 ml

1 mg in 200 ml = 0.1 mg in 20 ml

1:80000..= 0.1 mg in 8 ml5/2/2013 10

Plain mg/Kg With Adrenalinemg/Kg

Lidocaine 3 7

Prilocaine 6 9

Bupivacaine 2 2


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contraindication for Adrenaline containing

local anaesthetic agents:

agents

Absolute contraindication (should never be used)for: 1.infiltration around end-arteries i.e. ring

block of fingers, penis or other areas with a

terminal vascular supply as the intense

vasoconstriction may lead to severe ischaemia and

necrosis.

2. Intravenous regional anaesthesia (IVRA)

Relative contraindication:

1.Patient with severe hypertension

2.General anaesthesia with halothane5/2/2013 11


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Clinical Uses of Local Anaesthetics

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1. Topical Anaesthesia

2. Infiltration Anaesthesia

3. Intravenous regional anaesthesia

(IVRA)

4. Peripheral Nerve Blockade

5. Extradural Anaesthesia

6. Spinal Anaesthesia

7. Tumescent Anesthesia


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: op ca naes es a

LA may be applied to the skin, the eye, the ear, the nose

and the mouth as well as othermucous membranes.most

useful and effective: Lidocaine (i.e.gel 2%) and

prilocaine(i.e.EMLA)

2: Infiltration Anaesthesiaprovide anaesthesia for minor surgical procedures.

commonly used Amide LA are (Lidocaineprilocaine,mepivacaine and Bupivacaine).,The site of action is at unmyelinated nerve endings and

onset is almost immediate

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3: Intravenous regional anaesthesia (IVRA)

IVRA (BIER s Block) analgesia for minor surgical procedures. The

local anaesthetic agent is injected into a vein of a limb that

has been previously exsanguinated and occluded by a

tourniquet.

The site of action is probably the unmyelinated nerve

fibres,Prilocaine and Ldocaine are commonly used.Bupivacaine and etidocaineshould never be used for

IVRA! They are significantly protein bound and once thetourniquet is released there is a risk of cardiotoxicity. Several

deaths have been reported during IVRA with bupivacaine.

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4: Peripheral Nerve Blockade :

Regional anestheticprocedures that inhibit conduction in fibers ofthe peripheral nervous system. It can be devided into:

Minor nerve blocks involve the blocking of single nerveentities such as the inferior alveolar nerve, mental nerve, ulnaror radial nerve.

Major nerve blocks involve the blocking of deeper nerves or trunkswith a wide dermatomal distribution (e.g. brachial plexusblockade).

The commonly used LA agents are: Lidocaine, prilocaine,mepivacaine, and bupivacaine.

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epidural space between the dura mater and the

Lig.Flavum. The epidural space contains adipose tissue,

lymphatics and blood vessels. LA produces analgesia by

blocking conduction at the intradural spinal nerve roots.

usually used 0.5% Bupivacaine (mainly) or lidocaine (2.0%)6.: Spinal Anaesthesiainjction directly into the cerebrospinal

fluid (subarachnoid space) produces spinal anaesthesia.commonly used : Bupivacaine 0.5% (mainly hyperbaric), lidocaine (5%)

7.: Tumescent Anesthesia A technique most commonly employedby plastic surgeons during liposuction procedures

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Toxicity from Local Anaesthetic Drugs

when excessive blood levels occur. usually due to:

1. Accidental rapid intravenous injection.

2. Rapid absorption, such as from a very vascular site ie

mucous membranes. Intercostal nerve blocks will give a

higher blood level than subcutaneous infiltration,whereas plexus blocks are associated with the slowest

rates of absorption and therefore give the lowest blood

levels.

3. Absolute overdose if the dose used is excessive.

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Signs and Symptoms of LA Toxicity

It involves the CNS and CVS. In general (CNS) is more sensitive

to LA than the CVS. Therefore CNS manifestations tend tooccur earlier. Brain excitatory effects occur before the

depressant effects.

CNS signs & symptomsEarly or mild toxicity: light-headedness, dizziness, tinnitus,

circumoral numbness, confusion and drowsiness. Patients

often will not volunteer information about these symptoms

unless asked.

Severe toxicity: tonic-clonic convulsion leading to progressive

loss of consciousness, coma, respiratory depression, and

respiratory arrest.

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CVS signs & symptoms

Early or mild toxicity: if LAwith Adrenaline tachycardia

with Hypertension

If no Adrenaline : bradycardia with hypotension

Severe toxicity: Usually about 4 - 7 times the convulsant

dose needs to be injected before CV collapse occurs.

Collapse is due to the depressant effect of the LA acting

directly on the myocardium (e.g. Bupivacaine)

Severe and intractable arrhythmias can occur with

accidental iv injection.

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Essential Precautions and Treatment

Precautions: Secure intravenous access before injectionof any dose that . Always have adequate resuscitation

equipment and drugs available before starting to inject.

Treatment: stop the injection and assess the patient.Call for help while treating the patient

Ensure an adequate airway, give O2 in over facemask . Ventilate

the patient if there is inadequate spontaneous respiration

Intubation : if the patient is unconscious and unable to maintain

an airway.

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Treatment of circulatory failure

with I.V fluids and vasopressors:Ephedrin : If

not available or not effective in correctingthe hypotension .Adrenaline

Treat arrhythmias. Start chest

compressions if cardiac arrest occurs. Treat Convulsions with anticonvulsantdrugs

(Diazepam 0.2-0.4mg/kg , Thiopentone 1-4 mg/kg)

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Local Anesthetic Agent