la agent - lec 11 part 1

7/30/2019 LA agent - Lec 11 part 1

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The Pharmacology of Local

Anaesthetic Agents (LA):

- Local anaesthetic agents can be defined as: drugs whichinduce revesible loss of sensation in a circumscribed area ofthe body.

There are 2 types of anaesthesia:

1- General anaesthesia (GA) : reversible loss of concsiousnessinduced by our hypnotic drugs.

2- Local anaesthesia (LA): reversible loss of sensation whichdepends on: *the type of the LA , and *the duration of action.

so you should know the type of LA agent you use, the durationof action, the dose and safety , we'll talk about it.

In general, the molecule of LA agents consists of:1.A tertiary amine attached to an

2.Aromatic ring by an

3.Intermediate chain.

Now, There are 2 classes of local anaesthetic drugs defined bythe nature of the intermediate chain:

1.The ester LA agents include cocaine, procaine, andchloroprocainen


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2.The amide LA agents include lidocaine, prilocaine,bupivacaine, etidocaine, mepivacaine.

OK, Esters and amides have the same tertiary amines andaromatic ring, they only differ in the intermediate chain andthere is a big difference between them Clinically.

This picture shows the chemical structure of Lidocaine andProcaine , now Lidocaine is very common in dentistry it's asample of Amides and Procaine is a sample of Esters.

Both of them have the same aromatic group the same tertiaryamines, the difference is in the intermediate point, this is thedifference chemically.

There is a clear difference between them Clinically, and we'lltalk about it.

Again as we said before we have 2 classes of LA defined by


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the nature of intermediate chain: 1. Ester LA agents includegents Cocaine, Procaine and clorprocaine, you will not dealwith esters you'll deal with amides much more.

2. Amides LA agents include Lidocaine, dentists mainly useLidocaine, also we have prilocaine, bupivacaine, etidocaine,mepivacaine.

Dont confuse yourself with these Names (that's what the drsaid). you will mostly use Lidocaine.

The duration of action for Lidocaine is about 2-3 hours also weuse Bupivacaine, we use it commonly and it has a duration ofaction 6-8 hours or sometimes more depending onconcentration and site of injection.

we'll see now the differences between Esters and amides andwhy we use Amides Mainly.

* Esters are relatively Unstable in solution, Amides arerelatively stable.

stable in solution means when you dilute it, there will be Nochange in it's structure for longer time.

* Esters are rapidly hydrolysed in the body by plasma

cholinesterase (and other esterases) and that will affect theduration of action and make it very short.

Amides are slowly metabolized by hepatic amides which isgood.


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* 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 slide #5 this picture shows Sodium channels now wealready know that always when there is action potential in thebody it will pass from Brain through nerves now actionpotential will be induced and that will Open the sodiumchannels, so sodium will influx and potasium will go outside.that's called action potential

and it will go through nerve terminals to it's target which isMuscles, and Order them to contract.... Ok, this is the Normalsituation

Now, what about Sensation ? how do you feel pain?when you put your hands on something Hot for example youwill immediately move it, this happened according to actionpotential, when the brain recieved the sensation it will sendyou order to move your hand. (so we had sensation and motororders) all of this was through sodium channels.

Ok, the principle of Local anaesthesia is blocking the sodiumchannels.

when Sodium channels is blocked>>>> No action


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potential>>> no feeling of pain , (there is stimulation butwithout neurotransmitters)

Mode of action:

Here there is an important subject we'll talk about, as we saidbefore, after injection of tertiary amines base is liberated bythe relatively alkaline pH of tissue fluids:

Normally, when we inject the tissue normally it's alkaline.

in this equation:

B.HCl + HCO3 B + H2CO3 + Cl-

B is the base

HCo3 which is normally present in the tissue it will inducerelease of the base and th H in HCl will move to HCO3 to giveH2CO3.

and the chloride ion cl- will be alone .

Now this Base (B) is the part that Block the sodium channels,

If a patient came to your clinic and he was infected, what willyou do? will you start working directly?

No, because of the acidic media when infected, the LA won'twork.

to void the diselimination of infection usually we give


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antibiotics to the patient , he will be sent home and then comeback in a week after taking the antibiotic course, theinflammation will be reduced by that we avoid diseliminationof inflammation.

The main point I want you to understand is : Don't give LA toan infected tissue because it won't work in an acidic media(infected tissue = acidic media) , LA only work on alkalinemedia, if there is no alkaline media there will be No release ofthe base and LA will not be effective.

Preparations of LA:

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

1.reducing agent (e.g. sodium metabisulphite) to

enhance the stability of added vasoconstrictors.2.preservative and a fungicide: for allergy which is veryrare to have allergy to amides.

What does 1% Lidocain mean?In General pharmacology any drug and mainly LA whenyou see 1% on the drug

1% means >>>> 10mg per 1mlso 2% means >>>> 20mg per 1mlThe number of mg/ml can easily be calculated by multiplyingthe percentage strength by 10.


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vasoconstrictors:

why do we add vasoconstrictors to LA?

vasoconstriction of blood vessels will reduce the rate ofabsorption, so the risk of toxicity will decrease especially whenthere is rich blood supply in specific sites, like skull; ifsomeone had an injury in his head it will take long time toheal. WHY? because of the rich blood supply.

while in the hand for examlpe, there is poor blood supply, itwill heal faster.

Bleeding differ from a site to another according to the bloodsupply in the area of injury.

increase blood supply--------->> will induce increase inreabsorption of LA and vice versa.

Now, Adrenaline is the most common used vasoconstrictorwith LA, adrenaline added to LA will enhance it's potency and

prolong the duration of action. also the surgery itself will be ina bloodless field, for example, if you want to remove a nevus,you can use Lidocaine alone it will be OK, but if you addedadrenaline to lidocaine it will reduce bleedin.

we have to know the concentration of adrenaline, and how it isdiluted, sometimes adrenaline already diluted and that's okbut the problem is when you need to dilute it in the clinic, it'svery dangerous and you have to know the concentration anddilute it yourself, don't let anyone else do it.

as we said LA block all sensation including sympatheticnervous system,

LA---->> block Na channels---->> relaxation---->>


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vasodilation---->> increase bleeding in site of injection---->>reduce the duration of action.

so we add adrenaline (vasoconstrictor).

usually the concentration of adrenaline we use is 1: 200000

The table in slide#10 shows the most common LA and it'ssafety dose, this table is important you should memorize itespecially Lidocaine, now why did we increase the dose of LAwith adrenaline? because it's a vasoconstrictor, it will decreasethe absorption for safety to decrease toxicity.

Toxicity does NOT come from LA itself even if you inject thesame dose 3 times it will not do anything, the problem is inabsorption, it's in the plasma level in the circulation, that istoxicity.

and toxicity will not be locally it will inter the circulation andthen to CNS and CVS, so that, we need to know the dose.

Now, 3 mg\kg of lidocaine?? what does that mean?

a child patient came to your clinic, his weight is 20 kg, you willuse lidocaine 1% without adrenaline, how many ml are youallowed to use?

as we said 1% means 10mg\1ml ok?

lidocaine without adrenaline means the dose is 3mg\kg (in thetable slide#10).

now the child weighs 20 kg that means the dose is20kg*3mg\kg = 60mg

10mg ----->> 1 ml

60mg------>> ??


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60mg\10mg = 6ml.

if in the same example we used lidocaine with adrenaline itwill be.

7mg\kg * 20 kg = 140 mg

140mg\10mg = 14ml

The adrenaline that we use is 1:200000 , it means 1g in200000ml . 1g=1000mg. so 1g in 200000ml = 1000mg in200000ml = 1mg in 200ml = 0.1mg in 20ml.

in the same way, 1: 80000 will equal 0.1mg in 8ml.

you need to know how to dilute the solution when it comesnon-diluted, off-course you are not going to use 200000ml toput -shwayyet- lidocaine on them.

calculate it, it will be 0.1mg \20ml that's going to be easy touse (20ml), you bring a syringe with 20ml lidocaine and add

0.1mg adrenaline,, it's simple :)now adrenaline always comes in 1mg for 1ml that mean thepercentage is 0.1% . it's a standard anywhere in the worldyou'll get adrenaline percentage of 0.1%.

10mg in 1ml ------->>> 1%

1mg in 1mk--------->>> 0.1%

so the ampule comes in 1ml if I want 0.1mg in 20ml forexample, I'll take the adrenaline ampule (1ml) and dilute it in10cc of Normal Saline, then take 1ml from the solution andadd 20cc lidocaine to that 1ml of adrenaline------>> 20cclidocaine + 1ml adrenaline . that's it :D


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Contraindication for Adrenaline

containing local anaesthetic agents:

you should know that sometimes you can't use adrenaline withLA, why?

There is Absolute Contraindication (when adrenaline shouldnever be used with LA) for:

1. infiltration around end-arteries: for example I want toremove a nevus, i'll do infiltration for the skin around the

nevus, now in the region where I did the infiltration, with LAthere will be vasoconstrictor, and the blood supply mabeimpaired, no problem in this case because the blood supply inthe body start in aorta and the branches of aorta end witharteries then arterioles then capillaries just like a tree, so theregion of nevus will have blood supply from more than one siteit msy recieve blood supply from another site (here it's ok i'mnot afraid of any problem)

the problem is in the end-arteries like for example: ring blockof fingers (LA like a ring to anaesthetise the whole finger) whatwill happen now? maybe there will be No blood supply to thefinger because I blocked it with LA, no blood supply induceischemia, so in these cases we should never use adrenaline(absolute contraindication), if you used it and (la sama7aallah) you had a problem ---- 100% you'll be JAILED O_O ! (lafeeha laf wla dawaran) .

- the other absolute contraindication:

2. Intravenous regional anaesthesia (IVRA):You'll not use


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it as dentists but we'll talk about it in general, sometimeswhen doing a surgery to the hand like the carpel tunnelsurgery, instead of using General anaesthesia you put acanula in the hand and then squeezing by something likerubber, a big rubber, you squeeze the hand untill it drains allthe blood inside it, after that you put a tourniquet on the handwith a pressure over 300mmHg, then No more blood supplywill be there.. will that lead to ischemia??? YES, there might beischemia but the Limbal perepheries can stand ischemia u to2.5 - 3 hours. so till 2 hours I can impair the blood supply forhands and legs (extremeties), but centrally like kidney, brain

and heart, can they stand ischemia? they NEVER do, the braincan just stand ischemia for 3 min after that death will occur,because the nerve cells will not regenerate (death is death).

Now as I said in the intravenous regional anaesthesia when wesqueeze the hand, the veins became empty, We inject the LAinside them. (no blood in the viens but LA only) and thepatient will feel Numbness all over the hand instead of blood

there is LA.in these cases adrenaline is contraindicated, why? because ifany leak occured, there will be huge amount of adrenalinewithin the circulation,

So, we talked about absolute contraindications of adrenaline:

1. infiltration around end-arteries.2. intravenous regional anaesthesia (IVRA).

Now the Relative contraindications, this is more important to


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you as dentists because it include patients with severehypertension, and adrenaline use with these patient will causehypertension and tchycardia, when you have patient withsever hypertension you may take BP reading if its Normal(controlled) then you can use adrenaline but if it's uncontrolled(e.g BP= 150\100) it's better not to give him adrenaline that'sthe meaning of relative contraindication, you are the one whodecide to give or not, according to the patient condition.

another relative contraindication is General anaesthesia with

halothane:in anaesthesia we were using previously something which iscalled Halothane, halothane is given by inhalation, it causesensetivity to the heart, so the heart will be more sensetive toadrenaline, that's why we don't use halothane with adrenaline(this is not important that much to you).

Clinical Uses of Local Anaesthetics

1. Topical Anesthesia: like the spray we use when we feel pain,it's locally work on the mucous membrane.

2. Infiltration anaesthesia: doing infiltration on the surgecalfield (site) when you want to work on a specific teesh you

infiltrate the tissue that surround it, while working on thegingiva you do incision and infiltration on the site of incision.

3. Intravenous regional anaesthesia (IVBA).

4. Peripheral nerve blockade.


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5. Extradural Anaesthesia.

6. Spinal anaesthesia

7. Tumescent anaesthesia.

these are the routes of administration of LA, we'll talk abouteach one in details.

1. Topical anaesthesia: you can apply it to the skin,the eye, the ear, the nose and the mouth as well asother mucous membrnes.most useful and effective: Lidocaine (i.e.gel 2%) andprilocaine(i.e.EMLA) , now why gel and why EMLA cream? Imean if I use the LA that's used in the clinic and I spray itregionally, it will not work, because it's ionnized, it won't workexcept by injecting into tissue.

So. it's used externally on the mucous membrane or skin weuse gels or EMLA cream that is made in a way to be absorpedlocally.

sometime, if you want to be a gentle dentist you can usetopical LA before injecting the regional needle, to block nervesthen it will not be painfull because nerves will be blockedthat's the ide of topical anaesthesia.

2. Infiltration anesthesia:provide anaesthesia for minor surgical procedures. commonlyused Amide LA are (Lidocaine prilocaine,mepivacaine andBupivacaine)., The site of action is at unmyelinated nerveendings and onset is almost immediately.

3. Intravenous regional anaesthesia (IVRA): I've alreadytalked about, but you should know that it's not adrenaline


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which is not allowed with lidocaine, here we must not useanything with lidocaine (y3ne la adrenaline wla 3'airo).

the main 2 types of amide LA as we said :

1. lidocaine which is very common.

2. bupivacaine (longer acting) you don't use it in the clinicas a dentist but you may make a mix of lidocaine andbupivacaine, lidocaine will work immediately for surgery andbupivacaine is added so the patient will rest overnightbecause it's duration of action 8-9 hours.

Bupivacaine has very long acting duration but it's problem is ifit's entered the circulation it will induce irreversiblecombination with sodium channel in CVS. if it induced cardiacarrest there will be irreversible resistance for CVR, so it'scontraindicated to use bupivacaine or etidocaine in IV generalanaesthesia.

4. Peripheral Nerve Blockade:Regional anesthetic procedures that inhibit conduction infibers of the peripheral nervous system. It can bedevided into:

Minor nerve blocksinvolve the blocking of singlenerve entities such as the inferior alveolar nerve, mentalnerve, ulnar or radial nerve.

go to a specefic nerve supplying the site of surgery, likewhen you work on the first molar for example you shouldknow the nerve supply for that region to inject the LAthere and block the sensation (reversible loss ofsensation in the nerve) it differ from infiltration becausewe infiltrate at the site of surgery but the nerve block isnot in site of surgery, you make block a nerve in a finger


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to work in another region and that's the Minor nerveblock.

Major nerve blocks involve the blocking of deeper nerves or

trunks with a wide dermatomal distribution (e.g. brachialplexus blockade).

Brachial plexus blockade: a patient is having a surgery in hishand and his health status cannot stand general anaesthesiawe do brachial plexus block for him, brachial plexus is a groupof trunks (4 trunks) every one has it's own branches of nervesupply to the whole arm and hand, so the brachial plexus is

the whole nerve supply to the upper limbs. so we block thebrachial plexus.

The commonly used LA agents are: Lidocaine, prilocaine,

mepivacaine, and bupivacaine.

5. Extradural anaesthesia: like labor needle ( ) if youheared about it, it's commonly known, it mens that we injectthe needle in skin between the vertebrae in the ligmintumflavum, beneath ligamintum flavum will be the dura mate,there are 3 layers that cover the brain anad spinal cords: piamater, dura mater nd arachnoid mater. between the first 2layers there is CSF (Cerebrospinal fluid) which protect the

brain and spinal cord ( ). if trauma or injury occured,CSF will absorp it for protection. now while injecting the needlewe don't reach the CSF we just stop between the CSF and theligaminum flavum, in that area there is negative pressure,you'll feel resistance while injecting and pushing the Saline


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because of negative pressure, them a sudden loss ofresistance occur, then you feel that the syringe going insidewithout makng pressure on it that mean it reached theepidural space.

now all the nerves that supply let's say from the neck regionto down.

all of these nerves branch from spinal cord, we have vertebraeinside it the spinal cord which is protected by vertebrae (

). that means inside the vertebrae we have all nerves

that supply the whole body so they come from the spinal cord.

These layers when you give lidocaine or bupivacaine in thislayer we don't give high concentration because if theconcentration is high it will completely block the nerves, motorand sensory nerves and we don't want the motor nerves to beblocked, we just seek the sensory nerves blockade we needthe motor nerves to be active so the pregnant woman will still

have the force to push during delivery. so that we give her lowconcentration.

lower concentration will just affect the small in diameternerves which is sensory and sympathetic nerves, the motornerves will not be blocked because it has bigger diameter andneed higher concentration to be blocked OK?

So this is about Extradural anaesthesia which is used in labor,

6. Sinal anasthesia: it diifer from epidural in which: inepidural I control the concentration and blockade but in spinalanaesthesia. I inject the needle directly in the CSF which


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contain 2-3cc of LA and this will induce complete Blockade(sensory, motor and sympathetic from umbilicus to downward,we use it in surgeries which is below umbilicus like a surgery inprostate or leg and the patient has COPD, he can't stantgeneral anaesthesia we use the spinal block, there will becomplete block from let's say umbilicus downward.

7. Tumescent Anesthesia A technique most commonlyemployed by plastic surgeons during liposuctionprocedures.

Toxicity from Local AnaestheticDrugs

Toxicity depend on the blood level, to be toxic the LAshould be huge concentratd in the blood.Focus in this Note: YOU Shlould NEVER do any injectionof LA before Aspiration.even if you changed the needle you have to doaspiration again to avoid itravascular injection.Now when excessive blood levels occur usually due to:

1.Accidental rapid intravenous injection.

2.Rapid absorption, such as from a very vascular site iemucous membranes. Intercostal nerve blocks will give ahigher blood level than subcutaneous infiltration,

whereas plexus blocks are associated with the slowestrates of absorption and therefore give the lowest bloodlevels.

3.Absolute overdose if the dose used is excessive, like inchildren you gave 10cc to a child of 5kg weight,this isexcessive, but in adults it rarely occur.


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Signs and Symptoms of LAToxicityyou gave the patient the LA intravscularly, how wouldyou know?as I told you the systems that will be affected in LA areCVS and CNS, why? because they have Sodium channelsand LA may block the sodium channels.

CVS manifistation ( ) you'll not seethe CVS manifistations unless you gave a huge amount

of LA, for example if you gave 3-4cc of LA even if yougive them directly to blood this will not affect the CVSbut they will affct the CNS.

If ( ) toxicity occured you'll see the CNSmanifistation (Brain excitatory effects before thedepressant effect).at first, when you give LA and reach for example thebrain , it should induce depression, blockade of nerves

and depression, there is excitatory effect, the patient willbe irritant.So, CNS signs and sypmtoms:Early or mild toxicity: light-headedness (it may occurbecause of vasovagal attack or toxicity),dizziness,tinnitus, circumoral numbness (this sign is VERYimportant, it is a characteristic sign od LA if the patienttold you tht he feel of numbness around his lips you

immediately know that you gave him an overdose), aloconfusion and drowsiness. Patients often will notvolunteer information about these symptoms unlessasked.

after injecting the LA don't deal with patient as a


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machine or cushion, you should keep talking to him, askhim, how do you feel? is it painfull? don't ask him do youfeel numbness or drowsiness? ( ),,ask him indirect questions so you can visualise his

status, i.e if you ask him how are you? and he answeredyou normally: el7mdolellah, then it's ok he is consciousand there is no confusion.

Sever toxicity: it's rare to occur, if you inject 10cc of LAwithout aspirtion and you have a BAD luck that madeyou inject it in a vein directly, it will cause tonic clonicconvulsion ( ), leading to progressive loss ofconsciousness and Coma, if coma occured the patientwill sleep, airway obstruction will occur (tongue will blockthe airway), patient won't be breathing, which end toarrest and die. so you shloul be aware.

CVS signs: as we said it need a hugle plasma level tooccur, the size of CVS signs depend on Adrenalinepresence.if LA with adrenaline: we will see the signs of adrenalinetoxicity which is tachycardia and hypertension.if LA without adrenaline: we will see the signs of LAtoxicity which is bradycardia and ypotension.

Sever toxicity: Usually about 4 - 7 times the convulsantdose needs to be injected before CV collapse occurs. andthat's impossible in your occupation to deal with thishuge amount of dose.

Collapse is due to the depressant effect of the LA acting

directly on the myocardium (e.g. Bupivacaine),myocardium (the muscle itself) recieved the musclerelaxant, it will cause sodium channel block to the heartitself which cause arrest.


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Essential Precautions andTreatmentif toxicity occured, what will you do?

Precautions: Don't Do any procedure unless you secureintravenous access, so secure intravenous accessbefore injection of any dose that . Always have adequateresuscitation equipment and drugs available beforestarting to inject.

Treatment: while you're injecting the patient hebecame drowsy or he feel circumoral numbness, he had

signs of toxicity what will you do? the first thing is STOPinjection, because if you continued you'll increase thedose, after that you have to assess the patient and caalfor help while treating the patient.

Ensure an adequate airway, if coma occured you shouldbe afraid of airway obstruction>>> apnea>>Obstruction>> hypoxia during 3 min >> brain hypoxiaduring 6 min you'll lose the patient.

at least you should be able to deal with it, to assessairway.

Treatment of circulatory failureif, he had cardiac arrest or bradycardia or hypotension,what shall you do?first, give him IV fluid, huge amount of IV fluid to support

the circulation, even RTA patient when he come the firstprocedure we do is giving him IV fluid to support CVS.a;so patients with hypotension and bradycardia we givethem IV fluid.another thing we give is vassopressor like ephedrine oradrenaline, why? to increase the blood pressure.In hypotension and bradycardia patients, arms and legs


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can stand complete blood supply cutting up to 3 hoursas I told you before but what I concern about is thekidney, heart and brain, those are the vital organs, thecan't stand it, that's why the first thing to do is Support

the CVS, give the patient IV fluid if he is in the clinic andif you have adrenaline give him 0.2 mg of adrenaline toelevate his blood pressure if he is hypotensive or nearlyarrested.

Treat arrhythmias. Start chest compressions if cardiacarrest occurs.

Treat Convulsions with anticonvulsantdrugs (Diazepam

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

Done by: Safaa' R Shloul


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la agent - lec 11 part 1

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