2. Local Anesthesia II Flashcards
(33 cards)
Final Thoughts
• Kovanaze® = $22/Accuspray Dosing Unit
– 2 Sprays needed to numb = $44
– Occasionally need 3 sprays = $66
• Not covered by ____
• Only approved for a single ____ restorative procedure in patients ≥ ____ lbs
• To expand indication, future studies should include pediatric patients, multiple restorations and more invasive procedures
• Kovanaze got FDA approved ○ Expensive ○ Need two or three to work • 88 pounds > hasn't been studied in \_\_\_\_ ○ Young uncoop kids • Company is in trouble bc the sales are tough ○ The price and use is in question
insurance
maxillary
88
peds
Amides I
• Oral amides > \_\_\_\_ • Need water soluble end (amino terminus, tertiary or secondary amine) > the amides have taken over • Drug used mostly is \_\_\_\_ ○ Works and is cheap ○ Long history • Other drugs that will be picked up > mipovococaine is 3% > doen'st \_\_\_\_ as much as lido ○ Can get by for 20-30 min w/o a vasoconstrictor ○ \_\_\_\_ issues > don't need to give something that stimulates the heart / constricts BV • Higher blood levels w a drug likethis ○ Systemic toxicity > treating pediatric patients • Will use mepivacaine more than bupivacaine ○ Mepivocaine > added extra carbons > more \_\_\_\_ (doesn't make it better!) ○ 0.5% solution > 4x more powerful than \_\_\_\_ ○ W a vasoconstrictor > binds neuronal membranes vigorously > pulpal anesthesia for 4-5 hours, and can get soft tissue anesthesia/periosteal anesthesia for \_\_\_\_ hours (this is with bupivocaine!) § Not just used for long cases § For \_\_\_\_ control After \_\_\_\_ surgery > more to reduce opiod scripts
injectables lidocaine vasodilate CV potent mepivocaine 8-10 post op pain third molar
Amides I
• Maybe do the surgery w lidocaine and infiltrate the sockets w \_\_\_\_ (trade name) to reduce the onset of post surg pain > after remove 3-4 impacted third molars > while still numb you hit them w analgesics • \_\_\_\_ form of bupivocaine > solely approved (takes 2-3 hpurs to come on, and last for 24-48 hours) for infiltrated around incision for \_\_\_\_ control ○ The third molar data is not overwhelming • Etidocaine is no longer available ○ Supposed to be bupivocaines competitor > bad job at \_\_\_\_ it ○ Took lidocaine and added extra carbons > made it more powerful and marketed as a 1.5% solution ○ Long duration of pulpal and periosteal anesthesia • Issues w bupivocaine > all these locals have \_\_\_\_ effects ○ Treating cardiac arrhythmia > one local you give orally > procainamide > made it orally bioavailable ○ Some research that shows when you look at lidocaine > pref binds \_\_\_\_ channels when things are firing (like during an arrythmia) ○ Bupivocaine doesn't care > binds sodium channels in the heart as rigorously when hearts in a \_\_\_\_ rate > more \_\_\_\_ than other locals ○ Some people just appreciating the \_\_\_\_ of these agent > watch how much you give bc it's 4x more powerful § Bupivocaine is more cardiotoxic
marcaine liposomal post op pain marketing antiarrythmic Na noraml cardiotoxic potency
Amides II
• Prilocaine ○ Has same properties of \_\_\_\_ > doesn't vasodilate as much > can get by w a plain solution and get a decent duration of LA ○ Some studies > man block inj last the longest; some studies suggest 50-60 mins of tooth anesthesia; max arch is 30-40 mins • Both of these are 4% solutions > not that \_\_\_\_ soluble as the others • Articaine ○ Took prilocaine and took a \_\_\_\_ ring ○ Amides > no \_\_\_\_ formed > rare instances of allergies are even rarer w these ○ In one molecule you have an amide linkage and an ester side chain > the drug when it hits the BS > rapidly metabolized to \_\_\_\_ acid > inactive > may tamp down the potential of LA \_\_\_\_ • Ester becomes a \_\_\_\_ groups > no issue w PABA > when broken down you don't get it • 4% solutions > \_\_\_\_ ○ Someone says their tongue and lip is tingling and is fat after their injection
mepivocaine lipid thiofine PABA articanic acid overdoses COOH paresthestias
Frequency of Paresthesias in Ontario
• Long lasting paresthesia from LA > rare ○ 1/100k/500k • Uptick in paresthesias w the introduction of \_\_\_\_
articaine
FREQUENCY OF PARESTHESIAS BY ANESTHETIC AGENT
LOOK AT THE TABLE
* Some reported for lido and mepiv * 2-4% solutions > responsible for most of the \_\_\_\_ * Showing up w \_\_\_\_ injections
paresthesia
man block
Review of 1993 Paresthesia Data
• Most used local in Canada in 1993 = 1993 \_\_\_\_ • \_\_\_\_ was the third most used local ○ Endo uses a lot for block injections ○ Used in OS ○ More efficacy with \_\_\_\_
articaine
prilocaine
articaine
RED IS DEAD
• Nb cell line that expresses \_\_\_\_ channels ○ Dumped articaine on the Nb cells > more toxic than \_\_\_\_ • \_\_\_\_ is bad to nerves > all the Nb cells die ○ Positive control • Dentists > store cartridges in alcohol > last longer ○ Permanent nerve damage bc the alcohol leached it in there ○ Used for intractable \_\_\_\_ > kill the nerve • Articaine looks like its causing problems clinically, but in this model > the 2% \_\_\_\_ seems to be more toxic ○ Could be that > talking about \_\_\_\_ of Na channels > people w a variant > susceptible to the articaine neurotoxicity
Na lidocaine ethanol pain lidocaine SNPs
• Effects of pH on weak bases
○ LA are ____
○ When the pH becomes low > equil shifted from free base to the cationic form (charged)
○ When molecules are ____ > harder time penetrating barriers
○ With locals > has a hard time penetrating nerve sheets and membranes when cahrged > when inflamed pH is down > can calc how much in free base and cationic form (doesn’t pen nerve membrane really well)
• pKa = 50% of molecule is ____, and 50% is ____
• If lidocaine has a pKa of 7.4 (of blood) > and put in at normal physiolic pH = 1:1 cationic:fre base
○ Wit a pKa of 7.8 > ____ > still good enough to get enough over the membrane
• Drop the pH 2 units bc of an abscess > ____ cationic: free base > hard to get them numb
○ Pka’s of drugs never ____
○ To have a pka has to bea. ____ acid or base
• Don’t inject right into an infection > somene has an abcess > will spread via the needle track > injecting ____ it
• Nerves become ramped up > harder and sensitized and harder to get numb
• Will asking about this on the exam
• Diff locals have diff PKAs
weak base charged uncharged charged 30:70 100:1 change weak around
pKa, ionization and onset at pH 7.4 (LOOK AT THE TABLE)
• General trend ○ As pka goes up > you get more in the \_\_\_\_ form > slows down \_\_\_\_ ○ Problem w old novacaine > pka was almost 9; no infection > 97% in the cationic and 3% in the free base > had a \_\_\_\_ to get number (14-18 min) • Most rapid onset > pka below \_\_\_\_ • Free base is still less than 50% • Pka has the biggest effect on anesthetic onset • Bupivocaine has the longest \_\_\_\_ > don't like to use it in a busy practice even if it's. along procedure > has a long lag so it slows you down • \_\_\_\_ also has a high pka > don't just have to wait for up the nose and into the sinus, but also has a pka of 8.8/8.9 ○ Works at least for 45 mins
charged onset lag 8 duration tetracaine
TAKE A LOOK AT TABLE FOR LIPID SOLUBILITIES
• Why are some 0.5% and some 4% • Based on \_\_\_\_ > morph cxn to the lipid solubility • Prolacaine has a lipid sol of 55 and marketed as 4%; lidocaine is double the lipid soluble > need \_\_\_\_ • Bupivocaine is 1/5 lidocaine to 1/10 prilocaine; only need a 1/4 of lido and an 1/8 of prilocaine • Some of the prilocaine/articaine paresthesia has to do w the fact they're marketed as 4% > too \_\_\_\_ > knick of man nerve > have variant of Na channels > really gets in there and causes perm damage • Doesn't make bupiv better ○ Don't want to do this in a kid > will chew up their tongue ○ Third molars > you do each for this (initially, or for post op pain)
lipid solubility
half
cxn
The effects of lidocaine on the compound AP
• Siactic nerves from rats • Neurotoxicity w LA solution • \_\_\_\_ AP > not an individal nerve fiber (siatic nerve has thousands of nerve fibers, both pain and motor) ○ Dump lido on the nerve > abolish electrical activity ○ W the locals we use unless contam w ethanol > it's \_\_\_\_ ○ Took the local out in the drug bath > wash w physiologic solution > 3 hours activity has returned • Recovery in the body > \_\_\_\_ away from the site ○ Not metbaolism at the site ○ Most amide metab is in the \_\_\_\_ > numbness goes away • Slow it up > combine local with something that stimulates \_\_\_\_ receptors > vasoconstrictor and prolongs the duration ○ Dump alcohol on a nerve > nothing will recover or will rceover like 105'
compound reversible redistributed liver alpha1
Blockade of all sodium channels in 3 consecutive nodes of ranvier
• Demonstrate in the laboratory > diff sensitivity of nerve fibers to lcoals • Pain fibers and temp sensing fibers > \_\_\_\_ C and Adelta are more sensitive to locals > blocked \_\_\_\_ and reover \_\_\_\_ than fibers that are involved in proprioception ○ Most resistant: \_\_\_\_ fibers ○ Individual fiber preps int eh lab > take a siatic nerve and remove fibers and place mini electrodes > takes less local w a lightly myelinated than one that's high myelinated ○ Critical length hypothesis > knock out an Ap on a ind nerve fiber > puddle of local that covers \_\_\_\_ nodes of ranvier § \_\_\_\_ region, but most of the \_\_\_\_ channels are there ○ Clinically tough to show • Nerve trunk > where most of motor fibers are on outside and pain fibers are more in the core > locals will hit the \_\_\_\_ fibers first ○ Easy to show inlab, tough clinically • Can give a low enough of local that takes away the pain in an \_\_\_\_, but keeps the locals going
unmyelinated/light myelinated
quicker
slower
motor
3 unmyelinated Na motor epidural
Local anesthetic mechanisms
- sodium channel ____
- membrane ____• Either directly get into Na channels
○ When Na channels are open > more easily get in
• Or get itno lipids surrounding Na channels > expands lipids > squeezes Na channel closed
• Some people say that the true active form of the local is the ____ form > most of the time > to get ot the Na channel > entering retrograde > has to be ____ to get in > once into the axoplasm ____ is lwoer > charges up > charged form hits the inner sodium channel
○ In the real world if it’s charged before it gets in it won’t work
○ Need the ____ form
○ Fir this mech of action > uncharged form is better > esp for membrane expansion
blockade expansion charged uncharged pH uncharged
- epi
- levo
- norepi
- ephedrine
- tyramine• Potential vasoconstrictors
• The only two available in the US > 99% of the time is epi, and then there’s an epi analog > levo
○ Norepi used to be available, but a couple of cartirdges can cause pressor reactions > ____ increases
§ Solely stim alpha1 and beta1 > vasocon and inc HR > no opposing ____ effects elsewhere in the body
§ Other BV in skeletal muscle and internal organs > beta2 receptors > opens up
□ Why norepi isn’t used anaphycialcally > odens’t open up the ____
• Epi is 50 alpha1 and 50 beta1/2 > some systemically > some vessels constrict, but elsewhere you get ____
• Levo
○ The only solution this is in > 2% ____ solution w/ 1:20000 levo
Only reason it’s not 1:100k > levo is ____x less potent; need 5x more
BP vasodilatory bronchi vasodilation mepivocaine 5
• Took the epi molecule > moved methyl group one place over > makes it a more pure ____ > 80 alpha 1 and 20 beta1/2
○ Don’e like bc more of a cahnce of a pressor/hypertensive reaction
○ Other thing: three molecules (not epi and norepi)
§ NE: primary NT in ____ nerve fibers; impt in ____; a lot of ____ jack up NE
§ EPI: primarily released from ____
□ Catecholamins > ____ ring, 2 ____, and an amine end; pretty much restricted from the ____ (don’t cross the BBB); direct acting > directly stim ____ receptors (alpha, beta receptors)
• Look at two drugs (ephedrine and tyramine)
○ Eph: behind the counter > can convert to ____
○ These drugs are not catecholamines
§ ____ is an AA found in a lot of food products
○ A lot of ____ action > can directly stim alpha/beta receptors, but most of the action is causing the release of ____ (Ne and catecholamines)
○ If on ____ > don’t want to be consuming tyramine
vasoconstrictor postgang CNS antidepressants adrenal medulla benzene OH symp methamphetamine tyramine indirect NT MAOI
LA blood levels - 1 cartridge
• Advantages of vasocon added to LA ○ When given a local > do not want high blood levels > want godo levels at where it's injected ○ Blood levels of lido alone is 50% higher ○ \_\_\_\_ ug/ml > where starting to get into trouble • 3% mepivocaine > 15% more local inside ○ \_\_\_\_ blood levels ○ Still way below where you get itno trouble ○ Study in adults that average 150 pounds > 30 pound kid > at 1/5 the weight > 5x the blood levels > instead of 0.6mg/ml one cartridge may put into 3ug/ml > second may put on edge of local \_\_\_\_ • Great local in adults > where don't want epi > but easy to get toxicity in smaller kids
5
higher
toxicity
Anesthetic Success and Duration Maxillary Arch
LOOK AT THE TABLE
• Epi with lido > less in the blood • Anesthetic success after max lateral incisor infiltration injection ○ W this injection > 95-96% success > over the apex of the root • 2% lido by itself > used an electric pulp tester > measures tooth vitality ○ As you increase it > tingling > prepain, and then will start hurting ○ If you get it profoundly numb > you can bring it up to 80 and they won't feel anything • Lido alone > such a good \_\_\_\_ > as quickly as you put into the spot it goes away ○ When it works > tooth anesthesia is 6 mins (4 out of 10) ○ Add some epi > increase success to 97% > 35 mins > impeding \_\_\_\_ in the nerve • Inc cxn to 1:100k > same success rate; but you increase \_\_\_\_ and some soft tissue ○ W 3% mepivocaine plain > \_\_\_\_% isn't good enough for tooth; inc cxn you're >90% and add \_\_\_\_ (the only one is levo) > inc duration of action
vasodilator redistribution pulpal duration 2 vasoconstrict
• ____ 1:100k was already on the martket > looking at articaine plain > no epi and looking at half the cxn of epi > electric pulp testing
Articaine
• Articaine plain looked better than2% mepiv
○ Had success of ____% > no where as good as articaine w epi
• Success = ____ consecutive electric pulp test readings within 10 mins
○ Ramping every minute (from 0-80)
○ Three 80’s within 10 minutes >
• Slight advantage in success w ____ over 1/200
○ Once at 93-94% success it’s hard to beat
• Maybe everyone w articaine > want to lose lowest amount of drug > use the ____ solution
75
3
1/100
1/200k
• Duration of action
• 3 way cross over study > double blind, and everyone served as their own control (got all three xments w a week separation)
• Duration looks like ____
○ Plain articaine solutio development is out
• Duration is a little longer w the 1/100; but we’re talking ab 41 mins v 44 mins
• EPT challnege is severe (going to an 80)
○ Looking at ability to copmlete restorative procedure > these numbers would be higher
§ The clinical duration of the 1:200 solution is 45-60 mins
§ ____ is 65-70 mins
2% lidocaine
1/100
Maxillary LI infiltration EPT crossover
• Articaine 4% w 1:100 epi • Infiltration wise > more profound, and better spread of \_\_\_\_ • % of people at various timepoints after giving injection that went up to an 80 ○ If goes up to a 75 > complete restorative procedure • Look at lidocaine > max success is 60-65% in this study • Clearly, the articaine on the LI at every time point was \_\_\_\_ > not responding to the electric pulp tester ○ Put conducting material on the tooth > probe gets sunk into ○ \_\_\_\_ near the probe • Maxillary molar > should show up there (better infil anesthesia)
anesthesia
better
toothpaste
• What people started reporing that they were getting good man infiltration anesthesia
• If you’re going to anesthetize premolar back > ____ injection
○ Reports that you can doa. Filling on amolar/second PM by infiltrating around it
man block
What’s really intriguing is: this is giving an infiltration injection in mandibular first molar region between mesial and distal roots dropping a mL in there.
• This is the success rate over time - again by lack of response to EPT.
◦ Shows difference of 4% articaine w/ 1:100,000 epi vs w/ 2% lidocaine.
So here you are getting some profound ____ anesthesia with infiltration injections of articaine
• what’s interesting is that even though they gave the drug in the first molar region, this articaine has a very good ____ through the tissues
• so they were getting significant local anesthesia (lack of response to EPT) in the ____ region and 2nd molar region.
◦ At least at lot better than lidocaine with epi.
• So now clinicians are doing simple restorative procedures using ____ injections of articaine in the mandible instead of nasty mandibular block injection.
◦ Now can you take out an impacted ____ w/ an infiltration injection of articaine? I don’t think so.
mandibular spread 1st premolar infiltration third molar
