Flashcards in Anesthesia Part I Deck (198):
Difference btwn pharmakodynamics and pharmakokinetics:
Dynamics - how works
Kinetics - what body does to the drug
In LA, we are inhibiting Afferent or Efferent nn.
(efferent goes out)
Onset, Duration, Potency, no allergic rxns, Stably, Sterile, readily undergoes biotransformation - are all desireable properties of LA's and no LA meets ALL criteria
LA's prevent both the ____ and the _____- of a nerve impulse
What is the primary action of LA's in producing a conduction roadblock?
Decrease permeability of ion channels to sodium
*blocks sodium channels
Where do LA's work?
LA's prevent Sodium channels from assuming what state?
The primary effects of LA's occur during what phase?
LA's decrease the rate of ______ and prolong the rate of ________
Mostly LA works on C fibers, but we could go after myelinated fibers as well
What phospholipid bilayer membrane acts as a barrier to LA's
The outer layer of a neuron underlying its sheath:
The myelin sheath insulates the axon both electrically and pharmacologically
The Nodes of Ranvier are the only site where molecules of LA have access to the nerve membrane - lots of Na channels
How many Nodes of Ranvier must be blocked to ensure effective anesthesia?
How many mm?
What fiber carries information related to sharp pain?
What fiber carries information related to dull, aching pain?
*easier for LA to affect unmyelinated C fibers
What normally regulates the movement of Na ions across the nerve membrane?
*increase permeability of Na
LA molecules act by ______ antagonism with Calcium on the nerve membrane
LA produce a depolarizing nerve blockade
Mechanism of LA, displace _______
LA molecules have a ______ aromatic ring
An intermediate linkage of either _____ or ______
And a terminal _______
Only ____ containing LA's are available in the US and can be identified by a Nitrogen in the Intermediate Linkage
All LA's are weak _____
What chemical property of LA's correlates with Potency?
Lipid Solubility of the Aromatic Ring
Bupivacaine is more/less potent than Lidocaine
It is prepared at ___% concentration
*Lidocaine prepared at ____% concentration
In an LA molecule, what part is soluble in lipid?
What part of LA molecule is the "on-off switch" allowing LA to exist as either lipid or water soluble conformations?
Intermediate chain is either an Amide broken down in the _____
or and Ester broken down in the ______
What allows LA to be effective in tissues (chemical structure)?
Spacing between aromatic ring and secondary/tertiary amine
LA's are prepared as weak ______
Are combined with an acid to form a ______ (this makes stable/injectable solution)
All LA's are prepared as what?
Injected as what?
Acidic (HCl stored)
The salt form of LA exists as a ____ structure and will not penetrate the neuron
When exposed to physiologic pH (7.4), a proportion of molecules will convert to _______ structure that is lipid soluble
This determines what?
time of onset
What predicts the proportion of LA molecules in quaternary/tertiary structure when exposed to 7.4 physiologic pH?
pKa (ionization constant)
What speeds the onset of action and increases the clinical effectiveness of LA's?
pH varies a lot in extracellular fluids but remains constant where?
Changes in extracellular pH profoundly alter what?
Ability of LA to block nerve impulses
Without a vasoconstrictor (epi) what is the pH of LA's?
What does this explain?
burning sensation of LA's
LA's exist simultaneously as the base and the what?
RNH+ RN + H+
In order to get through the membrane, what form does the LA take?
In order to bind the receptor sites to block Na channels what form does the LA take?
Base molecule (RN) *lipophilic
Cation (RNH+) *hydrophilic
What form, Cation or Base, is the predominant in LA drug solutions?
What is the sequence of Form when injecting and LA - as injected?
In response to 7.4 tissue pH?
Once exposed to axoplasm?
Base (to pass through membrane)
Only ____ molecules can penetrate the nerve membrane
Only ____ molecules can bind receptor sites in channels
Low pH shifts LA to what form?
If this exists in tissues what happens?
decreases effectiveness b/c won't be able to penetrate membrane
The inclusion of more Cations in an injectable solution produces greater stability, increased solubility of powdered drug in water, and ease of sterilization
pH = pKa
50% Cation, 50% base
The higher the pKa, the more _____ form
This means what for the LA
pKa ranges for LA's are usually what (very narrow)?
7.7 to 8.1
What drug is very potent but very slow diffusing?
*slowest diffusing, but used in prolonged operations
*highest pKa of any LA
The higher the pKa, the more _____ the ____ the onset, the more _____ it will be once inside the membrane
The lower the pKa, the more ____ , the ____ onset, the less _____ will be once inside the membrane
cations, greater time of onset, more effective
base, faster the onset, less effective
What additive to LA's that prolongs shelf life can trigger rxn if allergic to sulfites?
What has a slower onset, LA's with or without vasoconstrictors?
*more base faster the onset - so acidic solutions take a longer time to buffer and cross membranes
LA's are effective on axons and free nerve endings and are can't penetrate skin
*except for EMLA, but slowly
Where can topicals diffuse to reach free nerve endings?
Why are topical nerve blocks ineffective in mucous membranes?
Low buffering capacity
Increasing the pH of a topical does what?
(less H+, less cation, more base)
Topicals are usually more concentrated than the injection version
Outside of nerve sheath:
Outside of nerve bundles:
Outside of nerves:
In a nerve sheath, what is the greatest barrier to the penetration of LA?
What are the 1st bundles in a fascisulus reached by LA?
What are the last?
Mantle bundles innervate something close by
Core bundles innervate something far away
In no clinical situation are all fibers in a peripheral nerve blocked
Relate pKa and onset of action:
Lower pKa, greater onset of action
*more diffusable through membrane
What relates to potency?
What relates to duration of action?
Degree of protein binding (bupivacaine)
Duration of action and potency are opposites
Cationic is related to duration of action
Lipid solubility is related to potency
What affects both potency and duration of LA's?
All LA's are vasodilators, this is why we add vasoconstrictors (like epi)
Mantle bundles lose LA more readily than core bundles and recovery is a slower process than induction
Increasing tolerance to a drug that is administered repeatedly
Tachyphylaxis is more likely to develop in what case?
If nerve function allowed to return prior to second injection
3 factors that affect the rate of removal of an LA:
Degree of protein binding
vascularity of injection site
presence or absence of vasoconstrictor
The first-in-class anesthetic reversal agent is called ______ .
It significantly shortens recovery time and is a _____
Injection site used:
When do LA's stop providing clinical effects?
When enter bloodstream
*can have other effects
The only LA that is a vasoconstrictor?
3 significant vasodilatory effects of LA:
Increase rate of absorption into blood
Decrease duration/quality of pain control
Increase blood conc. and potential for overdose (toxicity)
Once in the bloodstream, highly perfused organs receive more LA but the greatest percentage goes where?
LA readily crosses BBB and placenta
Elimination of LA's follow what order kinetics
1st order kinetics
half lives (time necessary to remove 50%)
Esters are hydrolyzed in the blood by ______
byproduct is _____ excreted in the urine
Inherited disorder (1 in 2800) unable to hydrolyze esters in blood and contraindication for LA esters:
Amides are metabolized where?
What is a relative contraindication to use of these LA's?
ASA IV to V liver dysfunction
What LA undergoes primary metabolism in the liver with some in the lung, and can induce the formation of methemoglobin?
What is the primary metabolite of Prilocaine (that leads to methemoglobin formation)
What metabolites of Lidocaine are responsible for producing sedation?
Systemic actions of LA's are related to the blood/plasma levels of the LA's
LA readily crosses the BBB and has what pharmacological action?
Overdose/Toxicity of LA's usually looks like what?
However, some LA's have ____ properties at lower/non toxic levels
Tonic-Clonic convulsions *inhibit inhibition
CVS effect of LA's
What LA is used as an anti-arrhythmic?
All LA's are vasodilators and create what in terms of BP?
LA's have negative CVS effects at what blood levels?
Slight increase BP due to symp activity at what levels?
Mild hypotension at what levels?
approaching od levels
When does LA produce profound hypotension?
What LA may produce fatal ventricular fibrillation at overdose?
What is more sensitive to irritating properties of LA than other tissues?
Most often associated with what?
At non-overdose levels LA's are a respiratory relaxant, and at overdose levels they can produce what?
Neuromuscular blockage is _____ when LA used w/ other relaxants
DDI's are ____ with other CNS depressants
Amides were once thought to contribute to what?
*there is no literature to support and is a genetic variant
We only use Amide LA's in dentistry in the US, but where do we use esters?
Short duration of action for LA's:
A nerve block will provide longer duration of pulpal/soft tissue anesthesia compared to supraperiosteal infiltration
A larger than recommended dose increases duration
2 drugs with long duration:
2 drugs with short duration:
bupivacaine 0.5%, prilocaine 4% w/ epi
mepivacaine 4%, prilocaine 4%
1:50k or 1:100k will be better for hemostasis
A true, documented, reproducible allergy is what for an LA?
When to use alternative or lowest dose w/ least conc?
You should have a minimum of 2 different drugs of varying duration of action in your practice
Short duration pulpal LA:
Intermediate pulpal LA:
Long pulpal LA:
The first synthetic LA was an Ester called...
It has the greatest _____ of LA's
It had a slow onset with means a high...
Novocain (procaine HCl)
What Ester combo LA was removed from the US market in 1996, was very toxic, and limited utility?
procaine HCl (novacaine) + propoxycaine
Norepinepherine isn't recommended why?
What is the Gold Standard LA - the drug against which all others are compared?
lidocaine is better than procaine (novacaine) in onset, potency, duration
worse in toxicity
Allergy to amide LA is common
What are the 2 pharmacologically active/potentially toxic metabolites to lidocaine HCl
Lidocaine onset of action
Effective dental concentration:
Safe for lactation?
Rapid, 2-3 minutes
safe - doesn't enter milk
What are the 3 formulations of lidocaine (w/ colors)
lidocaine 2% w/ epi 1:50k (green)
lidocaine 2% w/ epi 1:100k (red)
lidocaine 2% plain (light blue) *vasodilatory, few applications
The duration and depth of anesthesia differs how between Red and Green?
lidocaine 2% 1:100k vs. lidocaine 2% 1:50k
Why is Red lidocaine 2% 1:100k preferred for dental procedures?
*for hyper responders, elderly, ASA, cardiac risk
What are the 1st signs/symptoms of LA overdose?
drowsiness, loss of consciousness, resp arrest
B/c Licodane is a depressant, what other use does it have for the CNS?
What LA has similar actions to Lidocaine and lacks the duration of Bupivacaine?
What is the color/concentration of mepivacaine HCl
*similar to Lidocaine pharmacologically
mepivacaine HCl 3% w/o vasoconstrictor TAN
mepivacaine HCl 2% w/ levonordefrin 1:20k BROWN
What is the weakest vasodilator of all injectable LA?
mepivacaine w/ levonordefrin 1:20k provides same hemostasis as epi
Like Lidocaine, Mepivacaine has near non-existant allergy and also possesses anticonvulsant properties
Also, follows more classic OD presentation of CNS stimulation followed by crash
Relative potencies of LA's:
lidocaine, mepivacaine, prilocaine
Safe during lactation?
similar to Articaine and Lidocaine
Liver: hydroxylation & N-demethylation
1-2 minutes (rapid)
unknown, use w/ caution
What drug is similar to Mepivacaine pharmacologically?
prilocaine was thought to have decreased toxicity to lidocaine, but what was discovered?
reduces oxygen carrying capacity
Why is Prilocaine's end product CO2
What metabolite of Prilicaine induces formation of methemoglobin?
Because Prilocaine reduces blood Oxygen carrying capacity, this limits the dose that can be safely given
despite its complications, Prilocaine is metabolized much more rapidly/completely than Lidocaine
What LA has biotransformation take place in the Lungs and Kidney as well as the Liver?
What LA has faster Renal Clearance than all other Amides?
What LA is considered to be less toxic systemically than comparable potent amides?
*removed from circulation fast
The 2 formulations of Prilocaine:
4% Plain Black
4% w/ epi 1:200k Yellow
Why does Prilocaine 4% plain work well?
*but NOT as weak as mepivacaine
What LA is good for epi sensitive pts?
*least conc epi will produce lengthy anesthesia
Anything that produces ______ will be a relative contraindication to prilocaine
*this includes acetaminophen and phenacetin
Prilocaine HCl potency:
equal to lidocaine, mepivacaine
half as toxic as lidocaine
liver, lungs, kidneys - rapid/complete
kidneys - fast renal clearance
less than lidocaine, more than mepivacaine
use w/ caution - thought to enter breast milk
What LA is classified as an Amide but has a different ring structure?
This is a ______ ring - has a _____ atom on it that Increases solubility that has a ______ side chain
Thiophene - Sulfur, Ester
What LA is biotransformed in plasma and liver?
*rapidly in plasma
*ester off thiphene ring + amide
What has the fastest onset of the 5 injectable amide LA's?
Articaine has a high pKa, meaning fewer ____ molecules
Despite this, it's Sulfur/Ester ring makes it more _____
Articaine is available in what 2 formulations?
articaine 4% w/ epi 1:100k gold
articaine 4% w/ epi 1:200k silver
Because articaine has rapid metabolism and clearance, it presents ____ risk for systemic toxicity
What is the knock on articaine that probably isn't true?
Methemoglobiniemia may be a risk of articaine but no cases have been reported in dentistry
articaine HCl potency:
1/3 more potent than Lidocaine, mepivacaine, prilocaine
amide - liver ester - plasma cholinesterase
equal to lidocaine, greater than mepivacaine/prilocaine
What LA has a lengthy duration and is usually only used in OS?
Because bupivacaine lasts for so long, this decreases use of what?
The slowest onset LA due to high pKa
bupivacaine isn't recommende for what 2 demographics?
at risk for self injury (disabled)
What LA has the most profound vasodilating properties?
Overdoses with ____ are uncommon, but more severe and not easily reduces b/c it is ______
Adverse events with bupivacaine are rare b/c we use a lower dose than in medicine
bupivacaine formulation (and color)
bupivacaine 0.5% w/ epi 1:200k Blue
liver (slow by amidases)
most potent vasodilator
slowest (6-10 minutes)
longese - 2.7 hrs
Atrqumatic injections involve pre-injection numbing
Topical LA's don't contain what?
blood levels by topical LA's can be as high as those injected
Many LA's aren't used topically why?
concentrations would be too high - risk for OD
almost all LA's aren't used topically with what notable exception?
What ester is never injected, always Topical:
benzocaine may produce allergy w/ prolonged use why?
What topical is a ketone, equal in potency to cocaine, slow onset, unsuited for injection, and must be compounded at the pharmacy?
2 forms of topical lidocaine:
lidocaine base 5% (poorly soluble)
lidocaine hydrochloride 10% (soluble)
What is the most potent dental topical LA with that also has a long duration or 45 minutes?
What combo topical LA contains 3 esters and has a duration of up to 45 minutes?
benzocaine, butamben, tetracaine
What topical has higher concentrations of base forms of drugs, a long onset on skin, and a fast onset on mucosa?
2.5% lidocaine and 2.5% prilocaine Topical has what 2 formulations?
EMLA - medicine
Oraqix - dentistry
Where is Oraqix used?
It is a ____ mixture
Vasoconstrictors minimize the risk of LA toxicity, increase duration of action of LA, and provide hemostasis
2 Vasoconstrictors in Dental Anesthetics:
epinephrine (naturally occurring)
aromatic with a couple hydroxyls
*add a terminal amine = catecholamine
The dilution ratio:
grams drug dissolved: milliliters of solvent
Dilution ratio of epi used for anyphylaxis
1:100,000 epi used is 1 gram: 100,000 mL solvent
epi concentration can be 1:1k, 1:50k, 1:100k, 1:200k
What is the concentration of levonordefrin?
What is the only product that used levonordefrin?
mepivacaine 2% (brown)
Match colors: Lidocaine 2% epi 1:100k:
lidocaine 2% epi 1:50k
mepivacaine 2% levonordefrin 1:20k
prilocaine 4% epi 1:200k
bupivacaine 0.5% epi 1:200k
articaine 4% api 1:100k
articaine 4% epi 1:200k
most effective and widely used vasoconstrictor that affects heart and vasculature
peaks in plasma:
What is an absolute contraindication to epi
Epinephrine is especially prone to deterioration via...
Beta 1 = ______ effects
Beta 2 = ______ effects
coronary arteries, airway, skeletal
Epi always increases ____ BP
Epi decreases Diastolic pressure in what dose?
Increase in what dose?
small (beta 2)
What type of epi effects predominate in hemostasis?
In epi decline what type of effects predominate?
*vasodilation, post op bleeding
epi raises blood sugar levels
Endogenous epi is terminated by COMT and MAO in the liver
Exogenous epi is terminated by ______
A healthy pt can take how many mg of epi?
0.2 mg (200 mcg)
.04 mg (40 mcg)
Limit Epi dose with what Cardio pts? (2)
ASA III and ASA IV
1:50k epi cartridge max for healthy pt (0.2 mg):
ASA III/IV pt (.04 mg):
*double these for 1:100k, double again for 1:200k
1:50k dilution is most effective at hemostasis, but what is the dilution of choice for at risk individuals?
levonordefrin is a 75% _____ stimulator and a 25% ____ stimulator
levonordefrin is ___% as potent as epi
levonordefrin has more CNS/CVS effects compared to epi
less than epi
less than epi
less potent than epi
less than epi
COMT (no MAO)
levonordefrin max dose health pts:
1 mg = (20 ml 1:20,000) = 11 cartridges
0.2 mg = 4 ml of 1:20,000 = 2 cartridges