L3- Local Anesthetics Flashcards
Esters
not used in dentistry use as much - ones we will use are benzocaine - which is topical or maybe tetracain
benzocaine
type of LA that is an ester and is used as a topical
first anesthetics?
1884
- cocaine
amides
ones we are more familiar with and have more clinical importance
- articaine
- lidocaine
- mepivacaine
- prilocaine (sometimes)
most potent vasodilator?
procaine - used to get rid of a spasm - but not used in dentistry
all LA?
possess a degree of vasoactivity - most producing vasodilation
only LA that produces vasoconstriction?
Cocaine - vasodialates first and the does constriction
anesthetics with the least vasodialating properties? implicatins?
mepivicaine and prilocaine
- meaning they do not need the addition of a vasoconstrictor as much because they are not doing vasodialtion (more diffuse and will leave area with more dilation)
so given without a vasoconstrictor
oral route of LA
besides cocaine - these are poorly absorbed from the gastrointestinal tract following oral administration
not as effective because of first pass effect at liver
50-90% are taken up by liver so little left systemically to do anything
topical route of LA
absorbed at differeing rates after the application
used as topicals at certain concentration
tracheal mucosa
does work - almost as rapid uptake as IV administration
LA applied to intact skin?
does NOT WORK - they do not have an anesthetic action
EMLA?
‘Eutectic mixture of Local Anesthetic’
- surface anesthesia for intact skin
put on skin - wrap it and it has some effect as LA on the skin
can be effective before giving an injection or IV
intravenous pharmokinetics of LA
Iv administration provides the most rapid elevation of blood levels and is used in the primary treatment of ventricular dysrhythmias
- but wont get a ‘local’ effect
- used in medical emergencies
Pharmacokinetics - distribution once absorbed
vasodilating factors – more blood into area an LA reuptake into bloodstream (vasoconstrictor would prevent this)
once absorbed into the blood, local anesthetics are distributed throughout the body to all tissues
blood levels of LA depend on?
whereever most blood going - more LA
- rate of absorption into CVS
- rate of distribution
- elimination of the drug
wherever most blood goes - where you get most LA at first
ALL LA cross?
blood brain barrier AND the placenta - give local to pregnant make sure no effect - like class A? B is not as bad
more cardiac output =?
more blood flow and thus more LA to the area
Percentages/rank of Cardiac output distributed to different organ systems
- kidney - 22%
- GI system/spleen - 21%
- Skeletal muscle 15%
- Brain -14%
- skin - 6 %
- Liver - 6%
- bone
- heart muscle
- other
General first steps in LA once injected
- Uptake
- Distribution
- Biotransformation
Biotransformation of Esters
Ester LA are hydrolyzed in the PLASMA by the enzyme pseudocholinesterase
Biotransformation example of esters
procaine –> hydrolysis by pseudocholinesterase to para-aminobenzoic acid (PABA) – this can be excreted unchanges in the urine or to diethylamino alcohol then excretion
most common reason allergies to esters?
due to the PABA that is produced by the pseudocholinesterase –> THESE METABOLITES - not the parent compound (like procaine)
atypical pseudocholinesterase
implicatoins?
inability to hydrolyze the ester LA
incidence is 1 out of every 2800 persons
avoid esters
- so use amides
how do you know if patient has a pseudocholinesterase deficiency?
after they had exposure - not an allergic reaction
if first time had it - may have taken them a long time to come out of it but succinyl choline – used for general anesthetic
Amide Biotransformation and difference with them compared to esters
LIVER - primary site of biotransformation
*amidea have a more complex biotransformation and amides are usually present as the parent compound in greater precentage than esters
metabolized in liver – what effects liver will effect this
what would be effects and reasons for slower biostransformation of amides?
slower than normal biotransformation can lead to increased levels of LA in the blood stream (since less being metabolized) and can lead to increased toxicity
- hypotension
- congestive heart failure
- poor liver function like cirrhosis
take things to liver?
if slower rate – less LA to liver – less load to liver and longer time for metabolize
how many half lives does it usually take to eliminate a drug from the system?
about 6 half lives (not same thing as 6 hours)
normal half life for lidocaine?
with heart failure?
hepatic disease?
renal disease?
normal - 1.8 heart failure - 1.9 hepatic disease * - 4.9 - has almost double effect renal disease 1.3
defintion t 1/2
is the time necessary for a 50% reduction in the blood level
one half life = 50 % reduction, two half lives = 75 % reduction
two half lives is how much reduction?
75%
(50% = first)
second is half of 50 (25) so 50 + 25 = 75
pharmokinetics with excretion
- KIDNEYS
- the kidneys are the primary excretory organ for both the local anesthetics and its metabolites.
A percentage of a given dose local anesthetic drug will be excreted unchanged in the urine
what we will find is that the amide ones - parent compound will be excreted and esters the metabolites would be
systemic actions of LA
any membrane / nerve function is effected - so CNS and CVS are susceptible to their action and relates to the plasma levels of LA
- CNS is more susceptible
CNS effect systemic action
Anticonvulsant properties and preconvulsive phase
anticonvulsant properties
CNS systemic effect of LA
- raise the seizure threshold
doses 2-3 mg/kg given at a rate of 40-50 mg/min (0.-4 ug/ml
here there is a balance between inhibitory and facilitory impulses
then…. preconvulsive stage
preconvulsive phase
CNS effect
direct depressant action of the local anesthetic on the CNS (4.5-7ug/ml).
- slurred speech
- shivering
- muscular twitching
- tremor in muscle of face and distal extremities
FIRST there is a balance between inhibitory and facilitory impulses and then in the PRECONVULSIVE STAGE - inhibitory impulsee depressed-
selectively blocks out the inhibitory impulses – so the fascilitated takes over and gets shaking
then convulsive – could get to seizure
more? - both inhibitory and stimilatory are depressed
convulsive stage
with further elevation of the LA blood level produces clinical signs and symptoms consistent with a generalized tonic-clonic convulsive episode
*inhibitory impulses inhibited (vs. pre they are depressed)
greater that 7.5 ug/ml
Final stage in systemic effect of LA on CNS
Both the inhibitory and facilitory impulses are totally depressed, producing general CNS depression
- CVS will be effected next
effect of pCO2 on the convulsive threshold of various LA
with higher pCO2 – lower pH and more acidic so you need LESS of the LA to produce a toxic effect
- with seizure increase in metabolism is also occurring- so more acidic
with lower pH DURATION IS LONGER AND TAKES LESS TO REACH CONVULSIVE STATE
LA systemic effect on Cardiovascular system
LA drug action decreases electrical excitability of the myocardium, decreases conduction rate, and decreases the force of contraction
intravenous dose of LA agents required for Convulsive activity of CNS vs. Irreversible cardiovascular collapse
*effects to CNS will occur FIRST WITH LOWER AMOUNT NEEDED to produce toxic effect
so seizure CNS effects are going to occur at lower doses than CVS
example lidocain = 22 for CNS and 76 mg/kg for CNS
Step 1 - Sequence of LA - induced actions on CVS
(5 total steps)
- at non-overdose levels, a slight increase to no change in BP occurs because of increased CO and HR as a result of enhanced sympathetic activity -
- some vasoconstriction in peripheral vascular beds
Step 2 - Sequence of LA - induced actions on CVS
Levels are approaching but still below the overdose threshold - a mild degree of HYPOTENSION is noted - this is produced by a direct relaxant action on the vascular smooth muscle (due to vasodilation)
Step 3 - Sequence of LA - induced actions on CVS
AT OVERDOSE LEVELS - profound hypotension is caused by direct decreased myocardial contractility, cardiac output, and peripheral resistance
Step 4 - Sequence of LA - induced actions on CVS
AT LETHAL LEVELS - cardiovascular collapse is noted. this is caused by massive peripheral vasodilation and decreased myocardial contractility and heart rate
- sinus bradycardia
Step 5 - Sequence of LA - induced actions on CVS + which LA most associated with this - implications/why associated?
Bupivacaine (and lesser degree ropivacaine and etiodocaine) may precipitate potentially FATAL ventricular fibrillation
- these are LONG LASTING and can cause more problems with arrhythmia
- pt history of v-fib would not want to use
duration of anesthesia dependent on?
general
- individual patient variation
- accurate administration
- anatomical variation (IAN - look where mandibular canal is)
- type of injection administered (block lasts longer than infiltration)
doses of LA- given by? reflects?
manufacturer will give you the maximum dose for a specific drug usually in mg/kg or mg/lb/
these numbers reflect approximate values for there is a wide range in patient responses to blood levels of LA
maximum calculated dose should be decreased in who?
medically compromised, debilitated, or elderly patients
Factors in selection of LA and expand on each
- length of time that pain control is required
- potential for discomfort in the post-treatment period – *use a longer lasting LA
- requirement for hemostasis during treatment -*think about vasoconstrictors
- medical status of patient -*do not use ones that can cause adverse side effects
patient that ‘took a long time to wake up’ when went under general anesthesia
*atypical pseudocholinesterase
pseudocholinesterase deficiency?
- cannot effectivly break down the esters in the plasma – so use an amide which is metabolized in the liver - amide LA when working on the patient
absolute contraindication
implies that under no circumstance should the drug be administered to the patients because of the possibility of potentially toxic or lethal reactions is increased
relative contraindication?
the drug in question may be administered to the patient after carefully weighing the risk of using the drug to its potential benefit - and if an acceptable alternative drug is not an option - may use
benzocaine is? if contraindicated what can you use?
an ester- used as a topical anesthetic
could use lidocaine?
metabolism of articaine? Use it in patient with CHF?
LIVER AND BLOOD
90% liver
10% blood
not going to find articaine WITHOUT A VASOCONSTRICTOR
- but if use without it is okay to use in patient with history of CHF
use prilocaine in patient with CHF?
probably not - because takes longer to metabolize - higher risk of developing side effects
