Local Anesthetics Worksheet Flashcards
LA consists of a ____ and a _____ portion.
Lipophillic
hydrophilic
the lipophilic and hydrophilic portions of a LA are separated by a connecting:
hydrocarbon chain
LA’s are poorly soluble in
water
Because of the poor solubility in water, LA’s are marketed as water soluble:
Hydrochloride salts
hydrochloride salt solutions are acidic or alkalodic? pH?
Acidic
pH 6
hydrochloride salt solutions contribute to the LA’s what?
stability
what is it that contributes to the stability of LA’s?
the hydrochloride salt solutions
substituting a butyl group for the amine group on the benzene ring of procaine results in:
tetracaine
Tetracaine is water or lipid soluble?
Lipid soluble
Compared to procaine, tetracaine is more
lipid soluble
How many times more potent is tetracaine than procaine?
10 times more potent
Which LA has a longer duration; procaine or tetracaine?
tetracaine
the longer duration of tetracaine corresponds to a ___ fold decrease rate of _______.
4-5
fold decreased rate of
metabolism
compared to the commercially available racemic mixtures of bupivacaine and mepivacaine, what appears to be less toxic?
the S Enantiomers of bupivacaine and mepivacaine
what LA is known for cardio toxicity?
bupivacaine
the S enantiomers of Bupivacaine and mepivacaine produce less of this _____ _____ (two things) than the racemic mixtures or the R enantiomers of LA.
Neurotoxicity
Cardiotoxicity
What 2 LAs are available for clinical use as racemic mixtures (50:50) of the enantiomers:
Mepivacaine and bupivacaine
Mepivacaine, bupivacaine, ropivacaine, and levobupivacaine are all:
chiral drugs that may have S or R configurations
Name 4 LA that are chiral drugs that may have S or R configurations:
Mepivacaine,
bupivacaine,
ropivacaine,
levobupivacaine
Halogenation of procaine to _______
Chloroprocaine
Halogentation of procaine to chloroprocaine results in a ____ fold increase of what?
3-4 fold incease
in hyrolysis rate of chloroprocaine
hydrolysis of chloroprocaine is done by:
plasma cholinesterase
Etidocaine resembles:
Lidocaine
Etidocaine resembles lidocaine but has a 50 fold increase in:
lipid solubility
Etidocaine resembles lidocaine but has a 2-3 fold
increase in the duration of action
What LA is 35 times more lipid soluble than mepivacaine?
bupivacaine
Bupivacaine has a potency and DOA _____ times that of mepivacaine.
3-4 times
These drugs have been incorporated into liposomes to prolong the DOA and decrease toxicity:
Lidocaine, tetracaine, and bupivacaine
Lidocaine, tetracaine, and bupivacaine have been incorporated into liposomes to do what two things?
Prolong DOA
Decrease toxicity
The FDA has approved this for local infiltration of anesthesia for hemorrhoidectomy and bunionectomy:
bupivacaine extended release liposome injection
LAs bind to specific sites in:
voltage gated Na+ channels
Na+ channels are
the binding sites for LA
LA blocks what? (main moa)
Na+ current
LA blocks Na+ current reducing excitability of:
1) neuronal
2) cardiac
3) central nervous system tissue
LA prevents transmission of nerve impulses by inhibition passage of _______ through _______ in nerve membranes.
Sodium ions through ion-selective sodium channels
This is a specific receptor for LA molecules
The sodium channel itself
Describe how AP is not propagated d/t Na+ ion channels
- -failure of Na-channel permeability to increase slows rate of depolarization.
- Threshold potential is not reached thus,
- AP is not propagated
Pregnancy may do what to LA’s?
Increased sensitivity
*more rapid onset of conduction blockade
When might there be an increased sensitivity that would generate a more rapid onset of a LA blockade?
pregnancy
Name 3 esters :
table 10-1
Tetracaine
Procaine
Chloroprocaine
Name 2 rapid onset LA:
table 10-1
Chloroprocaine
Lidocaine
Chloroprocaine and Lidocaine both have:
a rapid onset
Procaine
Chloroprocaine
Tetracaine
Are all examples of:
esters
*in order of potency least to greatest
Which LA has the greatest protein binding?
Levobupivacaine (>97%)
Levobupivacaine has the greatest what?
protein binding
>97%
LAs are all weak:
bases
at physiologic pH what % of LA exists in a lipid soluble, non-ionized form?
< 50%
What type of environment would increase the ionized fraction of the LA if injected into it?
Acidic (as present with tissue infection)
*Acidosis
If LA is injected into an infected area, more of the drug becomes ________.
This is consistent with what kind of quality (of the block)?
Ionized (base in an acid)
–> poor quality blockade results; not as much being absorbed in ionized form
What 4 characteristics of LA effect the absorption of LA from its site of injection to the systemic circulation?
- site of injection
- dose
- use of epinephrine
- pharmacologic characteristics of the drug
The ultimate plasma concentration of LA is determined by what two factors?
- rate of tissue distribution
- rate of clearance of the drug
*p.287
Name 3 LA the lungs are able to extract from the circulation:
- Lidocaine
- bupivacaine
- prilocaine
*amides
Bupivacaine’s first-pass pulmonary extraction is
dose dependent
This LA has a dose dependent first pass pulmonary extraction:
bupivacaine
What drug impairs the extraction of bupivacaine from the lungs?
Propranolol
Propranolol is known to do what with certain local anesthetics?
- impair bupivacaine’s extraction by the lungs
- decrease plasma clearance of lidocaine and bupivacaine
What decreases the plasma clearance of lidocaine and bupivacaine?
Propranolol
Propranolol decreases the plasma clearance of which LA?
Lidocaine
bupivacaine
D/t their rapid hydrolysis, this classification of LA are not available to cross the placenta in significant amounts:
Ester LA
What causes LA molecules to accumulate in the fetus?
Acidosis
What is the process of ion accumulation in the fetus called?
ion-trapping
Ion trapping in a fetus, is a result of what type of environment?
acidosis
Do LA’s have good/limited/poor renal excretion?
limited renal excretion
Renal excretion of LA’s is limited because they are:
poorly water soluble
This LA has a 10-12% unchanged drug recovery in the urine
Cocaine
Less than what % of the LA is excreted in the urine unchanged?
< 5%
Cocaine is the exception to what?
renal excretion; unlike other LA’s 10-12% of cocaine is excreted unchanged.
Also it is an ester that is metabolized in the Liver instead of plasma.
Where are Amide LA’s primarily metabolized?
Liver
Name the most rapid metabolized amide(s):
Prilocaine
Name the intermediate metabolized amide(s):
Lidocaine
Mepivacaine
Name the slowest metabolized amide(s):
Bupivacaine
Etidocaine
Ropivacaine
What class of LA has the slower metabolism?
Amide
Amides have a slower ___________ compared to esters
metabolism
The principle metabolic pathway of Lidocaine is:
oxidative dealkylation
oxidative dealkylation of lidocaine occurs where?
Liver
Lidocaine metabolizes in the liver through oxidative dealkylation in to what?
monoethyglycinexylidide
Once lidocaine goes through oxidative dealkylation to monoethyglycinexylidide, what happens next?
hydrolysis
monoethyglycinexylidide hydrolyzes to this metabolite:
xylidide
xylidide has what % of the cardiac protection against dysrhythmias of lidocaine?
10%
Xylidide is hydrolyzed from
monoethyglycinexylidide
monoethyglycinexylidide is a result of
- Oxidative dealkylation of Lidocaine
- in the liver
In liver dysfunction, elimination half-time of lidocaine is
increased more than fivefold
There is more than a fivefold increase in the elimination half-time of lidocaine in patients with
liver dysfunction
Prilocaine is metabolized to
orthotoluidine
Prilocaine is associated with what life threatening complication?
methemoglobinemia
Orthotoluidine is the byproduct of what?
prilocaine metabolism
Orthotoluidine is an oxidizing compound capable of converting what?
hgb in to its oxidized form: methemoglobin
—> methemoglobinemia
What is the reversal drug and dose for methemoglobinemia?
methlyene blue
1-2mg/kg IV over 5 mins
-do not exceed 8mg/kg
Name the LA(s) lacking vasodilator activity:
- Mepivacaine
- Ropivacaine (added)
When adding epinephrine to a LA (in order to extend its DOA by vasoconstriction) is not recommended, what LA could you add to the mix as an alternative?
mepivacaine
Compare clearance and elimination half time of ropivacaine and bupivacaine:
-Ropivacaine has a shorter elimination half-time and higher clearance.
Ropivacaine has a shorter elimination half-time and higher clearance than bupivacaine. This may offer an advantage over bupivacaine in terms of :
systemic toxicity
In order of greatest to least LIPID solubility:
[lidocaine, bupivacaine and ropivacaine]
Bupivacaine
Ropivacaine
Lidocaine
Ropivacaine is metabolized by
P450
Which LA is the slowest eliminated amide?
Dibucaine
Dibucaine is known for its ability to inhibit the activity of normal:
butyrylcholinesterase by more than 70%
Dibucaine inhibits butytylcholinesterase activity by how much?
more than 70%
Atypical plasma cholinesterases account for prolonged effects and toxicity of drugs such as
succinylcholine
chloroprocaine
What LA is used for pseudocholinesterase difficency testing?
dibucaine
Cocaine undergoes metabolism where?
in the liver
All ester LA’s undergo hydrolysis by
cholinesterase enzymes
This ester LA is the only one that does not undergo hydrolysis by cholinestearse enzymes:
cocaine
Cocaine is metabolized by
plasma and liver cholinesterase
CSF contains little to no
cholinesterase enzyme.
Anesthesia produced by subarachnoid placement of Tetracaine will persist until
the drug is absorbed by systemic circulation
What contributes to the persistent effects of Tetracaine when injected into the CSF?
- CSF has no cholinesterase enzymes
- drug must be absorbed by systemic circulation
What is unique about benzocaine?
a weak acid (pka 3.5)
predominantely in non-ionized form
How long can cocaine remain in the urine?
24-36hrs
1-1.5 days
Alkalization of LA does what?
shortens onset of neural blockade
- enhances depth of sensory and motor blockade
- increases spread of epidural blockade
- increase the % of LA in the lipid soluble form that is available to diffuse across lipid cell barriers
The effect of the addition of epi to lidocaine and mepivacaine?
- prolongs duration of conduction blockade
- decreases systemic absorption of LA (by 20-30%)
The effect of the addition of epi to bupivacaine?
- prolongs duration of conduction
- decreases systemic absorption of LA (by 10-20%)
*slightly less than lidocaine and mepivacaine
Most LA possess intrinsic vasodilator properties except: (choose two)
Ropivacaine and mepivacaine
Ropivacaine and mepivacaine lack:
vasodilator properties like other LA’s
Most likely class of LA to have an allergic reaction to?
Esters
-b/c of metabolite paraaminobenzoic acid
Name the metabolite likely to evoke an allergic reaction in LAs
paraaminobenzoic acid
*ester metabolite
Is there a cross sensitivity b/w esters and amides?
NO
-more of a reflection of a sensitivity to the metabolite paraaminobenzoic acid
The plasma concentration of Lidocaine that causes:
ANALGESIA
1-5mcg/mL
The plasma concentration of Lidocaine that causes:
MYOCARDIAL DEPRESSION
5-10 mcg/ml
The plasma concentration of Lidocaine that causes:
TINNITUS
5-10 mcg/ml
The plasma concentration of Lidocaine that causes:
SEIZURES
10-15 mcg/ml
The plasma concentration of Lidocaine that causes:
APNEA
15-25 mcg/ml
The plasma concentration of Lidocaine that causes:
CARDIOVASCULAR DEPRESSION
> 25 mcg/ml
What is the recommended adult dose of lidocaine with epi for regional anesthesia:
7mg/kg
In tumescent liposuction the dose of lidocaine may range from
35-55mg/kg
What drug can be used to tx cocaine induced MI?
Nitroglycerin
What drug class should be used with caution with a cocaine overdose?
beta blockers
Beta blockers in the presence of catecholamine-induced HTN and tachycardia has been associated with:
profound cardiovascular collapse and cardiac arrest
What is the drug of choice for catecholaimine-induced HTN in cocaine OD?
Nitroprusside
There is evidence that Beta blockade accentuates [what] in the acute cocaine OD?
coronary artery vasospasm
