Local anesthetics 2 Flashcards
Select the true statement regarding the primary mechanism of action of local anesthetics.
a. the conjugate acid binds to the extracellular portion of the sodium channel
b. the conjugate acid binds to the intracellular portion of the sodium channel
c. the uncharged base binds to the extracellular portion of the sodium channel
d. the uncharged base binds to the intracellular portion of the sodium channels
b. conjugate acid binds to the intracellular portion of the sodium channel
Local anesthetics are
weak bases
After you inject local anesthetic around a nerve, the local anesthetic rapidly
dissociates into an uncharged base (LA) and an ionized conjugate acid (LA+)
Since local anesthetics are weak bases with pKa values higher than 7.4, we can predict that
> 50% of the local anesthetic will exist as the ionized, conjugate acid
Only ________- binds to the local anesthetic binding site
ionized, conjugate acid
The sodium channel remains in the closed, inactivated state until
enough local anesthetic diffuses away; during this time it’s resistant to depolariziation
Some of the non-ionized local anesthetic molecules diffuse thorugh
the lipid-rich axolemma
once inside, a new equilibrium between LA and La+ is established ;
What 3 paths can a local anesthetic travel after it’s injected near a peripheral nerve?
- diffuse into the nerve
- diffuse into surrounding tissue and bind to neighboring proteins
- diffuse into the systemic circulation
A patient states she experienced hypotension, tachycardia, and shortness of breath after receiving tetracaine during a previous surgery. Which drugs should be avoided in this patient? (select 3)
a. benzocaine
b. chloroprocaine
c. EMLA cream
d. articaine
e. cocaine
f. mepivacaine
a. benzocaine
b. chloroprocaine
e. cocaine
What are the two classes of local anesthetics?
esters & amides
The local anesthetic molecule is constructed from three key components:
benzene ring
intermediate side chain
tertiary amine
__________determines the local anesthetic’s drug class
the intermediate side chain
The intermediate side chain determines how
each drug class is metabolized
Amide-type local anesthetics are metabolized
in the liver by the P450 system
Ester- type local anesthetics are metabolized
in the plasma by pseudocholinesterase
What are the ester-type local anesthetics?
benzocaine
cocaine
chloroprocaine
procaine
tetracaine
What are the amide-type local anesthetics?
bupivacaine
dibucaine
lidocaine
mepivacaine
ropivacaine
All the amides have
two “i’s” in their names
Although true allergy to local anesthetics is rare, it is more common with
esters due to PABA
If a patient has experienced a true allergy with an ester, the safest course is to
change to a preservative free amide
Is there cross sensitivity between esters and amides?
no
What is PABA?
para-aminobenzoic acid
can be found in ester LA
Which characteristics correlate BEST with local anesthetic duration of action?
a. protein binding
b. lipid solubility
c. pKa
d. concentration
a. protein binding
What is the primary determinant of onset of action with LAs?
pKa
What is the secondary determinants of onset of action with LAs?
dose and concentration
What is the primary determinant of potency with LAs?
lipid solubility
What are the secondary determinants of potency with LAs?
intrinsic dilating effects
What is the primary determinant of duration of action?
plasma protein binding
What is the secondary determinants of duration of action?
lipid solubility & addition of vasoconstrictors
If the pKa of the local anesthetic is closer to the pH of the blood, then a larger fraction of molecules will exist as
the lipid-soluble uncharged base. More molecules diffusing across the axolemma translates to a faster onset of action
If the pKa of the LA is further away from the pH of the blood, there will be
fewer molecules available to penetrate the cell membrane which prolongs the onset of action
Explain why chloroprocaine is exception to the pKa & onset of action.
chloroprocaine has a high pKa in isolation this would suggest a slower onset; it is not very potent so large dose must be given creating a mass effect that has a rapid onset of action
Agents that are more liphophilic tend to be
more potent and have longer durations of action
Lipid solubility is increased with
alkyl group substitution on the amide group and the benzene ring
At higher concentrations (what we clinically use), LAs cause
vasodilation which removes the LA from its site of action and contributes to the termination of its effect
_________ is an exception to vasodilation because it inhibits NE reuptake and always causes vasoconstriction
cocaine
The pKA correlates with
the onset of action
The closer the pKa is to the pH of the blood, the ___________ the local anesthetic begins to take effect.
faster
Is a local anesthetic an acid or a base?
weak base
If you put a local anesthetic in an aqueous solution, a fraction
will remain non-ionized and the remaining fraction will ionize
When the drug’s pKa is closer to blood pH, then there’s a higher amount of
uncharged base
there’s more drug that can diffuse through the axolemma
What is the pKa of bupivacaine?
8.1
What is the pKa of levobupivacaine?
8.1
What is the pKa of ropivacaine?
8.1
What is the pKa of lidocaine?
7.9
What is the pKa of prilocaine?
7.9
What is the pKa of mepivacaine?
7.6
What is the pKa of procaine?
8.9
What is the pKa of chloroprocaine?
8.7
What is the pKa of tetracaine?
8.5
_______________ does not undergo protein binding.
chloroprocaine
The exception to the rule of the closer the pKa is to the pH of the blood, the faster the onset is
chloroprocaine
All ester local anesthetics have __________ pKa values
higher (8.5-8.9)
All amides have _________________ pKa values
lower (than the esters… highest is 8.1)
What is the pH of benzocaine?
3.5
The only local anesthetic with a pKa well below physiologic pH is
benzocaine
With benzocaine, ____________________ is a significant risk
methemoglobinemia
Benzocaine is useful for
topical anesthesia of mucus membranes during endoscopy, TEE placement, and bronchoscopy
In an acidic solution, weak bases are:
more ionized and water soluble
