Local anesthetics Flashcards
What are the three parts of a local anesthetic organically?
lipophilic aromatic group
intermediate chain of ester or amide
hydrophilic amine group
Do ester or amide local anesthetics have a longer duration of action? Why is this?
amides
esters are susceptible to esterases that break them down
What form of local anesthetic is required to penetrate the tissues and cell membrane to reach the site of action in the cytoplasm?
uncharged form (not ionized)
What is the charged form of local anesthetics required for?
to block the voltage-dependent Na channels
Charged LAs bind to…
open (active) Nav channels
At physiologic pH, what are LAs doing?
switching bt charged and uncharged forms
A decrease in tissue pH (acidosis) will cause an __________ in the amount of ionized drug.
increase
Diffusion of LA across the membrane is facilitated by an… pH
alkaline
LAs with high lipid solubility generally have the greatest… and …
What is an example of this?
potency and longest duration of action
bupivacaine
How can you speed the onset of LA block?
What drugs does this work best for?
make the pH of LA more basic (alkalization) by adding bicarbonate
less lipophilic LAs like lidocaine
The degree of Nav block by LA depends on the…
meaning with …
frequency of nerve impulses
increased AP frequency there will be increased Nav block
What type of axons are most difficult to block with LA?
large diameter myelinated (A type) axons
Anesthesia from a peripheral nerve block first develops ….
proximally
longer duration of LA block are achieved with drugs that are more… and in locations …
hydrophobic
with less vascularization
What alpha 1 agonists are usually used to prolong the duration of LA? What is their MOA?
epi and phenylephrine
vasoconstrictor
When should vasoconstrictors not be used with LAs?
in areas lacking collateral blood flow, like digital blocks or ears
Besides prolonging the duration of action of LA, what do vasoconstrictors do when given concurrently with LA?
limit LA toxicity by decreasing distribution into systemic circulation
Can LAs cross the BBB or placenta?
yes
How could LAs cause seizures if they are decreasing APs?
In the CNS, LAs block GABA before blocking excitatory neurons
increases restlessness and tremors leading to convulsions
What do LAs do to the heart if they get into systemic circulation?
decrease cardiac electrical excitability, conduction velocity, and force of contraction
Most LAs will cause vasodilation, what is the exception to this?
cocaine
Allergic reactions to LAs are much more likely to … because they are metabolized to …
esters
PABA (p-aminobenzoic acid)
How can a cardiac rescue be performed if too much LA is used?
intralipid - is a lipid emulsion that is typically used as an IV feeding supplement, but txs LA OD
intralipid absorbs the LA like a sponge to reduce the levels to below toxic - Nav channels become unblocked and are able to once again generate APs
bupivacaine has a longer duration of action than lidocaine bc it is …
more hydrophobic
Conventional cardiac resuscitation techniques often fail on pt with LA induced cardiac arrest bc…
cardiac APs cannot be generated
You want to do a long duration nerve block, but are concerned about cardiac toxicity. The best LA choice is…
ropivacaine
What are three LAs that can be used topially?
lidocaine
cocaine
benzocaine
Neuromuscular blocking drugs have no…
analgesic or anesthetic properties
What is the only depolarizing muscle blocking drug clinically available?
succinylcholine
What is the MOA of succinylcholine?
strong agonist for nAChR
Nondepolarizing muscle blocking drugs MOA
antagonists for the muscle nAChR
What is an AE of succinylcholine upon IV injection?
fasciculations which are non-synchronus contractions
What component of a succinylcholine block is phase I?
depolarizing, rending Nav channels inactive
What is phase II of succinylcholine block?
non-depolarizing component - desensitization
What are some AEs a/w succinylcholine use?
cardiac dysrrhythmias, fasciculations, hyperkalemia, myalgia, malignant hyperthermia
How do you tx malignant hyperthermia?
IV dantrolene
What is an AE of pancuronium?
increase in CO, HR, and MAP
What is an AE of atracurium?
histamine release at high doses induces hypotension and tachycardia
How do you reverse neuromuscular blockade?
When would this not work but why may it not matter much?
neostigmine - inhibits AChE activity (nondepolarizing agents), increasing ACh concentration at the NMJ
does not work for succinycholine, but phase I is enhanced, some reversal of phase II
sucs is such a short duration of action, you probably can just wait instead of reversing it
How is the action of succinylcholine terminated?
metabolism by plasma esterases
The nondepolarizing muscle blocking drug with the fastest onset of action is …
rocuronium
The bradycardia effect induced by succinylcholine can be blocked by pretx with…
atropine
