Local Anesthetics Flashcards
Local anesthetics are weak _____ and are partially ionized at pH 7.4.
bases
What form of the anesthetic binds to the Na+ channel pore?
both, but the cationic form has a stronger affinity
How does the local anesthetic reach its binding site?
via the intracellular pore entrance
Local anesthetics have a ____ structure, typically consisting of 1. a lipophilic aromatic portion; 2. an intermediate alkyl chain; 3. a hydrophilic amine portion.
tripartite
Name the toxin:
- one of the most potent toxins known
- found in marine dinoflagellates (red tide)
- binds to and blocks the extracellular entrance of voltage-gated Na+ channels –> death by paralysis of respiratory muscles
saxitoxin (STX)
What is the advantage of nerve block anesthesia?
large body regions can be anesthesized
What can local anesthetic toxicity cause?
- convulsions
- respiratory depression
- arrhythmias
- arterial dilation
When can local anesthetics reach their binding sites?
when the channel is open BUT they are also able to traverse the plasma membrane in the neutral form
Name 3 topical anesthetics.
- lidocaine
- tetracaine
- cocaine
How are amide local anesthetics terminated?
in the liver
Which local anesthetics are used in intravenous regional anesthesia/Bier’s Block?
lidocaine
Virtually all local anesthetics end in -_____.
-caine
Why are amide-linked local anesthetics contraindicated in pts with hepatic insufficiency?
the drug is only metabolized by the liver
Why is it important that local anesthetics are in the charged and neutral forms in the body?
the neutral forms can enter the cell in spite of a closed Na+ channel but the cationic form binds to the Na+ channel pore with a much higher affinity
Name 3 infiltration anesthetics.
- lidocaine
- procaine
- bupivacaine
Local anesthetics have a tripartite structure, typically consisting of 1. ______; 2. an intermediate alkyl chain; 3. a hydrophilic amine portion.
a lipophilic aromatic portion
What is a disadvantage of epidural anesthesia?
plasma level are high and can lead to toxicity
What opens Na+ channels?
membrane depolarization
What determines speed of conduction blockade in local anesthetics? Why?
pKa; lower pKa increases lipid solubility and tissue penetrance by increasing the fraction of local molecules that are uncharged –> enter membranes more readily
The intermediate chain in local anesthetics can either be an ____ or ____ moiety.
ester; amide
What determines the duration of action of local anesthetics? Why?
protein-binding capacity; it maintains the free concentration of anesthetic at an effective concentration for a longer period of time
What is use-dependent block?
the more the channel is open, the greater degree of local anesthetic binding and block; with more depolarization, the size of the inwards current decreases
What is a disadvantage of topical anesthetics?
the drug enters circulation
Name the toxin:
- one of the most potent toxins known
- found in Pufferfish, newts, and frogs
- binds to and blocks the extracellular entrance of voltage-gated Na+ channels –> death by paralysis of respiratory muscles
tetrodotoxin (TTX)
What is epidural anesthesia?
injection of local anesthetic just outside the dura of the spinal canal
What are the disadvantages of infiltration anesthesia?
- large doses are needed
- absorption into circulation
What can be used as an alternative anesthetic in pts allergic to amide and ester local anesthetics?
high dose promethazine
Is the fractional block greater in small diameter or large diameter axons? Why is this important?
small; therefore pain sensation is the first functionality lost
What is EMLA cream?
a mixture of lidocaine and prilocaine that exists as an oil at room temp and can thereby penetrate the skin
What protein do local anesthetics bind to?
α-1 acid glycoprotein (only amide anesthetics)
What is infiltration anesthesia?
injection of drug into tissue w/o consideration of the underlying nerves
Which is the only local anesthetic that produces local vasoconstriction? How?
cocaine; it blocks NE reuptake
What is saxitoxin (STX)?
- one of the most potent toxins known
- found in marine dinoflagellates (red tide)
- binds to and blocks the extracellular entrance of voltage-gated Na+ channels –> death by paralysis of respiratory muscles
Where does conduction block occur?
in smaller diameter, myelinated axons
Local anesthetics have a tripartite structure, typically consisting of 1. a lipophilic aromatic portion; 2. an intermediate alkyl chain; 3. ______.
a hydrophilic amine portion
What is nerve block anesthesia?
injection of a high conc of local anesthetic near a peripheral nerve or nerve plexus
How do local anesthetics work?
block voltage-gated Na+ channels in peripheral nerves
What happens in allergies to local anesthetics?
PABA is produced –> hypersensitivity
Local anesthetics increase the stability of the _____ to prolong the refractory period.
inactivated state of the channel
In local anesthetics, the names of the _____ have a single “I” whereas the names of the _____ have two “i’s.”
esters = 1 I amides - 2 i’s
Local anesthetics block conduction in small diameter, myelinated and unmyelinated axons, such as the ____ fibers that signal pain sensation.
C
What is intravenous regional anesthesia/Bier’s Block?
when blood is squeezed out of the limb or part of the body and a tourniquet placed, followed by injection of local anesthetic via a catheter
This is injection of drug into tissue w/o consideration of the underlying nerves.
infiltration anesthesia
What is tetrodotoxin (TTX)?
- one of the most potent toxins known
- found in Pufferfish, newts, and frogs
- binds to and blocks the extracellular entrance of voltage-gated Na+ channels –> death by paralysis of respiratory muscles
Where is the only place that blockade of APs can occur?
nodes of Ranvier
Local anesthetics have a tripartite structure, typically consisting of 1. a lipophilic aromatic portion; 2. ______; 3. a hydrophilic amine portion.
an intermediate alkyl chain
This is injection of a high conc of local anesthetic near a peripheral nerve or nerve plexus.
nerve block anestheisa
What makes a local anesthetic more potent?
higher lipid solubility
What is the binding site for local anesthetics?
the water-filled pore of the Na+ channel
What is spinal anesthesia?
injection of anesthetic into the CSF
What is the definition of local anesthesia?
loss of sensation in an area of the body
Which kinds of anesthetics have longer durations of actions?
the amides
Which local anesthetics are used for spinal anesthesia?
- lidocaine (short)
- bupivacaine (intermediate)
- tetracaine (long lasting)
Which vasoconstrictor often is added to local anesthetics?
epi
How are ester local anesthetics terminated?
they’re hydrolyzed by an esterase (pseudocholinesterase) and by the liver
Since block is use-dependent, unblock is _____.
also use-dependent
Which local anesthetics are used in epidurals?
- lidocaine (short)
- bupivacaine (longer)
- low conc bupivacaine + fentanyl for labor
What does local anesthetic binding to its site cause?
physical obstruction of Na+ ion flow through the Na+ channels, preventing membrane depolarization and terminating APs
How come cocaine analogs are safer than cocaine?
they are unable to block catecholamine reuptake
Local anesthetics block ____ and ____ of nerve impulses (APs) by blocking the voltage-gated Na+ channels.
initiation; conduction
Name 2 nerve block anesthetics.
- lidocaine (short duration)
- bupivacaine (longer duration)
Where does excretion of local anesthetics occur?
in the kidney
Why are vasoconstrictors added to local anesthetics?
- to prolong duration of conduction blockade
- reduce blood flow to the area (limit absorption)
- prevent toxicity
