Local Anesthetics Flashcards
Neurophysiology of pain involves what three things?
initiation
propagation
perception
Define local/peripheral analgesics
analgesia close to the source of the pain
ie) Novocaine, cocaine, NSAIDs
Define central analgesics
analgesia through supraspinal and spinal sites
ie) morphine, NSAIDs
Define general anesthetics
Loss of consciousness, amnesia, +/- analgesia
ie) propofol, etomidate, barbituates
What are pain receptors also called?
Nociceptors
Provide an example of a pain receptor
TRP channels
(transient receptor potential)
What are the two types of pain fibers?
C fibers and alpha delta fibers
What NT is released at synapse of alpha delta fibers?
Glutamate
What is the NT released at the synapse of C fibers?
Substance P
(and a little bit of glutamate)
Are C fibers unmyelinated or myelinated?
Do they have fast or slow AP propagation?
Unmyelinated
Slow propagation
Are alpha delta fibers unmyelinated or myelinated?
Do they have fast or slow AP propagation?
myelinated
fast, saltatory conduction
Character of first pain?
What fiber is responsible for first pain?
Sharp, Stinging, High Intensity Pain
fast alpha delta fibers
Character of second pain?
What fiber is responsible for second pain?
Dull, Aching, Low Intensity Pain
slow C fibers
How do NSAIDs work to decrease sensitization of C and alpha delta fibers?
NSAIDs inhibit production of PGs by blocking COX2 in proinflammatory cells
What is TTX?
tetrodotoxin
from pufferfish
How does TTX work?
it blocks Na+ channel via the extracellular side
extracellular Na+ channel blockage
THUS, since it is bound to the outer pore,
it blocks Na+ entry no matter what stage/state Na+ channel is in (resting, activated, inactivated)
How do local anesthetics bind differently than TTX to the Na+ channels?
local anesthetics are lipophilic so they get into cell and then wait around inside cell until Na+ channel is activated and then LAs go in and bind to Na+ channel and block Na+
So intracellular channel blockage
Blockage of Na+ channel occurs in what state for TTX?
resting and/or activated and/or inactivated
resting &
activated &
inactivated
Blockage of Na+ channel occurs in what state for local anesthetics?
resting and/or activated and/or inactivated
Blockade occurs when channel is in activated state
(M gate opens up and allows LA to gain entry into inner Na+ channel and block it)
Blockade can also occur during inactivated state
(LA can gain access to this inner pore of Na+ channel and block during inactivated state too)
Why do local anesthetics (and not TTX) lead to use-dependent blockade?
local anesthetics cannot bind and block during resting state
they can bind and block only in activated and inactivated states
Graph of use-dependent blockade of Na+ currents by local anesthetics
See picture
In the presence of TTX, the Na+ current trace following the 1st stimulation of the neuron would look like?
See Picture
trace 25
True or false:
Increased lipophilicity of local anesthetic means greater potency of local anesthetic and earlier onset of action of local anesthetic
true
What local anesthetics are esters?
Do they have a short or long duration of action?
See picture
What local anesthetics are amides?
Do they have a short or long duration of action?
See picture
True or false:
For every 10 local anesthetics that form as cationic,
one forms as uncharged and
can cross the membrane and block Na+ channels
True
Infected tissue has lower pH leading to more charged local anesthetic, so this anesthetic is more or less able to cross the cell membrane?
less
So less potency in these areas and takes longer to work/onset of action
The charged or uncharged local anesthetic can cross the membrane?
uncharged
The charged or uncharged local anesthetic blocks the Na+ channel?
charged
Small or large diameter fibers are blocked most easily by local anesthetics?
small
myelinated or unmyelinated fibers (of the same diameter) are blocked more readily?
myelinated fibers are blocked more readily
True or false:
The more the fiber fires, the more it is blocked by local anesthetics
True
use dependent thing
Are fibers in the interior or exterior more or less readily blocked by local anesthetics?
fibers in interior are less readily blocked by local anesthetics and fibers on the exterior are more blocked by local anesthetics
Name six routes of administration of local anesthetics
topical
infiltration
bier block
peripheral nerve block
epidural
spinal
When does systemic toxicity occur with local anesthetics?
when the LAs get absorbed into the vasculature and reach high enough concentrations in the heart and/or brain to disrupt cardiac and CNS function
probablility of this happening increases when LAs are administered into tissues with dense vasculature
(high vascularization) intercostal > caudal > epidural > brachial plexus > sciatic nerve (low vascularization)
Symptoms of systemic toxicity of brain
anxiety
confusion
tremors
convulsions
Symptoms of systemic toxicity of cardiovascular system
depressed myocardial contractility
bradycardia
vasodilation
hypotension
(exception: cocaine: tacycardia, vasoconstrction, and hypertension due to its abilit to block catecholamine reuptake at sympathetic nerve termini: that revolving door NET: NE transporter)
Administration of what reduces the likelihood of systemic toxicity by causing vasoconstrction and consequently prolongs duration of action of local anesthetics?
Epinephrine
(many LA formulations contain epinephrine)
What can direct injection into vasculature of local anesthetics cause?
temporary blindness
aphasia
hemiparesis
convulsions (treated with benzodiazepines)
respiratory depression
coma
cardiac arrest
What are some local adverse reactions to local anesthetics?
range from pain to tissue necrosis at site of injection
What are allergies most associated with, esters or amides?
rare but most associated with esters
(It is the PABA: para-aminobenzoic acid derivatives produced by metabolism of local anesthetic through pseudocholinesterases)
What drug given in adjunct therapy to reduce pain transmition?
Clonidine
See picture
Highlights of Cocaine
ester
used in nose and throat procedures
high abuse potential
can cause tachycardia
can cause vasoconstriction
Highlights of Procaine (Novocaine)
first sythetic local anesthetic
ester
slow onset
short duration
relatively low systemic toxicity
commonly used for infiltration and peripheral nerve blocks
Highlights of Lidocaine (Xylocaine)
most commonly used
amide
xylidine derivative
rapid onset
intermediate duration
causes vasodilation and is therefore combined with epinephrine
this compound is also used as a class 1B anti-arrhythmic due to its capacity to inhibit cardiac Na+ channels
Highlights of Ropivacaine (Naropin)
synthesized in only the S-isomer
S-isomer has low affinity for cardiac Na+ channels
(R-isomer has high affinity for cardiac Na+ channels)
lower cardiac toxicity compared to other local anesthetics
Drug Summary Table
See picture
Drug summary table
See picture
