Local Anesthetics Flashcards
Local Anesthetics are drugs that
reversibly block the conduction of electrical impulses along nerve fibers
Removal of the local anesthetic is followed by
spontaneous and complete return of nerve conduction, with no evidence of structural damage to nerve fibers.
The ability of the local anesthetic to produce a reversible conduction blockade of impulses along central and peripheral nerve pathways is dependent on:
Physiochemicalpropertiesofthelocalanesthetic
Anatomyofthenervebeingblocked
The Myelinated Sheath:
insulates the nerve and prevents electrical current from leaking out
The target of local anesthetics is the
sodium channel (blocks)
Resting membrane potential of a peripheral nerve is:
-70 mV
Voltage Gated Channels:
when at -70 mV Sodium moves in, and when at 35 mV Potassium moves out
The Na-K ATPase pump gives
energy to transport against the gradient
Resting potential value is
-70 mV
Action potential value is
35 mV
The mechanism of action of Local Anesthetics is
block sodium channels (reversible)
Sodium channel receptors are located
on the intracellular side of the cell membrane, and have a greater affinity for the charged form of the local anesthetics
Chemical structures of local anesthetics
an unsaturated aromatic ring system
an intermediate carbon group
a tertiary amine
Two types of local anesthetics include
Esters
Amides
Esters include
Procaine
Chloroprocaine
Tetracaine
Cocaine
AmIdes include
LIdocaine MepIvacaine PrIlocaine BupIvacaine LevobupIvacaine RopIvacaine EtIdocaine
The potency of local anesthetics have a direct correlation with
lipid solubility
the more lipid soluble, the more potent
Cm is the
minimum concentration of local anesthetic necessary to produce the conduction blockade of nerve impulses
Onset of action of local anesthetics depend on
Lipid Solubility- major determinant is amount of LA that is in non ionized form
pKa- pH of the LA at which the amount of non-ionized drug is equal
LA with a pKa closest to physiologic pH will have a higher concentration of non-ionized form that can readily pass through the nerve cell membrane
Once inside the cell, the ionized portion more avidly ….
binds the sodium channel inside the cell
Duration of action correlates with
lipid solubility (highly lipid soluble LA have a longer duration of action, because they are less likely to be cleared by blood flow)
LA that are highly lipid soluble are also typically highly protein bound
Sensitivity to blockade is determined by
Axonal diameter
(small>large) small more effective
Degree of myelination
(unmyelinated>myelinated) unmyelinated is more sensitive
-hard to get through myelinated sheath
In spinal nerves sensitivity to local anesthetics is
autonomic>sensory>motor
auto is more affected than sensory, sensory is more affected than motor
Nerve fibers are classified into 3 groups:
A, B, C
A-fibers are the _______ nerve fibers, so the they are the _______ sensitive
largest axonal nerve fibers
least sensive
B- fibers are the ________ nerve fibers
intermediate
more sensitive than A, less sensitive than C
C fibers are the ______ nerve fibers, they are _______
smallest
unmyelinated
Unlike other medications, local anesthetics are meant to
remain in the area of injection or application
The higher the concentration of drug injected that remain in the area of the nerves to be blocked, the ______ the onset of action
faster
Systemic absorption of injected LA depends on:
Blood Flow
- site of injection
- presence of vasoconstrictors
- specific local anesthetic agent
The addition of _______ to an LA, will prolong the duration of the anesthetic
epinephrine
All local anesthetics except _________, produce relaxation of vascular smooth muscle
cocaine= vasoconstrictor, used for ENT surgeries
Esters are predominantly metabolized by
pseudocholinesterase
Procaine and benzocaine (esters) are broken down into
PABA (associated with allergic reactions)
Patients with genetically abnormal pseudocholinesterase are at risk for
toxic side effects
Amides are metabolized by
microsomal P-450 enzymes in the liver
Amide metabolism is ______ than ester hydrolysis
slower
Decrease in liver function will reduce metabolism of ________ and increase toxicity
amides
Metabolites of prilocaine accumulate after large doses and convert Hgb to ________
methemoglobin (tx is methylene blue)
Methemoglobinemia S/S include
brownish gray cyanosis
tachypnea
metabolic acidosis
severe S/S ensue with: tissue hypoxia, headache, irritability, loss of consciousness
immediate reversal with methylene blue
The peak plasma concentration is dependent upon the __________ rather than the volume or concentration
total dose of local anesthetic
Additives to local anesthetic include
Opioids
Sodium Bicarbonate
Epinephrine
-these are added to increase the safety, quality, intensity, duration, and rate of onset of anesthetic
Ion trapping results from changes in
pH in relationship to the agents pKa
The more acidic the tissue (sepsis, infection = acidosis) the more
ion trapping (stuck in cell= longer duration of action) sticks around longer ( a base going into an acid)
Systemic toxicity of local anesthetics can occur from
inadvertent intravascular injection
administration of excessive dose
toxicity of LA include _____ and _____ side effects
cardiovascular and CNS
HTN/Tachy- brad/hypo - asystole
psychically abnormal - confusion - seizure
Esters / Amides have a higher rate of allergic reactions
esters
Topical cocaine has _________ properties
vasoconstrictor
Epinephrine should not be injected around end arteries such as
fingers/ toes
ears/ nose
genitals
Disadvantages of local infiltration anesthesia
large amount of local anesthetic must be used to block relatively small areas
pain on injection
-rate of injection
-alkalization of local (buffering)
