Flashcards in Unit 3 - Local Anesthesia Deck (32):
what is the definition of local anesthesia?
drug-induced reversible blockade of pain sensation in a specific part of the body that doesn't alter consciousness or block sensation in other parts
what are the ideal properties of local anesthetics?
1. fast onset
2. minimal absorption
3. minimal distribution
4. predictable and reversible action
5. large margin of safety
what are the three parts of local anesthetics?
1. aromatic ring (lipophilic portion)
2. intermediate linkage (ester or amide)
3. terminal amine (hydrophilic portion)
what is the aromatic ring/head of local anesthetics the primary determinant of?
lipid solubility, potency, and duration of action
-highly lipid soluble anesthetics are less likely to be cleared by blood flow and have a high degree of plasma binding, so elimination is prolonged
-greater lipid solubility enhances diffusion through nerve sheaths and neural membranes of individual axons which commprise a nerve trunk
-potency and lipid solubility increase with size
what is the middle part of a local anesthetic?
ester or amide link (creates the 2 classifications)
what are ester anesthetics metabolized by? examples? limits?
-metabolized by plasma esterases (but some patients have slow and fast metabolism)
-ex: cocaine, procaine, benzocaine, chloroprocaine, tetracaine
-limits: allergic potential and short duration
what are amide anesthetics metabolized by? examples? limits?
newer ones; maxed desirable properties (longer duration and sooner onset of action)
-metabolized by hepatic amidases
-ex: lidocaine, mepvivocaine, bupivicaine, etidocaine, prilidocaine, ropivicaine, dibucaine
-limits: less than esters
what does the terminal portion of a local anesthetic determine? types?
determines onset of action and how quickly it can cross a membrane
-can be tertiary form (lipid soluble) or quaternary form (positively charged, water soluble)
-depends on pKa and tissue pH (how much is converted to lipid soluble form)
--RNH- RN + H+
what state is a local anesthetic in when injected? which part is active?
-charged part is active, but then can't cross lipid cell membrane
-much change to uncharged form to become lipid soluble
-time for onset is thus determined by how much of it converts to lipid soluble form when exposed to physiologic pH
what is the ideal pKa of a local anesthetic? what is actually the case?
-ideal is 7.4, so that 50% of the molecular structure outside the cell is uncharged, and rapid diffusion across the lipid bilayer could occur
-actual are much higher, causing lower concentration of diffusable form in injection, and longer time for local anesthetic to take effect
what does the pKa of a local anesthetic determine?
how much of it is in a diffusible form on injection, and thus determines time of onset
-higher the pKa --> lower concentration of uncharged (diffusible) base, longer it takes to work
what happens to local anesthetic in an acidic environment? example?
pushes equation to left (RNH+), thus making less of diffusable form available, and slower onset of effect
-much of LA may be metabolized or taken away by circulation before it converts to lipid soluble form
-more ionized form is available, so less unionized form can diffuse
what happens to local anesthetic in an basic environment?
shifts equation to right (RN + H+), thus making more unionized diffusible form available to cross membrane
-faster onset of block
-ex: C-sections (mix with Na bicarb)
recall what the concentrations of sodium and potassium are in the resting neuron?
more sodium outside the membrane (positive charge) and more potassium inside the membrane (negative charge)
how do local anesthetics affect action potentials?
bind to and block intracellular portion of inactivated voltage gated Na channels, thus blocking conduction
-LA reduces Na influx and K+ efflux, thus inhibiting depolarization along nerve
how do the targets of local anesthetics and tetrodotoxin differ?
LA: intracellular portion of voltage-gated Na channel
TTD: extracellular portion of voltage-gated Na channel
which nerves are more sensitive to LA blockage?
smaller with higher firing rates
-smaller diameter = quicker to achieve high concentration of LA
-more firing means more inactivated channels are available secondary to depolarization
what are the 3 factors that determine the onset of block from LA?
1. degree of myelination (myelinated > unmyelinated)
2. firing frequency (more > less)
3. size of nerve fiber (smaller > bigger)
what is the ranking of nerve fibers affected by LA?
B (sympathetic tone) > C (temperature) = Adelta (pain) > Agamma (light touch) > A beta (sensory) > A alpha (motor)
explain the mechanism of differential blockade, and what this means if a patient's wrist is still "awake"
nerve fascicles are blocked from outside in, resulting in proximal to distal progression
-if after axillary LA, you just wait, because it will take some time for LA to move from shoulder to wrist
what happens if vasoconstrictors are added to LA?
diminishes localized blood flow
-prolongs duration of action
-limits potential for systemic toxicity
-allows for higher doses
what is the systemic toxicity of local anesthetics?
1. CNS - tends to occur at lower serum concentrations
-excitatory phase (talkative, muscle twitching, visual changes) followed by depression (seizures, coma, respiratory arrest)
2. cardiovascular system - tends to occur at higher serum concentrations
-direct cardiac toxicity (vasodilation, myocardial depression, bradycardia, ventricular fibrillation, cardiac arrest)
what is the local toxicity of LA?
1. transient neurologic symptoms with lidocaine for spinal anesthesia
2. neuronal injury
3. allergy (if ester anesthetic)
what can rescue the heart from LA toxicity?
co-administration of lipid emulstion (IV lipid emulsion = ILE)
what are the usual "false" allergies reported with lidocaine?
-passing out (vasovagal reaction to injection)
-heart palpitations (epinephrine in solution or released endogenously)
what is the "true" allergy with LA?
skin allergy from PABA (paraaminobenzoic acid) shared by all ester LAs
what are the 4 clinical applications for LA?
explain topical applications of LA?
direct application to eye, mouth, nose, trachea, GU
-absorbed rapidly from mucus membranes (risk of toxicity)
-cocaine is only used in mouth, nose, throat, and ear, where it uniquely produces vasoconstriction _ anesthesia
explain infiltration applications of LA?
injection directly into tissue
-does not consider course of cutaneous nerves
-often superficial (skin only)
-used as "preemptive analgesia" before surgical incision
explain regional applications of LA?
injection around individual nerves or nerve plexus
-blockade of peripheral nerves and plexi blocks somatic motor nerves (producing skeletal muscle relaxation)
spinal VS epidural applications of LA?
spinal: under dura, less LA, faster onset
epidural: above dura, bigger dose, slow/controlled onset