Local Anesthetics Flashcards
Hyperpolarization
Increase in cells resting membrane potential
Generally by diffusion of K to extracellular compartment
Depolarization
Decrease in cells resting membrane potential
Diffusion of sodium to intracellular compartment
Action potential generation
Trigger zone- initial segment, high concentration of sodium channels
Voltage gated triggered at -50mV
Action potential termination
NA channels inactivated, opening of K channels and hyperpolarization
Refractory period
Both Na and K channels are inactivated- no AP possible
Purpose to myelination
Increases speed of conduction, AP only conducted at nodes of Ranvier
MOA of Local Anesthetics
Antagonists at Voltage gated Na channels
Must penetrate nerve sheaths
Ionization of locals
Most pKas are slightly higher than physiologic pH= non-ionized on injection
Once local has entered cell it converts to ionized form which allows binding to Nav
Converts NAv to inactive state
Locals and duration of action
Direct relationship with degree of protein binding
Higher binding= longer duration
Vasoconstrictors (epi) and locals
Slow vascular uptake, prolonging effect
Variables in quality of block
Concentration
Volume
Potency
Characteristics of nerve fibers and type of block
Sympathetic/sensory nerves are typically easier to block because they are unmyelinated and smaller
Motor- larger and myelinated- more difficult
BICEPS
Highest to lowest rate of absorption
B lood
I ntercostal
C audal
E pidural
P lexus
S ubcutaneous
Metabolism of Locals
Ester- plasma esterases
Amide- hepatic
Elimination of amide local anesthetics
Amides are excreted via kidneys so higher risk of toxicity in renal failure
Toxicity of locals
Concentration and absorption time frame
IV injection- venous or arterial?
Arterial-undiluted brain bolus :(
Immediate cardiovascular collapse
Local CNS toxicity symptoms
Mild: anxiety, dizziness, tinnitus
Severe: seizure, twitching, altered LOC
Local Cardiac toxicity mechanism
Blockade of cardiac sodium channels- neg inotropy- lethal arrhythmias or arrest
Which locals are more cardiotoxic?
Higher potency, lipophilic
Cardiovascular considerations in neuraxial
Sympatholytic- blockade of sympathetic nerve fibers
Blockade above T-4 dermatome blocks cardiac accelerator nerves=hypotension/bradycardia
Treating LAST
Support circulation and cardiac function
Seizure- midazolam/lorazepam/propofol
ACLS with severe bradycardiawith following adjustments:
Epi bolus < 1mcg/kg
Lipid emulsion in LAST
Lipids act as a “sink” sequestering local from cardiac myocytes
> 70kg- bolus 100 ml lipid emulsion 20% over 2-3 min, then 200 ml over 20min
<70kg 1.5ml/kg emulsion bolus
Then 0.25 ml/kg/min infusion over 20 min
Why types of solutions do we use for neuraxial anesthesia??
PRESERVATIVE free
Cocaine
Only naturally occurring local
Current use as topical
Only local that causes vasoconstriction
Sympathomimetic effects if absorbed systemically
Benzocaine
Low potency topical- slow onset/short duration
Can lead to methemoglobinemia- just use lidocaine
Chloroprocaine
Extremely short plasma half-life
Common in neuraxial for rapid onset/ short duration
Often combined with longer acting amides to set up the block
Amide locals
Two I’s
Lidocaine
Prilocaine
Mepivacaine
Bupivacaine
Levobupivacaine
Ropivacaine
Ester Locals
One I
Procaine
Chloroprocaine
Tetracaine
Cocaine
Benzocaine
Tetracaine
Very potent, slow onset, long acting
Lidocaine
IV/topical/peripheral never block
No longer used in neuraxial
Anti-arrhythmic effects with IV as well as systemic analgesia although mechanism unknown
Bupivacaine
Prolonged/intense sensory analgesia
Concentrations greater than 0.5% are no longer used due to LAST
Levobupivacaine
Reduced CNS and CV toxicity
Similar profile- significantly more expensive
Ropivacaine
Structurally similar to Bupivacaine but less potent
Neuraxial- greater block differentiation/ selectivity for sensory over motor block
Locals with low potency/ short duration
Procaine, Chloroprocaine
Locals with intermediate potency/duration
Mepivacaine, lidocaine
Locals with high potency/long duration
Bupivacaine, Ropivacaine, Tetracaine
Block onset based on nerve fiber/type
B- autonomic
C- sympathetic/dorsal root=pain/temp/touch
A- Motor
Why are type B fibers blocked before unmyelinated C fibers?
Only have to block 3 nodes instead of the entire unmyelinated fiber
Normal Sodium/potassium concentrations in and out of cell
Na out- 140
Na in- 14
K out- 4
K in- 140
Explain action potential
RMP= -70
Stimulus- influx of Na to reach -50
Threshold reached= opening of voltage gated Na channels and depolarization
Repolarization- closure of Na and opening of K voltage gated channels allow rapid outflow of K
Hyperpolarization=refractory period
Normal epi concentration
1:200,000
Or 5mcg/ml
Treating ventricular arrhythmias in LAST
Preferential to Amiodarone
Ion trapping in LAST
May develop acidosis in setting of resp depression
=local becomes more ionized and less likely to diffuse across membranes
=trapped in brain or by placental barrier
Exparel
Controlled release local anesthetic
Liposomal suspension of Bupivacaine
72hr release
Max dose- 266mg
Specific guidelines if using in combination with other locals
Hyperkalemia risk in local anesthetic
Raises RMP, neurons more likely to depolarize-seizure
Metabolic acidosis with locals
Favors ion trapping- in cns
LAST treatment
Manage airway
Benzos for seizures
Modified ACLS, <1mcg/kg epi, amiodarone for vent dysrhythmias, avoid vaso/other locals
Emulsion therapy
PABA
Metabolite of ester anesthetics, known to be immunogenic
This local causes methemoglobinemia
Benzocaine
Anti-emetics acting on vestibular center
Anticholinergics and H1
