Local Anesthetics Flashcards
Local anesthetic uses?
Infiltrated around the nerve
Applied topically to the skin
Injected into blood vessels that are first exsanguinate
Injected into the subarachnoid or epidural spaces
What is the general difference between A, B, and C fibers? (which are myelinated, speed, and size)
A fibers: myelinated, size 1-22 micrometers, FAST
B fibers: myelinated, 1-3 micrometers, slower than A, but faster than C
C fibers: unmyelinated fibers, 0.1-2.5 micrometers, SLOW
List each fiber from fastest to slowest and list what it senses.
(A: alpha, beta, delta, gamma; B; C)
A-alpha: motor and proprioception
A-beta: motor, touch, pressure
A-gamma: motor/muscle tone (fine motor modulation)
A-delta: pain, temp, touch
B: PREganglionic autonomic
C: dull pain, temp, touch, POSTganglionic autonomic
Large fibers have the _____ conduction velocity, _____ capacitance, and _____ threshold for excitability
(highest/lowest)
Highest conduction velocity
Highest capacitance
Lowest threshold for excitability
Between sensory, motor, and autonomic, which is blocked first when given an LA?
Autonomic blocked first, more on the outside/mantle of the nerve (C fibers)
Sensory blocked next, then motor blocked last because it is at the core/inner surface and hardest for the LA to reach
More specifically, what is the clinical sequence of local anesthesia blockade (5 steps), what is blocked?
1- sympathetic block (vasodilation, warm skin) 2- loss of pain and temp 3- loss of proprioception 4- loss of touch and pressure 5- motor blockade
Which ion establishes and maintains resting membrane potential?
K
Local anesthetics MOA?
LAs bind to the Na channel alpha subunit when it is in the inactivated closed state
Impulse conduction blockade is caused by inhibition of the influx of Na ions (during depolarization phase of action potential)
Do locals change the threshold potential, the ability to reach threshold, or both?
ONLY the ability to reach threshold
Describe the typical structure of a LA
Lipophilic head (aromatic ring) Intermediate chain containing an amide (NH) or an ester (COO-) Hydrophilic tail (tertiary amine)
How can the name of a LA identify it as an amide vs ester?
One eyed ester (procaine)
Two i’s amide (lidocaine)
How are esters vs. amides metabolized?
Esters: hydrolyzed by non-specific esterase’s in the plasma and tissues (mostly liver), metabolite = PABA (para-aminobenzoic acid), except for cocaine
Amides: metabolized in the liver, CP450, slower than esters, aromatic hydroxylation, N-dealkylation, amide hydrolysis
Highly lipid soluble anesthetics are ___ (more/less) potent and have a ____ (shorter/longer) DOA than water soluble anesthetics
More potent
Longer
Increase in the length of an intermediate chain, more carbons, _____ (inc/dec) potency and toxicity
Increases
Also increased with length of the terminal groups on the tail and aromatic ring
What is exparel?
Bupivacaine extended release liposome injection, only approved for bunionectomy and hemorrhoidectomy
When mixed with another local, it will change the effects and increase chance of toxicity
How many nodes of ranvier must be blocked by LA to stop the propagation of action potentials?
THREE
What characteristics govern LA systemic absorption?
Physiochemical factors: pKa, pH, and lipid solubility, blood flow
Physiologic conditions: tissue pH, pCO2, temp, characteristics (age, pregnancy)
Note: elderly and pregnant are more at risk for toxicity
Absorption by type of block from high to low?
I Think I Can Place Epidural Blocks So Smooth
Intravenous, Tracheal, Intercostal, Caudal, Paracervical, Epidural, Brachial plexus, Subarachnoid, Subcutaneous
Do ionized or non-ionized drugs cross a lipid membrane?
NONionized
What are the pros/cons of ionized LAs vs. non-ionized?
Ionized binds to the receptor easier
Nonionized gets through the barrier easier
The ideal LA drug would be 50/50 (half ionized, half nonionized)
The ionized form is favored when?
The non-ionized form is favored when?
(acid/base drug in acid/case environment)
Ionized favored when acidic drug in basic environment, basic drug in acidic environment
Nonionized favored when acidic drug in acidic environment, basic drug in basic environment
Local anesthetics are strong/weak acids/bases
Weak bases
Packaged in acidic formulations but basic upon injection
When looking at %non-ionized and onset, which LA doesn’t follow the rule?
Rule: higher % non-ionized = faster onset
Chloroprocaine is the exception to the rule because it is only 2 % non-ionized and has a fast onset (we give it in higher concentrations to have this effect)
Which LAs have slow, moderate, and fast onsets?
Slow: procaine, tetracaine (esters)
Intermediate: bupivacaine
Fast: chloroprocaine, lidocaine, etidocaine, mepivacaine
What does adding bicarb do to the LA effect?
Increases onset
Enhances block depth
Increases spread of block
What factor of an LA is most important in determining potency? Which drugs are highly potent?
Lipid solubility
Highly potent: etidocaine, bupivacaine, tetracine
What factor of an LA is most important in determining DOA? What other factors are there?
Most important: protein binding (more protein bound, inc DOA)
Other: blood flow, addition of vasoconstrictors, lipid solubility, vasodilator activity, uptake of lungs, metabolism
Note: lidocaine has a fast onset, but has an intrinsic vasodilator activity (short DOA), so epi is commonly added to have a longer DOA
Adding vasoconstricor to LA has what three effects?
- Inhibits systemic absorption
- Prolongs DOA
- Detects intravascular injection
Potency is most influenced by _____
DOA is most influenced by _____
Onset is most influenced by ______
Potency - Lipid solubility
DOA - protein binding
Onset - pKa
List max doses of LAs
Bupivacaine, ropivacaine, etidocaine, lidocaine, mepivacaine, choroprocaine, cocaine, tetracaine
Bupivacaine 2.5 mg/kg Cocaine 3 mg/kg Tetracaine 3 mg/kg Ropivacaine 3 mg/kg (3.5 w epi) Etidocaine 4 mg/kg Lidocaine 4 mg/kg (7 w epi) Mepivacaine 4 mg/kg (7 w epi) Chloroprocaine 12 mg/kg
LA toxicity s/s?
CNS: circumoral numbness, tinnitus, vision changes, dizzy, slurred speech, restless, muscle twitching, seizures (which cause CNS depression, apnea, hypotension)
CV: hypotension, myocardial depression, AV block
Note: bupivacaine is most CV toxic
What treats LA toxicity CV collapse?
CPR
Modified ACLS
Intralipid 20% 1.5 mL/kg rapid bolus immediately; follow with infusion 0.25 mL/kg/min x 10 min
Cardio-pulmonary bypass
What is TNS (transient neurologic symptoms), aka transient radicular irritation?
Neuro-Inflammatory process causes pain in lower back, butt, posterior thigh, 6-36h after full recover from SAB, lasts about a week
Associated more with lidocaine
What is caudal equina syndrome?
Diffuse lumbosacral injury, numbness in LE, loss of bowel and bladder control, paraplegia, this is PERMANENT
Causes: lidocaine 5%, tetracaine, chloroprocaine
What is anterior spinal artery syndrome?
LE paralysis with/ without sensory deficit
Unknown cause, advanced age is a risk factor
Allergy to LA is usually due to what?
Allergy to PABA, esters
Other: preservative reaction
LA interactions?
Pseudocholinesterase inhibitors may prolong the duration of ester anesthetics
Cimetidine and propranolol decrease hepatic blood flow, decrease clearance of amide LA and cocaine
Analgesia promoted by opioids, clonidine, and epinephrine added to LA
Lidocaine uses?
Regional/ neuraxial block
Cough suppression
Attenuate ICP/BP raise during laryngoscopy
Attenuate reflex bronchospasm that may occur with airway instrumentation
Suppress ventricular dysrhythmias
How is cocaine metabolized?
Liver and plasma esterases
NOT PAVA like the other esters
What is chloroprocaine used for?
OB epidurals, it has an ultra rapid serum hydrolysis (metabolism) which reduces toxicity risk to mom and baby
Does lidocaine have an active metabolite?
YES. 2
Monoethylglycinexylidide (80% activity) and xylidide (10% activity)
Why is lidocaine avoided in spinals?
Linked to caudal equina syndrome
Epidural ok to use
Talk about metabolism of prilocaine.
Rapid metabolism
TOXIC metabolite ortho-toluidine
Must be avoided in OB due to metabolite
Big doses will convert hgb to methemoglobin (treated with methylene blue)
Bupivacaine pros and cons?
Pro: highly protein bound so low incidence of neuro complications with spinal, longer DOA so good for post-op pain and labor. Also, A alpha, beta, and gamma fibers are not completely blocked, so sensory is blocked and motor is not completely blocked.
Con: TOXICITY! very cardio toxic; pressure is still felt, that can freak people out
Peripheral nerve blocks are dosed based on what?
VOLUME
Choose concentration based on limits of max dose
Epidurals are dosed based on what?
VOLUME
1.25-1.6 mL/segment
Choose concentration based on limits of max dose
Spinals are dosed based on what?
DOSES. Just know them.
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