Local Anesthetics - concepts Flashcards
What is anterior spinal artery syndrome?
LE paralysis with/ without sensory deficit
is a clinical subset of spinal cord injury syndromes, due to ischemia/infarction of the anterior two-thirds of the spinal cord, typically sparing posterior third of the spine
Unknown cause, maybe vasoconstrictors (epi)?, PVD, advanced age ↑ the risk
What is the general difference between A, B, and C fibers?
(which are myelinated, speed, and size)
A fibers: myelinated, large, size 1-22 micrometers, FAST
- important for afferent and efferent somatic (they have motor and sensory)
B fibers: myelinated, size 1-3 micrometers, slower than A, but faster than C
- important for autonomic function (Motor only)
C fibers: unmyelinated fibers, small, size 0.1-2.5 micrometers, SLOW
- motor only
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
when do you redose lidocaine (epidural)?
lidocaine lasts about 1.5-2 hours etc
Potency is most influenced by _____
DOA is most influenced by _____
Onset is most influenced by ______
Potency - Lipid solubility
DOA - protein binding
Onset - pKa
What is caudal equina syndrome?
causes?
Diffuse lumbosacral injury, numbness in LE, loss of bowel and bladder control, paraplegia
this is PERMANENT
Causes: lidocaine 5%, tetracaine, chloroprocaine
what impact does the terminal group have on potency and toxicity
↑ length of terminal groups located on the tertiary amine (tail) & aromatic ring = ↑ potency & ↑ toxicity
What influences DOA of LAs
Duration proportional to amount of time LA is in contact with the nerve fiber
- protein binding - most important
- tissues blood flow
- addition of vasoconstriction
- lipid solubility
- intrinsic vasodilator activity (ex: lidocaine can vasodilate)
- Uptake by the lungs
- Metabolism
How many nodes of ranvier must be blocked by LA to stop the propagation of action potentials?
3
≈ 1 cm
what influences Cm (concentration minimum)
- Nerve fiber diameter (the farther the nodes of Ranvier the harder to block)
- Tissue pH (determines how much remains non-ionized)
- Frequency of nerve stimulation
- Potency of particular LA (determines how many molecules you need)
Epidurals are dosed based on what?
VOLUME
1.25-1.6 mL/segment
Choose concentration to use based on MAXIMUM DOSE, density of block required and toxicity profil
The dose really depends on the level that you want to achieve (for example, T4 vs T10 sensory level)
How can the name of a LA identify it as an amide vs ester?
One eyed ester (procaine)
Two i’s amide (lidocaine)
or amide has an “i” in from of “caine”
Local anesthetic uses?
- Infiltrated around the nerve
- Applied topically to the skin & mucous membranes
- Injected into blood vessels that are first exsanguinated
- Injected into the subarachnoid or epidural spaces
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)
Why are vasoconstrictors added to LAs
- Inhibition of systemic absorption of LA
- Prolongation DOA of the LA effect → ↓ chance of toxicity d/t slowing systemic absorption
- Detection of intravascular injection
pH - effects on onset
pH of the local anesthetic solution & the pKa of the drug determine proportion of drug in the non-ionized state
high/normal pH values, the rate & amount of absorption is higher
lower pH, the rate & amount of absorption are lower
Do locals change the threshold potential, the ability to reach threshold, or both?
NO
they ONLY change the ability to reach threshold
(they inhibit reaching the threshold)
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
Motor blocked last because it is at the core/inner surface and hardest for the LA to reach
onset relies on location of nerve fibers
autonomic and smaller fibers go first
Cm (concentration minimum)
the min number of molecules needed to block a certain nerve
analogous to MAC
Peripheral nerve blocks are dosed based on what?
VOLUME
Choose concentration based on limits of max dose
Are local anesthetics triggers for MH?
Nope
which nerve roots has the sensory nerves
dorsal roots = sensory = afferent neurons
Adding vasoconstricor to LA has what three effects?
- Inhibits systemic absorption
- Prolongs DOA
- Detects intravascular injection
What treats LA toxicity CV collapse?
- CPR
- Modified ACLS
- limit medications to epinephrine 10-100 mcg
- use amiodarone
- avoid CCB, ß blockers, lidocaine
- Intralipid 20% 1.5 mL/kg rapid bolus immediately; follow with infusion 0.25 mL/kg/min x 10 min
- Cardio-pulmonary bypass
Local anesthetics MOA?
LAs bind to the Na+ channel alpha subunit when it is in the inactivated closed state
(in the inner portion of the channel)
Impulse conduction blockade is caused by inhibition of the influx of Na+ ions (during depolarization phase of action potential)
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 drug 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
what drug is the exception to the pKa-onset rule
Chloroprocaine
although the pKA is high (8.7) it has the fastest onset because it’s given in higher concentrations (has more molecules crossing the membrane)
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
LA toxicity s/s?
CNS
circumoral numbness, tinnitus, vision changes, dizzy, slurred speech, restless, muscle twitching (especially in the face), seizures (which cause CNS depression, apnea, hypotension)
CV
hypotension, myocardial depression, AV block
Note: bupivacaine is most CV toxic
which nerve roots has the motor neurons?
ventral = efferent = motor
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)
Do ionized or non-ionized drugs cross a lipid membrane?
NON-ionized
What factor of an LA is most important in determining potency? Which drugs are highly potent?
Lipid solubility
Highly potent: etidocaine, bupivacaine, tetracine
pKa - effects on onset
the closer the pKa is to 7.4 (closer to physiological pH) will be FASTER ONSET than a drug with pKa of 9
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)
What does adding bicarb do to the LA effect?
Increases onset
Enhances block depth
Increases spread of block
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 impact does the intermediate chain have on potency and toxicity
↑ in the length of the intermediate chain (↑ number of carbon atoms) → ↑ potency & ↑ toxicity
LA lipid solubility & potency, toxicity, DOA
highly lipid soluble = More potent, higher risk of toxicity, longer DOA
Which ion establishes and maintains resting membrane potential?
K+
when do you redose chloroprocaine (epidural)?
chloroprocaine lasts about an hour before you have to redose
Allergy to LA is usually due to what?
Allergy to PABA, esters
Other: preservative reaction (ex: Methylparaben additive)
Spinals are dosed based on what?
DOSES.
Just know them. :’(
how does temp affect onset
↓ temperature = ↓ drug absorption across the nerve membrane = ↓ onset
hwat do you do if your pt has seizures r/t LA toxicity
- airway
- seizure = lots of metabolism → they need more O2
- get CO2 normalized
- benzos - anticonvulsant properties
What characteristics govern LA systemic absorption?
Physiochemical factors
- pKa, pH, and lipid solubility
- ex: water soluble will be removed faster from site
- blood flow
Physiologic conditions:
- tissue pH
- pCO2
- temp
- characteristics
- Note: elderly and pregnant are more at risk for toxicity
volume of solution or vehicle used (ex: epi)
concentration of local anesthetic
Conditions that increase the risk for LA toxicity
- Pregnancy
- hypoxia
- pH abnormalities
- CV modulating drugs (ex: β-blockers)
action potential - absolute refractory period
when? why is it important?
when the voltage gated Na+ channels are in inactivated state
regardless of how strong the stimuli, no action potential can be generated
LA absorption by type of block from high to low?
I Think I Can Place Epidural Blocks So Smoothly
- Intravenous
- Tracheal
- Intercostal
- Caudal
- Paracervical
- Epidural
- Brachial plexus
- Subarachnoid
- Subcutaneous
Local anesthetics are strong/weak acids/bases
Weak bases
Packaged in acidic formulations (to make them water soluble & not precipitate) but basic upon injection
concept of frequency or use dependent blockade
the more frequently the nerve cycles through actio potential, the more readily the Na++ channels are found in ianctive state, the more rapidly the blockade occurs
resting nerves are less sensitive than repetitively stimulated nerves
How are esters vs. amides metabolized?
Esters: hydrolyzed by non-specific esterase’s in the plasma and tissues (mostly liver)
- metabolized faster w/ low chance of toxicity
- metabolite = PABA (para-aminobenzoic acid), except for cocaine
Amides: metabolized in the liver, CP450
- slower than esters
- aromatic hydroxylation
- N-dealkylation
- amide hydrolysis
in a neuron, where are the voltage gated Na+ channels found?
in the axon
concentrated in the nodes of Ranvier
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
More specifically, what is the clinical sequence of local anesthesia blockade (5 steps), what is blocked?
1- sympathetic block (autonomic block: vasodilation, warm skin)
2- loss of pain and temp
3- loss of proprioception
4- loss of touch and pressure (pressure is difficult to block)
5- motor blockade
