Flashcards in Local Anesthetics Deck (51):
MOA of local ansthetics
site- Sodium ion channels
Block conduction of neural transmission by decreasing rate of depolarization in response to excitation (prevent reaching threshold potential)
Does NOT change resting potential, or actual threshold potential value
Describe normal nerve conduction:
Resting potential of neural membrane = -90mV (via Na out, K+ in)
Excitation = increase in permeability to Na = depolarization (more +) = hit threshold = self sustaining influx of Na (massive depolarization)
Form of local anesthetic most helpful for causing activity
neutral form = can cross lipophillic membrane to Na channel receptor (ie site of action)
Ionized form inside nerve causes activity
Describe conformations of Na channel, and conformations most helpful for local anesthetic activity
Resting-closed : NO ACTIVITY
Activated - Open: ACTIVITY
Inactivated - Closed: ACTIVITY
Repeated depolarization (which cauases activated/inactivated states vs resting) more effective anesthetic binding = enhancement of conduction blockade
USE DEPENDENT / FREQUENCY DEPENDENT BLOCK
Role of pH on LA activity
pKa of LA determines proporation of neutral to ionized forms
lower pKa= greater % of unionized (active) drug
Why would you add bicarbonate to LA?
Increase pH of environment = more neutral/ionized form (for any given pH)
Why may infected tissue be difficult to anesthetize?
infection = low pH
less proportion of neural/ionized form for given pKa of LA
What does the lipid solubility of a LA confer?
describes uptake into neural membrane
lipid solubility generally correlates to POTENCY, DURATION OF EFFECT, and sometimes INVERSELY WITH LATENCY/TIME TO ONSET
ETIDOCAINE OR BUPIVUCAINE
more motor blockade?
Describe relationship between location of nerve fibers in nerve bundle, and onset of effect.
Mantle (external) = 1st = effects proximal structures
Core (internal) = 2nd = effects distal structures
How do lipophilicity and protein binding effect LA uptake into blood stream?
higher lipo/PB = slower uptake
LA effect on vasoactivity
Vasodilators at clinically relevant concentrations
Why add vasoconstrictors to LA?
prolongation of anesthesia by decreased uptake into blood stream
less likelihood of toxicity (uptake is slower than metabolism)
Adding epi to which of the following LA will have greater effect on activity?
Bupivicaine, Tetracaine, Lidocaine
Has vasodilation (greater), so epi will have greater effect on general activity
Cocaine, Procaine, chlorproacaine
lidocaine, bupivicaine, mepivicaine, ropivicaine
Metabolism of esters
hydrolysis in plasma
metabolism of amides
metabolism by hepatic microsomal enzymes, and lung extraction
Site with highest systemic absorption of LA
( > caudal >epidural > brachial plexus) for the most part
LA w/ highest potency (greatest to least)
Bupivacaine/Tetracaine > ropivacaine > prilocaine/mepivacaine/lidocaine/chlorprocaine > procaine
Max dose of lidocaine for infiltration (in mg)
Max dose of Mepivacaine for infiltration
Max dose of prilocaine for infiltration
Max dose of Bupivacaine for infiltration
Max dose of Ropivacaine for infiltration
Max dose of Procaine for infiltration
Max dose of Chlorprocaine for infiltration
Major LA for IV anesthesia
Chlorprocaine, Lidocaine, Prilocaine
Major LA for local anesthesia
Major LA for peripheral nerve block
Procaine, Chlorprocaine, All amides
Major LA for epidural anesthesia
Chlorprocaine, all amides
Major LA for spinal anesthesia
Procaine, tetracaine, Bupfivacaine, ropivacaine
CNS toxicity symptoms
circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, TC seizures
How do LA cause seizures?
depression fo cortical inhibitory neurons, letting excitatory pathways rule
How can LA seizures propogate LA toxicity?
acidosis propogates LA toxicity
Tx for CNS toxicity of LA
-Benzos vs Propofol
Cardiovasular toxicity of LA effects
profound hypotension (relax arteriolar SM relaxation)
direct myocardial depression
impaired cardiac automaticiy/conduction = prolonged PR, wide QRS
LA with highest cardiac toxicity?
How do interlipids help reduce toxic events?
provide lipid sink that binds to LA and pulls it out of active circulation = diminish toxicity
Esters vs amides; more allergic reactions
esters = produce PABA metabolites = hypersensitivity
Does cross sensitivity between esters and amides for hypersensitivity exist?
Esters make PABA (allergen)
some amides contain methylparaben as preservative (cross reacts w/ PABA); it is not the amide itself but the preservative
Major use of Tetracaine
spinal anesthesia (high risk of TNS)
RARELY used for epidural/PNB (slow onset, profound motor blockade, high toxicity at high conc)
Major uses of lidocaine
topical, local, IV, PNB, epidural/spinal (restricted 2/2 side effects)
What form of lidocaine infusion has highest risk of neurotoxicyt and neural injury?
spinal anesthesia (via continuous spinal) = cauda equina syndrome
maldistribution and high does through small gauge catheter
What is TNS?
transient neurologic syndrome =
pain and dysesthesia following intrathecal doses of lidocaine
occurs in up to 1/3 of patients, lasts up to 3 days
Factors increasing risk of TNS?
knee arthroscopy positioning
1st line treatment for TNS
How does mepivacaine vary from lidocaine?
piperdine ring = less vasodilation = longer duration of action
Major limitation of mepivacaine?
ineffective as topical anesthetic
Major limitation of prilocaine
At high doses may result in clinically significant of ortho-toluidine = can convert hgb to methemoglobin
antidote = methylene blue