Local Anesthetics Flashcards
Lightheaded ness, oral parenthesis, tinnitus, muscular twitching
5-10mcg/ml
Would you give propofol if signs of CV compromise?
No bc propofol drops BP more
High tissue protein binding with distribution
Remains in neural tissues longer
What is prilocaine and benzocaine metabolized to?
O-toluidine (methemiglobinemia)
What does pKa determine with LA?
Partially determines the speed of onset
Respiratory effects of IV infused lidocaine or systemic toxicity
Depressed hypoxia drive (response to low PaO2)
Dissociation from binding site impacted by:
Molecule size, charge, and lipophilicity
1-5mcg/ml
Analgesia
Are myelinated or unmyelinated more sensitive to LA block?
Myelinated axon
Does lipid solubility or protein binding have a greater impact to duration of action?
Protein binding
When does LA gains access during VG Na+ state?
Open/activated state
PK absorption of mucous membranes
Provides minimal barriers
What impacts the duration of action for LA?
Lipid solubility and protein binding
What does increasing lipophilicity do?
- increasing LA potency
- slower onset
- delay absorption into systemic circulation
Vasoconstrictors with epinephrine?
Prolonged duration of action and reduced peak serum concentration
What does lipophilicity favor?
Entry of LA molecule into the cell membrane
Is less lipid soluble more or less potent?
Less potent so faster onset
How are esters metabolized?
Hydrolysis by plasma esterases (pseudocholinesterase) into inactive metabolites
How does methylene blue treatment work?
Reduces metHb to Hb in 20-60min
What kind of pH does epinephrine containing LA have?
Acidic pH
How long are amides metabolized?
Longer elimination half-life
What are amides metabolized by?
Hepatic CYP 450 enzymes
Do smaller molecules dissociate from Na channels more or less rapidly?
More
What increases the risk of accumulation of unmetabolized drug and systemic toxicity?
Amide metabolism
LAST at risk
Neonates and infants (increase free fraction)
Elderly
Pregnancy - women in labor
cardiovascular depression
> 25mcg/ml
What does peak serum concentration correlates with?
- LA concentration
- region administrated
- protein binding
How fast does esters metabolism occurs?
Within minutes
Major CV toxicity requires how much local anesthetic blood concentration
3x the required to produce seizures
Lipid solubility distribution
More slowly
Who is most at risk for methemiglobinemia?
Neonate
What other channel blockade may contribute?
Potassium channel
Are phasic blocks stronger or weaker in sensory than motor nerves?
Stronger
If more lipid soluble, what will happen with duration of action?
More slowly diffuse from a lipid rich environment to aqueous blood stream
Treatment of LAST
Lipid emulsion
-early administration of 20% IV lipid emulsion
Onset and action with mixing LA
Fast onset and long acting (lidocaine and bupivacaine)
What kind of pKa and pH will have the greater amount of non-ionized (neutral) form that more readily permeates the nerve cell membrane?
pKa closest to physiologic pH (7.4)
When is the greatest effect of LA?
When most of nerve fibers are firing
What kind of distribution do you get from injection at target/local site
Distribution within that compartment
CC/CNS low ratio
More cardiotoxic (bupivacaine)
Which LA agent is the only exception to pKa closest to physiologic pH will have fast onset?
Chloroprocaine
Structure activity relationship of lipophilic region-aromatic region
Onset
Potency
Duration of action
What is the minimum of nodes that must be blocked to prevent AP propagation?
3
LA esters drugs name?
All names have 1 i
2 general intent of local anesthetics
- Produce local or regional effect
2. Avoid systemic effects
What is methemiglobinemia?
- reduced O2 carrying capacity
- reduced Fe2+ combines with O2
- oxidized to Fe3+ state
What 4 factors effect pharmacokinetic?
- Molecule size
- % ionionized
- Lipid solubility
- Serum/tissue protein binding
Do sensory or motor nerves fire at increased rates?
Sensory nerves
What 2 structures affect activity relationship?
Amino-ester
Amino-aside
-linkage aromatic ring to the hydrocarbon chain
Nerves with higher baseline firing rates will demonstrate greater blockade vs nerves with lowering firing rates
Phasic block
What kind of pH do LA’s have?
Weak bases and high pKa
Is some degree of lipid solubility needed for cross membrane to site of action?
Yes to some degree
What is used to treat methemiglobinemia?
Methylene blue
Extreme lipophilicity favors what kind of binding and duration of action?
- continued binding
- increases duration of action
Treatment of LA toxicity for seizures?
Benzodiazepines
Are smaller or larger axon diameter more sensitive to LA action?
Smaller
PK absorption with intact skin
Requires high concentration of lipid soluble agent for permeation and analgesia
What is the exception to esters metabolism?
Cocaine metabolized by liver
Potency of LA action (3):
- Correlates with lipid solubility
- Increased by adding large alkyl groups
- No single measure to compare potency
Coma, respiratory arrest
15-25mcg/ml
Structure activity relationship of hydrophilic amine group
3 or 4 amine depending on PKA &pH
What kind of charge can pass through membrane
Neutral (nonionized) LA
CC/CNS high ratio
Greater safety margin bc recognizes earlier presenting CNS before CV collapse ensures (lidocaine, mepivacaine)
Structure activity relationship of ester or amide linkage
Hydrolysis - duration of action
Local anesthetic systemic toxicity (LAST)
1/3 begin with CNS and progress to CVS
-occurs immediately following LA injection
LA amides drug name?
All names have 2 i’s
Onset of LA action depends on (6):
- Lipid solubility
- Ease of diffusion through connective tissue
- Charged form
- Epi added
- pH of tissue
- pKa
Duration of action for LA
- correlates with potency and lipid solubility
- rate of dissociation from Na channel
- correlated with tissue protein binding
Distribution from systemic distribution?
2 compartment
- initial phase (organs of high blood flow)
- brain and heart, liver, kidneys
- delayed absorption from adipose phases
What kind of PK distribution correlate with toxicity risk?
Cmax and time to Cmax
Onset and duration of transient neurological symptoms after spinal anesthesia
Onset 6-36hrs
Lasts 1-7days
Highest to lower peak concentrations with vascularity?
IV>tracheal>intercostal>caudal>Paracervical>epidural>brachial plexus>subarachnoid/femoral>subcutaneous
Conduction of nerve impulse through non-myelinated nerve fiber requires what?
More LA exposure for similar block in myelinated axon
What is the minimum concentration that will block nerve impulses conduction impacted by?
- fiber size, type, myelination
- pH
- frequency of nerve stimulation
- electrolyte concentration (less K+ and more Ca+)
When is distribution the greatest?
Both lipid solubility and protein binding are high
MOA of local anesthetics
Inhibit VG Na+ channels
Do you use max dose when you combine LA?
No because toxicity is additive
Seizures, unconsciousness
10-15mcg/ml
