Local Anesthetics Flashcards
Mechanism of Action of Local Anesthetics
Local Anesthetics (LA) produce reversible blockade of conduction of electrical impulses along nerve fibers
Reversibly block voltage-gated sodium channels in neurons (primary site of action)
- Penetrate/enter inner cell membrane of neuron
- Bind receptors within/near site of action
- Preventing influx of sodium ions
- Blocking propagation of the action potential
The mechanism of local anesthetics depend on what factors?
Nerves being blocked
Chemical structure of local anesthetic
Properties of local anesthetic
Local anesthetics cause reversible and transient loss of sensation (analgesia) in a portion of the body without _____
loss of consciousness
What is the sequence of sensory function blockade?
Pain → Temperature → Touch → Pressure → Motor
*recovery occurs in reverse order
Differential blockade is dependent on ___ and determined by ___.
Dependent on nerve sensitivity to local anesthetics
Determined by nerve fiber
oType
oDiameter
oMyelination
Lipid solubility is determined by ___
Aromatic ring and its substitutions
Tertiary amine substitutions
Greater lipid solubility equals ____
Increased potency (concentrations range 0.5-4%)
Increased protein binding
Longer duration of action
Slower onset of action
Higher tendency for cardiac toxicity
Greater protein binding for LAs equals _____
Longer duration of action
Higher pKa equals _______
Slower onset of action
Greater inherent vasodilation equals _____
Increases systemic absorption
Increases chances of toxicity
Decreases duration of action
Decreases onset of action
Systemic absorption/distribution dependent on ______
Site of injection
Dose
Addition of vasoconstrictor
Patient related factors
What are the two phases of diffusion?
Rapid disappearance phase – uptake by rapidly equilibrating tissue with high vascular perfusion
Slow phase of disappearance – individual local anesthetic distribution, biotransformation and excretion
Called the two compartment model
Metabolism/Excretion of Amide-Type LAs
Metabolized in the liver by CYP1A2 and CYP3A4 à can result in significant systemic levels with rapid absorption, increases potential for toxicity
Excreted by the kidneys
Metabolism/Excretion of Ester-Type LAs
Metabolism catalyzed by plasma and tissue cholinesterase via hydrolysis à rapid and occurs throughout body, reduces potential for toxicity
Results in water soluble metabolites that are excreted in urine
Mixture of local anesthetics are used to ____
achieve quick onset and long duration
Potency, spread/depth of epidural anesthesia is increased during ____
pregnancy
Newborn and elderly patients exhibit ____
prolonged half lives (decreased metabolism)
Hepatic dysfunction reduces metabolism of ____ LAs
amide type
Addition of sodium bicarbonate increases _____ resulting in _____.
increases pH
resulting in more drug in nonionized state and accelerated onset of action
What is the most commonly used vasocontrictor added agent to LAs?
Epinephrine
How does adding epinephrine to a LA decrease the chance of toxicity?
It decreases vascular absorption which results in reduced blood concentrations and reduced risk of toxicity
Epinephrine concentration 1:100,000 = ___
10 mcg/mL
Epinephrine concentration 1:200,000 = ____
5 mcg/mL
LAs that have a low potency and a short duration of action include ____
Procaine
- Slow onset
- DOA: 60-90 minutes
Chloroprocaine
- Fast onset
- DOA 30-60 minutes
LAs that have an intermediate potency and duration include ___
Mepivacaine
- Fast onset
- DOA 120-240 minutes
Lidocaine
- Fast onset
- DOA 90-120 minutes
LAs that have a high potency and long duration include ____
Bupivacaine
- Slow onset DOA 180-600 minutes
Ropivacaine
- Slow onset DOA 180-600 minutes
For site of injection, areas with high vascularity result in ___
greater uptake and higher blood concentrations
Drugs that alter/compete for plasma cholinesterase activity ____
Decrease hydrolysis of ester type
Examples: succinylcholine, neostigmine, pyridostigmine
Drugs that inhibit hepatic enzymes/decrease hepatic blood flow ____
Result in increased accumulation of amide type (such as lidocaine)
Examples: cimetidine, propranolol
What interaction do opioids/alpha adrenergic agonists have on LAs?
Potentiate analgesic effects
Which type of local is associated with increased allergic response?
Ester-type
Derivatives of and metabolized to PABA (para-aminobenzoic acid)
Cross reactivity within class
Treatment of LA allergy
Mild reactions: PO/IV diphenhydramine, famotidine
Severe: epinephrine, corticosteroids
What causes Local Anesthetic System Toxicity (LAST)?
Increased systemic concentrations of local anesthetic
oIntravascular injections
oHigher doses
oHigher absorption
oDecreased metabolism and elimination
Which LAs are at higher risk for causing LAST?
Long acting and potent LAs
S/S of LAST
Neurological Symptoms
- lightheadedness, visual disturbances, muscle twitching, convulsions, unconsciousness, coma, respirartoy arrest, CVS depression
Cardiac Symptoms
- Ventricular fibrillation
- Ventricular tachycardia
- ST changes
- Wide complex
- Hypotension
- Tachycardia
- Bradycardia/asystole
Prevention of LAST
Ensure appropriate access
Adhere to maximum dose recommendations
Be aware of concentration calculations
Choose agent that is suitable with least necessary potency and toxicity profile
Addition of vasoconstrictor
Careful patient observation following injection
Immediate discontinuation upon recognition of toxic symptoms
Treatment of LAST
Immediately stop injection/aspirate if possible and do not administer any additional local anesthetics
Supportive care to treat signs and symptoms
Airway management: 100% oxygen
Seizure suppression: benzodiazepines
BLS/ACLS algorithms
Avoid vasopressin, CCBs, beta-blockers, propofol
Lipid emulsion 20% infusion
For treatment of LAST with lipid emulsion 20% infusion, what is the dosing guidelines?
Bolus 1.5 mL/kg (lean body mass) IV over 1 minute
Continuous infusion 0.25 mL/kg/min
Repeat bolus once/twice after 5 minutes for persistent cardiovascular effects
Double infusion rate if blood pressure remains low
Continue infusion for at least 10 minutes after attaining stability
Upper limit: 10 mL/kg over first 30 minutes
What causes aquired methemoglobinemia?
LA metabolites include o-toluidine derivatives, which are responsible for inducing hemoglobin oxidation
Metabolite causes iron atom in hemoglobin to be oxidized from a ferrous form (Fe2+) ferric form (Fe3+) (conversion of hemoglobin to methemoglobin)
Methemoglobin is incapable of binding and transporting oxygen
Methemoglobin accumulation leads to tissue hypoxia
What agents can cause methemoglobinemia?
Prilocaine
Lidocaine
Tetracaine
Benzocaine
What pre-existing factors place a patient at higher risk for development of methemoglobinemia?
G6PD deficiency
Congenital or idiopathic methemoglobinemia
Cardiac or pulmonary compromise
Exposure to oxidizing agents or their metabolites
Infants < 6 months
Signs/Symptoms of Methemoglobinemia?
Onset: Immediate or delayed
Cyanotic skin discoloration, lightheadedness, headache, tachycardia, fatigue, confusion, tachypnea, seizures, arrhythmias, acidosis, death, chocolate-brown discoloration of blood
Treatment of Acquired Methemoglobinemia
Immediate discontinuation of LA and other oxidizing agents
Methylene blue 1-2 mg/kg administered over 5 minutes
oAt lower doses, increases conversion of methemoglobin to hemoglobin
oMay repeat dose in 1 hour if needed
oMaximum dose 7-8 mg/kg
Maximum dose of Bupivacaine and Levobupivacaine
Plain: 2mg/kg
With epinephrine: 3mg/kg
Total max dose Bupivicaine Plain: 175mg
Total max dose Bupivicaine with epinephrine: 225mg
Maximum dose of Lidocaine
Plain: 5mg/kg
With epinephrine: 7mg/kg
Total max dose Plain: 350mg
Total max dose with epi: 500mg
Maximum dose of Mepivacaine
Plain: 5mg/kg
With epinephrine: 7mg/kg
Maximum dose of Ropivacaine
Plain: 3mg/kg
With epinephrine: 3mg/kg
Total max dose Plain: 200mg
Total max dose with Epi: 250mg
Maximum dose of Prilocaine
Plain: 6mg/kg
With epinephrine: 8mg/kg
Total max dose Plain: 400mg
Total max dose with Epi: 600mg
Maximum dose of Procaine
7mg/kg
Total max dose: 350-600mg
Maximum dose of Chloroprocaine
Plain: 11mg/kg
With epinephrine: 14mg/kg
Total max dose Plain: 800mg
Total max dose with Epi: 1000mg
Class of Procaine = ____.
Potency, Onset, Duration
Ester
Low Potency
Slow Onset
Short DOA
Class of Tetracaine = ____.
Potency, Onset, Duration
Ester
High Potency
Slow Onset
Intermediate/Long DOA
Class of Lidocaine = ____.
Potency, Onset, Duration
Amide
Intermediate potency
fast onset
intermediate DOA (long with epi)
Class of Bupivacaine = ____.
Potency, Onset, Duration
Amide
High potency
Slow onset
Long DOA (longer with epi)
Class of Ropivacaine = ____.
Potency, Onset, Duration
Amide
High potency
Slow Onset
Long DOA
1G = ___mg = ___mcg
1mg = ___mcg
1G = 1,000mg = 1,000,000 mcg
1mg = 1,000mcg
Which LAs are administered topically?
lidocaine (both IV and topical)
Benzocaine
Cocaine
Increased CNS concentrations of LAs will lead to what symptoms?
- Lightheadedness, tinnitus, tongue numbness
- visual disturbances
- muscular twitching
- convulsions
- unconsciousness
- coma
- respiratory arrest
- cardiovascular system depression
The larger, myelinated, nerve fibers for motor, proprioception are how sensitive to LAs?
Not very sensitive (AKA it takes a lot of medication to penetrate those fibers)
The smaller unmyelinated nerve fibers are how sensitive to LAs?
very sensitive, it takes less of the drug to penetrate them
