Local Anesthetics Flashcards

1
Q

Mechanism of Action of Local Anesthetics

A

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)

  1. Penetrate/enter inner cell membrane of neuron
  2. Bind receptors within/near site of action
  3. Preventing influx of sodium ions
  4. Blocking propagation of the action potential
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2
Q

The mechanism of local anesthetics depend on what factors?

A

Nerves being blocked

Chemical structure of local anesthetic

Properties of local anesthetic

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3
Q

Local anesthetics cause reversible and transient loss of sensation (analgesia) in a portion of the body without _____

A

loss of consciousness

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4
Q

What is the sequence of sensory function blockade?

A

Pain → Temperature → Touch → Pressure → Motor

*recovery occurs in reverse order

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5
Q

Differential blockade is dependent on ___ and determined by ___.

A

Dependent on nerve sensitivity to local anesthetics

Determined by nerve fiber

oType

oDiameter

oMyelination

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6
Q

Lipid solubility is determined by ___

A

Aromatic ring and its substitutions

Tertiary amine substitutions

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7
Q

Greater lipid solubility equals ____

A

Increased potency (concentrations range 0.5-4%)

Increased protein binding

Longer duration of action

Slower onset of action

Higher tendency for cardiac toxicity

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8
Q

Greater protein binding for LAs equals _____

A

Longer duration of action

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9
Q

Higher pKa equals _______

A

Slower onset of action

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10
Q

Greater inherent vasodilation equals _____

A

Increases systemic absorption

Increases chances of toxicity

Decreases duration of action

Decreases onset of action

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11
Q

Systemic absorption/distribution dependent on ______

A

Site of injection

Dose

Addition of vasoconstrictor

Patient related factors

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12
Q

What are the two phases of diffusion?

A

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

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13
Q

Metabolism/Excretion of Amide-Type LAs

A

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

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14
Q

Metabolism/Excretion of Ester-Type LAs

A

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

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15
Q

Mixture of local anesthetics are used to ____

A

achieve quick onset and long duration

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16
Q

Potency, spread/depth of epidural anesthesia is increased during ____

A

pregnancy

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17
Q

Newborn and elderly patients exhibit ____

A

prolonged half lives (decreased metabolism)

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18
Q

Hepatic dysfunction reduces metabolism of ____ LAs

A

amide type

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19
Q

Addition of sodium bicarbonate increases _____ resulting in _____.

A

increases pH

resulting in more drug in nonionized state and accelerated onset of action

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20
Q

What is the most commonly used vasocontrictor added agent to LAs?

A

Epinephrine

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21
Q

How does adding epinephrine to a LA decrease the chance of toxicity?

A

It decreases vascular absorption which results in reduced blood concentrations and reduced risk of toxicity

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22
Q

Epinephrine concentration 1:100,000 = ___

A

10 mcg/mL

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23
Q

Epinephrine concentration 1:200,000 = ____

A

5 mcg/mL

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24
Q

LAs that have a low potency and a short duration of action include ____

A

Procaine

  • Slow onset
  • DOA: 60-90 minutes

Chloroprocaine

  • Fast onset
  • DOA 30-60 minutes
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25
LAs that have an intermediate potency and duration include \_\_\_
**Mepivacaine** * Fast onset * DOA 120-240 minutes **Lidocaine** * Fast onset * DOA 90-120 minutes
26
LAs that have a high potency and long duration include \_\_\_\_
**Bupivacaine** * Slow onset DOA 180-600 minutes **Ropivacaine** * Slow onset DOA 180-600 minutes
27
For site of injection, areas with high vascularity result in \_\_\_
greater uptake and higher blood concentrations
28
Drugs that alter/compete for plasma cholinesterase activity \_\_\_\_
Decrease hydrolysis of ester type Examples: succinylcholine, neostigmine, pyridostigmine
29
Drugs that inhibit hepatic enzymes/decrease hepatic blood flow \_\_\_\_
Result in increased accumulation of amide type (such as lidocaine) Examples: cimetidine, propranolol
30
What interaction do opioids/alpha adrenergic agonists have on LAs?
Potentiate analgesic effects
31
Which type of local is associated with increased allergic response?
Ester-type ## Footnote Derivatives of and metabolized to PABA (para-aminobenzoic acid) Cross reactivity within class
32
Treatment of LA allergy
Mild reactions: PO/IV diphenhydramine, famotidine Severe: epinephrine, corticosteroids
33
What causes Local Anesthetic System Toxicity (LAST)?
**Increased systemic concentrations of local anesthetic** oIntravascular injections oHigher doses oHigher absorption oDecreased metabolism and elimination
34
Which LAs are at higher risk for causing LAST?
Long acting and potent LAs
35
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
36
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
37
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
38
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
39
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
40
What agents can cause methemoglobinemia?
Prilocaine Lidocaine Tetracaine Benzocaine
41
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
42
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
43
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**
44
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
45
Maximum dose of Lidocaine
Plain: 5mg/kg With epinephrine: 7mg/kg Total max dose Plain: 350mg Total max dose with epi: 500mg
46
Maximum dose of Mepivacaine
Plain: 5mg/kg With epinephrine: 7mg/kg
47
Maximum dose of Ropivacaine
Plain: 3mg/kg With epinephrine: 3mg/kg Total max dose Plain: **200mg** Total max dose with Epi: **250mg**
48
Maximum dose of Prilocaine
Plain: 6mg/kg With epinephrine: 8mg/kg Total max dose Plain: **400mg** Total max dose with Epi: **600mg**
49
Maximum dose of Procaine
7mg/kg Total max dose: 350-600mg
50
Maximum dose of Chloroprocaine
Plain: 11mg/kg With epinephrine: 14mg/kg Total max dose Plain: **800mg** Total max dose with Epi: **1000**mg
51
Class of Procaine = \_\_\_\_. Potency, Onset, Duration
Ester Low Potency Slow Onset Short DOA
52
Class of Tetracaine = \_\_\_\_. Potency, Onset, Duration
Ester High Potency Slow Onset Intermediate/Long DOA
53
Class of Lidocaine = \_\_\_\_. Potency, Onset, Duration
Amide Intermediate potency fast onset intermediate DOA (long with epi)
54
Class of Bupivacaine = \_\_\_\_. Potency, Onset, Duration
Amide High potency Slow onset Long DOA (longer with epi)
55
Class of Ropivacaine = \_\_\_\_. Potency, Onset, Duration
Amide High potency Slow Onset Long DOA
56
1G = \_\_\_mg = \_\_\_mcg 1mg = \_\_\_mcg
1G = 1,000mg = 1,000,000 mcg 1mg = 1,000mcg
57
Which LAs are administered topically?
lidocaine (both IV and topical) Benzocaine Cocaine
58
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
59
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)
60
The smaller unmyelinated nerve fibers are how sensitive to LAs?
very sensitive, it takes less of the drug to penetrate them