Local anesthetics Flashcards
1
Q
General intent of local anesthetics
A
- Produce local or regional effects
2. Avoid systemic effects
2
Q
Mechanism of action of local anesthetics
A
- Inhibit voltage gated Na channels
- Bind to inactivated state
- Prevents neural cells from generating action potentials in response to slight depolarization
3
Q
Phasic or use dependent block
A
Affinity for activated > resting
4
Q
What impacts dissociation from Na channels?
A
- Smaller molecules dissociate from Na channel more rapidly
- Extreme lipophilicity (bupivicaine) favors continued binding and increases duration of action
5
Q
What happens when you increase lipophilicity?
A
- Favors entry of local anesthetics into molecule
- Increasing potency
- Slower onset (slower to leave nerve membrane for intracellular fluid)
- Delays absorption into systemic circulation
6
Q
How do substitutions change lipophilicity?
A
More substitutions = more lipophilic
7
Q
Ester local anesthetics
A
- Shorter duration of action
- Benzocaine
- Chloroprocaine
- Cocaine
- Procaine
- Tetracaine
8
Q
Amides local anesthetics
A
- Longer duration of action
- Bupivicaine
- Lidocaine
- Prilocaine
- Ropivacaine
9
Q
Absorption of local anesthetics
A
Administer close to target nerve tissue
Smallest volume and dose
10
Q
Factors that effect absorption
A
Drug molecule size
% ionized
Lipid solubility
serum/tissue protein binding
11
Q
How does pH and pKa effect local anesthetics?
A
- Neutral form readily crosses phospholipid cell membrane, but most local anesthetics are weak bases and have a pKa > physiologic pH
- 50% of molecules are cations are physiologic pH when administered
- pKa partially determines speed of onset
12
Q
Onset time of procaine and tetracaine
A
Slow
13
Q
Onset time of bupivacaine and ropivacaine
A
Moderate
14
Q
Onset time of chloroprocaine, lidocaine, etidocaine, and mepivacaine
A
Fast
15
Q
How does pH and pKa change with administration of local anesthetics?
A
- Neutral to pass through the membrane
- Lipophilic to penetrate the membrane
- Ionized to bind to Na channel
- Inside cell non-ionized to ionized equilibrium
- lower pH of intracellular fluid shifts towards ionized
16
Q
Characteristics of local anesthetics with epi
A
- Acidic pH
- 100% ionized
- Accelerates onset
- Vasoconstricts to prevent redistribution away from nerve fibers
- Prolongs duration of action and reduce peak serum concentrations
17
Q
Highest to lower peak concentrations for vascularity
A
IV > tracheal > intercostal > caudal > paracervical > epidural > brachial plexus > subarachnoid/sciatic/femoral > subcutaneous
18
Q
Duration of procaine, chloroprocaine
A
Short due to low protein binding and lipid solubility
19
Q
Duration of lidocaine and mepivacaine
A
Moderate
20
Q
Duration of tetracaine, etidocaine, bupivicaine, and ropivacaine
A
Long
21
Q
Metabolism of esters
A
- Hydrolyzed by plasma esterases (except cocaine is metabolized by liver)
- occurs within minutes
- Metabolized to inactive metabolites
- para-aminobenzoic acid metabolite can cause allergic reactions
22
Q
Metabolism of amids
A
- Hepatic CYP450 enzymes
- Longer elimination half life
- Increased risk for accumulation of unmetabolized drug and system toxicity
23
Q
Can cause methemiglobinemia, should be avoided in labor and delivery, patients with limited cardiopulmonary reserve, and endoscopies
A
Prilocaine, bupivacaine and sometimes lidocaine
24
Q
Treatment for methemiglobinemia
A
Methylene blue
Reduces methemiglobin to hemoglobin
Short duration of effects
Normalizes within 20- 60 minutes
25
How is potency increased?
More large alkyl groups to parent molecule = more potent = more lipid soluble
26
What impacts the minimum concentration that will block nerve conduction?
Fiber size (smaller is more sensitive), type, myelination (myelinated is more sensitive)
pH (acidic pH antagonizes block)
Frequency of nerve stimulation
Electrolyte concentration (dec K+ and inc Ca++ antagonize block)
27
A minimum of _ nodes must be blocked to prevent AP propagation
3
28
Implies nerves with higher baseline firing rates will demonstrate a larger blockade compared with lower firing rates
Phasic block
29
True/false: sensory nerves fire at a higher rate than motor
True
30
Exceeds sensory block during spinal and epidural anesthesia
Sympathetic block
31
Exceeds motor block during spinal and epidural anesthesia
Sensory block
32
Associated with sharp, fast pain
Adelta fibers
33
Associated with burning or slow pain
C fibers
34
More susceptible fibers to local anesthetic
Adelta fibers
35
LA with selectivity for sensory nerves over motor during onset and offset
Bupivacaine and ropivacaine
36
Route of administration of LA
1. Topical
2. Injection in vicinity
3. Major nerve trunks
4. Epidural or spinal
37
Adverse neurological effects of local anesthetics
1. tongue paresthesia
2. dizziness
3. blurred vision
4. restlessness/agitation
5. seizures
6. dysesthesia
7. burning pain
8. Aching in lower extremities/buttock
38
Adverse respiratory effects of local anesthetics
1. depressed hypoxic drive
2. apnea from phrenic and intercostal nerve paralysis
3. Depressed medullary respiratory center
4. apnea after "high" spinal or epidural hypotension
39
Adverse cardio effects of local anesthetics
1. suppressed phase 4 depolarization
2. slowed conduction velocity
3. depressed contractility
4. vasodilation (except with cocaine)
5. tachycardia or HTN in awake pts
6. arrhythmias
40
What is Local Anesthetic Severe Toxicity (LAST)?
- most commonly seizures
- 1/3 begins with CNS and progresses to CVS features
- Typically occurs immediately following LA injection
41
LAST risk factors
1. Drugs
2. Patient age (neonates, infants, elderly)
3. Pregnancy
42
CC/CNS ration
drug dose required to cause catastrophic cardiovascular collapse to the drug dose required to produce seizures
2. low ratio = more cardiotoxic (bupivacaine)
3. High ratio = greater safety margin to recognize early onset CNS issues before cardiac collapes (lidocaine, mepivacaine)
43
Treatment of LAST
Lipid emulsion 20% IV early,
100ml bolus over 2-3 minutes followed by 200-250 ml over 15-20 min
Rebolus up to 2 additional times
44
May lead to prolonged action/slower systemic absorption in LAST
Vasoactive drugs; ropivacaine, levobupivacaine
45
May lead to more rapid systemic absorption
Bupivacaine; vasodilating
46
How much should you reduce the LA dose in neonates and infants
15% <4 months of age
47
How much should you reduce the LA dose in elderly?
10 to 20%
48
Why are women in labor at risk for LAST?
- reduced alpha 1 acid glycoprotein
- Increased CO
- Rapid absorption, high Cmax
49
Benzocaine: techniques, available concentrations, max dose, typical duration
Technique- topical
Available concentration-20%
Max dose-N/A
Typical duration-N/A
50
Chloroprocaine techniques, available concentrations, max dose, typical duration
Technique- epidural, infiltration, peripheral nerve block, spinal
Available concentration- 1, 2, 3%
Max dose-12 mg/kg, 600 mg
Typical duration-short due to rapid metabolism
rapid onset
51
Cocaine: techniques, available concentrations, max dose, typical duration
Technique: topical, ENT
Available concentration: 4, 10%
Max dose: 3mg/kg
Typical duration: NA
52
Procaine (Novocain): techniques, available concentrations, max dose, typical duration
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Technique: spinal, local infiltration
Available concentration: 1, 2, 10%
Max dose: 12 mg/kg, 500mg
Typical duration: short
slow onset
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53
Tetracaine (amethocaine) techniques, available concentrations, max dose, typical duration
Technique: spinal, topical (eye)
Available concentration: 0.2, 0.3, 0.5, 1, 2%
Max dose 3mg/kg, 100mg topical
Typical duration: long as far as esters go
Slow onset
54
Bupivacaine: techniques, available concentrations, max dose, typical duration
Technique: epidural, spinal, infiltrations, peripheral nerve block (sensory>motor **cardiotoxic)
Available concentration: 0.25, 0.5, 0.75%
Max dose: 3mg/kg, 175 mg
Typical duration: long
Slow onset
55
Lidocaine: techniques, available concentrations, max dose, typical duration
Technique: epidural, spinal, infiltration, peripheral nerve block, IV, regional, topical
Available concentration: 0.5, 1, 1.5, 2, 4, 5%
Max dose: 4.5 mg/kg (7 mg/kg with epi), 300 mg
Typical duration: medium
Rapid onset
56
Mepivacaine: techniques, available concentrations, max dose, typical duration
Technique: epidural, infiltration, peripheral nerve block, spinal
Available concentration: 1, 1.5, 2, 3%
Max dose: 4.5 mg/kg (7 mg/kg with epi), 300 mg
Typical duration: medium
Slow onset
57
Prilocaine: techniques, available concentrations, max dose, typical duration
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Technique: EMLA (topical), epidural, IV, regional (outside US)
Available concentration: 0.5, 2, 3, 4%
Max dose: 8 mg/kg, 400 mg
Typical duration: medium
Slow onset
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58
Ropivacaine: techniques, available concentrations, max dose, typical duration
Technique: epidural, spinal, infiltration, peripheral nerve block
Available concentration: 0.2, 0.5 0.75, 1%
Max dose: 3mg/kg, 200mg
Typical duration: long
Slow onset
