Local Anesthetics Flashcards

(112 cards)

1
Q

Local anesthetics definition

A

Drugs that reversible block conduction of electrical impulses along nerve fibers

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2
Q

Schwann cells

A

Support and insulate each axon

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3
Q

What type of cells surround each axon

A

Schwann cells

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4
Q

Unmyelinated nerves and Schwann cells

A

Small nerves, single Swann cells cover several axons

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5
Q

Myelinated nerves and Schwann cells

A

Larger nerve, Schwann cell covers only one axon and has several concentric layers of myelin

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6
Q

nodes of ranvier

A

Periodic segments between Schwann cells along the axon that do not contain myelin

There are VGNa channels in these segments and are the primary site of LA action - action potentials jump from nerve to nerve aka saltatory conduction

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7
Q

What is saltatory conduction

A

APs jump from nerve to nerve via nodes of ranvier

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8
Q

How many nodes must LAs inhibit VGNa channels in to block impulses

A

Three successive nerves

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9
Q

What are bundles of axons called

A

Fasiculi

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10
Q

What are the layers of the connective tissue that cover fasciculi

A

There are 3
Endoneurium - thin, delicate collagen that embeds the axon in the fascicule
Perineurium - consists of layers of flattened cells that binds groups of fascicules together
Epineurium - surrounds the perineurium and is composed of connective issue that holds fascicles together to form a peripheral nerve

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11
Q

Falyar’s explanation of the neuriums

A

The endoneuriums surround individual axons

The perineurium binds fasicicles together

The epineurium holds all of those bundles of fascicles together to form a peripheral nerve

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12
Q

RMP of axon

A

-70mV to -90mV

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13
Q

What physiologic mechanisms help create RMP

A

Na-K pump in axolemma

Intracellular K ratio of 30:1

Membrane impermeable to other ions

Excess of negatively charged ions in axoplasm

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14
Q

Nernst equation

A

Expresses the charge created by K+ concentration gradient

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15
Q

What charge puts VGNa into active states (end of depol)

A

20mV

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16
Q

What restores RMP

A

NA - K pump

3 Na’s leave for each 2 K’s that enter

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17
Q

LA mechanism of action

A

Bind to VGNa channels preferentially to those in open, inactive states

They also block K, Ca, and GPCRs to a lesser extent

This blocks transmission of nerve impulses

They DO NOT alter the RMP or threshold potential

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18
Q

Modulated receptor hypothesis of LA action

A

Preference to attach during active or inactive states

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19
Q

Frequency dependent blockade

A

Resting nerve is less sensitive to LA than one repeatedly stimulated

AKA = use-dependent or phasic block

“Works better when its doing something”

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20
Q

Are LAs acids or bases? And describe the mechanism of how they enter the cell

A

All LAs are weak bases

Unionized (unprotonated) base form of the LA diffuses through cell membrane and then becomes re-ionized once inside cell and is able to attach to the inner portion of the VGNa channel

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21
Q

Which type of nerves to LAs preferentially bind to

A

Smaller, unmyelinated nerves

Aka larger, myelinated nerves are harder to block

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22
Q

Differential blockade order?

A

Preganglionic (think sympathetic nerves) are blocked first, followed by small C fibers and small A fibers

= loss of pain and temp

Touch and proprioception can still be present

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23
Q

Type A - Alpha fiber characteristics

A

Proprioception, motor
Diameter = 6-22 um
Heavy myelination
Last to be blocked

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24
Q

Type A beta fiber characteristics

A

Touch, pressure
Diameter 6-22 um
Heavy myelination
Intermediate time to block

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25
Type A gamma fibers
Muscle tone Diameter 3-6 um Heavy myelination Intermediate time to block
26
Type A delta fibers
Pain, cold temp, touch Diameter 1-5 um Heavy myelination Intermediate time to block
27
Type B fiber characteristics
Preganglionic autonomic vasomotor Diameter <3 um Light myelination Blocked early
28
Type C sympathetic fiber characteristics
Postganglionic vasomotor Diameter 0.3-1.3um No myelin Blocked early
29
Type C dorsal root fiber characteristics
Pain, warm and cold temp, touch Diameter 0.4-1.2 um No myelin Blocked early
30
Halsted
Recognized LA as a potential for regional and spinal anesthesia
31
Koller
Introduced cocaine as the first LA in 1884
32
LA used for neural blockade structure
3 characteristics ``` Unsaturated aromatic ring (lipophillic) Tertiary amine (hydrophilic) Ester or abide linkage that binds the aromatic ring to the carbon group (this is how we designate class) ```
33
List the amides
Look for the i!!! ``` Lidocaine Mepivicaine Prilocaine Bupivicaine Ropivacaine Articaine ```
34
List the esters
``` Procaine Chloroprocaine Tetracaine Cocaine Benzocaine ```
35
Ester LA metabolism
catalyzed by plasma and tissue cholinesterases via hydrolysis, rapidly occurs throughout body
36
Amide LA metabolism
Hepatic metab by CYP1A2 and CYP3A4 and thus a significant blood level may develop with rapid absorption Severe hepatic disease can prolong metab of these drugs and increase risk for toxicity
37
Which of the classes of LAs have higher allergic potential
Esters because they break down into PABA (para aminobenzoic acid) which is an allergen
38
What is the longest acting ester LA
Tetracaine
39
Which of the LA classes are more lipophillic
Amides
40
Which of the LA classes are more protein bound
Amides
41
Minimum effective concentration
Cm The minimum concentration of LA necessary to produce conduction blockade of a nerve impulse Analogous to MAC
42
Cm of motor fibers in comparison to sensory fibers
Motor fibers are twice that of sensory fibers Aka sensory anesthesia may not always be accompanied by paralysis
43
Do you need more or less LA for intathecal vs epidural anesthesia
You need less ***For epidural you give higher volume of a lesser concentration
44
What type of nerve fiber is most readily blocked
Pre-ganglionic B fibers
45
How can you increase onset of LA
Give more
46
How is the effect of LA terminated
Systemic absorption Places that are more highly vascularized will last for less time
47
What increases risk of toxicity of LA
Faster absorption aka highly vascularized area
48
Good falyar tip for injecting local
Only inject 5ml at a time and aspirate before you inject
49
If an LA is more lipid soluble, what other characteristics would you expect
Increased protein binding Increased potency Longer duration of action Tendency for severe cardiac toxicity
50
What plasma proteins do LAs bind to?
Alpha1-acid glycoproteins To a lesser extent - albumin
51
Basic drugs become more ionized in what type of solution
A solution where pH is less than pKa
52
Do drugs with a pKa closer to physiologic pH have a faster or slower onset
Faster
53
Physiochem properties of Procaine
``` Pka: 8.9 % ion @ pH 7.4: 97 % protein bound: 6 Onset: slow DoA: 60-90 ```
54
Onset and doa of chloroprocaine
This one doesn’t intuitively make sense but falyar said its due to the high concentration you give he also said it has a similar profile to procaine but he didn’t list the numbers Onset: fast DoA: 30-60
55
Physiochem props of tetracaine
``` Pka: 8.5 % ion @ pH 7.4: 93 % protein bound: 94 Onset: slow DoA:180-600 min ```
56
Physiochem props of lidocaine
``` Pka: 7.9 % ion @ pH 7.4: 76 % protein bound: 64 Onset: fast DoA: 90-120min ```
57
Onset and doa of mepivicaine
Onset: fast DoA: 120-240 min
58
Onset and doa of ropivicaine
Onset: slow DoA: 180-600 Min
59
Physiochem props of bupivacaine
``` Pka: 8.1 % ion @ pH 7.4: 83 % protein bound: 95 Onset: slow DoA: 180-600 mins ```
60
Vasomotor action of LAs and exceptions
LA causes relaxation of smooth muscle Exceptions = lidocaine, ropivacaine, cocaine Relaxation = vasodilation = decreased doa and increased plasma concentration aka potential toxicity
61
Rank the uptake of LAs based on regional technique from highest to lowest
``` IV Tracheal Caudal Paracervical Epidural Brachial Sciatic Subq ```
62
Why do we add epi to LA
It’s a vasoconstrictor that decreases rate of vascular absorption Increased duration and potency of block Decreased risk of systemic toxicity
63
Sodium bicarbonate with LAs
Raises pH of LA solution resulting in more drug in the non-ionized state May result in less pain on injection Limitation: precipitation can occur
64
When LA is being distributed, where does it go first
Brain, heart, lungs receive most initially Risk for toxicity Then muscle and it receives most
65
How does renal dysfunction affect LAs
Affects clearance but far less than hepatic failure But it will affect protein binding
66
Changes in pregnancy
Mechanical - reduction in epidural spaces Hormonal - progesterone levels affect LA sensitivity
67
Local anesthetic systemic toxicity (LAST)
Most commonly occurs from an inadvertent intravacular injection - initial blocking of inhibitory neurons thought to cause seizures - blocking of cardiac ion channel = Brady or vib if severe Presents rapidly - agitation, tinnitus, circumoral numbness, blurred vision, metallic taste in mouth - then muscle twitching, unconsciousness, seizures - if levels are very high = seizures and respiratory arrest Incident rate is 0.4 per 10,000 -most commonly seen in epidural, axillary, interscalene blocks
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How to prevent LAST
Test dosing Incremental injection with aspiration Use of pharmacologic markers Ultrasound
69
treatment of LAST
Prompt recognition Airway management - suppress seizure: benzo and succ - prevent hypoxia and acidosis Lipid emulsion therapy Vasopressors - epinephrine < 1mg/kg - no vasopressin
70
Lipid emulsion dosing
Lipid emulsion 20% - precise volume and flow rate are not crucial Pt > 70kg - bolus 100 ml rapid over 2-3 minutes - gtt 200-250ml over 15-20 minutes Pt < 70 kg - bolus 1.5 ml/kg rapid over 2-3 min - gtt 0.25 ml/kg/min (ideal body weight) Re-bolus once or twice at the same dose and double infusion rate if patient remains unstable DOSE LIMIT = 12 ml/kg Be aware that total volume of lipid emulsion can approach 1 L in a prolonged resuscitation (>30min)
71
Lipid emulsion therapy moa
Capture local anesthetic in blood (lipid sink) Increased fatty acid uptake by mitochondria Interference of Na channel binding Promotion of calcium entry Accelerated shunting
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Max dose of lidocaine
In mg/kg No epi: 4 Epi: 7
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Max dose of mepivacaine
In mg/kg No epi: 4 Epi: 7
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Max dose of bupivacine
In mg/kg No epi: 3 Epi: n/a
75
max dose of ropivacaine
In mg/kg No epi: 3 Epi: N/A
76
Max dose of procaine
In mg/kg No epi: 12 Epi: N/A
77
Max dose of chloroprocaine
In mg/kg No epi: 11 Epi: 14
78
Max dose of prilocaine
In mg/kg No epi: 7 Epi: 8.5
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Max dose of tetracaine
In mg/kg No epi: 3 Epi: n/a
80
Amide related allergies
Related to preservative Paraben, methylparaben, metabisulfite
81
Methemglobinemia
A conduction of high concentration of methemoglobin in blood Ferris form of hgb converted to ferric form Reduced oxygen carrying capacity - hypoxemia not responsive to therapy
82
Which LAs can cause methemoglobinemia
Benzocaine - rise in cases since 2006 r/t otc spray mostly involving infants <2 Prilocaine - d/t one of its metabolites o-toluidine - dosing should not exceed 2.5mg/kg - should be avoided in children under 6, pregnancy, pts taking other oxidizing drugs
83
Treatment of methemoglobinemia
Methylene blue 1-2 mg/kg over 3-10 minutes High levels may require transfusion or dialysis
84
Cauda equina syndrome
Manifests as bowel and bladder dysfunction with lower extremity weakness and sensory impairment related to cord ischemia - r/f includes supernormal doses of LA - maldistribution of LA within intrathecal space
85
Transient neurologic symptoms
Associated with intrathecal lidocaine Presents as burning, aching, cramp like pain in the low back and radiating down the thighs for up to five days post op Other risk factors include lithotomy and outpatient surgery
86
When was lidocaine discovered
1943 by nils Lofgren in sweden
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Labor epidural test dose lidocaine concentration
1.5% with epi 1:200,000
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Lidocaine and the ACLS algorithm
Why? Depress myocardial automaticity - class IB Dose? - 1-1.5 mg/kg IV/IO - 0.5-0.75 mg/kg (refractory) - 3 mg/kg total - 1-4 mg/min or 30-50 mcg/kg/min (maintenance infusion)
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EMLA cream
Eutetic mix of LA 1:1 lidocaine:prilocaine Don’t give - mucous membranes - broken skin - infants < 1 month - hx methemoglobinemia
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Why give lidocaine during induction
Decrease pain of prop Attenuate CV response to intubation Attenuate increase in ICP in patients with decreased compliance Dose on ideal body weight
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Lidocaine and pain of propofol
20 mg lidocaine in 10 mL with venous occlusion for 60 seconds
92
Attenuation of SNS with lidocaine
1.5 mg/kg IV administration 1-3 minutes prior to laryngoscopy
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Topical lidocaine (trachea)
Decreases emergence phenomenon aka coughing, sore throat, dysphonia LTA - administer 30 minutes prior to extubation for best effect Jelly Fill cuff with low-dose alkalized lidocaine (40mg) - seeps out over time - need 60 min minutes to achieve desired effect (add bicarbonate to increase non-ionized fraction) Or just more IV at end of case
94
Technique for adding alkalized lidocaine to the ETT tube
``` Achieve correct pressure using air Remove and record amount of air required Add 2ml lidocaine Add 1-2ml sodium bicarbonate Add saline to match cuff volume ``` USE MANOMETER Case has to last at least an hour
95
Airway block
Nebulized lidocaine =.4% lidocaine applied directly to oropharynx Transtracheal block - 4% lidocaine injected through the cricothyroid membrane Higher risk of aspiration because pt cannot tell if they are even swallowing or not
96
Lidocaine infusions
Used as part of multimodal analgesia Bolus: 1.5 mg/kg bolus dose Infusion: 2mg/kg/hr Shown to reduce post op pain and speed up return of bowel function in open and laparoscopic procedures Decreased pain and improve outcomes in prostatectomy, thoracic, and spine procedures Accumulation is a concern so monitor patients
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Cochrane’s review on lidocaine infusion
Quality of evidence is limited | Benefits uncertain
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Bier block
IV regional anesthesia Indicated for short procedures 25-50ml of 0.5% lidocaine injected into an IV distal to a tourniquet Onset time 5-10 minutes Tourniquet pain at 20 minutes
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Plasma concentration of lidocaine 1-5 ug/ml effects
Analgesia
100
Plasma concentration of lidocaine 5-10 ug/ml effects
``` Circumoral numbness Tinnitus Skeletal muscle twitching Systemic hypotension Myocardial depression ```
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Plasma concentration of lidocaine 10-15ug/ml effect
Seizures unconsciousness
102
Plasma concentration of lidocaine 15-25ug/ml effect
Apnea coma
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Plasma concentration of lidocaine >25ug/ml effect
CV depression
104
Liposomal local anesthetics: exparel
Injected directly into surgical site shown to reduce opioid requirements for up to 72 hours Bupivacaine combined with liposomal agent depofoam Lipid membranes separate chambers of bupivicaine in a honeycomb structure
105
Administration of exparel
Single dose infiltration only Admin with a 25g or larger bore needle Not to exceed 266mg (20ml 1.3% undiluted drug) - dilute up to 0.89 mg/ml (1:14 by vol) Invert vial multiple times to re-suspend particles Inject slowly via infiltration into surgical site with frequent aspiration Do not admin if its not white You will need some sort of adjunct to deliver with it because it is going to take a while to start working - but don’t mix with lidocaine because it will break down the liposome If you do mix it, use within 4 hours
106
Exparel what not to do
Don’t - mix with non-bupivacaine LAs - use for OB cervical blockade - give to patients under a8 - use for epidural/intrathecal - use for peripheral nerve block - administer if vial has been frozen or exposed to high temp Do - use caution for patients with hepatic disease
107
Adverse effects of exparel
>10% N/V | <10% dizzy, tachycardia, HA, somnolence, bradycardia, hypoesthesia, lethargy
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Cocaine
The original LA and the only one that is naturally occurring
109
How does cocaine cause SNS stimulation
Blocks monoamine transporter in the adrenergic system which blocks reuptake of catecholamines to cause vasoconstriction
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Cocaine use
Primarily used for topical anesthesia of nose and throat
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Max dose cocaine
5ml of 5% solution
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When should cocaine be used cautiously
Use cautiously with other epi containing solutions, MAOi’s, tricyclics