Local Anesthetics Flashcards
(80 cards)
1
Q
What was the first local anesthetic? When was it developed?
A
Procaine (1905)
2
Q
Clinical applications of local anesthetics:
A
- anesthesia
- analgesia
- acute and chronic pain management
- decrease perioperative stress
- improve perioperative outcomes
- treat cardiac dysrhythmias
- anti-inflammatory
3
Q
List the sections of a peripheral nerve from innermost to outermost:
A
- endoneurium
- perineurium
- epineurium
4
Q
Influx of which ion produces a neuronal action potential?
A
Na+
5
Q
Influx of which ion generates the wave of depolarization down a nerve axon?
A
Na+
6
Q
Resting membrane potential of a nerve:
A
-70mV
7
Q
How many nodes of Ranvier must be blocked to reliably interrupt impulse propagation?
A
3
8
Q
Define salutatory conduction:
A
in myelinated axons, the AP is conducted only at the nodes of Ranvier, skipping the distance between adjacent nodes
9
Q
Describe how LAs work:
A
- reversibly bind to voltage-gated Na+ channels in the nerve’s axon
- no entrance of Na+ into the cell
- no depolarization
- no propagation of the AP down the axon
10
Q
List the 3 other channels/receptors that local anesthetics block beyond their primary mechanism:
A
1) voltage-dependent K+ channels
2) L-type Ca2+ channels
3) some G-protein coupled receptors
11
Q
During which states do LAs preferably bind to Na+ channels?
A
activated & inactivated state
12
Q
Which portion of the LA diffuses through the skin/membrane? Which portion binds to the receptor in the Na+ channel?
A
- non-ionized/lipid soluble portion diffuses through the membrane
- ionized portion binds to the receptor inside the voltage-gated Na+ channel; this portion cannot penetrate the cell membrane
13
Q
What is the order in which nerve fibers are blocked?
A
- B
- C
- A-delta
- A-gamma
- A-beta
- A-alpha
(Beer & Cheese AnD A Game Are Better than An Apple)
14
Q
How does diameter of nerve fibers correlate to sensitivity?
A
smaller diameter = most sensitive (C fibers)
larger diameter = least sensitive (A-alpha fibers)
15
Q
How does myelin affect sensitivity?
A
more myelin = less sensitive
16
Q
What is the clinical order of loss of function?
A
Pain
Temperature
Touch
Proprioception
Skeletal muscle tone
(Pregnancy TEsts Take PRecise SKills)
17
Q
Axon diameter is (inversely/proportional) to LA resistance.
A
proportional
Larger diameter = more resistance
18
Q
Sensory & sympathetic nerves are blocked (first/last).
A
first
19
Q
Motor nerves are blocked (first/last).
A
last
20
Q
Define minimum effective concentration:
A
the minimum concentration of LA needed to produce a conduction block of an impulse
*different for different nerve fibers (larger fibers require higher concentrations)
21
Q
How does tissue pH affect Cm?
A
- increased tissue pH –> decreased Cm
- decreased tissue pH –> increased Cm
(why a typical dose is less effective in acidic/infected tissue)
22
Q
List bodily tissues from highest to lowest blood flow:
I Think I Can Please Everyone But Susie & Sally
A
Intravenous
Tracheal
Intercostal
Caudal
Paracervical
Epidural
Brachial plexus
Subarachnoid
Subcutaneous
23
Q
How are ester LAs metabolized? Excreted?
A
- metabolized: plasma esterases
- excreted: renal
24
Q
How are amide LAs metabolized? Excreted?
A
- metabolized: hepatic enzymes
- eliminated: renal
25
LAs are weak (acids/bases), which means they are (more/less) nonionized at physiologic pH.
- weak bases
- more nonionized at physiologic pH
26
When the pKa of a drug is closer to physiologic pH, more of the drug exists as...
lipid-soluble, uncharged, base
27
Compare the pKa, ionization, and onset of Lidocaine and Procaine:
Lidocaine
- pKa 7.9
- 3:1 ionized:unionized
- 2-3 min onset
Procaine
- pKa 8.9
- 32:1 ionized:unionized
- 6-12 min onset
28
How is onset related to pKa?
the closer the drug is to physiologic pH, the more of the drug exists in the unionized/active state and the faster it works
29
Which factors, in addition to pKa, affect onset?
dose & concentration
(higher dose/concentration = faster onset d/t more molecules given)
30
Which LA is an outlier when it comes to pKa and onset?
Choloroprocaine;
really high pKa so should have a slower onset BUT it is not very potent so a large dose must be given --> more molecules --> rapid onset
31
Describe how LAs work in infected tissue?
infected tissue has a lower pH; many LAs are bases and thus more ionized/less active at low pH; poor penetration of nerve tissue and less effective nerve block
32
How is potency related to lipid solubility?
More lipid soluble the drug, the easier it is to diffuse through the epineurium
33
How does the vasodilating effect of LA affect potency?
greater vasodilating effects = faster vascular uptake = less potent as the drug is not sequestered to the area it was injected into.
34
How is duration of action of LAs related to protein binding?
- drug bound to tissue proteins acts as a reservoir that extends the DOA
- LAs = weak bases that primarily bind to AAG (secondary binding to albumin)
35
What other characteristics of LAs affect duration of action?
- lipid solubility (more soluble = longer DOA)
- vasodilating effect (increases rate of vascular uptake = shorter DOA)
- addition of vasoconstrictors (decreases ability of drugs to diffuse away = longer DOA)
36
Which LAs have low potency and short DOA?
Procaine (Novocaine)
Choloroprocaine (Nesacaine)
37
Which LAs have intermediate potency and DOA?
Mepivacaine (Carbocaine)
Lidocaine (Xylocaine)
38
Which LAs have high potency and a long DOA?
Bupivacaine (Marcaine)
Ropivacaine (Naropin)
Tetracaine (Pontocaine)
39
2 structural classes of LAs:
- aminoester
- aminoamide
40
How do you differentiate between the 2 structural classes of LAs?
- amino esters has one "i" and one "i" in the generic names
- amino amides has 2 "i"s and 2 "i"s in the generic names
41
Differences in metabolism of 2 classes of LAs:
amino esters = hydrolysis in the plasma
amino amides = biotransformation in the liver
42
Which structural class of LAs is more stable and associated with fewer allergic reactions?
amino amides
43
4 facts about Procaine:
1) amino ester LA
2) earliest developed injectable LA
3) unstable, potential for allergic reactions
4) spinal procaine --> increased nausea
44
4 facts about Tetracaine:
1) amino ester LA
2) commonly used for spinal anesthesia
3) more slowly metab than Procaine/Choloroprocaine
4) rarely used for epidurals or PNBs
45
Which LA is rarely used for epidurals or PNBs? Why?
Tetracaine
- slow onset
- profound motor blockade
- potential toxicity
46
4 facts about Chloroprocaine:
1) amino ester LA
2) popular epidural anesthetic d/t short duration
3) rapid hydrolysis = minimal risk to fetus
4) often used to quickly load epidural for crash C-sections
47
What characteristic is important when considering drugs being used in the intrathecal space?
preservative-free
48
4 facts about Lidocaine:
1) amino amide LA
2) most commonly used & most versatile
3) potential neurotoxicity (cauda equina syndrome) w/ continuous spinal use
4) Transient Neurological Symptoms (TNS) with spinal use
49
4 facts about Mepivacaine:
1) amino amide LA
2) less vasodilation than other LAs (slightly longer DOA)
3) similar uses as Lidocaine except ineffective topically
4) lower incidence of TNS than Lidocaine
50
4 facts about Prilocaine:
1) amino amide LA
2) metabolite = ortho-toludine
3) rapid metabolism
4) 40% less CNS toxicity than Lidocaine
51
Effects of the metabolite of Prilocaine:
ortho-toludine
- converts Hgb to methemoglobin
- may spontaneously subside
- OR may be reversed with Methylene Blue
52
Prilocaine is rapidly metabolized & has low acute toxicity (40% less than Lidocaine). Why is it not widely used?
metabolite (ortho-toludine)
53
4 facts about Bupivacaine:
1) amino amide LA
2) most commonly used LA for labor epidurals and PO pain mgmt
3) also used for PNBs and spinals
4) SE = refractory cardiac arrest
54
Describe how Bupivacaine can lead to refractory cardiac arrest:
- prolonged recovery from Bupivacaine blockade makes it more potent in depressing the maximum upstroke velocity of cardiac AP and ventricular cardiac muscle
*dilute solutions for epidural, small doses for spinal reduce this risk
55
4 facts about Ropivacaine:
1) amino amide LA
2) S(-) enantiomer of the homolog of Bupiv & Mepiv
3) less pronounced motor block, C fibers preferentially blocked, may produce greater differential block
4) lower lipid-solubility = less potent than Bupiv
$$$$$
56
4 facts about Levobupivacaine:
1) amino amide LA
2) S (-) enantiomer of Bupiv
3) less cardiotoxic than Bupiv
4) no advantage over Bupiv r/t differential blockade
57
When is it most advantageous to utilize Ropivacaine or Levobupivacaine?
cases in which relatively high doses of anesthetic are administered
58
Patients who receive Exparel should not receive any other form of Lido for ___ hours
96 hours
59
Describe how Liposomal Bupivacaine works:
- Bupivacaine is encapsulated by liposomes
- nearly identify to cell membranes (made of phospholipids)
- deliver drug via diffusion
60
Dose/onset/duration of Exparel:
- dose = max of 266mg
- onset = 15min-2hours
- DOA = up to 72 hours
61
What % solution is a solution containing 1 gram of drug per 1 mL of fluid?
100% solution
62
What % solution is a solution containing 10 mg/mL?
1%
1000mg in 100mL
1g in 100mL
63
What % solution is a solution containing 1mg/mL?
0.1%
100mg in 100mL
0.1g in 100mL
64
What % is a solution with a 1:100 dilution?
1% solution
65
How many mg are in 1 mL of a 0.6% solution?
6mg/mL
66
Describe tumescent anesthesia:
- plastic surgeon technique during liposuction
- subcutaneous injection of large volumes of dilute LA + epi
- may peak up to 20 hours after infusion
67
List the potential adverse effects of LAs:
- allergic reaction
- direct neurotoxicity
- intraneural injection
- local anesthetic systemic toxicity (LAST)
- methemoglobinemia
- transient neurologic syndrome (TNS)
68
Allergic reactions to LAs:
- very uncommon
- more common with amino esters d/t metabolism to paraminobenzoic acid (PABA)
- cross sensitivity between groups is absent
69
Describe cauda equina syndrome (CES):
- bowel/bladder dysfunction with bilat LE weakness and sensory impairment
- d/t supranormal doses of intrathecal LA OR maldistribution of LA spread within intrathecal space
- Chloroprocaine (large dose)
- Lidocaine (continuous spinal anesthesia)
70
Describe Transient Neurologic Symptoms (TNS):
- back & LE pain x5 days postop
- burning, aching, crampy, radiating pain in anterior & posterior thighs
- d/t spinal Lidocaine?
- surgical positioning?
- treat symptomatically and include NSAIDS
71
Describe methemoglobinemia:
- Ferrous Hgb (Fe2+) oxidized to Ferric form (Fe3+)
- reduced O2 carrying capacity
- shifts oxyhemoglobin curve to the L
- common culprits: Bezocaine, Procaine, Dapsone, Nitrites
- treat with methylene blue (1-2mg/kg) over 3-10 min
- level >70 may need transfusion or dialysis
72
Clinical signs of methemoglobinemia:
- hypoxia not improved with increased FiO2
- abnormal blood coloration
- saturation gap (blood gas paO2 is OK but low pulse ox)
- new-onset cyanosis or hypoxia after ingestion of an oxidative agent
73
Causes of LAST:
- inadvertent intravascular injection of LA
- absorption of large amounts of LA
- continuous infusion/accumulation of drug + metabolites x several days
74
Effects of LAST:
- depression of voltage-gated Na+, K+, and Ca2+ channels in excitable tissues of CNS and cardiac system
- depression of inhibitory CNS neurons --> seizures
- decreased cardiac contractility, several arrhythmias
75
Describe the progression of symptoms of LAST:
- numbness of tongue (2-4mcg/mL)
- dizziness/tinnitus (4-6mcg/mL)
- visual problems (6-8mcg/mL)
- muscle cramps (8-10mcg/mL)
- seizures (12-16mcg/mL)
- decreased consciousness (16-18mcg/mL)
- coma (16+mcg/mL)
- respiratory/cardiovascular arrest (24+mcg/mL)
76
LAST treatment:
- stop injecting the LA
- lipid emulsion therapy
- manage airway
- control seizures
- treat hypotension & bradycardia
77
How does addition of opioids to LA affect blocks?
- increased duration
- increased quality of surgical anesthesia & analagesia
78
How does addition of Dexamethasone affect blocks?
increases duration
79
How does addition of clonidine or dexmedetomidine affect blocks?
- multiple sites of action
- increase duration of block
- increase anesthesia
80
How does bicarbonate affect blocks?
- increases % of nonionized drug
- increases membrane penetration
- decreases onset time
- reduces pain during SQ infiltration
