Local Anesthetics Flashcards
What was the first local anesthetic? When was it developed?
Procaine (1905)
Clinical applications of local anesthetics:
- anesthesia
- analgesia
- acute and chronic pain management
- decrease perioperative stress
- improve perioperative outcomes
- treat cardiac dysrhythmias
- anti-inflammatory
List the sections of a peripheral nerve from innermost to outermost:
- endoneurium
- perineurium
- epineurium
Influx of which ion produces a neuronal action potential?
Na+
Influx of which ion generates the wave of depolarization down a nerve axon?
Na+
Resting membrane potential of a nerve:
-70mV
How many nodes of Ranvier must be blocked to reliably interrupt impulse propagation?
3
Define salutatory conduction:
in myelinated axons, the AP is conducted only at the nodes of Ranvier, skipping the distance between adjacent nodes
Describe how LAs work:
- 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
List the 3 other channels/receptors that local anesthetics block beyond their primary mechanism:
1) voltage-dependent K+ channels
2) L-type Ca2+ channels
3) some G-protein coupled receptors
During which states do LAs preferably bind to Na+ channels?
activated & inactivated state
Which portion of the LA diffuses through the skin/membrane? Which portion binds to the receptor in the Na+ channel?
- 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
What is the order in which nerve fibers are blocked?
- B
- C
- A-delta
- A-gamma
- A-beta
- A-alpha
(Beer & Cheese AnD A Game Are Better than An Apple)
How does diameter of nerve fibers correlate to sensitivity?
smaller diameter = most sensitive (C fibers)
larger diameter = least sensitive (A-alpha fibers)
How does myelin affect sensitivity?
more myelin = less sensitive
What is the clinical order of loss of function?
Pain
Temperature
Touch
Proprioception
Skeletal muscle tone
(Pregnancy TEsts Take PRecise SKills)
Axon diameter is (inversely/proportional) to LA resistance.
proportional
Larger diameter = more resistance
Sensory & sympathetic nerves are blocked (first/last).
first
Motor nerves are blocked (first/last).
last
Define minimum effective concentration:
the minimum concentration of LA needed to produce a conduction block of an impulse
*different for different nerve fibers (larger fibers require higher concentrations)
How does tissue pH affect Cm?
- increased tissue pH –> decreased Cm
- decreased tissue pH –> increased Cm
(why a typical dose is less effective in acidic/infected tissue)
List bodily tissues from highest to lowest blood flow:
I Think I Can Please Everyone But Susie & Sally
Intravenous
Tracheal
Intercostal
Caudal
Paracervical
Epidural
Brachial plexus
Subarachnoid
Subcutaneous
How are ester LAs metabolized? Excreted?
- metabolized: plasma esterases
- excreted: renal
How are amide LAs metabolized? Excreted?
- metabolized: hepatic enzymes
- eliminated: renal
LAs are weak (acids/bases), which means they are (more/less) nonionized at physiologic pH.
- weak bases
- more nonionized at physiologic pH
When the pKa of a drug is closer to physiologic pH, more of the drug exists as…
lipid-soluble, uncharged, base
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
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
Which factors, in addition to pKa, affect onset?
dose & concentration
(higher dose/concentration = faster onset d/t more molecules given)
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
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
How is potency related to lipid solubility?
More lipid soluble the drug, the easier it is to diffuse through the epineurium
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.
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)
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)
Which LAs have low potency and short DOA?
Procaine (Novocaine)
Choloroprocaine (Nesacaine)
Which LAs have intermediate potency and DOA?
Mepivacaine (Carbocaine)
Lidocaine (Xylocaine)
Which LAs have high potency and a long DOA?
Bupivacaine (Marcaine)
Ropivacaine (Naropin)
Tetracaine (Pontocaine)
2 structural classes of LAs:
- aminoester
- aminoamide
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
Differences in metabolism of 2 classes of LAs:
amino esters = hydrolysis in the plasma
amino amides = biotransformation in the liver
Which structural class of LAs is more stable and associated with fewer allergic reactions?
amino amides
4 facts about Procaine:
1) amino ester LA
2) earliest developed injectable LA
3) unstable, potential for allergic reactions
4) spinal procaine –> increased nausea
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
Which LA is rarely used for epidurals or PNBs? Why?
Tetracaine
- slow onset
- profound motor blockade
- potential toxicity
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
What characteristic is important when considering drugs being used in the intrathecal space?
preservative-free
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
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
4 facts about Prilocaine:
1) amino amide LA
2) metabolite = ortho-toludine
3) rapid metabolism
4) 40% less CNS toxicity than Lidocaine
Effects of the metabolite of Prilocaine:
ortho-toludine
- converts Hgb to methemoglobin
- may spontaneously subside
- OR may be reversed with Methylene Blue
Prilocaine is rapidly metabolized & has low acute toxicity (40% less than Lidocaine). Why is it not widely used?
metabolite (ortho-toludine)
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
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
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
$$$$$
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
When is it most advantageous to utilize Ropivacaine or Levobupivacaine?
cases in which relatively high doses of anesthetic are administered
Patients who receive Exparel should not receive any other form of Lido for ___ hours
96 hours
Describe how Liposomal Bupivacaine works:
- Bupivacaine is encapsulated by liposomes
- nearly identify to cell membranes (made of phospholipids)
- deliver drug via diffusion
Dose/onset/duration of Exparel:
- dose = max of 266mg
- onset = 15min-2hours
- DOA = up to 72 hours
What % solution is a solution containing 1 gram of drug per 1 mL of fluid?
100% solution
What % solution is a solution containing 10 mg/mL?
1%
1000mg in 100mL
1g in 100mL
What % solution is a solution containing 1mg/mL?
0.1%
100mg in 100mL
0.1g in 100mL
What % is a solution with a 1:100 dilution?
1% solution
How many mg are in 1 mL of a 0.6% solution?
6mg/mL
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
List the potential adverse effects of LAs:
- allergic reaction
- direct neurotoxicity
- intraneural injection
- local anesthetic systemic toxicity (LAST)
- methemoglobinemia
- transient neurologic syndrome (TNS)
Allergic reactions to LAs:
- very uncommon
- more common with amino esters d/t metabolism to paraminobenzoic acid (PABA)
- cross sensitivity between groups is absent
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)
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
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
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
Causes of LAST:
- inadvertent intravascular injection of LA
- absorption of large amounts of LA
- continuous infusion/accumulation of drug + metabolites x several days
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
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)
LAST treatment:
- stop injecting the LA
- lipid emulsion therapy
- manage airway
- control seizures
- treat hypotension & bradycardia
How does addition of opioids to LA affect blocks?
- increased duration
- increased quality of surgical anesthesia & analagesia
How does addition of Dexamethasone affect blocks?
increases duration
How does addition of clonidine or dexmedetomidine affect blocks?
- multiple sites of action
- increase duration of block
- increase anesthesia
How does bicarbonate affect blocks?
- increases % of nonionized drug
- increases membrane penetration
- decreases onset time
- reduces pain during SQ infiltration
