Local Anesthetics Flashcards
Conduction velocity is increased by nerve:
Myelination and Diameter
A Delta Fibers
Fast pain
Temperature
Touch
A Gamma Fibers
Skeletal Muscle Tone
A Beta Fibers
Touch
Pressure
A Alpha Fibers
Skeletal Muscle Motor
Proprioception
B Fibers
Preganglionic ANS Fibers
C Fibers
SNS: Postganglionic ANS fibers
Dorsal Root: Slow Pain, Temperature, Touch
What is Cm?
The minimum effective concentration
Similar to ED50 for IV anesthetics or MAC for inhaled anesthetics
Fibers that are easily blocked have a ______ cM
Fibers that are resistant to block have a _____ cM
Easy: Low
Resistant: High
Local anesthetics inhibit nerve fibers in what order?
B
C
Small A
Large A
Cm is reduced by:
Higher tissue pH
High Frequency of Nerve Stimulation
Local anesthetics reversibly bind to:
the alpha subunit of voltage-gated sodium channels
When can local anesthetics bind to the alpha subunit?
Only during active and inactive states. They cannot bind during the resting state.
What is a phasic blockade?
Since local anesthetics cannot bind with alpha subunits during the resting state, the more frequently a nerve is depolarized, the more quickly it will be blocked
How do local anesthetics impact the resting membrane potential?
They don’t. They only affect nerve conductance.
Potassium control resting membrane potential
Calcium controls threshold potential
What is the resting membrane potential for peripheral nerves?
-70
______ is the primary determinant of resting membrane potential
serum K level
How do serum potassium levels impact nerve resting membrane potentials?
Decreased serum potassium → RMP more negative (harder to depolarize)
Increase serum K → RMP more positive
(easier to depolarize)
What is the threshold potential of nerve fibers?
-55 mV
How does serum Ca impact threshold potential?
Decreased Ca → TP more negative
Increased Ca → TP more positive
When the RMP is close to the TP, what happens?
The cell is easier to depolarize
When the RMP is further from the TP, what happens?
The cell is harder to depolarize
A cell repolarized when:
K leaves the cell
Cl enters the cell
What determines a local anesthetic’s speed of onset?
Its pKa
What determines a local anesthetic’s potency?
Its lipophilicity
Local anesthetics are weak ______
bases
When local anesthetics are injected, they dissociate into:
an uncharged base
AND
a conjugate acid
How much local anesthetics dissociates in tissues?
Since all of them have pKa’s that are higher than 7.4, more than 50% will dissociate
When local anesthetics ionize in the tissues, which portion enters the cell?
The uncharged base
What happens once the uncharged base enters the axoplasm?
Since the pH is lower, it picks up a H+ ion and becomes a conjugate acid
It is this conjugate acid that binds to the alpha subunit on the INSIDE of the axon membrane
A true local anesthetic allergy is more likely with a _____ than a ______
more likely with an ester than an amide because esters are derivatives of PABA
A patient with an allergy to an ester can receive an amide so long as:
the preparation is preservative free (because that may have been what caused the allergy rather than the ester itself)
Which structure in a local anesthetic determines give it lipophilicity?
Which structure in a LA is hydrophilic?
Which LA structure determines its drug class?
What determines the duration of onset of an LA?
Its protein binding capacity
How do local anesthetics affect vasculature?
At subclinical doses, they are vasoconstrictors because they inhibit nitric oxide
at clinical doses, they are vasodilators
Which LA is exception to the effects of LAs on vasculature?
Cocaine
It inhibits NE reuptake and ALWAYS causes vasoconstriction, no matter what the dose is
Which class of LA has higher pKa’s?
All esters have higher pKa values than amides
There is only one LA that does not undergo protein binding:
Chloroprocaine
There is only one LA with a pKa that is well below physiologic pH:
Benzocaine
pKa 3.5
What is special about benzocaine?
It is non-ionized at physiologic pH, and yet it still has anesthetic properties
Usually it’s only the ionized portion of LAs that can interact with the sodium channel
Which serum proteins do LAs bind to?
Prefer Alpha - 1 - acid glycoproteins
but will also bind to albumin
How is cocaine metabolized?
Both pseudocholinesterases and hepatic
What factors increase the risk of CNS toxicity from lidocaine?
What determines the extent of cardiotoxicity from increased LA serum levels?
Degree of affinity for the sodium channel receptor
Rate of dissociation from the receptor during diastole
This is why drugs that have a high affinity (like bupivicaine) carry a higher risk of cardiac toxicity
The risk of cardiac toxicity from bupivicaine is increased by:
calcium channel blockers
Digitalis
Pregnancy
Beta Blockers
What drug should be given to a patient with a cocaine overdose?
NOT a beta blocker, since this will cause unopposed Alpha 1 activity
Preferably nitroglycerin or another straight vasodilator, or labetalol which has alpha 1 blocking capabilities
How do you calculate the lipid emulsion BOLUS to give to a patient with suspected LAST?
1.5 ml/kg
Which drugs should NOT be given during a LAST code?
beta blockers and calcium channel blockers
They enhanced cardiac disturbances
Which ACLS drugs should be avoided in LAST patients?
Vasopressin
Lidocaine (duh)
Procainamide
Epinephrine
How do you calculate the lipid emulsion INFUSION for a patient in LAST?
0.25 ml/kg/min
Can be increased to 0.5 if ineffective
How many times can you repeat the lipid bolus?
Twice
What is the recommended max dose of lipid emulsion therapy?
10 ml/kg in the first 30 min
What is the most common cause of death from liposuction?
PE
What is the maximum amount of lidocaine that can be used in tumescent anesthesia?
50-55 mg/kg
When is general anesthesia recommended for patients undergoing liposuction?
If 2-3 L of tumescent anesthesia is going to be needed
Methemoglobin is formed when:
the iron on the hemoglobin molecule becomes oxidized to Fe3+ decreasing the oxygen carrying capacity of the molecule
Which LAs can lead to methemoglobinemia?
Benzocaine
EMLA
Cetacaine
Besides LAs, what other drugs can cause methemoglobinemia?
Nitric Oxide
Sulfonamides
Nipride
Nitroglycerin
Phenytoin
What are the classic manifestations of methemoglobinemia?
The blood takes on a chocolate color
A decreased SpO2 in the setting of a normal PaO2
Slate grey cyanosis
How does methemoglobinemia effect SpO2 waveforms?
Tends to push it toward 85%
Which patients should NEVER receive methylene blue?
G-6-PD
They need an exchange transfusion instead
What is the treatment for methemoglobinemia?
Methylene Blue
Are neonates at a higher or lower risk of methemoglobinemia?
Higher
Their blood cells have very low levels of methemoglobin reductase
Which direction does methemoglobinemia shift the dissociation curve?
To the left
BECAUSE
Methemoglobin can’t bind O2, but that actually increases the affinity of HgbA for O2
This means the HgbA hangs onto O2, leading to tissue hypoxia and metabolic acidosis
Myelinated nerve fibers are surrounded by ____ in the PNS and _____ in the CNS
PNS: Schwann Cells
CNS: Oligodendrocytes
Which two organ systems are most susceptible to effects from systemic absorption of local anesthetics?
The heart and the brain, for two reasons:
- They are extremely vascular and therefore receive a lot of the drug
- They are both highly electrical, and they’re more susceptible to sodium ion changes
The potential for CNS toxicity correlates directly with:
the potency of the LA
Does CV toxicity occur at higher or lower plasma levels than CNS toxicity?
Way higher. Generally you’ll see CNS effects at much lower plasma concentrations
Which local anesthetics are most likely to cause cardiovascular collapse?
All LAs cause hypotension, dysrhthmias, and myocardial depression
BUT
the most potent agents (bupivacaine, ropivacaine, levobupivacaine) tend to cause the devastating outcomes
How do plasma concentrations of local anesthetics impact the pulmonary vasculature?
In general, LAs at high doses cause vasodilation. BUT in the pulmonary vasculature, high dose LA results in severe pulmonary hypertension
Why is bupivacaine so cardiotoxic?
It has a greater affinity for binding with resting and inactivated sodium channels than lidocaine
Bupivacaine dissociates off the sodium channel much more slowly than lidocaine
Why is it so important to secure the airway if LAST occurs?
To prevent further exacerbation of the toxicity by hypoxemia, hypercapnea, and acidemia
If you give a benzodiazepine to stop a seizure from LAST and it isn’t effective, what should be the next drug given?
An NMBA
It won’t stop the seizure but it will facilitate pulmonary ventilation and disrupt the muscular activity, preventing lactic acidosis which would worsen LAST
