Local Anesthestics Flashcards
Conduction - Myelinated vs. Unmyelinated Fibers:
-Propogation of impulses is ___ in both.
\_\_\_ = impulses travel along the length of the fiber in a continuous fashion (spans entire length) \_\_\_ = conduction is "\_\_" so fast (50x) that it appears as if impulses leap from one node of Ranvier (no myelin) to the next
-similar
Unmyelinated fibers
Myelinated fibers
“saltatory”
*Both rely on movement of ___ but a little differently.
myelinated - “jumping” from node to node
unmyelinated - spans entire length
Local can’t get to the nerve at the ___. In order for a local to really block a nerve it has to block at least ___ if not ___ or will not be effective.
ions
myelinated section
2 nodes, 3
Nerve Fibers:
- The velocity an impulse travels is proportional to the ___.
- The ___ the ___, the higher the conduction velocity.
- Fibers classified according to ___.
- 3 Types???
diameter of the fiber
larger the diameter
diameter
A, B and C fibers
Receptors fluctuating btw active and inactive states, agonist or antagonist will hold it in a certain conformation. Locals keep the ion channel in the ___.
Cell or neuronal membrane important - allows us to develop an ___ across the 2 sides of the membrane (___ more permeable in a resting neuron). ___ can not really move until channels open. Electric charge (negative charge inside becomes too strong) and ___ will no longer leak out.
inactivated-closed state electrochemical gradient potassium sodium potassium
Nerve Fibers that sense pain, temperature and touch and their differences?
What nerve fiber is associated with the preganglionic autonomic?
A delta fibers - fast pain
C fibers - dull pain, POSTganglionic autonomic, no myelin
B-fibers
Differential Blockade:
- Clinically, the sensitivity of a peripheral nerve to local anesthetic is ___ related to size. Why you see __-first, __-second, __-last.
- HOWEVER THIS IS NOT A CAUSE AND EFFECT!
- In a lab, larger fibers __ and __ are actually more sensitive to local anesthetics than the __ fibers which are unmyelinated and small.
inversely autonomic blockade sensory motor A delta A gamma C fibers
Differential Blockade continued:
- Difference btw clinical observation and research theories =
- anatomic issues (__ found deeper in nerve bundles - harder for the LA to reach)
- variable activity in different nerves - __ fire at higher frequency)
(ex: frequency dependent blockade) - variable ___ mechanisms
- larger nerves
- pain fibers
- variable ion channel mechanisms
Differential Blockade:
___ are the easiest fibers to block, then sensory, then motor. Will see ___ first.
But in lab this is the opposite - easier to block ___.
***Leading theory is the ?
Autonomic
BP change
large A fibers
***anatomy and the location of the nerves
Spread of Local Anesthetic-LOCATION, LOCATION, LOCATION:
- Outer surface of a peripheral nerve is known as the ___ (usually more ___ structures)
- Inner surface known as ___ (these fibers usually serve more ___ structures)
- THE SEQUENCE OF ONSET AND RECOVERY FROM A LA BLOCK IN A MIXED PERIPHERAL NERVE RELIES HEAVILY ON ???
- This factor is much more important than the ___ of the nerve fiber to local anesthetics.
-mantle proximal -core distal -WHERE IT IS LOCATED -inherent sensitivity
Local anesthetic has the most access to the ___ nerves, LA hits the nerves on the outer surface aka the mantle of the bundle and then need more LA to penetrate into core where you have the ___.
peripheral
larger fibers
Achieve deeper block (loss of touch and pressure and then finally motor blockade) by giving more, but going for a ___.
higher concentration (Ex: lidocaine sensory go for 1%, even deeper block go for 2%)
The difference in the concentration of positive and negative ions when the cell is at rest? Approximately?
Resting Membrane Potential
-70 to -90 millivolts
The Action Potential:
- ___ state = ___ space has a relatively ___ compared to the ___ space.
- __ = result of impermeability of the resting cell membrane to ___ outside the cell.
*Polarized state intracellular negative charge extraceullular *Polarity sodium
Action Potential:
- Membrane is more permeable to ___, BUT as ___ exits the cell, a higher proportion of negative ions remain.
- ___ becomes more positive (___ ions) and the electrical gradient favors movement of ___ back into the cell.
- IT IS THIS MOVEMENT OF ___ THAT ESTABLISHES AND MAINTAINS ???
-Potassium potassium -Extracellular fluid potassium ions potassium potassium Resting membrane potential (RMP)
Action Potential:
An action potential is a ___ of the membrane, lasting ___.
- Occurs when a specific physiologic stimulus is received by the ___.
- Stimuli nerve receptors respond to = ????
rapid depolarization
1-2 milliseconds
nerve receptor
mechanical, chemical, thermal and pressure
Action Potential:
- Stimulus causes ___ of the nerve membrane to open, ___ rushes into the cell, causing the ___ of the membrane.
- Influx of sodium causes membrane potential to increase to __ to __.
- As permeability of ___ decreases, ___ permeability increases –> efflux of ___ from the cell and return to ___.
sodium channels sodium rapid depolarization \+20 to +40 millivolts sodium potassium, potassium RMP
___ = a schwann cell wraps itself around the axon several times, enveloping the axon in a myelin sheath. (speeds conduction)
___ = a single schwann cell surrounds several axons
Myelinated nerve fiber
Unmyelinated nerve fiber - not entirely unmyelinated, but not enough to the degree to provide fast conduction
Blockade of Nerve Conduction by Local Anesthetics:
Bind the ___, binds when it is in the ___ (no AP will occur, sodium channel blocked no longer able to conduct ions).
-This blocks impulse conduction during the ___ of the action potential.
sodium channel on the alpha subunit
inactivated closed state
depolarization phase
Locals only change the ___, they do not change the resting membrane potential or the threshold itself - JUST THE ??? With local do not reach threshold, will see it rise up just under threshold line.
ability to reach threshold
ABILITY TO REACH IT
Good strong binding in ___. An ___ is much easier to block than a ___ not firing at a fast rate. ___ and ___ firing at a more frequent rate normally compared to a ___, possibly why they are blocked first.
-___ does play a part.
- inactivated closed state
- active nerve
- resting nerve
- Autonomic and sensory
- motor
- Lipid solubility
Aminoamides vs. Aminoesters:
Distinction is important because they are ___ - with ___ have much more of an issue with allergies!!!
metabolized differently
esters
___ = has only been approved for bunionectomy and hemorrhoidectomy, no other dosing available for any application because it has not been approved! Lots of concern about toxicity because safe doses have not been established for other surgeries.
- This is a bupivacaine extended release ___ injection. FDA approved.
- Dose depends on?
- Max dose?
Exparel
- liposome injection
- surgical site
- 266 mg or 20 mL
Minimum Blocking Concentration = ?
- this is a conceptual issue, no values exist that guide our anesthetics)
- minimal concentration to actually block a nerve!
- this is very variable therefore no values (unlike MAC).
- Surgeons do not understand that local anesthetics are ___! If you give a max dose of lidocaine, can’t use anymore locals period.
Cm
-Additive!
Cm depends on (4)?
- nerve fiber diameter
- tissue pH
- frequency of nerve stimulation
- potency of particular LA
Distance btw Nodes of Ranvier in myelinated fibers contributes to?
-Ability to block certain nerves easier than others
-the internodal distance increases with?
Differential nerve block
-fiber diameter
___ gives you some really nice sensory block with limited motor block! This is great for post-op pain control-patient can still move! Also for woman in labor!
This is a reason this drug remains popular despite its toxicity.
Bupivacaine
Absorption of locals is not something we want to occur quickly, this absorption will limit the DOA and increase potential toxicity. Most important factor is ___, also the ___ (ionization?), ___ (___ will want to stay in the tissues), highly ___ will stay in the tissues longer.
blood flow to the tissue physiologic pH lipid solubility very lipid soluble protein bound
- ___ tissues tend to not absorb locals as well
* ___ and ___ much higher risk of toxicity!
Cold tissues
Pregnant and elderly
Do ionized or non-ionized drugs cross a lipid membrane?
non-ionized
- ___ = important for metabolism and for allergy risk
- ___ = this is the only ester with some liver metabolism. All of the other esters are metabolized by ___, by ___ and ___. Ester class = fast metabolism! This is nice because it limits the toxicity potential (worried about the brain and the heart).
-Amides rely on ___ which tends to be more cumbersome.
- intermediate chain
- Cocaine
- ester hydrolysis
- nonspecific esterases
- acetylcholinesterase
- hepatic metabolism
___ anesthetics are more potent, thus more toxic and have a longer DOA than do ___ anesthetics.
Highly lipid soluble
water soluble
Enantiomers of a chiral drug may vary in terms of the pharmacokinetics, pharmacodynamics and toxicity.
Ex: ___ and ___ (racemic) vs. ___ and ___(pure S enantiomer, more expensive but better with toxicity)
Bupivacaine and Mepivacaine
Ropivacaine and Levo-bupivacaine
Physiologic pH relatively ___ to local anesthetics because their pka is above 7.4. The higher you are the higher the mismatch, pka of 9 = ___.
Make these ___ by bringing down the pH of the solution - packaged in acidic formulations. However, as soon as the drug is injected it will behave like a ___. Also packaged in acidic formulations because ___ degrades in higher pH and we add this to a lot of our locals.
acidic more ionized soluble weak base epinephrine
If you mix ___ with any other local it can change the pharmacokinetics of ___ and really increase the toxicity (ex: mixing it with lidocaine or bupivacaine).
Exparel
Exparel
pH at which a drug exists?
Ideal pKa?
pKa
7.4
LA Onset:
- Because the __ crosses the lipid rich nerve cell membrane
- The __ of the local anesthetic solution and the __ determine proportion of drug in the __ state.
- In areas of high/normal pH values the rate and amount of absorption is __; conversely at lower pH the rate and amount of absorption are __.
- Non-ionized form
- pH
- pKa
- non-ionized state
- higher
- lower
Onset and pKa:
___ is the exception to the rule pKa = 8.7, with a fast onset. This is because we are giving much higher concentrations (2-3%) of this drug d/t its low potency. Thus giving more molecules which increases the chance of these molecules crossing the membrane.
Chloroprocaine
- Babies tend to have lower pHs than their mothers, particularly during labor. Weak base (local) goes across will now re-equilibrate and because baby is much more acidic than mom, drug will become much more __ = __.
- Adding __ = change the local pH to more alkalotic - increases onset, enhances block depth, and increases the spread of the block.
Ionized
Ion trapping
Bicarb
Never give a LA in an ___ - will have lower pH and much more of the drug will be ionized, no drug will cross, not effective.
Infected tissue
Onset most influenced by = ?
Potency most influenced by = ?
DOA most influenced by = ?
Highly potent LAs???
pKa
Lipid solubility
Protein binding
Bupivacaine
Etidocaine
Tetracaine
Duration of Action:
- Most important factor?
- Intrinsic vasodilator activity -
- __ = fast onset but intrinsic dilator activity, gets carried away, add epinephrine to counteract
- __ = fast onset with no intrinsic vasodilator activity, good to give to patients you would not want to give epinephrine to (ex: diabetics)
- Protein binding
- Lidocaine
- Mepivacaine
Duration of Action:
*??? = taken up pretty significantly in the first pass by the lung. Buffer with these drugs, huge bolus, lung can take up some.
*??? = also taken up by the lungs - may not have as much of a buffer if patient is also on these drugs.
Bupivacaine Lidocaine Prilocaine Fentanyl Sufentanil Propranolol
- Tissue richest in esterases is the __. Esters are metabolized everywhere, we have esters in the liver and the plasma.
- Use __ with atypical cholinesterase issues - concerned of high risk of toxicity in these patients.
- liver
- amide
___ is the most important drug to stick to the max dose - it can be catastrophic!
*Need to be able to do these calculations in your head on the spot!
*Use ideal body weight plus 20% with an obese patient. Normal weight patient use ideal body weight.
Depends, if dosing an intercostal block will probably just stick to ideal body weight.
Bupivacaine
Local Anesthetic Toxicity - CNS:
What do you do if that patient has a seizure?
-Administer __ - usually __ (can also give __). Propofol may be a disadvantage due to CV issues.
Seizure - AP after AP, using tons of ATP and CO2 being produced. This person really needs a supportive airway, oxygen and have benzos on board!
Benzodiazepine
midazolam
ativan
Local Anesthetic Toxicity - Treatment of CV collapse:
Can compete for Bupivacaine with __, can have really good outcomes.
If hospital does not stock this, Carrie would not perform blocks there!
Dose?
Intralipid 20%
Rapid bolus of 1.5 mL/kg followed by infusion with
0.25 ml/kg/min x 10 minutes
Local Anesthetic Toxicity - CNS:
__ = Usually occurs after a __ resolves (__ hours after full recovery), develop extreme pain in the days following (EXTREME PAIN). Pain in thighs and buttocks, lasts about 7 days and then resolves. This is highly associated with __ (subarachnoid blocks now steering away from __ because of this).
Transient Neurologic Symptoms (TNS) aka Transient Radicular Irritation
- SAB
- 6-36 hours
- lidocaine
- lidocaine
Local Anesthetic Toxicity - CNS:
This is a permanent deficit. Rare. Spinals give small volumes, high concentrations. More common when they were using micro-catheters with spinals not used as much now but if do use stick with __.
-__, __, __ have been implicated
Cauda Equina Syndrome Bupivacaine lidocaine 5% tetracaine chloroprocaine
- Diffuse lumbosacral injury, numbness in LE, loss of bowel and bladder control, paraplegia?
- Unknown cause? These factors increase the risk ???
*Cauda Equina Syndrome
*Anterior Spinal Artery Syndrome LE paralysis with +/- sensory deficit
advanced age
PVD
vasoconstrictors?
Local Anesthetic Drug Interactions:
- Can increase the toxicity of ester locals?
- Amide toxicity can increase with these 2 drugs on board?
- Analgesia promoted by ????
Pseudocholinesterase inhibitors
Cimetidine and propranolol
opioids, precedex, clonidine, epinephrine
Long DOA for an ester, especially with epi added can be up to __.
Tetracaine
6 hours
Toxic metabolite - ortho-toluidine. Avoid in OB!?!
Great for OB patients for post-op pain?
Prilocaine
Bupivacaine
Dosing Main Points:
___, ___ and ___
- Peripheral Nerve Block:
- ___ dictated by type of block.
- Choose concentration based on limitations of ___ balanced with ___ desired.
Concentration, Volume and Total Dose Administered
- Volume
- max dose
- density of blockade desired
Dosing Main Points:
- Epidural - volume dictated to what level of block desired
- __-__ = per segment desired
- Choose concentration based on ___ (ex: labor vs. surgical epidural)
*Spinal - these doses you just have to know
- 1.25-1.6 mL/segment desired
- density of block desired
Concentration will tell you depth of block (? - more pain related,
? - more significant/motor block)
lower concentration
higher concentration
- __ = dosing on volume, volume for each block. Amount you can give is limited based on max dose and what you are giving it for (pain vs. motor block). Volume, concentration, max dose.
- __ = also based on volume. Determine what level of block you want (how many segments - 4 segments = 4 x 1.25 for small person and 4 x 1.6 for large person) and then determine what volume you would give as starting dose. Then look at patients response. Remember we are doing incremental dosing. With epidurals will find you are getting close to max doses when giving!
- __ = you just need to know the doses!
- PNB
- Epidural
- Spinal
