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NU 600

Exam 5 - Local Anesthetics

Nerve cells communicate w/other cells via _________ messages. ionic
What are nerve cells known as? Excitable cells
What is the excitability of a cell based on? Structure of the cell membrane and components
All the parts within a cell are called _________. Organelles
What are the 3 primary structures of the nerve cell anatomy? Dendrites, nerve cell body, axon
The area where information from neurons communicates with other nerve cells is called the _________. Dendritic zone
The charge of the extracellular environment is __________, and the intracellular environment is _________. Positive; negative
The elongated portion of the nerve cell body is called the ___________. Axon
What are dendrites? Outfoldings and branched projections of a neuron that conduct electrochemical stimulation rec'd from another neuron to the cell body from which the dendrites project
What is axoplasm? What is its function? Intracellular fluid; movement of energy and waste material
Transport of materials within the axoplasm is facilitated through what structure? Microtubules
Microtubules transport intracellular contents between what two structures? Cell body and end of the axon
What is the receptive part of a neuron referred to as? Dendritic zone
The dendritic zone is often (small/larger) than the cell body. Larger
The outfoldings of the nerve cell membrane are called ______. Dendrites
Where is the site for initiation of excitability? Dendrites
The original sensory signal (is/is not) modified as it travels from peripheral sensory and motor neurons to the brain. Is—the original signal is modified by dendritic anatomy
Nerve cells are dependent on what substance in order to transmit electrochemical signals? ATP
Both the extracellular fluid and intracellular fluid of the neuron are (water/lipid) based. water
What does the nerve cell membrane serve as a barrier against? Ionic movement
Where does ionic movement occur? Gaps, called ion channels, formed by lipoproteins
The cells that protect axons are called ________ in the PNS, and _____________ in the CNS. Schwann cell; oligodendrocyte
What does the distance between gaps of a myelinated axon related to? Local anesthetic action
What are Schwann cells responsible for? Enzyme and myelin synthesis, metabolic needs
How many times do Schwann cells wrap myelin around an axon? B/w 50-200 revolutions
What are the functions of the myelin sheath? Insulates and protects the neuron
Intervals between the nodes of Ranvier occur at intervals of about _______ mm. 1
The density of Na channels within the nodes of Ranvier is (high/low). High
What is saltatory conduction? The propagation of action potentials along myelinated axons from one node of Ranvier to the next, increasing conduction velocity of action potentials
The terminal end of the axon is also called the ______. Synaptic terminal
What part of the nerve cell is involved w/electrical conduction? Nerve cell membrane
What is the main structural component of the nerve cell membrane? Rows of phospholipid molecules
What are the most active ions for excitable membranes? Potassium, sodium, calcium
How does movement in sodium channels differ from movement in potassium channels. Sodium=channels are either opened or closed and determined by changes in voltage; potassium=moves freely down electrical gradients
Describe how the nerve cell membrane is a semipermeable membrane. Freely allows for potassium to accumulate in the axoplasm, but blocks the movement of sodium
What serves as the basis for conduction? Na-K gradient and the energy dependent enzyme systems that maintain the gradient
The movement of potassium is (free/restricted), while the movement of sodium is (free/restricted). Free; restricted
Why does an electrical gradient exist between the intra- and extra- cellular environments? The free movement of potassium creates the gradient against the restricted movement of sodium
How fast does peripheral nerve conduction occur? 45-60meters/sec
How fast do unmyelinated fibers conduct impulses? As low as 0.7meters/sec
Voltage is mainly determined by the movement of what electrolyte? Potassium
What is the charge on the inside of the cell? -70 to -90mV -70 to -90mV
What is the equilibrium potential? The state of equilibrium maintained by the balance of chemical forces that move cations in one direction and equal electrical forces in the opposite direction
Stimuli that generate an impulse are created through what three means? Mechanical, chemical, electrical
What does the neuron membrane generate in response to environmental stimuli? Action potential
How is an action potential triggered? Depolarization of the membrane beyond threshold
How else are action potentials referred as? Impulses or nerve impulses
Depolarization occurs until what voltage is reached? 15mV
What is the total excursion of amplitude? 110mV (-70mV to 40mV)
What initiates the rapid reversal of depolarization? The movement of potassium down its concentration gradient
What ultimately restores the cell back to its baseline polarized state and ready for the next propagation? Energy dependent transport of sodium out of the cell, and passive movement of potassium back into the cell.
What does “propagation” of an action potential refer to? Depolarization that occurs at one node causes voltage changes that initiate the process at the next distal site
Define nerve conduction. The propagation of a signal that occurs throughout the length of an intact nerve
Nerve fibers are divided into three groups based on what three characteristics? Diameter, conduction, velocity
“A” nerve fibers are (unmyelinated/myelinated) and (rapid/slow) conductors of nerve signals. Myelinated; rapid
What functions do “A” fibers process? Sensory, motor, and muscle impulses
“B” fibers are (larger/smaller) than “A” fibers. Smaller
“B” fibers are (myelinated/unmyelinated) and (rapid/slow) conductors. Myelinated; slow
What functions do “B” fibers process? Pre-ganglionic, autonomic
Which nerve fibers are the smallest? Are they myelinated or unmyelinated? C fibers; unmyelinated
What are the subgroups of “A” fibers? Alpha, beta, gamma, delta
What part of the nerve cell membrane is most responsible for nerve signal propagation? Sodium channel
Sodium channels (are/are not) selective for sodium. Are
Ion selectivity, specifically for sodium, is provided by what feature? Filters
How are sodium channels opened and closed? Through voltage-controlled gating
How many times does sodium move more freely through a sodium channel compared to potassium? 100x
How much sodium is able to move through a potassium channel? Almost none
Why is sodium unable to pass through a potassium channel? It is highly charged and associated w/more water molecules
How is the opening and closing of sodium channels physically controlled? By confirmational changes in structural proteins
*BONUS* LA best bind to sodium channels when the channels are in what two states? Open or inactive
What is an amphiphatic molecule? A molecule that results from the combination of 2 diverse groups
What are the two diverse groups of an LA and how are they joined? One end of the LA is lipophilic and the other is hydrophliic; they are joined by an intermediate chain
The lipophilic end of the LA is composed of a _______. Benzene ring
Which end of the LA is the first to enter the neuron? Lipophilic, or benzene ring
The intermediate chain is composed of a _______. Hydrocarbon
The hydrophilic end of the LA is composed of a ________. Tertiary amine
Where does the differentiation occur that creates either an ester or amide LA? The linkage within the intermediate chain that connects it to the benzene ring
The majority of LA are classified as ______. Tertiary amines
Tertiary amines are derivatives of what chemical? Ammonia
Ammonia is a (weak/strong) base. Weak
The blockade of what type of channel leads to the interruption of neural activity? Sodium channel
How is the ability of a LA to block a sodium channel determined? Affinity of the hydrophilic end of the LA for the axoplasmic side of the sodium channel
How does increasing the length of the hydrocarbon substitutions of the tertiary amine affect the characteristics of a local anesthetic? Increases the lipophilicity and potency
What part of an LA molecule can be altered to increase its potency? The tertiary amine by lengthening it
The length of the intermediate chain must be b/w what two carbon lengths? 3 and 7
How much activity will an LA have with an intermediate chain length of 2? None
Where does the first step in the biotransformation of an LA occur? The intermediate bond
What part of the LA determines its metabolism? Intermediate bond
What chemical is the aminoester group derived from? Benzoic acid
The intermediate bond of an aminoester is subject to what type of metabolism? Rapid hydrolysis w/plasma cholinesterase
The ½ life of aminoesters is (short/long). Short
The amide group is derived from what organic compound? Aniline
What two steps does the metabolism of an amide require? Biotransformation conjugation
Where does the metabolism of an aminoamide occur? Liver
How is potency and toxicity of the aminoamide determined? First by redistribution then elimination
What component of the LA is required to facilitate uptake into the neuron? Lipophilic component (benzene ring)
The potency of the LA is r/t to the ________. Lipid solubility
What portion of the LA occupies the sodium channel of the nerve cell? Tertiary amine
What determines the alignment of the tertiary amine to the sodium channel? Opposing forces of the ends of the LA, and the length of the intermediate chain
The occupation of the sodium channel by the LA occurs on which side of the nerve cell? Axoplasmic, or intracellular
What is the onset of LA action related to? The ability of the LA to diffuse into a lipid matrix
How are the majority of LA solutions prepared and what does their specific gravity resemble? Prepared plain w/sp. gravity close to H20
What does baricity refer to? The density of a substance compared to the density of CSF
How is baricity used in anesthesia? Determines the manner in which a drug will spread in the intrathecal space
______ is added to a LA to make it heavier. Glucose
LA solutions are (hypo/hyper)baric compared to CSF at body temperature. Hypo
The typical LA molecule is a __________ and a __________. Tertiary amine; weak base
The typical LA molecule is (highly/poorly) soluble in water. Poorly
When combined with a strong acid, the typical LA molecule will form a ______. Salt
How are LAs manufactured in the US? As hydrochloride salts
In solution, the LA salt exists between what two states? Neutral salt (base) and ionized (cation)
The cation is the ______ state of an LA molecule. Ionized
LAs are weak bsaes with a pKa in the _______ to _______ range. 7, 9
What is a conduction block? Block where the LA enters sodium channels in sufficient quantity to interrupt activity
How great does the potential peak sodium current of each nerve cell membrane have to be in order to propagate an action potential? 5-6x greater than necessary
The conduction block is (reversible/irreversible). Reversible
When does impulse propagation occur? When sodium channels are opened or activated
LAs prevent conduction by converting sodium channels into a/an (open/active/inactive) state. Inactive
Identify 3 intermediate acting LA. Lidocaine, procaine, mepivicaine
Identify 1 long acting LA. Bupivicaine
How much of an unmyelinated nerve has to be covered w/a LA in order for an effect to occur? The full circumference and length
Place each block in order from highest to lowest: sensory, motor, sympathetic. Highest to lowest: sympathetic, sensory, motor
Place each block in order of onset from fastest to slowest: sensory, motor, sympathetic. Fastest to slowest: sympathetic, sensory, motor
(Larger/Smaller) fibers take longer to block than (larger/smaller) nerve fibers. Larger; smaller
A sympathetic block occurs with blockade of what types of nerve fibers? B
Which fibers are the smallest and most easily blocked? B
What type of nerve fibers are associated with spinal anesthesia? All nerve fibers (B, C, and all of A and the A subgroups)
Which fibers are the largest in the body? A-alpha
A-alpha fibers are associated with what types of blocks? Motor
Where does the spinal cord end? L1-L2
The superior aspect of the iliac crest is a landmark for what level of the spine? L3-L4
Which side of the sodium channel allows for reversible binding? Axoplasmic (intracellular)
LA (can/cannot) move through sodium channels from the extracellular environment. Cannot
The lipid soluble portion of the LA, the benzene ring, is also known as the _______. Base
The base portion of the LA is the (lipophilic/hydrophilic) section of the LA molecule. Lipophilic
pH of the intracellular is more (basic/acidic). Acidic
The pH of the intracellular environment favors the (basic/cationic) form of the LA. Cationic
What is the best chemical state for diffusion into a neuron by a LA? Intermediate lipid solubility
What two conditions slows down movement of an LA into the intracellular environment of a neuron? Very high or low lipid solubility
Once inside the neuron, what form of the LA favors the sodium channel? Cationic (ionized)
Alternative structures of the same protein are referred to as _______, and the transitions between them are called ________. Conformations; conformational changes
What causes a conformational change of the sodium channel to allow for sodium movement into the nerve cell? Depolarization
Subsequent impulses (do/do not) influence a sodium channel that has been inactivated by a LA. Do not
Potency is directly proportional to _______. Lipid solubility
The ability of a LA to cross a neural membrane is directly r/t its __________. Lipid solubility
Any alteration of the lipid solubility of a LA alters its ________. Potency
What is created from the addition of a 4-carbon aliphatic chain to the intermediate chain of procaine? Tetracaine
What is created from the addition of 3 carbons to the methyl group on the tertiary amine of mepivicaine? Bupivicaine
The addition of _________ prior to the injection of an LA increases the amount of (ionized/non-ionized) drug. Sodium bicarbonate; non-ionized
How can the potency of an LA be increased without affecting its lipid solubility? Increasing the non-ionized portion of the drug
What determines the blocking action of an LA? What determines its duration? Blocking=ionic activity of hydrophilic portion of the LA; Duration=lipid solubility and protein binding
Which two LA are the most lipophilic and what is unique about them? Bupivicaine and tetracaine; have the longest duration of action
What determines the speed of onset of a LA? Location of injection
How do spinals and epidurals differ in onset of effect and why does this occur? The effect of spinals occurs sooner because they are injected directly into the spinal nerves, whereas epidurals require movement of the LA across the dura to achieve anesthetic effect
The active form of the LA is the ________ form. Nonionized
Biotransformation, deactivation, and elimination start in the ______ section of the LA. Intermediate chain
Movement away from the target neural structure starts what three processes? Deactivation, biotransformation, and elimination
What does the accuracy of regional anesthetic technique depend on? The proximity of the injection to the nerve w/o intraneural injection
True/False: The LA that is absorbed into the bloodstream is not readily absorbed into the CNS. False – the small molecular structure of the LA makes the nonionic form readily absorbed
What are five possible scenarios of CNS toxicity from LA injection? Direct injection into the CNS with a dose intended for epidural anesthesia; cytotoxicity; intraneural injection; IM; additives creating toxicity
What is the purpose of a test dose in an epidural? To gauge whether the catheter is located in the spinal canal or a blood vessel
All spinals have to be free of what substance? Methylparaben
Identify clinical signs of toxicity with increased CNS concentrations of lidocaine. Visual disturbances, muscular twitching, convulsions, unconsciousness, coma, respiratory arrest, CVS depression
Adequate ventilation in the event of lidocaine toxicity helps prevent what two conditions? Acidosis and ion trapping
What two types of medications can be used to prevent or treat seizures associated w/lidocaine toxicity? BZDs or sodium thiopental
True/False: Long-term sequelae are common with lidocaine toxicity. False
What occurs with the most severe cases of LA toxicity? Plasma levels of the agent causes hemodynamic instability d/t direct action on the myocardium and ANS
What are the CV consequences of lidocaine toxicity? Negative inotropy, arrhythmia, cardiac arrest
True/False: The effects of a LA on the heart is dose and medication specific. True
The effect of bupivicaine accumulation is due to what factor? The fast movement into and slow movement out of a nerve cell
Toxicity of a local anesthetic may ultimately lead to depression of what system? Depression of myocardial conduction system
What is the antibody of anaphylaxis? IgE
What are the two classes of body responses to a foreign substance? Systemic and cellular
What does systemic exposure lead to? What can repeat systemic exposure lead to? Creates antibodies; can lead to anaphylaxis
What is the slow-reacting substance of anaphylaxis? Neutrophil
When does cell mediated immunity occur? With the sensitization of cells
A local response to exposure is often known as _________. Contact hypersensitivity
Several (days/weeks/months) must pass between initial exposure to a potential allergen and the potential for anaphylaxis. Weeks
What do neutrophils potentiate? Constrictive effects of histamine on smooth muscle
What do the constrictive effects of histamine result in? Bronchospasm and increased capillary permeability
Identify the aminoester local anesthetics and their trade names. (5) procaine (Novacaine), chloroprocaine (Nesacaine), tetracaine (Pontocaine), cocaine, benzocaine (Cetacaine)
What is the trade name for procaine? Novocaine
______ is the least toxic LA. Procaine
Procaine is a derivative of ______. Para-aminobenzoic acid (PABA)
Why is procaine the least toxic of all LA? Rapidly metabolized
What does metabolism of procaine begin with? Exposure to plasma cholinesterase
What is the clinical application of procaine? Cutaneous or mucus membrane infiltration (mostly dental practice)
What is the trade name for chloroprocaine? Nesacaine
How is chloroprocaine metabolized? Ester hydrolysis
Chloroprocaine, like procaine, is used for what purpose? Infiltration of cutaneous or mucus membranes
What can occur with subarachnoid injection of chloroprocaine? Severe neurologic injury
What is the trade name for tetracaine? Pontocaine
What is the most popular agent for spinal anesthesia? Tetracaine
Tetracaine has a (high/low) lipid solubility factor. High
What is added to tetracaine to prolong its duration. 1% solution of epinephrine
How much is the duration of tetracaine increased with the addition of 1% epi? 20-30%
How much 1% epi is usually added to tetracaine to prolong its duration? 80-100mg
What is the onset/offset profile of tetracaine? Slow onset and long duration d/t high pKa and lipid solubility
Cocaine is an (ester/amide). Ester
What was the first agent used for local anesthesia? Cocaine
What properties lead to the abuse of cocaine? Oral ingestion identified excitatory and euphoric properties
Besides local anesthesia, what other effect does cocaine have? Intense vasoconstriction
The vasoconstrictive properties of cocaine make it useful for application on _______. Mucus membranes
What is the max dose of cocaine for an adult? 200mg (~3mg/kg)
Where is cocaine commonly used and how is it applied? ENT; applied to mucus membranes w/sponges saturated w/4-5% sol.
What is the trade name for benzocaine? Cetacaine
Benzocaine, like cocaine, is useful in direct application of _______. Mucus membranes
Toxicity of benzocaine surfaces with amounts > ______mg. 200-300
The use of which local anesthetic can result in methemoglobinemia? Benzocaine
Benzocaine is ideal for what type of anesthesia? Topical
Identify the 7 aminoamide anesthetics and their trade names. Lidocaine (Xylocaine), Mepivicaine (Carbocaine), Prilocaine (Citanest), Etidocaine (Duranest), Bupivicaine (Marcaine, Sensorcaine), Ropivicaine (Naropin), Dibucaine
What is the most widely used local anesthetic in the world? Lidocaine
What is the trade name for lidocaine? Xylocaine
What is the most widely used and most versatile of all LA? Lidocaine
What is the most popular agent for infiltration? Lidocaine
What does eutectic mean? Melts quickly
Which LA can be nebulized into the airway? Lidocaine
What reflexes can lidocaine suppress? Hiccups and cough
What preservative contributes to the allergy profile of lidocaine? Methylparaben
What is the test dose of lidocaine used to r/o intravascular injection? 3cc MPF 2% lidocaine w/epi 1:200,000
Which LA is associated with cauda equina syndrome? Lidocaine
How is lidocaine used in obstetrics? Spinals for C-sections
*BONUS* What is the cauda equina? Bundle of spinal nerves and nerve roots, consisting of the 2-5 lumbar, 1-5 sacral, and the coccygeal nerves.
*BONUS* What does the cauda equina innervate? Pelvic organs and lower limbs
*BONUS* The termination of the spinal cord is known as the ______. Conus medullaris
What is cauda equina syndrome? Serious neurologic condition w/acute loss of function of the lumbar plexus
Cauda equina syndrome may be a result of anesthesia in what conditions? Iatrogenic lumbar punctures, catheter trauma from spinals, high local anesthetic concentrations around the cauda equina
What is the trade name for mepivicaine? Carbocaine
Which local anesthetic has properties comparable to lidocaine? Mepivicaine
What is a unique property of mepivicaine? Diffuses through tissues proximate to the site of injection
The unique property of mepivicaine makes it ideal for what application? Field blocks
What is the ideal LA for field blocks? Mepivicaine
The application to clinical practice for mepivicaine is in ________ anesthesia. Infiltration
What other applications, besides infiltration anesthesia, is mepivicaine used in? Spinals and epidurals
What is the trade name for prilocaine? Citanest
Which amide has been associated w/methemoglobinemia? Prilocaine
Which LA is a common alternative to lidocaine? Prilocaine
Prilocaine is not used in which application of anesthesia? Spinals
Prilocaine acts in a manner similar to _______. Lidocaine
What is the trade name for etidocaine? Duranest
What is etidocaine derived from? Lidocaine
How does etidocaine compare to lidocaine? More potent and longer acting
The increased lipid solubility of etidocaine also makes it ____ and ____. Potent; toxic
Which LA is used for topical anesthesia, with application to the cornea and trachea? Etidocaine
Like prilocaine, etidocaine is not used in what aspect of anesthesia? Spinals
What are the two trade names for bupivicaine? Marcaine, Sensorcaine
Which LA is the most cardiotoxic? Bupivicaine
Bupivicaine is a LA used for when a (long/short) duration of analgesia is important. Long
Bupivicaine is used in spinals with (hypo/hyper)baric techniques. Hyper
When is bupivicaine used in anesthesia? Effect with long-duration sensory anesthesia, spinals (hyperbaric), epidurals, nerve blocks
What is the trade name of ropivicaine? Naropin
Ropivicaine is chemically similar to which local anesthetics? Bupivicaine and mepivicaine
Which medication is the replacement LA for bupivicaine? Ropivicaine
Which is safer in regards to cardiotoxic effects: bupivicaine or ropivicaine? Ropivicaine
Ropivicaine has a (high/low) level of potency and lipid solubility. High
What is the replacement medication for bupivicaine? Ropivicaine
In what clinical applications is ropivicaine used? Infiltration and epidural anesthesia
Which LA has a high affinity for plasma cholinesterase? Dibucaine
Dibucaine inhibitis up to _____% of plasma cholinesterase activity in its normal genetic form, and as little as _____% of the atypical variants. 80; 15
Provide the dibucaine numbers for normal, heterozygous, and homozygous forms of plasma cholinesterase expression. Normal=80%, heterozygous=50-60%, Homozygous=10-20%
Which 5 local anesthetics are most commonly used in anesthesia? Lidocaine, mepivicaine, bupivicaine, ropivicaine, tetracaine (per Joseph)
*BONUS* Which two LA are beneficial in topical anesthesia? Tetracaine, lidocaine
*BONUS* Which LA is not used for local infiltration? Tetracaine
*BONUS* Tetracaine is used in what two anesthetic applications? Topical and spinal anesthesia
*BONUS* Lidocaine can be used in any aspect of regional anesthesia. True
*BONUS* What are three regional applications of procaine? Infiltration, nerve block, spinals
*BONUS* Chloroprocaine, like procaine, can be used for infiltration and nerve blocks but where does it differ from procaine? Ok for epidurals and not for spinals
*BONUS* True/False: All of the aminoamide anesthetics can be used in epidural anesthesia as well as nerve blocks. True
*BONUS* Which two aminoamides can be used for spinal anesthesia? Lidocaine, bupivicaine
*BONUS* What two LA can be used for IV regional anesthesia? Lidocaine, prilocaine
What three solutions serve to increase the speed of onset of LAs? Dextran, carbonate, bicarbonate
How does the addition of dextran influence LA? Increases speed of onset and depth of the conduction block
The addition of carbonate to a LA has (variable/consistent) outcomes. Variable—carbonation is rarely seen today
How does bicarbonate influence the LA? Speeds the onset of the conduction block
What benefits does epinephrine have as an additive to a LA? Prolongs duration, marker for intravascular injection, decreases blood loss
What is a field block? Block where the LA is infiltrated around the border of the surgical field, leaving the operative area undisturbed
What is a nerve block? Block where the LA is injected directly adjacent to the nerve supplying the surgical field
Name the 5 aminoamide anesthetics along with their plain dose max 24hr totals. Lidocaine 300mg, mepivicaine 300mg, prilocaine 500mg, bupivicaine 175mg, ropivicaine 250mg
Name the 5 aminoamide anesthetics along with their epi dose max 24hr totals. Lidocaine 500mg, mepivicaine 500mg, prilocaine 600mg, bupivicaine 225mg, ropivicaine 300mg
Created by: philip.truong