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