! Local Anesthetics Flashcards
Learning objectives
Describe the pharmacokinetic and pharmacodynamic properties of local anesthetics
Discuss clinical pharm of local anesthetics, including toxicity and effects on organ systems \
List the common routes of administration of local anesthetics
Describe chemical make up and how TI effects pharmacological properties
Ok
List local anesthetics
Benzocaine Bipivacaine Cocaine Dibucaine Lidocaine Procaine
Articaine Chlorprocaine Levobuoivacaine Mepivacaine Proparacaine Ropivacaine Tetracaine
Amides
LIdocaine MepIvacaine BupIvacaine RopIvacaine ArtIcaine
Iiiiii
Esters local anesthetic
Benzocaine
Cocaine
Procaine
Tetracaine
Short lasting local anesthetics
Procaine with potency of 1
Medium lasting local anesthetic
Lidocaine (4)
Mepivacaine (2)
Articaine (?)
Cocaine (2)
Long acting local anesthetics
BupIvacaine (16)
Ropivacaine (16)
Tetracaine (16)
Typical local anesthetics contain both hydrophilic and hydrophobic components that are separated by an __ or __ link
Ester or amide
Agents with ester links are more prone to __ that amides, so have a shorter duration
Hydrolysis
How does use of a vasoconstrictor effect absorption of local anesthetics like epinephrine
Reduce intermediate and short duration absorption
Cocaine is unique that it has intrinsic symapthomimetic ___ properties
Vasoconstriction
Amide IV bolus
Widely distributed after intravenous bolus administration
Tissue distribution ester type agents
Extremely short plasma half life
Ester metabolism
In plasma by circulating butyrylcholinesterase/plasma cholinesterase enzymes
Amide type metabolism
In liver and then excreted int he urine as charges substances CYP450
MOA local anesthetics
Block voltage gates Na currents and stop the spread of AP across nerve axons (the receptor site for local anesthetics is at the inner vestibule of the Na channel); block nerve conduction by decreasing or preventing the large transient increase in the permeability of excitable membranes to sodium that normally is produced by a depolarization of the membrane
The smaller and more lipophilic the local anesthetic, the __ the rate of interaction with the sodium channel and the more __ the agents actions
Faster
Potent
What are some lipophilic local anesthetics
Tetracaine
Bupivacaine
Ropivacaine
More potent and longer durations
Local anesthetics preferentially block __ fibers because the distance over which such fibers can passively propagate an electrical impulse is shorter
Small
__ nerves tend to become blocked before unmyelinated nerves of the same diameter, so preganglionic B fibers are blocked before smaller unmyelinated C fibers
Myelinated
Fibers that fire at a __ frequency of depolarization are blocked before those that fire __
Higher
Slower
Type A delta and C fibers are blocked ___ than the large alpha A fibers
Earlier
In bundles of large mixed nerves in large nerve trunks, it is not uncommon for motor nerve block to occur before sensory block because motor nerves are usually located circumferential
Motor nerves are the first nerves to be exposed to the local anesthetic when it is administered into the tissue surrounding the nerve
In the extremities, proximal sensory fibers are located in the outer portion of the nerve trunk and distal sensory innervation is located in the __ of the nerve
Core
Type A fibers
Alpha(proprioception, motor)
Beta (touch, pressure)
Gamma(muscle spindles)
Delta (pain, temperature)
- listed thickest to thin
- all heavily myelinated and
- listed increasing sensitivity to block
Type B fiber
Preganglionic autonomic
Small diameter
Light myelination
Huge sensitivity to block
Type C fiber
Dorsal root (pain) Sympathetic (postganglionic)
Both small diameter
Both non myelinated
HUGE sensitivity to block
Routes of local anesthetic administration
Topical
IV
Injection
Infiltration anesthesia injection
Directly into tissue in the vicinity of peripheral nerve endings without taking into consideration the course of cutaneous nerves; can be superficial enough to include only the skin and deep enough to include intraabdominla organs
Block anesthesia injection
Injection in major nerve trunks; the purpose is to anesthetize a region distal to the site of injection; examples: femoral nerve block for surgery distal to the knee, brachial plexus block for procedures on the upper extremities or shoulders
Spinal anesthesia injections
Injection into CSF in lumbar space ; produces anesthesia over a considerable fraction of the body with a dose of local anesthetic that produces negligible plasma levels
Epidural anesthesia injection
Injection into epidural space can be performed in the sacral hiatus or int he lumbar, thoracic, or cervical regions of the spine; current popularity has arisen from the development of catheters tat can be placed into the epidural space, allowing either continuous infusions or repeated bolus administration
IV regional anesthesia
For short surgery
Distal vein given
While circulation of the limb is isolated with a proximally placed tourniquet; large doses of local anesthetics are used, so the tourniquet should remain long enough to ensure that high circulating drug levels do not cause systemic toxic events
___ prolong actions of anesthetics
Vasoconstrictors
Why do vasoconstrictors prolong duration(epi activates a adrenergic and causes vasoconstriction)
Decreases the rate of anesthetic absorption into circulation, reduces the rate at which the local anesthetic is metabolized, and reduces systemic toxicity
Why should epinephrine containing solutions not be injected into tissues supplied by end arteries (ears, toes, nose, fingers, penis)
Resulting vasoconstriction may cause gangrene
Why use caution when injecting vasoconstrictor into muscle
Epi can activate B 2 receptor in skeletal muscle vascular beds and cause dilation, increasing the potential for systemic toxicity
Cocaine
Potentials effects of NE on a receptors by blocking the norepinephrine transporter and results in localized vasoconstriction, eliminating the need for combining the drug with epi
What are the two types of local anesthetic toxicity
Toxicity following systemic absorption
Direct neurotoxicity from local effects when given in close proximity to the spinal cord and other major nerve trunks
Low concentrations have the ability to produce what CNS issues
Sleepiness, light headedness, visual and auditory disturbances, and restlessness (early signs of toxicity include circumoral and tongue numbness and a metallic taste)
High concentrations may cause what
Nystagmus , muscle triwthcing, convulsions
What do you do when large doses of anesthetics are needed
Premedication with a parenteral benzodiazepine can provide prophylaxis against CNS toxicity by raising the seizure threshold (local anesthetics cause depression of cortical inhibitory pathways, thereby allowing unoppposed activity of excitatory neurons pathways)
Central stimulation is followed by depression; death is usually caused by __ __
Respiratory failure
Undesired CV system effects of local anesthetics
Direct effects on cardiac and smooth muscle and from indirect effects on the autonomic nervous system
Local anesthetics block cardiac __ channels and decreases electrical excitability, conduction rate, force of contraction and cause arteriolar dilation, leading to systemic hypotension
Sodium
Cocain
NOT THE CASE
Inhibits NE reuptake and results in vasoconstriction (ischemia), hypertension, and cardiac arrhythmias)
BupIvacaine
Most cardiotoxic due to its long duration of action
Lidocaine
Class Ib antiarrhythmic
Lidocaine suppresses autonomicaity of conduction tissue by increasing electrical stimulation threshold of __ , ___ and ______
Ventricle, His-Purkinje system, and spontaneous depolarization of the ventricles during diastole by a direct action on the tissues
Lidocaine blocks the initiation and conduction of nerve impulses by __, which results in inhibition of depolarization with resultant blockage of conduction
Decreasing the neuronal membranes permeability to sodium ions
Most common adverse effect of IV lidocaine is what
CNS toxicity-usually mild, dose dependent and always resolves upon discontinuation
Why are allergic reactions to ester type local anesthetics more common
Metabolism to allergy causing compounds (allergies to amide type local anesthetics are rare)
Ester local anesthetics have _ i and amide have _ i
One
More than 2
T/F patients allergic to one ester type agent will most likely be allergic to another
T
Benzocaine
Poor solubility in water, used only as sa topical agent; used topically for dermatological conditions, hemorrhoids, premature ejaculation, and as an anesthetic lubricant
BupIvacaine
Long duration of action capable of producing prolonged anesthesia;has a tendency to provide more sensory block than motor block
Cocaine
Clinically desired properties of cocaine are the blockade of nerve impulses and local vasoconstriction get actions secondary to its ability to inhibit local NE reuptake; euphoric properties are primarily due to inhibition of catecholamine reuptake (mainly dopamine in the CNS) used primarily as a topical anesthetic of the URI
Dibucaine
Due to toxicity associated with injections, now used only as a topical cream for use on the skin
Lidocaine
Prototypical amide local anesthetic; alternative choice for individuals sensitive to ester type local anesthetics; produces faster, more intense, longer lasting, and more extensive anesthesia than an equal dose of procaine; used as an antiarrhythmic
Procaine
Compared to newer agents , procaine generally has lower potency, slower onset, and shorter duration of action; only used for infiltration anesthesia (local anesthesia produced by injection of the anesthetic solution directly into the area of terminal nerve endings) metabolized to a para-aminobenzoic acid, which inhibits the action of sulfonamide antibiotics
