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153 Cards in this Set

  • Front
  • Back
local anesthesia
-the loss of sensation in a discrete region of the body caused by disruption of impulse generation and propagation
what was the first local anesthetic?
cocaine
problems with cocaine
-has irritant properties when placed around nerves
-has the potential for physical and psychological dependence
progression of local anesthetics after cocaine
-cocaine is a benzoic acid ester, so strategies to develop new locals focused on this class
next local identified
benzocaine
problem with benzocaine
-its poorly water soluble so its use is restricted to topical use
what was the first useful injectable local anesthetic?
procaine
procaine
-considered the prototypical local anesthetic on which all modern locals are based
procaine molecule
-the molecule is derived from an aromatic acid, para-aminobenzoic acid), and an amino alcohol, yielding a structure with 3 distinct regions:

1. an aromatic head, which imparts lipophilicity
2. a terminal amine tail, a a proton acceptor that imparts hydrophobicity
3. a hydrocarbon chain attached to the aromatic acid by an ester linkage
other PABA derivatives developed as local anesthetics in the 20th century
-include both esters and amides
-most notably tetracaine and chloroprocaine, both of which embody modifications of the aromatic ring
what local was introduced in 1984?
lidocaine
what was unique about lidocaine?
it was the first departure from the amino-ester series
lidocaine structure
-because its derived from an aromatic amine, xylidine, and an amino acid, the hydrocarbon chain and aromatic head are linked by an amide bond (rather than an ester), imparting greater stability
-the structure also averts the allergic reactions commonly seen with ester anesthetics (which is due to the sensitivity t the cleaved aromatic acid)
-due to this lidocaine became the template for development of a series of amino-amide anesthetics
what are most amino-amide local anesthetics derived from?
xylidine
amide locals
include of course lidocaine, and also:

mepivacaine
bupivacaine
ropivacaine
levobupivacaine
how do the newer compounds compare to lidocaine?
-the terminal amino portion is contained within a piperidine ring, so they are commonly referred to as pipecholyl xylidines
what other feature do ropivacaine and levobupivacaine share?
-they are single enantiomers rather than a racemic mixture, a strategy which takes advantage of the differential steroselectivity of neuronal and cardiac sodium ion channels to reduce the potential for cardiac toxicity
how do the amides differ from the esters?
-the amides require biotransformation in the liver, rather than undergoing ester hydrolysis in the plasma
mecahnism of action of local anesthetics
block action potential conduction bu blocking voltage-gated Na channels
resting membrane potential of neurons
-normally the neural membrane has a negative potential of -90 mV (meaning the potential inside the nerve cell is negative relative to the ECF)
how is this potential created?
-by the combination of active outward transport of Na and inward transport of K, and the membrane being relatively permeable to potassium and impermeable to Na
action potential propagation
-excitment of the nerve causes an increase in the permeability of the membrane to Na, causing the membrane potential to become increased, and if a critical potential is reached (the threshold potential) there will be a rapid influx of Na ions causing depolarization, and then afterwards the resting membrane potential is reestablished
so local anesthetic mechanism of action from an electrophysiologic standpoint
-block neural transmission by decreasing the rate of depolarization in response to excitation, preventing the threshold potential from being achieved
-do not alter resting transmembrane potential or the threshold potential
activation and mechanism of action of local anesthetics
-the ability of locals to block Na conduction occurs by their interaction with specific receptors on the inner vestibule of the Na ion channels
-locals exist in 2 forms in dynamic equilibrium, an uncharged base and a protonated or charged quatrinary amine
-while it is the charge form that has the ability to interact with the Na channels, it is extremely hydrophilic so cant cross the cell membranes, so its the neutral base which crosses the cell membranes and once in side reequilibrium occurs allowing the charged form to interact with the receptors
other way local anesthetics can reach the Na receptors
-laterally, through the hydrophobic pathway
evidence of the complexity of local anesthetic actions
-these mechanisms cant completely account for local anesthetic effect, as an example benzocaine only exists in the uncharged form and isnt affected by pH, yet still has local anesthetic toxicity
unproven hypothesis on other ways local anesthetics work
-could cause the nerve membrane to expand causing constriction of the Na ion channels
Na channel receptor conformational states
the modulated receptor model states that Na ion channel exist in several different states:

-during rest the channel is in the resting-closed state, then during excitation it moves from a resting-closed state to an activated-open state, where sodium ions pass through and cause depolarization
-after depolarization the channel goes to an inactivated-closed state

-the importance of these states are that local anesthetics bind with different affinities to the different states
local anesthetic binding to the different Na ion channel conformational states
-local binds to the activated and inactivated states more readily than the resting, causing them to attenuate changes in conformation of the receptor
-also, drug dissociates slower from the inactivated state than the resting
what is the consequence of drug dissociating slow from the inactivated state than the resting?
-repeated depolarization causes more effective anesthetic binding, which means there is progressive enhancement of blockade with repeated stimulation of that nerve, called use-dependent or frequency-dependent block
-this may be the reason for the selective block of different types of nerve fibers, depending on their characteristics and frequency of activity of the nerve
proportions of charged and uncharged local anesthetics
-is a function of both the dissociation constant of the drug and the environmental pH
dissociation constant of local anesthetics
-due to the Henderson-Hasselbalch equation, is expressed as:

pKa= pH - log [base]/[conjugate acid]
what if the concentration of the base and conjugate acid are equal?
the latter part of the equation cancels, since log 1=0
pKa
-a good way to describe whether local anesthetics exist in the charged or uncharged form
a low pKa
-the lower the pKa, the greater to unionized fraction for a given pH

Ex: benzocaine is highly lipophillic and has a pKa of 3.5, and it exists solely as a neutral base under normal physiologic conditions
pKa of the commonly used local anesthetics
-most are between 7.6 and 8.9
-this means that less than half of the molecules are in the unionized form at physiologic pH
local anesthetic formulations
-because theyre poorly soluble in water, they are marketed as water-soluble hydrochloride salts, solutions which are acidic, which contributes to the stability of local anesthetics, but also potentially slowing the onset of the block
how can the onset of the block be spead up?
by adding bicarbonate to the solution to increase the unionized fraction
other conditions that can lower pH and have a negative impact on the onset of a block
anything that causes tissue acidosis, such as infection
local anesthetic lipid solubility
-affects their tissue penetration and uptake into nerve membranes
-is expressed as a partition coefficient
how is the partition coefficient determined?
-by comparing the solubility of the drug in a nonpolar solvent , like n-heptane or octanol, with the solubility in the aqueous phase, such as water or buffered solution
what does lipid solubility of local anesthetics generally correlate to?
-to potency and duration of action, and to a lesser extent varies inversely with latency or time to onset
what other factor correlates with the duration of action of local anesthetic?
-protein binding, which serves to retain the drug within nerves
ester local anesthetics
procaine
chloroprocaine
tetracaine
amide local anesthetics
lidocaine
mepivacaine
prilocaine
bupivacaine, levobupivacaine
ropivacaine
pKa of local anesthetics
ester

procaine: 8.9
chloroprocaine: 8.7
tetracaine: 8.5

amide

lidocaine: 7.9
mepivacaine: 7.6
prilocaine: 7.9
bupivacaine, levo: 8.1
ropivacaine: 8.1
nonionized % at ph 7.4
ester

procaine: 3
chloroprocaine: 5
tetracaine: 7

amide

lidocaine: 24
mepivacaine: 39
prilocaine: 24
bupivacaine, levo: 17
ropivacaine: 17
local anesthetic potency
ester

procaine: 1
chloroprocaine: 2
tetracaine: 8

amide

lidocaine: 2
mepivacaine: 2
prilocaine: 2
bupivacaine, levo: 8
ropivacaine: 6
max dose (mg) for infiltration
(the dose should take into account the site of injection, use of a vasoconstrictor, and patient-related factors)

ester

procaine: 500
chloroprocaine: 600
tetracaine: N/A

amide

lidocaine: 300
mepivacaine: 300
prilocaine: 400
bupivacaine, levo: 150
ropivacaine: 200
duration after infiltration (min)
ester

procaine: 45-60
chloroprocaine: 30-60
tetracaine: N/A

amide

lidocaine: 60-120
mepivacaine: 90-180
prilocaine: 60-120
bupivacaine, levo: 240-480
ropivacaine: 240-480
topical?
ester

procaine: no
chloroprocaine: no
tetracaine: yes

amide

lidocaine: yes
mepivacaine: no
prilocaine: no
bupivacaine, levo: no
ropivacaine: no
infiltration
ester

procaine: yes
chloroprocaine: yes
tetracaine: no

amide

lidocaine: yes
mepivacaine: yes
prilocaine: yes
bupivacaine, levo: yes
ropivacaine: yes
IV regional
ester

procaine: no
chloroprocaine: no
tetracaine: no

amide

lidocaine: yes
mepivacaine: no
prilocaine: yes
bupivacaine, levo: no
ropivacaine: no
peripheral block
ester

procaine: yes
chloroprocaine: yes
tetracaine: no

amide

lidocaine: yes
mepivacaine: yes
prilocaine: yes
bupivacaine, levo: yes
ropivacaine: yes
epidural
ester

procaine: no
chloroprocaine: yes
tetracaine: no

amide

lidocaine: yes
mepivacaine: yes
prilocaine: yes
bupivacaine, levo: yes
ropivacaine: yes
spinal
ester

procaine: yes
chloroprocaine: yes (?)
tetracaine: yes

amide

lidocaine: yes (?)
mepivacaine: yes (?)
prilocaine: yes (?)
bupivacaine, levo: yes
ropivacaine: yes

?: the use of these is controversial and the recommendations are evolving
nerve fiber classification
are classified based on:

-diameter
-the presence (type A and B) or absence (type C) of myelin
-function
type A fibers
split into 4 subtypes:

alpha
beta
gamma
delta
alpha type A fibers
large diameter, fast conducting fibers, whose function is proprioception and large motor
beta type A fibers
somewhat large and fast conducting, function is small motor, touch, and pressure
gamma type A fibers
medium size and conduction velocity fibers, whose function is muscle tone
delta type A fibers
medium diameter and conduction velocity fibers, whose function is pain, temperature, and touch
type B fibers
-small myelinated fibers with medium/slow conduction velocity, whose function is preganglionic autonomic
type c fibers
unmyelinated, small slow conducting fibers, whose function is dull pain, temperature, and touch
what does nerve fiber diameter influence?
conduction velocity, with larger diameter correlating to rapid nerve conduction
what else influences nerve conduction?
the presence of myelin, which insulates the axolemma from surrounding media, making current flow through periodic interruptions in the myelin sheath, called nodes of ranvier
local anesthetic action and myelin
-conduction blockade is predictably absent if at least 3 successive nodes of ranvier are exposed to adequate concentrations of local anesthetic
nerve fiber diameter and local anesthetic blockade
-it has been observed that blockade is inversely correlated to nerve fiber diameter, meaning that larger myelinated nerve fibers are more sensitive than smaller unmyelinated ones, and there is evidence of this
-however, in practice increasing concentrations of local will cause block of motor, sensory, and autonomic fibers
-the discrepancy is poorly understood, but might be due to anatomy arrangement of nerve fibers, variability in the longitudinal spread required for block, effects on other ion channels, and inherent impulse activity
different propensities of local anesthetics to induce differential blockade
-local anesthetics all differ in their ability to produce differential blockade

for example: etidocaine gives a more profound motor block than bupivacaine, causing the former to have a limited value clinically, and the latter to be good for labor and post op pain control

-attempt to get mostly sensory affecting local anesthetics have been unsuccessful, so you have to use other things to do it such as intrathecal opioids
spread of local anesthesia once its injected
-when local is injected around a nerve, it has to diffuse from the outer surface (mantle) to the nerves center (core) along a concentration gradient, which means fibers in the mantle are blocked first
-mantle fibers are usually innervating more proximal structures, while the core fibers go to more distal ones, accounting for first getting proximal anesthesia and then distal afterwards
other implications of this anesthetic spread
-if motor fibers are more peripheral there will be skeletal muscle paralysis before getting sensory block
onset and recovery of motor, sensory, and autonomic nerves
-in light of the prior facts, the sequence of onset and recovery between autonomic, sensory, and motor block depends as much if not more on the location of the nerve fibers in a mixed bundle as on the sensitivity of the fibers to local anesthetics
unique thing about local anesthetic pharmacokinetics
-differ from most drugs in that they are deposited right at the target site, and that systemic absorption results in ending of their action, rather than them being delivered to target sites and the start of their action as with other drugs
peak plasma concentrations of local anesthetics
-are determined by the rate of systemic uptake, and to a lesser extent the rate of clearance
factors that affect the rate uptake of local anesthetics
-several things related to the physiochemical properties of the local, and local tissue blood flow
what local anesthetic characteristics will cause delayed uptake?
its delayed for local anesthetics with high lipophilicity and protein binding
vasoactivity of local anesthetics
-they differ in their vasoactivity, but most are vasodilators at clinically relevant concentrations, though this varies with site of injection
clinical importance of this effect
-the lower systemic toxicity of S (-) ropivacaine compared to R (+) may result from its vasoactivity

-also, the differing effect that adding vasoconstrictors such as epinephrine to local for spinals is another example: when given intrathecally tetracaine, in contrast to lidocaine or bupivacaine, causes a significant increase in spinal cord blood flow, so as you would predict adding epi or pother vasoconstrictors to tetracaine has a more dramatic prolongation of effect than to the other locals
metabolism of local anesthetics
-amino-esters are metabolized by hydrolysis, whereas amino-amides are metabolized by hepatic microsomal enzymes
in what other way are local anesthetics metabolized?
the lungs can extract some amount of local, such as with lidocaine, bupivacaine, and prilocaine
metabolism and local anesthetic toxicity
-the rapid hydrolysis of the ester chloroprocaine makes it less likely to be able to achieve sustained elevated plasma concentrations and cause toxicity, in comprison to the amide locals
-patient swith atypical plasma cholinesterase, though, may have an increased risk of developing toxicity from chloroprocaine and the other esters due to decreased or absent plasma hydrolysis
lidocaine metabolism
-hepatic metabolism of it is extensive, and clearance of lidocaine parallels hepatic blood flow, with liver disease or diseases which cause a decrease in hepatic blood flow, such as CHF or with general anesthesia, decrease the rate of metabolism of lidocaine
renal excretion of local anesthetics
-due to these drugs low water solubility, it is usually limited to <5% of the dose
adding vasoconstrictors to local anesthetics
-its usually 1: 200,000 epi, or 5 ug/ml
-causes local vasoconstriction which limits systemic absorption and prolongs the duration of action, while having little effect on the onset of anesthesia
advantages of vasoconstrictors with local
-the decreased systemic absorption increases the chance that the rate of metabolism will match or be higher than the rate of absorption, decreasing the possibility of systemic toxicity
-it also decreases local bleeding
disadvantages of vasoconstrictors with local
-systemic absorption of epi can cause cardiac dysrhythmias, or accentuate hypertension in vulnerable patients
-also need to avoid epi in peripheral nerve blocks in areas without good collateral blood flow, such as in digital blocks
systemic toxicity of local anesthetics
usually occurs after accidental intravascular injection, less commonly can be from absorption of the local from the tissues
-
what does the amount of local absorbed depend on?
-the dose given
-the site of injection
-the use or not of a vasoconstrictor
systemic absorption for the different sites of injection
-is greatest with intercostal nerve blocks and caudal anesthesia
-is intermediate after epidural anesthesia
-and is least after brachial plexus blocks
what causes the clinically significant adverse effects caused by local?
toxicity of the CNS and cardiovascular system
max doses for local anesthetics
-the max acceptable doses for regional anesthesia were given in the prior table, and while they provide a good starting point for limiting plasma concentrations and preventing systemic toxicity, they are not evidence based and dont take into account injection site and patient factors
CNS toxic effects of local anesthetics
-cicumoral numbness and facial tingling
-restlessness
-vertigo
-tinnitus
-slurred speech
-this all culminates in tonic-clonic seizures, since locals are neuronal depressants its thought that they selectively block cortical inhibitoy pathways while leaving the excitatory ones intact, causing seizures
-it can progress, however, to the blockade of both inhibitory and excitatory pathways, causing coma (usually at higher doses)
what can occur with the seizure activity?
-it can cause arterial hypoxemia and metabolic acidosis, which further potentiates the CNS toxicity of the local
management of local anesthetic CNS toxicity
-early intubation and ventilation to maintain oxygenation may be wise
-muscle relaxants can stop the peripheral manifestations of the seizures, but dont stop the central seizures, for this you need a drug that acts centrally to stop seizures:

diazepam 0.1 mg/kg IV
small doses of thiopental 1-2 mg/kg

-can also consider hyperventilation to reduce PaCO2 causing a decrease in CBF to decrease the delivery of local anesthetic to the brain
cardiovascular toxicity by local anesthetics
-the CV system is less susceptible than the CNS to the toxic effects of local, this is why need higher doses to get the CV effects
-get hypotension due to relaxation of arteriolar smooth muscle and direct myocardial depression
-also, local can directly block cardiac Na channels, interfering with the conduction system, and causing an increased PR interval and widened QRS
direct cardiac toxicity between the local anesthetics
-the ability of each to do this is not equal
-the ratio of the dose required to produce CV collapse to that for seizures for lidoacaine is 2x that of bupivacaine, illustrating that bupivacaine has greater cardiotoxicity (which has been the driving force for developing single-enantiomer anesthetics like ropivacaine and levobupivacaine)
allergic reactions to local
-rare, accounting for <1% of the adverse effects seen with these drugs
cross-sensitivity of allergies to local
-esters, which produce metabolities similar to PABA, are more likely to produce hypersensitivity reactions than amides
-there is no cross-sensitivity between the 2 classes of local, so if someone has an ester allergy you can give amides and vice cerse, though it has to be noted that the allergic reaction could be caused by methylparaben or other compounds which resemble PABA which are used as preservatives for both esters and amides, so if the rxn was caused by a preservative, not the ester local anesthetic, it could still occur with amides if they have the same preservative
documenting local anesthetic allergies
-is usually done clinically be the local inducing the common signs f hypersensitivity (rash, laryngeal edema, hypotension, and bronchospasm)
-tryptase is a serum marker of mast cell degranulation, and might be used as confirmation and intradermal testing to establish if local or other drugs are the culprit if tings like opioids or IV anesthetics have been given concurrently
what are the common amino-esters?
-procaine
-tetracaine
-chloroprocaine
what was the earliest injectable local anesthetic, which enjoyed extensive us eduring the first half of the past century?
procaine
why is procaine use limited now that lidocaine has been intriduced?
because of its instability and tendency to produce hypersensitivity reactions
why has procaine started to make a comeback, and what are the problems with this?
-its starting to make a comeback for use in spinal anesthesia due to lidocaine causing TNS (transient neurologic symptoms)

-the problem is that procaine offers only a small advantage with respect to TNS over lidocaine, and there is a high incidence of nausea following its use intrathecally
tetracaine
-ester commonly used for spinal anesthesia due to its long duration of action, especially with a vasoconstrictor
what is the problem with the combo of tetracaine and a vasoconstrictor?
its surprisingly high rate of TNS
tetracaine solutions
-available as a 1% solution, or as niphanoid crystals
which form is preferable and why?
the crystal form, due to the instability of the solution
tetracaine for epidurals or peripheral nerve blocks
is rarely used because of its toxicity at higher doses, slow onset, and profound motor blockade
tetracaine metabolism compared to the other esters
the rate of metabolism is 1/4 that of procaine, and 1/10 of chloroprocaine
chloroprocaine
-ester that is popular in epidurals for OB since its rapid hydrolysis limits the possibility of systemic toxicity and fetal exposure
chloroprocaine and neurologic injury
-due to inadvertent injection intrathecally when intended for the epidural space
-was initially thought to be due to the preservative sodium bisulfate as shown by some early studies, but later studies showed that intrathecal bisulfate did not cause neurotoxicity, but may actually be neuroprotective
-either way, preservative free chloroprocaine exists
problems with epidural chloroprocaine
-it imapirs the anesthetic and analgesic action of epidural bupivacaine and opioids
chloroprocaine for spinals
-has been recently looked at due to lidocaine and TNS, and the thought is the low dose required isnt predicted to produce toxicity
-initial reports are not enough to use it for this right now
amide local anesthetics
-lidocaine
-mepivacaine
-prilocaine
-bupivacaine
what is the most versatile and popular local?
lidocaine, used for everything: topical, IV, regional, epidural, and still spinal though this is controversial due to TNS
lidocaine neurotoxicity
includes:

-cauda equina syndrome
-TNS
lidocaine and cauda equina syndrome
-neurotoxicity caused when its given for spinal anesthesia, especially continuous infusion
-was most often seen when neurotoxic concentrations were given in the caudal region of the subarachnoid space due to maldistribution and high doses given through a small gauge needle
-recently, though, smaller doses routinely given for spinal anesthesia (75-100mg) have been associated with it
TNS
-pain following even modest doses of spinal lidocaine
-was initially called transient radicular irritation, but since the cause of the syndrome is unclear was changed to TNS
what other things predispose to TNS?
-lithotomy position
-positioning for knee arthroscopy
-being outpatient
things that do nt predispose to TNS
-drug concentration
-presense of glucose
-using epi
-needle size
TNS timecourse
-usually occurs 12-24 hours after surgery, and most resolve within 3 days, rarely last >1 week
TNS symptoms
-can be more severe than the pain caused by the surgery itself, and hospitalization is rarely needed for pain control
-is NOT associated with sensory loss, motor weakness, or bowel or bladder dysfunction
first line treatment of TNS
NSAIDs
mechanism
unclear, but looks like it is not the same thing that causes persistent neurologic defecits (cauda equina syndrome)
what local was the first in the series of pipecholyl xylidines that combined the piperidine ring of cocaine and the xylidine ring of lidocaine?
mepivacaine
mepivacaine
-use paralells lidocaine as it produces similar effects to it, except for it is a little longer acting, and with less vasodilation; the only exception is its an ineffective topical anesthetic
advantage versus lidocaine
has a lower, though not insignificant, risk of TNS when used spinally
prilocaine
-once thought to be promising due to its rapid metabolism and low acute toxicity (40% less CNS toxicity than lidocaine), not used much because high doses (>600mg) are associated with buildup of its metabolite, ortho-toluidine
ortho-toluidine
-an oxidizing compound that can convert hemoglobin to methemoglobin
prilocaine induced methemoglobinemia
-will subside spontaneously, and can be reversed with methylene blue (1-2 mg/kg IV over 5 minutes)
prilocaine use
-as stated before, the ability to produce methemoblobinemia has limited its clinical use, and in fact it isnt even approved for use in the US
-has shown some interest in using it for spinals as an alternative to lidocaine, with some studies showing it has a similar duration of action to lidocaine, with less TNS, but no formulation in existence would even be adequate for intrathecal use
what local anesthetic is a congener of mepivacaine, with a nutyl rather than a methyl tail off the piperidine ring, which imparts a longer duration of action?
bupivacaine
bupivacaine characteristics and uses
-longer duration of action tha lidocaine
-gives a high quality sensory block compared to motor, which is why it is the most commonly used local for epidurals during labor
-also a commonly used peripheral nerve block local, and a good record for spinals
problems with bupivacaine
-refractory cardiac arrest is associated with using 0.75% bupivacaine for epidurals when accidentally injected IV, so this concentration isnt recommended for epidural anesthesia
mechanism of bupivacaine's cardiotoxicity
-due to its interaction with cardiac Na ion channels: when compared to lidocaine, which enters and leaves sodium channels quickly, recovery from bupivacaine (which is fast in slow out) block during diastole is prolonged, so its more potent at depressing the maximum upstroke velocity of the cardiac AP (Vmax) in ventricular muscle, creating conditions for unidirectional block and reentry
other mechanisms for bupivacaines cardiotoxicity
-disruption of AV nodal conduction
-depression of myocardial contractility
-indirect effect mediated by the CNS
concerns for bupivacaine's cardiotoxicity
-places an importance on the total dose of the drug given, and using fractional dosing during regional
-cardiotoxicity is not a concern when dilute solutions are given for labor epidurals or for post-op pain, or when small doses are given for spinals
single-enantiomer local anesthetics
include ropivacaine and levobupivacaine
isomers
different compounds which have the same molecular formula
stereoisomers
-the subset of isomers that have atoms connected by the same subset of bonds, but have different spacial orientations
enantiomers
a particualr class of steroisomers that exist as mirror images
chiral
-from the Greek for "hand", because the forms are considered non-superimposable mirror images
properties of enantiomers
-have identical physical proterties, except for the direction of rotation of the plain of polarized light
-the direction is used to classify enantiomers as dextrorotatory (+) if the rotation of light is right or clockwise, and levorotatory (-) if left or counterclockwise
racemic mixture
-a mix of equal parts of enantimomers, which is optically inactive since the rotation from one isomer is cancelled by the opposing rotation of another
how else can chiral compounds be classified?
on the basis of absolute configuration, as R (rectus) or S (sinister)
enantiomer's action
-can differ in their biologic activity
-for example: S (-) bupivacaine has less cardiotoxicity than R (+)
ropivacaine
(levopropivacaine)
-the S(-) enantiomer of the homolog of mepivacaine and bupivacine, with a propyl tail on the piperidine ring
advantages of ropivacaine
-more favorable interaction with cardiac sodium ion channels
-produces more vasoconstriction, which may contribute to its reduced cardiotoxicity compared to bupivacaine
-motor block is less pronounced, and studies show it may preferentially block C fibers
caveat to the advantages of ropivacaine over bupivacaine
-it is less potent than bupivacaine, which is important when comparing the drugs because if more drug needs to be given to get the desired effect, the supposed benefits with respect to less cardiotoxicity and differential block may not be true
-in fact, it appears ropivacaine DOES show advantage over bupivacaine with respect to less cardiotoxicity, but not so with differential block
ropivacaine use in light of this
-since its more expensive, use can only be justified when large doses of local are needed, such as with peripheral nerve blocks and epidurals for surgical anesthesia
levobupivacaine
-the single S(-) enantiomer of bupivacaine
-has reduced cardiotoxicity, but no advantage on differential block compared to bupivacaine (similar to ropivacaine-think the single-enantiomer locals are the same in this regard)
-also similar to ropicavaine, its use due to the advantages are restricted to situations when large doses of local are needed
local anesthetic eutetic mixture
-normally the keratinized layer of skin provided a good barrier against diffusion of topical anesthetic, making anesthetizing intact skin with only topical local difficult
-but, a combo of 2.5% lidocaine and 2.5% prilocaine cream (EMLA) (ie. eutetic mixture) achieves this
eutetic mixture properties
-has a lower melting point than either of the components, and exists as an oil at room temperature which can overcome the barrier of the skin
-especially good in kids to relieve pain from venipuncture or IVs, though it can take up to an hour to start working