Chapter 10 LA Flashcards
amides
- lidocaine
- prilocaine
- ropivicaine
- bupivicaine
- articaine
- mepivacaine
esters
- cocaine
- procaine
- chloroprocaine
- tetracaine
- benzocaine
miscellaneous LA
- EMLA cream
- hyaluronidase (wydase, virtase, others) –> sometimes added to LA to help spread
intermediate chain is an
ester or amide linkage
T/F benzene ring is lipophilic
True
T/F Quaternary amide is hydrophilic
True
LA have 3 things always
- lipid soluble side
- water-soluble side
- amide/ester linkage
amide’s have a __ in chain
nitrogen
ester’s have a __ in chain
oxygen
how are esters broken down?
catalyzed by plasma and tissue cholinesterase via hydrolysis; occurs throughout the body
IS RAPID
esters have a __ allergy potential
higher
if patients exhibit an allergy to any ester drug, all other esters should be
avoided
what is the longest acting ester?
tetracaine
amides are metabolized in the
liver by CYP1A2 and CYP3A4
and thus a significant blood level may develop witha rapid absorption
T/F allergy to amides are extremely common
false
extremely rare
amides are longer acting because they are more
lipophilic and protein-bound and require transport to the liver for metabolism
absorption =
offset
absorption of LA offsets its action, its done working
there is no __ __ among amide class or between the ester and amide agents
cross allergy
just allergic to that amide NOT all the amides
Type A beta fiber:
function, myelination/diameter, anesthetic block onset
- touch, pressure
- heavy 5-12 µm
- intermediate
Type A gamma fiber:
function, myelination/diameter, anesthetic block onset
- muscle tone
- heavy 3-6 µm
- intermediate
Type alpha A fiber:
function, myelination/diameter, anesthetic block onset
- proprioception, motor
- heavy, 12-20 µm
- last
Type A delta fiber:
function, myelination/diameter, anesthetic block onset
- pain, cold temperature, touch
- heavy 1-5 µm
- intermediate
Type B fiber:
function, myelination/diameter, anesthetic block onset
- preganglionic autonomic vasomotor
- light, < 3
- early
Type C dorsal root fiber:
function, myelination/diameter, anesthetic block onset
- pain, warm and cold temperature, touch
- none, 0.4-0.12
early
Type C sympathetic fiber:
function, myelination/diameter, anesthetic block onset
- postganglionic vasomotor
- none, 0.3-1.3
- early
which LA are chiral drugs because the molecules possess an asymmetric carbon atom
mepivacaine, bupivacaine, ropivacaine
which amide LA’s have a long DOA
bupivicaine
ropivicaine
which amide LA’s have a medium DOA
lidocaine
mepivacaine
prilocaine
which ester LA has a medium DOA
cocaine
which ester LA has a short DOA
procaine
which ester LA has a topical only DOA
benzocaine
which ester LA has a long DOA
tetracaine
LA cause temporary loss of __ __ without loss of consciousness by blocking conduction along __ nerve fibers
pain sensation; sensory
some selectivity for pain afferents is acheived partly by using the agent close to
target neurons
LA are either strong acids or weak bases?
weak bases
all currently used drugs block
voltage-dependent Na channels in excitable cells
which decreases the likelihood of an action potential
the target site of the drugs is on the
cytoplasmic side of the neuron membrane
so drug molecules must pass through the membrane
LA exist in __ between ionized and nonionized forms
equilibirum
lipophilic forms diffuse more __ through the membrane
readily
hydrophilic diffuse more readily though
cytoplasm
because LA act on excitable cells then can cause toxicity including:
fatal cardiovascular effects or seizures
what characteristics of LA increases when epi is added?
- degree of motor blockade
- degree of sensory blockade
- duration of blockade
- area of blockade
does onset time increase or decrease when epi is added to LA?
decreases
*except during spinal anesthesia
what characteristics of LA increase when the dose is increased (volume or concentration)?
- degree of motor blockade
- degree of sensory blockade
- duration of blockade
- area of blockade
- peak plasma concentration
does onset time increase or decrease when the dose is increased of LA (volume or concentration)?
decrease
peak plasma concentraiton __ with the addition of epi to LA
decreases
what is the usual dose of epi when added to a LA?
5 µm/mL or 1:200,000
epi is usually added to LA to __ the __ of vascular absorption
decrease; rate
allowing more anesthetic molecules to reach the nerve membrane and improve the depth and duration of A
adding epi can also be used as a __ for inadvertent intravascular injection
marker
dose mg/kg for procaine 1%
14
dose mg/kg for tetracaine 1%
1
MOST TOXIC LA
dose mg/kg for chloroprocaine 3%
11 (14)
dose mg/kg for cocaine 4%
3 (topical) –> 200mg total
dose mg/kg for lidocaine 1%
4 (7)
dose mg/kg for lidocaine 2%
4 (7)
dose mg/kg for mepivacaine 2%
4 (7)
dose mg/kg for prilocaine 3%
7 (8.5)
dose mg/kg for bupivacaine 0.75%
2.5 (3.2)
dose mg/kg for ropivaciane 0.75%
3 (3.5)
variation occurs in single injection dose depending on
the type of LA and the location of the block
in the event of LA overdose, respiratory depression may occur resulting in __ & __
hypoxia; acidosis
the acidosis may increased the
ionized fraction of LA within the cerebral circulation thereby DECREASING its ability to cross the blood/brain barrier
cannot leave the brain to reenter systemic circulation!! very bad!!
LA accumulation in the fetal circulation is enhanced by
fetal pH is lower than the maternal pH this may result in high fetal levels of LA
LA injected into acioditic, infected tissues are __ due to the loss of lipid solubility
ineffective
LA lipid solubility is diminished in an acidotic environment d/t
increased concentration of the ionized (water-soluble) form of the drug
loss of lipid solubility prevents ABSORPTION INTO THE NERVE thereby preventing access to the site of action
carbonation of LA __ the onset and intensity of of action of neural blockafe
speeds
CO2 readily diffuses into the nerve __ the pH within the nerve
lowering
the lipid-soluble form of the LA after passing through the neuronal membrane will receive
protons from the intra-neuronal environment and ionize
increasing th eionized fraction within the neuron produces
higher concentration of the active form of the anesthetic available at the Na channel (site of action)
T/F CO2 makes the outside of the nerve more acidic
false
inside of the nerve
commercialy available LA are prepared in a slightly
acidic formulation
improves stability by increasing the concentration of the ionized form of the drug
addition of Na bicarb to the LA mixture increased the
pH of the solution thereby increasing the concentration of the non-ionized form of the drug
improving lipid solubility of the LA improves
diffusion of the LA through the neuronal membrane leading to a more rapid onset of action
Basic solution make the __ of the nerve more __ and easier for LA to __ onset of action
outside; basic; increase
fetus has a more __ environment than mom
acidic
one of the most important factors of how fast a LA will work it its
pKa
the lower the pKa the ___ the onset
faster
the greater the portion of nonionized drug available, and the drug needs to be non-ionized to penetrate the nerve
the exception is __ the pKa is 8.7
chloroprocaine
but its still the fastest LA because we give it a high concentration 3%
the more protein bound a LA =
the longer the duration of action
how does a more protein-bound LA make it last longer?
if it binds to stronger proteins, it binds to tissues/nerves and therefore takes longer to be released
Why do we add epinephrine to locals?
to increase the duration of action and decrease toxicity!
unique properties of cocaine
- naturally occurring
- comes from coca plants
- sigmund freud introduced it into medicine
T/F cocaine is extremely potent
True
- can only be used as a topical NOT injectable (Max dose 200mg)
- blocks the reuptake of norepinephrine and epinephrine –> sympathomimetic effects
LA accumulation in the fetal circulation is enhanced by
the fact that the fetal pH is lower than the maternal pH
this may result in high fetal levels of LA
lipid solubility correlates with
potency
*greater lipid solubility enhances diffusion through neural coverings and cell membranes allowing a lower mg dosage
dissociation constant (pKa) correlates with
time of onset
*determines the portion of an administered dose that exists in the lipid-soluble, tertiary molecular state at a given pH. Agents having a lower pKa have a greater proportion in the tertiary, diffusible state, and the hastens onset
chemical linkage correlates with
metabolism
*esters are principally hydrolyzed in plasma by cholinesterases. Amides are primarily biotransformed within the liver
protein binding correlates with
duration
*affinity for plasma proteins also corresponds to affinity for protein at the receptor site within Na channels, prolonging the presence of anesthetic at the site of action
symptoms of the therapeutic level of LAST
- lightheadedness
- tinnitus
- circumoral and tongue numbness
Stage 2 of LAST
visual disturbances and muscular twitching and convulsions
stage 3 of LAST
coma and unconsciousness
bupivacaine binds to
certain cardiac proteins
- binds to the heart preferentially over any other tissue
stage 4 of LAST
respiratory arrest & CVS depression
T/F bupivacaine can be used for IV regional
FALSE
binds to the cardiac proteins causing cardiac arrest
the spectrum of presenting signs:
CNS: CV: combination
45%: 11%: 44%
spectrum of CNS signs
- seizure 68%
- dizziness, drowsiness, tinnitus, perioral, confusion,dysphoria, dysarthria 11%
- loss of consciousness 7%
- agitation 11%
spectrum of CV signs
- bradycardia/asystole 27%
- hypotension 18%
- tachycardia 16%
- wide complex 12%
- VT/VF 13%
when does LAST usually occur in 50% of cases?
in less than 1 minute
when does LAST usually occur in 25% of cases?
1 to 5 mins
