pharm 4 Flashcards
what is conduction velocity
a measure of how fast an axon transmits the action potential
how is conduction velocity increased
myelination (AP skips along nodes of ranvier- salatory conduction)
or lg fiber diameter
what fiber type has first onset
B
what fiber has second block onset
C
what fiber has 3rd block onset
A gamma (skeletal muscle tone) and A delta (fast pain, temp, touch)
what fiber has 4th block onset
A alpha (skeleta muscle/ proprioception) and A beta (touch and pressure)
explain walking epidural
low concentration of bupivicaine- analgesia with sparing motor function
as concentration is increased- it anesthetizes mroe resitant nerve types such as those that control motor function and proprioception
what is min effective concentration
unit of measurement that quantifies the concentration of local anesthetic that is required to block conduction
fibers that are more easily blocked have lower min effective concentration
fibers more resistent to blockade have higher
rank nerve fibers according to their sensitivity of local anesthetics (most- least sensitive)
b fibers > c fibers > small diameter A fibers (gamma and delta) > lg diameter A fibers (alpha and beta)
na channel can exist in 3 possible states
resting- channel is closed and able to be opened if neuron depolarizes
active- channel is open and na is moving along its gradient into the neuron
inactive- channel is closed and unable to be opened (refractory)
when do LA bind to voltage gated Na channel
guarded receptor hypothesis: LA can only bind to sodium channels in their open (active and inactive - closed refractory) states
LA do not bind to Na channels in their resting states
how do LA affect neuronal depolarization
when enough na channels are blocked- there arent enough open channels for Na to enter cell in sufficient quantity
cell cant depolarize and AP cant propagate
what does LA not affect
RMP or threshold potential
over 50% of LA will exist in what form after injection
LA are weak bases with pka higher than 7.4 - so we can predict most of them will exist as ionized conjugate acid after injection
what happens to the non ionied fraction of LA
diffuses into nerve through lipid rich axolemma
how can you tell form the name if it is an ester or amide
ester: one i
amide: 2 i’s
how are esters metabolized
pseudocholinesterase
how are amides metabolized
hepatic carboxylesterase/ p450
what type of LA is more common to have allergy cross sensitivity
more common with esters - b/c of PABAs
if allergic to one avoid all others
pka determines
onset of action!!
if pka is closer to ph… onset is faster
if pka is further from ph.. onset is slower
what disobeys pka rule?
chloroprocaine!
high pka- shich should mean slow onset
but pka is not very potent- so you have to give it in a higher concentration- giving more creates a mass effect- so it has a rapid onset of action even though it has a high pka
lipid solubility is prime determinant of
potency
the more lipid soluble a LA- the easier it is for the molecule to transverse the neuronal membrane
intrinsic vasodilating effect is a secondary determinent of
secondary determinent of potency
vasodialtion increases uptake into systemic circulation- reducing amount of LA avaliable to anesthetize the nerve
what factors determine DOA
-protein binding- primary!
-lipid solubility and intrinsic vasodilating activity- secondary! - higher lipid soluble- longer DOA; vasodilating activity increases vascular uptake and shortens DOA
do most LA cause vasoconstriction or vasodialtion
vasodilation! except cocaine - vasoconstriction
factors that influence vascular uptake and plasma concentration
-site of inection
-tissue blood flow
-physiochemical properties of LA
-metabolism
-addition of vasoconstrictor
rank lowest to highest LA toxicity risk
think least vascular to most
subcut- sciatic - femoral- brachial plexus- epidural- caudal - intercostal- interpleural- tracheal - IV
max dose of bupivicaine
w/o 2.5 mg/kg (175 mg)
w/ 3 mg/kg (300 mg)
max dose of ropivicaine
3 mg /kg (200 mg)
max dose of liodcaine
w/o 4.5 mg/kg
(300 mg)
w/ 7 mg/kg (500 mg)
most common sign of LA toxicity
seizure
unless!! bupivicaine- cardiac arrest occurs before seizure
lidocaine toxicity effects
1.analgesia
2.tinnitus, restlessness, skeletal muscle twitching, numb lips, blurred vision, hypotension, myocardial depression
3.coma, resp arrest
4. cv collapse
factors increasing risk of cns toxicity in LAST
hypercarbia, hyperkalemia, metabolic acidosis
hypercarbia- increases cbf and increases drug delivery to the brain. decreases protein binding so more free drug can enter brain
hyperK- raises rmp, makes neurons more likely to depolarize
met acidosis- decreses convulsion threshold; favors ion trapping in brain
why is bupivicaine more cardiotoxic compared to lidocaine
- greater affinity for Na receptor
- slower rate of dissociation from receptor during diastole
more bupiv stays at receptor
cv morbidity is higher- resuscitation more difficult
what do you modify during ACLS for LAST
epi- can hinder resuscitation- reduces effectiveness of lipid emulsion therapy
give < 1 mcg/kg if need to give
what is choice for v arrythmias in LAST ACLS
amiodarone
what to avoid in ALCS treatment LAST
vasopressin, lidocaine, procainamide
what does lipid emulsion do during LAST
acts as lipid sink
intravascular reservoir- sequestors LA and reduces plasma concentration of LA
how much lipid emulsion do you give
if pt over 70 kg:
bolus: 100 ml over 2-3 min
infusion 250 over 15-20 min
can repeat bolus and or double infusion
if pt under 70 kg
1.5 ml/kg of LBW (2-3 mins)
infusion 0.25 ml/kg/min
can repeat bolus and or double infusion
max dose of lidocaine for tumescent anesthesia
55 mg/kg
other complications with tumescent anesthesia (other than LAST)
pulmonary edema- from the large volume
if over 2-3 L of tumescent solution is given- recomended GA
what LA are more likely to cause L shift of oxyhemoglobin dissociation curve
prilocaine and benzocaine- can cause methemoglobinemia
oxygen binding site on heme portion of hemoglobin molecule- causes iron molecule in its ferrous form (Fe2+)
oxidation of the iron molecule to its ferric form- creates methemoglobin
impairs o2 binding and unbinding from the hgb molecule- shits oxyhemoglobin dissociation curve to the L- creating physiologic anemia
what drugs can cause methemoglobinemia
benzocaine, cetacaine, prilocaine, EMELA, nitroprusside, nitroglycerin, sulfonamides, phenytoin
signs and symptoms of methemoglobinemia
hypoxia, cyanosis, chocolate colored blood, tachycardia, tachypnea, mental state changes, coma and death
methemoglobinemia treatment
methylene blue (1-2 mg/kg over 5 minutes
max dose: 7-8 mg/kg
methemoglobin reductase metabolizes methylene blue to form leucomethylene blue
