pharm 4 Flashcards
1
Q
what is conduction velocity
A
a measure of how fast an axon transmits the action potential
2
Q
how is conduction velocity increased
A
myelination (AP skips along nodes of ranvier- salatory conduction)
or lg fiber diameter
3
Q
what fiber type has first onset
A
B
4
Q
what fiber has second block onset
A
C
5
Q
what fiber has 3rd block onset
A
A gamma (skeletal muscle tone) and A delta (fast pain, temp, touch)
6
Q
what fiber has 4th block onset
A
A alpha (skeleta muscle/ proprioception) and A beta (touch and pressure)
7
Q
explain walking epidural
A
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
8
Q
what is min effective concentration
A
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
9
Q
rank nerve fibers according to their sensitivity of local anesthetics (most- least sensitive)
A
b fibers > c fibers > small diameter A fibers (gamma and delta) > lg diameter A fibers (alpha and beta)
10
Q
na channel can exist in 3 possible states
A
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)
11
Q
when do LA bind to voltage gated Na channel
A
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
12
Q
how do LA affect neuronal depolarization
A
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
13
Q
A
14
Q
what does LA not affect
A
RMP or threshold potential
15
Q
over 50% of LA will exist in what form after injection
A
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
16
Q
what happens to the non ionied fraction of LA
A
diffuses into nerve through lipid rich axolemma
17
Q
how can you tell form the name if it is an ester or amide
A
ester: one i
amide: 2 i’s
18
Q
how are esters metabolized
A
pseudocholinesterase
19
Q
how are amides metabolized
A
hepatic carboxylesterase/ p450
20
Q
what type of LA is more common to have allergy cross sensitivity
A
more common with esters - b/c of PABAs
if allergic to one avoid all others
21
Q
pka determines
A
onset of action!!
if pka is closer to ph… onset is faster
if pka is further from ph.. onset is slower
22
Q
what disobeys pka rule?
A
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
23
Q
lipid solubility is prime determinant of
A
potency
the more lipid soluble a LA- the easier it is for the molecule to transverse the neuronal membrane
24
Q
intrinsic vasodilating effect is a secondary determinent of
A
secondary determinent of potency
vasodialtion increases uptake into systemic circulation- reducing amount of LA avaliable to anesthetize the nerve
25
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
26
do most LA cause vasoconstriction or vasodialtion
vasodilation! except cocaine - vasoconstriction
27
factors that influence vascular uptake and plasma concentration
-site of inection
-tissue blood flow
-physiochemical properties of LA
-metabolism
-addition of vasoconstrictor
28
rank lowest to highest LA toxicity risk
think least vascular to most
subcut- sciatic - femoral- brachial plexus- epidural- caudal - intercostal- interpleural- tracheal - IV
29
max dose of bupivicaine
w/o 2.5 mg/kg (175 mg)
w/ 3 mg/kg (300 mg)
30
max dose of ropivicaine
3 mg /kg (200 mg)
31
max dose of liodcaine
w/o 4.5 mg/kg
(300 mg)
w/ 7 mg/kg (500 mg)
32
most common sign of LA toxicity
seizure
unless!! bupivicaine- cardiac arrest occurs before seizure
33
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
34
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
35
why is bupivicaine more cardiotoxic compared to lidocaine
1. greater affinity for Na receptor
2. slower rate of dissociation from receptor during diastole
more bupiv stays at receptor
cv morbidity is higher- resuscitation more difficult
36
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
37
what is choice for v arrythmias in LAST ACLS
amiodarone
38
what to avoid in ALCS treatment LAST
vasopressin, lidocaine, procainamide
39
what does lipid emulsion do during LAST
acts as lipid sink
intravascular reservoir- sequestors LA and reduces plasma concentration of LA
40
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
41
max dose of lidocaine for tumescent anesthesia
55 mg/kg
42
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
43
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
44
what drugs can cause methemoglobinemia
benzocaine, cetacaine, prilocaine, EMELA, nitroprusside, nitroglycerin, sulfonamides, phenytoin
45
signs and symptoms of methemoglobinemia
hypoxia, cyanosis, chocolate colored blood, tachycardia, tachypnea, mental state changes, coma and death
46
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
47
who is at risk of developing methemoglobinemia
g6p reductase definiciency- dont have methemoglobin reductase- exchange transfusion may be needed
neonates- fetal hemoglobin is deficint in it
48
whats in emela cream
50/50 lidocaine and prilocaine
can cause methemoglobinemia
49
what shortens LA onset of action
sodium bicarb
50
what extends LA duration
epi (b/c its a vasoconstricter- decreases systemic uptake)
51
what can be added to LA to provided analgesia
clonidine (a2 agonist)
epi (a1 agonist)
opioids (mu agonist)
52
what drug improves LA diffusion through the tissue
hyaluronidase- spreads
53
what are the 2 types of nicotinic receptors at the NMJ
prejunctional Nn receptor: on the presynaptic nerve (n= nerve) - regulates ach release
postynaptic Nm receptor- on muscle (motor end plate)- responds to Ach- depolarizes the muscle
54
what happens when ach activates post synaptic nicotinic receptor
na and ca enter the cell- k leaves
makes cell interior more positive- activates voltage gates na channels- depolarizes muscle cell, iniates action potential; releases ca into cytoplasm initating muscle contraction
55
how does ach signal get turned off at neuromusclar junction
achetylcholinesterase hydrolyzes ach almost immediately
56
whats the deal with extrajunctional receptors
more sensitive to sux- open for longer- allows more K leak (hyperkalemia)
normal receptors increase it 0.5-1 for 10-15 mins
57
what conditions have more extrafunctional receptors
spinal cord injury
burns
cva
tetanus
severe sepsis
muscular dyrtrophy
upper or lower motor neuron injury
58
what about nondepolarizers and extrajunctional receptors
resistant- need higher dose
59
how does fade work
2 supplies of ach:
1. ach for immediate release
2. ach that needs to be mobilized before it can be released
nondepolarizers competitively antagonize- no more mobilization - so less is released which is why you see fade
sux binds and facilitates mobilization and there is akways ach for release- this is why you see no fade- same effect as ach
60
phase 1 vs 2 block
phase 1 block- no fade
phase 2 block- fade present
the only time sux causes fade is with a phse 2 block
need very high dose of sux or cont infusion
61
what Tof ratio means full recovery
> 0.9
62
where is best spots for onset and recovery of block monitoring
onset: orbicularis occuli facial nerve
recovery adductor pollicis ulnar nerve
63
what clinical sign means only 50% of the receptors are occupied with nmb
inspiratory force >-40, sustained head lift >5 sec, hand grip >5 sec, holding tongue blade in mouth
64
which means 60% of receptors are occupied
sustained tetany, double burst
65
which means 70% of receptors occupied
TOF no fade, >20 ml/kg vital capacity
66
which means 80% receptors
vt >5 ml/kg
67
what does sux do to your HR
can cause bradycardia or tachycardia
bradycardia: stimulating M2 receptor on SA node
tachycardia and HTN: mimicking action of ach at sympathetic ganglia
(tachycardia is more common than bradycardia in adults)
68
how long (time wise) does sux increase K
10-15 mins
69
can you give sux to renal patients
yes if their k is normal (the dont have a change in response- just if their k is high it may get too high)
70
sux and iop
increases it 5-15 for up to 10 min
concern if OPEN GLOBE injury
controversial if ndmb pretreat changes response
71
sux and intragastric pressure
contracts abd muscles
raises lower esophogeal sphincter tone
cancels eachother out so barrier pressure is unchanged
no increased risk of aspiration
72
what are the names of the enzymes that metabolize ach
acetylcholinestase
genuine cholinesterase
type 1 cholinesterase
true cholinesterase
specific cholinesterase
73
what are the names fo what metabolizes succinylcholine, mivacurium and ester LA
btylcholinesterase, pseudocholinesterase, t2 cholinesterase, false cholinesterase, plasma cholinesterase
74
where is the prime location of aceylcholnestase
NMJ
75
where is the prime location of pseudocholineserase
plasma
76
results of dibucaine test
normal number is 80- meaning dibucaine has inhibited 80% of pseudocholinesterase in the sample- suggests normal enzyme is present
but dibucane wont inhibit atypical plasma cholinesterase so if pt has a number of 20- it means dibucaine didnt inhibit pt pchee and atypical value is present
77
what is the worst variant of pseudocholinesterase
atypical homozygous- succinylcholine lasts 4-8 hrs
78
why does sux have black box
risk of cardiac arrest and sudden death. - linked to hyperkalemia in children with undiagnosed muscular dystroophy (rhabdo)
not!! MH!!
79
why do you use calcium to treat cardiac arrest from sux
hyperkalemia raises RMP so excitable tissues are closer to threshold potential- iv calcium raises threshold potenial- reestablishes the normal distance
80
how do you treat someone who is hyperK from sux
1. stabilize myocardium with calcium chloride 20 or calcium gluconate 60
2. shift k into cells - hyperventilate, glucose and insulin, bicarb
3. k elimination- lasix, volume, HD, hemofiltration
81
who is at highest risk of myalgia following succinylcholine- who is lowest
highest: young adults undergoing ambulatory surgery- women > men
non strenous activity
(thiink: those who are not used to being sore)- young female dont workout
82
are myalgias eliminated by pretreating with nmba
no
83
how else can you reduce risk of myalgias
NSAIDs, lidocaine 1.5 mg/kg, use of higher dose rather than lower dose of sux!!!
opioids will not reduce incidence of myalgia
84
who should not get defasiculation dose of nmb
preexisting skeletal muscle weakness- myasthenia gravis
85
who is at risk for hyperkalemia after succinylcholine
ALS, charcot marie tooth, duchennes muscular dystrophy, guillian barre, hyperkalemic periodic paralysos, MS, upregulation of extrajunctional receptors
86
non depol muscular blockers smallest ED95 to largest
cis, vec, mivac, atracurium, roc
87
what is ed95
dose for optimal conditions of tracheal intubation is 2-3 x ed95
ed95 is dose at which there is 95% decrease in twitch height
88
what are the 2 classes of NDMB
benzylisoquinoquinium and aminosteroids
89
name the benzlisoquinolium compounds
atracurium, cisatracuium and mivacurium
-curium!!
90
name the aminosteroids
roc, vec, pancuronium
91
what does it mean to be a benzylisoquinium compound
undergo spontaneous degregation in the plasma
not dependent on hepatic or renal function for metabolism and elimination
92
atracurium
hydrolyzed by hoffman elimination (33%) and non specific plasma esterases (66%)
non specific plasma esterases are not the same with pseudocholinesterase!!! - people with pseudo.. def do not have prolonged block
this is the same as the ones thta get rid of esmolol and remi
93
cisatracurium
hoffman onlY!!
"the hoff is a cisy"
94
mivacurium
metabolized by pseudocholinesterase- same as sux
relatively short DOA
95
what is hoffman elimination
BASE catalyzed reaction- dependent on normal blood ph and temp
96
what makes hoffman elimination faster
alkalosis and hyperthermia
97
what type of patient is slower to reverse with hoffman
cold and or hypercarbic patient
98
active metabolite of atracurium and cisatracurium
atracurium makes more!
laudanosine- produces seizures
more of a concern with prolonged infusion in icu
mo muscle relaxant properties
99
does mivacurium have active metabolite
no
100
what drugs potentiate effects of nmb
voltatiles, antibiotics, antidysrhythmics, LA, diuretics
101
electrolyte distrubances that can potenitate effects of NMB
increased: lithium and mag
decreased: calcium and K
102
what NMB has vagolytic effect
pancuronium
inhibits M2 receptor at sa node, stimulates release of catecholamines and inhibits catecholamine reuptake in adrenergic nerves
increases hr and co with no or minimal effect in svr
103
what nmb do you avoid in someone with hypertrophic cardiomyopathy
-pancuronium (vagolytic)
-atracurium and mivacuronium (histamine release)
104
what NMB is most likely to cause anaphylaxis
sux! not roc
105
how do cholinesterase inhiitors reverse paralysis caused by nondepol nmb
aceylcholinesterase hydrolyzes ach
edrophonium, neostigmine, pyridostigmine- inhibit ache- indirectly increases ach concentration- making it able to competitively compete for sites at nicotinic receptor and antagonize the blcok
106
how does renal failure affect the dosing of ache inhibitors and aminosteroid nmb
it will prolong both so dose adjustment is not needed
107
side effects of ache inhibitors
dumbbells
diarrhea, urination, miosis, bradycardia, bronchoconstriction, emesis, lacrimation, laxation, salivation
108
which one has the most sedation, antisialog, prevention in motion nausea, mydriasis
all scopalamine
109
what antimuscarincs pass through BBB
atropine and scopalamine- tertiary (lipophilic)- easily pass
glyco does not
110
does atropine ever cause bradycardia
yes- can cause paradoxial bradycardia in doses under <0.5 mg
111
ht transplant and antimuscarinic
intrinisc firing rate of SA node now soley determines HR
muscarinic antagonists do not affect hr of pt with previous ht transplant- but they will still get other effects so they should still get antimuscarinic
112
MOA of sugammadex
gamma cyclodextran- ring encaposlates nmb so it cannot engage with nicotinic receptor
113
what nmb does sugammadex work best with
roc > vec > panc
works on aminosteroids
no effect on benzylisoquinolones
114
how does sugmmadex get metabolized
it is excreted unchanged by kidneys
115
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