Unit 5 - Neuromuscular Blockers Flashcards
1
Q
what are the 2 types of nicotinic AChRs at NMJ
A
- prejunctional Nn receptor: regulates ACh release
- postsynaptic Nm receptor: responds to ACh (depolarizes muscle)
2
Q
enzyme in synaptic cleft
A
AChE
3
Q
5 subunits of postsynaptic nicotinic receptor
A
- 2 alpha
- 1 beta
- 1 delta
- 1 epsilon
4
Q
what causes postsynaptic nicotinic receptor to open
A
when 2 ACh molecules simultaneously occupy both alpha subinits
Na+ and Ca2+ enter cell, K+ exits
4
Q
what causes postsynaptic nicotinic receptor to open
A
when 2 ACh molecules simultaneously occupy both alpha subinits
Na+ and Ca2+ enter cell, K+ exits
5
Q
electrolyte movement when ACh activates Nm
A
Na+ flows down concentration gradient and enters cell
6
Q
how is muscle contraction initiated after ACh binds to Nm receptor
A
- Na+ enters cell
- muscle cell depolarization instructs SR to release Ca2+ into cytoplasm
- engages in myofilaments, initiates muscle contraction
7
Q
why don’t anions pass through Nm
A
repelled by negative charge
8
Q
what is acetylcholinesterase metabolized to
A
choline + acetate
9
Q
what terminates action of ACh
A
metabolism and diffusion away from receptor
10
Q
what allows extrajunctional receptors to return later in life
A
denervation
prolonged immobility
11
Q
where are EJRs distributed
A
NMJ & sarcolemma
12
Q
conditions that increase EJRs
(avoid succs)
A
- Upper or lower motor neuron injury
- Spinal cord injury
- Burns
- Skeletal muscle trauma
- Cerebrovascular accident
- Tetanus
- Severe sepsis
- Muscular dystrophy
- Prolonged chemical denervation (Mg, long term NMB infusion, clostridial toxin)
13
Q
how does succs affect serum K+
A
can transiently increase serum K+ by 0.5-1.0 mEq/L for up to 10-15 minutes
14
Q
why can conditions that increase EJR cause life-threatening hyperkalemia
A
EJRs remain open longer than postjunctional receptors - allows more Na+ to enter & augments K+ leak
15
Q
how is alpha 7 subunit (pathologic variant of nicotinic receptor) depolarized
A
succs and choline
16
Q
general rule for avoiding succs with denervation injuries
A
- avoid for 24-48 hours after injury
- at least 1 year after
exception - burns (risk can exist for several years)
17
Q
Primary treatment of succs-induced hyperkalemia
A
- IV CaCl
- hyperventilation
- sodium bicarbonate
- glucose + insulin
18
Q
patient response to NDNMBs with increased EJRs
A
resistant
More receptors = more NMB needed to effectively antagonize Nm at NMJ
19
Q
patient response to NDNMBs with increased EJRs
A
resistant
More receptors = more NMB needed to effectively antagonize Nm at NMJ
20
Q
what causes fade with TOF
A
- when a NDNMB competitively antagonizes the presynaptic nicotinic receptor (Nn), ACh mobilization is impaired so only vesciles for immediate release can be used
- nerve stimulation can quickly exhaust this supply
- less ACh released with each successive stimulus
21
Q
2 supplies of ACh at NMJ
A
1) some available for immediate release
2) some that must be mobilized before available for immediate release
22
Q
what propagates AP along nerve axon
A
Na+ channels
23
Q
how do ACh vesicles exit nerve
A
via exocytosis
each vesicle releases 5,000-10,000 ACh molecules into synaptic cleft
24
structure of
24
structure of postsynaptic nicotinic receptor at NMJ
* pentameric ligand-gated Na+ channel in motor endplate at NMJ
* 5 subunits that align circumferentially around an ion-conducting pore
25
what happens when ACh activates post-synaptic nicotinic receptor at NMJ
* ACh binds to alpha subunits, which prompts channel to open
* Na+ and Ca2+ enter cell, K+ leaves
* Na+ flows down concentration gradient and enters muscle cell
* voltage-gated Na+ channels activated, muscle cell depolarizes & generates AP
* myocyte depolarization instructs ER to release Ca2+ into cytoplasm to engage with myofilaments and cause muscle contraction
26
how is the ACh signal "turned off" at NMJ?
AChE positioned around pre- and postsynaptic nicotinic receptors hydrolyzes ACh almost immediately
27
where are EJRs distributed
at NMJ and also throughout sarcolemma
28
receptors stimulated by succs
prejunctional receptors
29
MOA of nondepolarizing NMBs
competitvely antagonize presynaptic Nn receptors
30
why is there no fade with succs
* succs facilitates mobilization of ACh when it binds to presynaptic Nn receptor
* there's always ACh available for immediate release
31
what distinguishes between a phase 1 and phase 2 block
presence or absence of fade
| phase 2 - ACh mobilization impaired, nerve terminal can only release imm
32
NMBs that cause phase 1 block
depolarizing NMBs
| succs
33
NMBs that cause phase 2 block
nondepolarizers
| succs in certain situations
34
2 situations that can create phase 2 block with succs
1. dose > 7-10 mg/kg
2. IV gtt
35
how is phase 2 block characterized
fade with tetany, prolonged duration
36
why can high dose succs cause phase 2 block
likely inhibits presynaptic nicotinic receptor, impairs ACh mobilization/release from presynaptic terminal, and/or creates conformational change in postsynaptic receptor
37
how many twitches will a patient have with succs
either 1 or 4
38
how to reverse a phase 2 block with succs
wait it out
| (don't give reversal)
39
best site to measure NMB onset with TOF
orbicularis oculi (closes eyelid) or corrugator supercilia (eyebrow twitch)
| CN 7
40
Relying on flexion of the 5th finger over- or underestimates NMB recovery
over
41
best site to measure NMB recovery
adductor pollicis (thumb adduction) or flexor hallucis (big toe flexion)
| Nerve = ulnar n. or posterior tibial n.
42
when is full recovery from NMB assumed
TOF ratio is > 0.9 at adductor pollicis
43
what is residual blockade
defined as TOF ratio <0.9
44
what Vt value suggests NMB recovery
5+ mL/kg
45
max receptors occupied when pt Vt 5+ mL/kg
80%
46
max % receptors occupied when pt reaches no fade with TOF
70
47
vital capacity that suggests NMB recovery & max receptors blocked
20+ mL/kg
70%
48
max % receptors blocked when pt has no fade with 50 Hz tetanus
60
49
inspiratory force that suggests NMB recovery
max % receptors blocked
better than -40 (more negative is better)
50%
50
max % receptors blocked with 5 second headlift
50
51
clinical endpoints of NMB evaluation that suggest max 50% receptors blocked
* head lift > 5 seconds
* hand grip same as preinduction
* holding tongue blade in mouth against force
52
best qualitative test of neuromuscular function
holding a tongue blade in the mouth against force
| Limitation: can’t be performed with oral ETT in place
53
structure of succs
2 ACh molecules joined together
54
how can succs cause bradycardia
by stimulating M2 receptor in SA node
55
increases risk of bradycardia with succs admin
2nd dose
| probably r/t primary metabolite succinylmonocholine
56
how can succs cause tachycardia
by mimicking ACh at sympathetic ganglia
57
how do adults vs. kids typically respond to succs in terms of HR
* Adults: tachycardia more common than bradycardia
* Kids: more susceptible to bradycardia d/t higher baseline vagal tone
58
how does succs affect IOP
Transiently ↑ IOP by 5-15 mmHg for up to 10 minutes
59
how to prevent increased ICP with succs
defasciculating dose
60
how does succs affect intragastric pressure
temporarily increases
prevent or minimize with defasciculating dose
61
how does succs affect barrier pressure
net unchanged (increases intragastric pressure, decreases LES tone)
| does not increase risk of aspiration
62
how does succs affect barrier pressure
net unchanged (increases intragastric pressure, decreases LES tone)
| does not increase risk of aspiration
63
side effect of succs that may or may not be related to an MH reaction
massetter spasm
64
black box warning of succs
risk of cardiac arrest and sudden death 2/2 hyperkalemia in children with undiagnosed skeletal muscle myopathy
65
function of dystrophin
| (absence of protein in DMD)
* critical for structure of cytoskeletal on skeletal & cardiac muscle cells
* helps anchor actin and myosin to cell membrane
66
patho of DMD that results from absence of dystrophin
* sarcomma destabilized
* allows creatine kinase and myoglobin to enter systemic circulation & cause inflammation, fibrosis, cell death
67
why are patients with DMD predisposed to hyperkalemia with succs
Absence of dystrophin alters type and number of postjunctional nicotinic receptors on muscle cell
68
s/s DMD assoc. with dystrophin absence
* skeletal muscle weakness
* conduction abnormalities
* cardiomyopathy
* sometimes cognitive impairment
69
marker of skeletal muscle breakdown
Creatine phosphokinase
70
EKG changes with mild hyperkalemia
peaked T waves, prolonged PR
71
treatment of cardiac arrest in a child after induction with succs
immediately start treating for hyperkalemia:
1. Stabilize myocardium: CaCl 20 mg/kg or CaGluc 60 mg/kg
2. Shift K+ into cells: hyperventilation, glucose + insulin, sodium bicarbonate, albuterol
3. Enhance K+ elimination: Lasix 1 mg/kg, volume resuscitation, dialysis, hemofiltration
72
elemental calcium in 10% CaCl vs. 10% CaGluc
10% CaCl = 27.2 mg/mL elemental calcium
10% CaGluc = 9 mg/mL
73
how much 10% glucose to use when treating cardiac arrest from succs
0.3-0.5 g/kg 10% glucose solution + 1 unit insulin per 4-5 g IV glucose
74
s/s postoperative myalgia assoc. with succs
muscle soreness in neck, shoulders, subcostal region, upper abd/trunk muscles
75
MOA of postop myalgia with succs
Believed to be r/t uncoordinated muscle contraction (fasciculations) before paralysis
76
pts at highest risk of postoperative myalgia with succs
young adults undergoing ambulatory surgery (women > men), those who don’t routinely engage in strenuous activity
77
do opioids decrease myalgia with succs
nope
78
pts with lowest incidence of postop myalgia with succs
Children, elderly, and pregnant pts seem to have lowest rates of occurrence
79
methods to decrease risk postop myalgia with succs
* NDNMB pretreatment
* NSAIDs
* lidocaine 1.5 mg/kg
* higher vs lower dose of succs
80
defasciculating dose
1/10th ED 95 dose of non-depolarizer
| 2mg roc, 1.5 mg atracurium, 0.3 vec 3-5 min before succs
81
why is a higher dose of succs needed if defasciculating dose of NDNMB used
* Nondepolarizer will competitively antagonize nicotinic receptor
* more succs needed to overwhelm effect
82
primary location of AChE
NMJ
83
synonyms for AChE
* Acetylcholinesterase
* Genuine cholinesterase
* Type 1 cholinesterase
* True cholinesterase
* Specific cholinesterase
84
primary location of pseudocholinesterase
plasma
85
synonyms for pseudocholinesterase
* Butyrylcholinesterase
* Pseudocholinesterase
* Type 2 cholinesterase
* False cholinesterase
* Plasma cholinesterase
86
enzyme that metabolizes succs, mivacurium, and ester LAs
pseudocholinesterase
87
where is pseudocholinesterase produced
liver
88
how does pseudocholinesterase activity serve as an indicator of hepatic function
produced in liver
89
reference concentration range of pseudocholinesterase
2900-7100 units/L in plasma
90
how does plasma concentration of Pseudocholinesterase affect symptoms
Neuromuscular symptoms begin at 60% of normal, prominent at 20% of normal
91
where is pseudocholinesterase located
liver, smooth muscle, intestines, white matter, heart, pancreas (not CSF)
92
drugs that reduce Pseudocholinesterase activity
* **Metoclopramide**
* **Esmolol**
* **Neostigmine** (not edrophonium)
* Echothiopate
* Oral contraceptives/estrogen
* Cyclophosphamide
* MAOIs
* Nitrogen mustard
93
diseases that decrease pseudocholinesterase activity
* **Atypical PChE**
* **Severe liver disease**
* Chronic renal disease
* Organophosphate poisoning
* **Burns**
* **Neoplasm**
* Advanced age
* Malnutrition
* **Pregnancy** (late stage)
94
definitive diagnosis of atypical acetylcholinesterase
dibucaine test
95
what is dibucaine
amide LA that inhibits normal plasma cholinesterase (no effect on atypical PChE)
96
what does dibucaine number reflect
% of normal enzyme inhibited by dibucaine
97
normal dibucaine no.
80 (dibucaine has inhibited 80% of pseudocholinesterase in sample)
98
genotype, dibucaine no., and succs duration assoc. with typical homozygous pseudocholinesterase
* genotype = UU
* dibucaine no = 70-80
* succs duration = 5-10 min
99
genotype, incidence, dibucaine no., and succs duration assoc. with typical heterozygous pseudocholinesterase
* genotype = UA
* incidence = 1/480
* dibucaine no = 50-60
* succs duration = 20-30 min
100
genotype, dibucaine no., and succs duration assoc. with atypical homozygous pseudocholinesterase
* genotype = AA
* incidence = 1/3200
* dibucaine no = 20-30
* succs duration = 4-8 hours
101
what is atypical plasma cholinesterase
Pseudocholinesterase is produced in sufficient quantity but not functional
| qualitative defect
101
what is atypical plasma cholinesterase
Pseudocholinesterase is produced in sufficient quantity but not functional
| qualitative defect
102
methods to restore levels in atypical pseudocholinesterase
Whole blood, FFP, or purified human cholinesterase
103
treatment of choice for atypical pseudocholinesterase
postop mechanical ventilation
104
diseases assoc. with hyperkalemia from succs
* DMD
* **Guillain-Barre**
* **MS**
* ALS
* Charcot-Marie-Tooth
* **Hyperkalemic Periodic Paralysis**
105
diseases assoc. with nondepolarizing NMB sensitivity
* DMD
* **Guillain Barre**
* **MS**
* ALS
* **Huntingdon**
* **Myasthenia gravis**
* myotonic dystrophy (may have normal response)
106
what is the ED95 of a non-depolarizing NMB
dose at which there’s a 95% decrease in twitch height
107
relationship between ED95 and NDNMB potency
inversely related
measure of potency
108
how can ED95 of NDNMB be used to predict onset
higher ED95 = lower potency = faster onset
109
mivacurium:
- ED95
- intubation dose
- onset
- duration
- ED95: 0.067 mg/kg
- intubation dose: 0.15 mg/kg
- onset: 3.3 min
- duration: 16.8 min
110
cisatracurium:
- ED95
- intubation dose
- onset
- duration
- ED95: 0.04 mg/kg
- intubation dose: 0.1 mg/kg
- onset: 5.2 min
- duration: 45 min
111
vecuronium:
- ED95
- intubation dose
- onset
- duration
- ED95: 0.043 mg/kg
- intubation dose: 0.1 mg/kg
- onset: 2.4 min
- duration: 45 min
112
atracurium:
- ED95
- intubation dose
- onset
- duration
- ED95: 0.21 mg/kg
- intubation dose: 0.5 mg/kg
- onset: 3.2 min
- duration: 45 min
113
rocuronium:
- ED95
- intubation dose
- onset
- duration
- ED95: 0.305 mg/kg
- intubation dose: 0.6 mg/kg
- onset: 1.7 min
- duration: 35 min
114
pancuronium:
- ED95
- intubation dose
- onset
- duration
- ED95: 0.067 mg/kg
- intubation dose: 0.08 mg/kg
- onset: 2.9 min
- duration: 85 min
115
short-acting NDNMB
mivacurium
116
intermediate-acting NDNMBs
cisatracurium, vecuronium, atracurium, rocuronium
117
NMBS in benzylisoquinolinium class
Atracurium
Cisatracurium
Mivacurium
| -curium
118
NMBs in aminosteroid class
Rocuronium
Vecuronium
Pancuronium
| -ronium
119
are NMBs ionized or unionized
ionized
120
which NDNMB class is more affected by renal failure
aminosteroids (may prolong duration)
121
metabolism of atracurium
Ester hydrolysis 66%
Hofmann 33%
122
elimination of atracurium
10-40% renally eliminated
(no liver)
123
metabolite of atracurium & cisatracurium
laudanosine
124
metabolism of cisatracurium
77% hoffman
125
elimination of cisatracurium
* mostly hofmann
* renal elim. is 16% of total clearance
* no liver
126
what is Hofmann elimination
base-catalyzed reaction dependent on normal blood pH and temperature
127
how do pH & temp affect Hofmann elimination
* Faster with alkalosis & hyperthermia
* Slower with acidosis & hypothermia
128
potential adverse effect of laudanosine accumulation
seizures
129
metabolism & elimination of roc
* metabolism: none
* > 70% liver elim
* 10-25% renal elim
* no metabolites
| primarily eliminated via biliary excretion as unchanged molecule
130
metabolism & elimination of vec
* 30-40% liver metabolism
* 40-50% hepatic elim.
* 50-60% renal elim
* metabolite: 3-OH vecuronium
131
metabolism & elimination of pancuronium
* metabolism: 10-20% liver
* 15% hepatic elim
* 85% renal elim
* metabolite: 3-OH pancuronium
132
how can elim 1/2 times of aminosteroid NDNMBs be prolonged
* hepatic dysfunction
* renal failure
* age extremes
133
greatest to least NMB potentiation with volatiles
Des > Sevo > Iso > N2O > Propofol
134
antibiotics that potentiate NMB
Aminoglycosides, polymyxins, clindamycin, lincomycin, tetracycline
135
antidysrhythmics that potentiate NMBs
* Verapamil
* amlodipine
* lidocaine
* quinidine
136
how does lasix affect NMBs
potentiates
137
how does lithium potentiate NMB
↑ activates potassium channels
138
how do Mg, Ca, and K affect NMB
* Mg ↑ = ↓ ACh release from presynaptic nerve
* Ca ↓ = ↓ ACh release from presynaptic nerve
* K ↓ = ↓ RMP
139
how does hypothermia affect NMB
↓ metabolism & clearance
140
how does cyclosporin affect NMB
potentiates
141
NMBs that can cause histamine release & how to minimize
succinylcholine, atracurium, mivacurium
minimize with slow admin.
142
NMB that can stimulate autonomic ganglia
succs
## Footnote
not affected by rate of admin.
143
NMB with slight vagolytic effect
pancuronium
144
MOA of vagolytic effect with pancuronium
Inhibits M2 receptors in SA node, stimulates catecholamine release, inhibits catecholamine reuptake in adrenergic nerves
| ↑ HR & CO, minimal effect on SVR
144
MOA of vagolytic effect with pancuronium
Inhibits M2 receptors in SA node, stimulates catecholamine release, inhibits catecholamine reuptake in adrenergic nerves
| ↑ HR & CO, minimal effect on SVR
145
NMB pts with HCOM should not get and why
pancuronium - vagolytic effect can cause LVOTO
146
most common cause of periop allergic reactions
NMBs
| 1st - succs
2nd - roc
147
how do NMBs cause allergic reactions
* NMB structures contain 1 or more antigenic quaternary ammonium groups that interact w IgE
* Causes mast cell and basophil degranulation
148
lab value that reflects allergic reaction to NMB
elevated tryptase level (peaks at 15-120 min)
149
assoc. between exposure to soap/cosmetics and NMB allergy
* NMB structures contain 1 or more antigenic quaternary ammonium groups that interact w IgE
* Possible to develop following exposure to soap or cosmetics (contain quaternary ammonium)
150
What characterizes a phase II block following succs administration?
Inhibition of presynaptic nicotinic receptors
151
do NMBs treat bronchospasm
No - they relax skeletal muscle, NOT smooth muscle
152
possible explanations for why des potentiates NMB the most of volatiles
* central alpha effect on motor neurons
* inhibition of postjunctional nicotinic receptors at NMJ
* increased NMB affinity at postjunctional nicotinic receptors at NMJ
