Exam 2- NMBAs Flashcards
1
Q
where are lower motor neuron cell bodies located?
A
in the ventral horn of the spinal cord and the motor nuclei of cranial nerves
2
Q
how do lower motor neurons project their axons?
A
via the ventral roots to control effector organs
3
Q
what are effector organs?
A
muscles and glands
4
Q
what are the characteristics of somatic motor neurons (3)
A
large diameter, myelinated, and fast conducting
5
Q
what happens to an axon as it approaches its ending?
A
they lose their myelin sheaths before branching into terminal fibers
6
Q
where does each terminal fiber supply a muscle fiber via a specialized connection?
A
the NMJ
7
Q
what does the NMJ consist of?
A
the presynaptic motor neuron, the postsynaptic muscle fiber, and the senaptic cleft
8
Q
what contains the enzyme acetylcholinesterase?
A
the synaptic cleft
9
Q
what does the NMJ convert
A
the electrical signal of the motor nerve into a chemical signal which in turn is converted into an electrical event leading to a mechanical response
10
Q
what does the motor unit consist of?
A
the motor neuron and the muscle fiber it innervates
11
Q
what subunits are capable of binding ACh?
A
only the 2 alpha subunits
12
Q
what kind of receptors for acetylcholine?
A
nicotinic
13
Q
what is the primary purpose of muscle relaxation?
A
to achieve adequate relaxation of the upper airway, vocal cords, and diaphragm to facilitate intubation and surgery
14
Q
NMBAs are NOT
A
anesthetics
15
Q
do NMBAs cause amnesia?
A
no
16
Q
is complete paralysis required for all surgical cases?
A
no
17
Q
main site of action of NMBA is on what receptor?
A
the nicotinic cholinergic receptor
18
Q
what is the twitch monitor?
A
a device used to measure how much muscle relaxation is caused by the dose of a muscle relaxant
19
Q
only depolarizer used in anesthesia?
A
succinylcholine
20
Q
ACh mediates transmission of
A
an impulse from nerve to muscle
21
Q
what happens when depolarization of the motor nerve reaches the nerve terminal?
A
voltage-gated Ca2+ channels open, and the vesicles (quanta) that contain ACh are released
by exocytosis from the nerve terminal into the cleft
22
Q
K+ channels in the nerve terminal area limit
A
the extent of Ca2+ entry into the terminal, and regulate the transmitter quantal release, initiating nerve membrane repolarization
23
Q
the release of ACh quanta is antagonized by (2)
A
hypocalcemia and hypermagnesemia
24
Q
where is ACh synthesized?
A
in the presynaptic nerve terminal
25
what is ACh synthesized from?
acetate and choline
26
where is most of the ACh contained?
in the reserve pool
27
Once nerve depolarization occurs and the intracellular
Ca2+ concentration increases, ACh quanta are released into
the synaptic cleft
28
what is ED50
what dose corresponds to a 50% twitch reduction
29
what is ED95?
corresponds to 95% block
30
anesthesia focuses on ED50 or ED95?
ED95
31
duration of action related to muscle blockers?
time of injection to return of 25% twitch height
32
what is the recovery index?
time interval between 25% and 75% twitch height
33
is rocuronium a depolarizer?
no, it is a nondepolarizer
34
where does a depolarizer work?
at the postsynaptic nAChRs
35
provide an example of a depolarizer
succinylcholine
36
define nondepolarizing drugs
competes for active binding sites on nAChRsp
37
examples of nondepolarizing
everything except succinylcholine
38
what does succinylcholine activate?
the prejunctional receptors to release ACh
39
what does succinylcholine mimic?
ACh
40
what does succinylcholine do to the postjunctional membrane and extrajunctional receptors?
produces sustained depolarization
41
what does prolonged depolarization of the motor end-plate do?
inactivates Na channels & increases influx of K
42
what drug may cause fasiculations before total paralysis?
succinylcholine
43
what is the typical IV dose for succinylcholine?
1-1.5 mg/kg
44
what is succinylcholine onset?
about 1 minute
45
what is succinylcholine duration?
5-15 minutes, dose dependent
46
almost 90% of SCh is...
hydrolyzed in the plasma before reaching the myoneural junction
47
where does hydrolysis of SCh occur?
in the plasma
48
what hydrolyzes SCh?
butyrylcholinesterase (pseudocholinesterase or plasma cholinesterase)
49
what is SCh broken down into?
succinylmonocholine and choline
50
how much of SCh releases the NMJ?
only 10%
51
where is Butyrylcholinesterase/Pseudocholinesterase/Plasmacholinesterase sythesized?
in the liver
52
where are Butyrylcholinesterase/Pseudocholinesterase/Plasmacholinesterase found?
in the plasma
53
what factors lower pseudocholinesterase?
severe liver disease, advanced age, pregnancy, malnutrition, burns, anticholinesterase drugs and Reglan, oral contraceptives
54
what does neostigmine do to pseudocholinesterase activity?
profoundly decrases activity
55
what can cause prolonged muscle relaxation after succinylcholine and mivacurium?
abnormal genetic variant of butyrylcholinesterase mutation
56
how do you test for abnormal genetic variant of butyrylcholinesterase?
check the dibucaine number
57
dibucaine number
results can help to identify individuals at risk for prolonged paralysis following the administration of succinylcholine.
58
Phase 1 block
expected w succinylcholine
59
with continued dosing of a depolarizing NMBA what can occur?
a phase I block can develop into a phase II block
60
what can cause a phase 2 block?
repeated SCh doses or an IV continuous infusion
61
phase 2 block
muscles are no longer receptive to acetylcholine released by the motor neurons
62
cardiovascular side effects of SCh
Sinus bradycardia, junctional and arrest PARTICULARLY IN CHILDREN
Premature ventricular contractions
reflect the actions of succinylcholine at cardiac muscarinic cholinergic (M2) receptors where the drug mimics the physiologic effects of acetylcholine
63
when is arrest common with SCh?
more common if a second dose is given within 5 minutes of first dose and in children
64
what do you treat SCh arrest with?
atropine
65
what can SCh do to plasma levels of potassium?
increase potassium by 0.5 mEq/dL in healthy patient
66
renal patients should avoid
Succinylcholine
67
SCh can cause severe hyperkalemia in what patients?
pts with burns, severe abd infections, severe metabolic acidosis
68
risk of SCh in children?
severe rhabdo, hyperkalemia, and death
69
what pre treatment can you give a patient to reduce cardiac effects
anticholinergics
70
Myoglobinuria
from muscle damage after SCh (most of the patients with rhabdomyolysis and myoglobinuria were subsequently found to have malignant hyperthermia or muscular dystrophy)
71
malignant hyperthermia can be caused by
SCh
72
masseter spasm
increase in tone of the masseter muscle may be an early indicator of malignant hyperthermia (especially in children)
73
what can SCh do to intragastric pressure?
increase intragastric pressure and lower esophageal tone (LES)
74
when does SCh increase intraocular pressure? (time)
2-4 min after administration
75
what drug is a contraindication a open eye injury?
SCh
76
malignant hyperthermia receptor
ryanodine
77
what activates the ryanodine receptor
halogenated agents & succinylcholine
78
what does MH cause release of?
massive uncontrolled release of Ca ++ from the sarcoplasmic reticulum
79
2 classes of nondepolarizing muscle relaxants
aminosteroids and benzylisoquinolinium
80
aminosteroids
pancuronium, pipercuronnium, vecuronium, rocuronium
81
benzylisoquinolinium examples
atracurium and cisatracurium
82
nondepolarizing muscle relaxants mechanism of action
Competitively antagonize the presynaptic receptors to decrease release of Ach (fade on TO4)
83
what do non depolarizing muscle relaxants compete with?
ACh for binding on one or both of the alpha subunits
84
rocuronium action
intermediate dose dependent
85
rocuronium histamine release?
rare
86
rocuronium effects on BP or HR?
none
87
what can be used to defasiculate with SCh?
rocuronium
88
rocuronium potency (low or high)
low
89
rocuronium intubating dose
0.6 mg/kg
90
highest anaphylaxis drug
rocuronium
91
rocuronium onset
good for RSI, variable onset
92
rocuronium metabolites
no real metabolites
93
rocuronium RSI dose
1.2 mg/kg
94
rocuronium comes in a ______. vial
50 mg
95
maintenance/repeat dose of rocuronium
0.1 mg/kg
96
rocuronium defasiculating dose with SCh?
5 mg
97
where is rocuronium mostly eliminated?
by the liver
98
vecuronium induction dose
0.1 mg/kg
99
vecuronium comes in a ______ mg vial
10
100
pretreatment of vecuronium for intubation dose is given when?
3 to 5 min before intubation dose
101
vecuronium maintenance dose for surgical relaxation
0.01 mg/kg
102
pancuronium acting time
long acting
103
pancuronium histamine release?
none
104
pancuronium vagolytic effects
modest tachycardia due to antimuscarinic stimulation
105
pancuronium direct sympathomimetic effects
norepinephrine release and reduced uptake of norepinephrine by adrenergic nerves
106
what drug has potential for significant postoperative residual blockade?
pancuronium
107
pancuronium initial dose
0.06-0.1 mg/kg
108
pancuronium maintenance dose
0.02 mg/kg
109
pancuronium onset
2-5 min
110
pancuronium duration
60-100 min
111
what drugs undergo hoffmann elimination?
Benzylisoquinolines
112
what is Hofmann elimination
Spontaneous, non-enzymatic, non-organ dependent chemical breakdown at physiologic temperature and pH
113
does mivacurium have histamine release?
yes when given quickly
114
mivacurium recovery
spontaneous recovery from the block is rapid
115
mivacurium metabolism
hydrolysis by plasma cholinesterase
116
mivacurium intubation dose
0.2 mg/kg
117
mivacurium infusion dose
5-8 mcg/kg/min
118
mivacurium onset and duration
1 min onset, 20 to 30 min duration
119
atracurium: short/intermediate/long acting
intermediate acting
120
atracurium histamine release?
yes
121
atracurium cardiovascular effects
skin flushing, tachycardia, and hypotension
122
atracurium metabolism
hofmann elimination and ester hydrolysis
123
atracurium dose
0.5 mg/kg
124
atracurium onset
2-3 min
125
atracurium duration
20 to 25 min
126
atracurium primary metabolite
laudanosine
127
what can laudanosine produce?
rare seizure activity
128
cisatracurium: short/intermediate/long acting
intermediate
129
cisatracurium metabolism
30% hofmann elimination
130
cisatracurium histamine release
no
131
cisatricurium cardiovascular changes
none
132
what is a potent cis-cis isomer of atracurium
cisatracurium
133
cisatricurium dose
0.15-0.2 mg/kg IV
134
Cisatracurium onset
2-3 min
135
Cisatracurium peak
4-7 min
136
Cisatracurium duration
40-70 min
137
what does hypothermia do the NMBA?
prolongs the duration by decreasing receptor sensitivity and ACh mobilization
138
what happens to renal and hepatic metabolism w hypothermia?
renal and hepatic metabolism are reducesd
139
what does hypothermia do to Hofmann elimination?
reduces Hofmann elimination
140
what does aging do to the volume of distribution of NMBA
reduced volume of distribution due to decreased total body water and serum albumin
141
what potentiates NMBAs
hypokalemia
142
AChASe can catalyze ACh at _____ molecules per active site per second
4,000
143
Anticholinesterase/Acetylcholinesterase Inhibitors
neostigmine, edrophonium, pyridostigmine
144
Selective Relaxant Binding Agent
sugammadex
145
what blocks the breakdown of ACh by AChAse
Acetylcholinesterase Inhibiting Agents/Anticholinesterase
146
high dose of neostigmine
maximal inhibition
147
Edrophonium: short/ intermediate/ long acting
short duration
148
what drug is endrophonium used with?
atropine
149
Enlon-Plus
is a mixture of Edrophonium and atropine together in the same vial
150
edrophonium is mostly ineffective when?
given for deep blocks
151
edrophonium onset
rapid, 1-2 minutes
152
Edrophonium dose
.5-1 mg/kg mixed with atropine 7-10 mcg/kg (0.014 mg/mg of edrophonium)
153
enlon-plus dose
Enlon-plus: .05-.1 mg/kg slowly over a minute
154
endrophonium given without atropine
causes bradycardia
155
what conditions are associated with upregulation of extrajunctional AChR
hemiplegia, paraplegia, muscular dystrophies, Guillian-barre syndrome, and burns
155
is sugammadex water soluble
yes, highly
156
what drug can encapsulate steroidal NBMA drugs
suggamadex
157
what drug has 8 sugars arranged in a ring
sugammadex
158
what are undesireable affects of sugammadex
nothing really
159
does sugammadex effect acetylcholinesterase or cholinergic receptors?
no
160
what drug when injected over 10s immediately captures free molecules of rocuronium or vecuronium?
sugammadex
161
where is sugammadex filtered out
by the glomerulus
162
when should you avoid sugammadex
patients with decreased creatinine clearance
163
what drug should be avoided in ESRD?
sugammadex
164
sugammadex routine reversal of modertate block dosing
2mg/kg
165
sugammadex routine reversal of deep neuromuscular block dose
4mg/kg
166
sugammadex dose for immediate reversal after rocuronium
16 mg/kg
167
sugammadex and hormonal contraceptives
decreased effectiveness of birth ocontrol
168
sugammadex hypersensitivity reactions
sneezing, nausea, rash and urticaria
169
which reversal agent has a risk of anaphylaxis
sugammadex- airway edema, bronchospasm and CV collapse
170
when is sugammadex anaphylaxis seen most often?
higher dosing
171
when does sugammadex anaphylaxis occur?
within 5 min of admin
172
how to treat sugammadex reactions?
small boluses of epinephrine (10-20 mcg) titrated to response, Benadryl, dexamethasone and famotidine
173
what is the only anticholinesterase that crosses the BBB?
physostigmine
174
what is not used for the reversal of muscle relaxants
physostigmine
175
what are fasiculations
involuntary rapid muscle twitches that are too weak to move a limb but are easily felt by patients and seen or palpated by clinicians
176
fasiculations with SCh
80-90% if not pretreated w non-depolarizer or NSAIDs for myalgias
177
myalgias with SCh
usually big skeletal muscles; 50-60% for 1-2 days
178
a defasiculating dose of _________________ administered prior to succinylcholine decreases its side effects
non-depolarizing muscle relaxant
179
what is the onset of rocuronium
1-2 min depending on dose
180
what is the duration of rocuronium
about 30-70 min after RSI dose
181
what is rocuronium elimination
primarily by the liver (70%)/ 30% renal
182
vecuronium: short/intermediate/long
intermediate NMB
183
vecuronium histamine release
none
184
vecuronium cardiac implications
cardiac stable
185
what drug might precipitate with thiopental
vecuronium
186
what kind of potency does vecuronium have
medium potency
187
what is vecuronium onset
2-3 min for good intubating conditions
3-5 min for maximal blockade
188
what is vecuronium duration
25-40 min you will see 25% recovery; 45-60 min you will see 95% recovery
189
vecuronium metabolite
3-desacetyl (60% potency of vecuronium)
190
pancuronium direct sympathomimetic effects
norepinephrine release and reduced uptake of norepinephrine by adrenergic nerves
191
pancuronium cautions
in any patient that will not tolerate increased HR and cardiac output
192
what drug poses the potential for significant postoperative residual blockade?
pancuronium
192
what drug is used in cardiac surgery to counteract the bradycardia associated with high-dose opioid dosing
pancuronium
192
what is the primary metabolite of atracurium
laudanosine
192
patients with what condition might have an altered response to NMBAs?
myasthenia gravis
192
what can laudanosine produce
rare seizure activity
193
acidosis interferes with
effects of anticholinesterases
194
hypercarbia leads to _______ and interferes with _________
acidosis; antagonism
195
hypermagnesemia prolongs NMBA duration of action by
inhibiting calcium channels
196
hypokalemia potentiates ___________ and can __________ the effectiveness of anticholinesterases on reversal
NMBAs; decrease
197
what drugs can cause bronchoconstriction, increased salivation, increased bowel motility
Acetylcholinesterase Inhibiting Agents/Anticholinesterase
198
Acetylcholinesterase Inhibiting Agents/Anticholinesterase drugs are usually given in combination with
an anticholinergic / antimuscarininc
199
what drugs can cause significant parasympathetic effects
Acetylcholinesterase Inhibiting Agents/Anticholinesterase
200
maximal inhibition occurs when
100% of acetylcholinesterase has been inhibited
201
at maximal inhibiton
* Additional doses of acetylcholinesterases will not improve recovery
* Can lead to paradoxical muscle weakness
* Resultant weakness may be due to desensitization of Ach receptors leading to transmission failure and depolarization block
202
what does neostigmine inhibit
hydrolysis of ACh by AChAsE
203
neostigmine is used with
glycopyrrolate
204
what does using glycopyrrolate with neostigmine do ?
decreases muscarinic side effects of neostigmine
205
does neostigmine penetrate the BBB?
not very well
206
when to reverse with neostigmine
recommendations include waiting until 4 tactile TOF counts are visible at the adductor pollicis before administering
shouldn’t be given until spontaneous recovery evident (TOF)
207
neostimine is more effective in
moderate blocks but it is slow acting
208
neostigmine dose
0.04-0.08 mg/kg
209
max neostigmine dose
5 mg
210
for every 1 mg of neostigmine,
mix with 0.2 mg glyco
211
neostigmine onset
15 min, dependent on twitches
212
neostigmine duration
1-2 hours
213
neostigmine metabolism
hepatic, urinary excretion
214
sugammadex removes
the relaxant from the NMJ and moves it into the plasma
215
high dose of sugammadex (16mg/kg) has the potential for
bradycardia/ cardiac arrest, headache, hypotension, N/V, anaphylaxis and hypersensitivity (pruritus and urticaria)
216
how many mg of sugammadex is required to encapsulate 1mg of rocuronium
4 mg
217
what is sugammadex physically incompatible with
verapamil, ondansetron and ranitidine
218
how long should you wait after sugammadex administration before readministering Roc or Vec?
24 hours after reversal
219
high dose (16mg/kg) sugammadex coagulation affects
increased aPTT, PT and INR
220
high dose sugammadex caution in patients (3)
with coagulopathies
treated with therapeutic anticoagulation
receiving thromboprophylaxis other than heparin and LMWH
221
is physostigmine used for reversal of muscle relaxants?
no
222
what is physostigmine used to treat
anticholinergic toxicity
223
S&S anticholinergic toxicity
flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status, fever and urinary retention
224
CNS symptoms anticholinergic toxicity
restless, shivers, agitation, disoriented
225
provide examples of anticholinergics
atropine, scopolamine, antihistamines, antipsychotics, cyclic antidepressants
226
anticholinergic drug side effects
227
treatment for cholinergic crisis
Atropine 35-70 mcg/kg
Pralidoxime 15 mcg/kg every 20 min
Benzos
228
S&S cholinergic crisis
miosis, salivation, bronchoconstriction, bradycardia, abdominal cramping, weakness, lacrimation,
229
CNS effects of cholinergic crisis
dysphoria, confusion, seizures, coma
230
cholinergic crisis muscarinic symptoms
231
cholinergic crisis nicotinic symptoms
232
cholinergic crisis vs. myasthenic crisis
Cholinergic crisis: excess activity of Ach
Myasthenia Gravis: decrease in Ach activity due to auto-reactive antibodies that attack the nicotinic Ach receptors on postsynaptic membranes
233
how do you differentiate between cholinergic crisis and myasthenic crisis
Give edrophonium... muscle strength will improve if myasthenic crisis
| more strength = myasthenia (M&M)
234
muscle strength will improve with endrophonium in?
myasthenia gravis
235
does edrophonium cross the BBB?
no
236
cholinergic crisis has _________ secretions while myasthenic crisis has __________ secretions
increased; normal
237
cholinegic crisis: bradycardia or tachycardia?
bradycardia
238
myasthenic crisis: bradycardia or tachycardia?
tachycardia
239
what test relieves myasthenic crisis symptoms?
tensilon test
240
pupils are constricted in
cholinergic crisis
| constriction = cholinergic
241
pupils are normal or dilated in
myasthenic crisis
242
increased cholinergic activity
cholinergic crisis
243
decreased cholinergic receptors
myasthenic crisis
244
tensilon test makes symptoms worse in
cholinergic crisis
245
clinical signs of muscle weakness
Blurry vision, double vision
Facial weakness, facial numbness, and general weakness
Most common signs in the PACU:
Generalized weakness
Patient reported difficulty completing 5-second eye opening
Difficulty visually tracking or speaking
Indicative of ocular and pharyngeal muscle sensitivity
246
complications of residual neuromuscular blockade
Need for tracheal reintubation
Impaired oxygenation and ventilation (may be blamed on Opioids)
Impaired pulmonary function
Increased risk of aspiration and pneumonia
Pharyngeal dysfunction
Delayed discharge from the PACU
247
clinical signs of neuromuscular recovery
Tidal volume
Negative inspiratory force
Grip strength
5-second head lift (not a sensitive test for residual block)
Ability to protrude the tongue
Take home: these are unreliable signs of the return of muscle strength
248
depolarizing NBMAS produce muscle relaxation by
directly depolarizing the nAChRs
249
SCh acts as a __________, mimicking ___________
false transmitter; ACh
250
Nondepolarizing NMBAs compete with
ACh for the two α-subunits
251
define onset of action for an NMBA
the time from administration (usually intravenously, IV) until maximal neuromuscular block (disappearance of ST).
252
onset time is _________ related to dose
inversely
253
is the only depolarizing NMBA available clinically
succinylcholine
254
succinylcholine has the fastest _________, shortest __________, and greatest ________ of any NMBA
fastest onset, shortest duration, and greatest reliability
255
SCh has molecular similarity to
ACh
256
is SCh degrated by acetylcholinesterases?
no
257
is SCh fade or no fade
no fade because of progressive but equivalent decrease in the force of contractions
258
when may spontaneous breathing resume after 1mg/kg SCh dose
may resume as fast as 5 minutes after 1 mg/kg SCh administration
259
characteristics of depolarizing block
decrease in train-of-four (TOF) amplitude without fade in response to depolarizing agent administration
260
what can be given to decrease the incidence of postoperative myalgia?
lidocaine and rocuronium, but carry a risk of heavy side-effects
261
what drugs can attenuate IOP increase if given pre-treatment?
lidocaine and sufentanil
262
treatment of hyperkalemia
hyperventilation, IV calcium chloride, and glucose/insulin to shift potassium intracellularly.
263
drug with a black box warning in the pediatric population
Succinylcholine
264
patients receiving ____________ (drug) may be particularly susceptible to muscle injury from administration of SCh
statin therapy
265
In obese individuals who need RSI, the dose of SCh should be calculated on
the basis of actual body weight rather than ideal body weight.
266
when is the use of SCh contraindicated
hx or family hx of malignant hyperthermia
267
where are nondepolarizing NMBAs distributed mostly
in the ECF
268
larger nondepolarizing NMBAs may need to be administered in patients with
renal/hepatic failure, and in burn patients
269
vecuronium recovery time may be prolonged significantly in the patient with
diabetes mellitus
270
Adding depolarizing and nondepolarizing NMBAs results in
mutual antagonism
271
what does the dibucaine number reflect?
the QUALITY of cholinesterase enzyme (ability to hydrolyze SCh) not the quantity that is circulating in plasma
272
what is a normal dibucaine number range?
70-80
273
which NMBA is associated with an increase in potassium?
succinylcholine
274
which 2 NMBAs are associated with histamine release
mivacurium and atracurium (less in atracurium)
275
what does neostigmine inhibit
acetylcholinesterase
276
what is used to treat myasthenia gravis
neostigmine
277
what is the function of neostigmine in anesthesia
reversal of effects of non-depolarizing NMBA drugs after surgery
