Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology for Anesthesia > 06 - NMB Agents and Reversal > Flashcards

06 - NMB Agents and Reversal Flashcards

1
Q

what is the neuromuscular junction?

A

the narrow gap between neuron and muscle fiber

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

when the nerve depolarizes, which ions and neurotransmitters are involved?

A

Ca ions enter neuron and ACh is released from vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

where does ACh bind?

A

ACh binds nicotinic cholinergic receptors on motor end-place of muscle fiber

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

how does ACh work?

A

ACh receptor opens ion channel to generate end-plate potential
potential propogates along muscle membrane leading to contraction
amt of ACh released far exceeds (by 10-fold) amount needed for depolarization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

how is ACh hydrolyzed? what are the products?

A

ACh is hydrolyzed into acetate and choline by acetylcholinesterase (AChE)
embedded in motor end-plate membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what happens to the muscle when ACh receptors close and end-plate repolarizes?

A

muscle begins to relax

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

describe NMB agents and reversal

A

quaternary ammounium compounds with affinity for nicotinic ACh receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what happens with depolarizing NMBs?

A

cloely resemble ACh and bind to ACh receptors (agonist)

generate muscle action potential

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

T/F depolarizing NMBs are metabolized by AChE

A

False

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is a Phase I block?

A

end plate cannot repolarize, muscle becomes flaccid.

peripheral nerve stimulation: constant but diminished twitch, no fade, no post-tetanic potentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is a Phase II block?

A

prolonged depolarization causes abnormal response to ACh

resembles non-depolarizing block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what happens with non-depolarizing NMBs?

A

bind ACh receptor but cannot induce ion channel opening (competitive agonist)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

where do non-depolarizing NMBs bind?

A

bind to a subunit of ACh receptor so ACh cannot bind, but receptor is not activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

T/F non depolarizing NMBs do not generate end-plate potential

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what percentage of receptors are blocked before fade is observed?

A

> 70%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what percentage of receptors are blocked before complete twitch suppression is observed?

A

> 90%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is peripheral nerve stimulation?

A

fade effect during prolonged/repeated stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

why would there be fade of twitches?

A

less ACh available in nerve terminal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

when is fade most obvious?

A

sustained tetanus or double-burst stimulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

how are depolarizing agents reversed?

A

diffuse away from NMJ -> hydrolysis by plasma pseudocholinesterase

Phase I block: no reversal agent exists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what happens if you try to reverse a depolarizing agent with AChE inhibitor?

A

reversal of Phase I block with AChE inihbitor can lead to prolonged depolarization
reversal of Phase II block with AChE inhibitor may be appropriate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

how are non-depolarizing agents eliminated?

A

redistribution, metabolism, excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

how will the amount of ACh be affected if you inhibit AChE?

A

increase amount of ACh in NMJ

increased AChe will compete with the NMB drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the only available depolarizing muscle relaxant?

A

succinylcholine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what is the structure of succinylcholine?

A

two joined ACh molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what is the onset of sux? duration?

A

rapid onset - 30-60sec

short duration - <10min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is sux metabolized by?

A

pseudocholinesterase (only a small fraction actually reaches NMJ)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what factors would cause prolonged action of sux?

A

hypothermia
pregnancy
liver disease
renal failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how long will sux last with a 1:50 heterozygous abnormal pseudocholinesterase gene?

A

20-30min block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

how long will sux last with a 1:3000 homozygous abnormal pseudocholinesterase gene? how do you treat it?

A

4-8 hour block

treat with mechanical ventilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

how does dibucaine affect sux?

A

dibucaine is a LA that inhibits pseudocholinesterase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what is the dibucaine number? normal values?

A

% inhibition = dibucaine number
normal = 80
heterozygous = 40-60
homozygous = 0-20

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what do cholinesterase inhbitors do? how?

A

prolong phase 1 depolarizing block

inhibition of AChE -> high conc of ACh -> intensify depolarization

inhibition of pseudocholinesterase -> reduced hydrolysis of sux

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what’s an example of a cholinesterase inhibitor?

A

organophosphate pesticides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

which nondepolarizing NMBA inhibits pseudocholinesterase?

A

pancuronium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what can small doses of nondepolarizing NMBA do to sux?

A

small doses can antagonize depolarizing block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what is the IV dose of sux?

A

1-1.5 mg/kg

as low as 0.5 mg/kg if defasiculating dose not used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

will higher or lower doses of sux increase likelihood that spontaneous breathing will resume after desaturation?

A

lower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

do you use true body weight or ideal body weight to calculate dose of sux?

A

true body weight

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

T/F boluses (10mg) can be repeated

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

how would you run an infusion of sux?

A

0.5-10mg/min (mix 1-2 vials in 100mL bag)
titrate to effect
use nerve stimulator to prevent Phase II block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what is the IM dose of sux?

A

4-5 mg/kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

what is the dose of sux for layngospasm?

A

0.1 mg/kg IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

T/F the side effects of sux are related to its resemblance to ACh

A

true

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

what are the CV side effects of sux?

A

binds muscarinic cardiac ACh receptors:
bradycardia, decr contractility

opposite effect at highser doses (binds nicotinic ACh receptors in autonomic ganglia ?)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

when is bradycardia especially seen with sux?

A

children and 2nd dose in adults

consider prophylactic treatment with atropine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

how can fasiculations be prevented?

A

small dose of non depolarizing durg, 5 min in advance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

how is hyperkalemia caused with sux?

A

sustained opening of ion channels and membrane depolarization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

how much is serum K+ increased with sux?

A

0.5 mEq/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

when will there be a significant K+ release? why?

A

trauma, denervation
rapid proliferation of extrajunction ACh receptors with neural injury
widespread depolarization -> significant K+ release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

T/F pre-tretament with nondepolarizer will prevent hyperkalemia

A

FALSE

pre-treatment with nondepolarizer will NOT prevent hyperkalemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

when can higher instances of hyperkalemia be seen?

A 
3rd degree burn injury
massive skeletal trauma
upper motor neuron injury
denervation -> muscle atrophy
myopathies (myotonia, muscular dystrophy)

potential risk within 96 hrs
peaks 7-10 days after injury
lasts 6 mos or longer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

how can myalgia with sux be prevented?

A

defasiculating dose of nondepolarizer

54
Q

how is ICP and gastric pressure affected by sux?

A

increased ICP and gastric pressure
not consistently observed

both can be attenuated with defasiculating dose

55
Q

how is IOP (intraocular pressure) affected by sux/

A

increased
no reports of extrusion of ocular contents with succinylcholine

IOP not attenuated with defasiculating dose

56
Q

when will a phase II block occur with sux?

A

after 2-4 mg/kg IV or after a single dose, in pts with atypical plasma cholinesterase

57
Q

how does a phase II block occur?

A

presynaptic block reducing the synthesis and mobilization of ACh, and postjunctional receptor desensitization

58
Q

do inhalation anesthetic drugs accelerate or decelerate onset of Phase II block?

A

accelerate

59
Q

how can you antagonize a Phase II block?

A

anticholinesterase drugs but response is difficult to predict

60
Q

how do you treat a Phase II block?

A

advisable to allow spontaneous recovery

61
Q

T/F sux is a potent trigger for malignant trigger

A

malignant hyperthermia

62
Q

what can look like MH?

A

young pt with undiagnosed muscular dystrophy going into hyperkalemic cardiac arrest

neuroleptic malignant syndrome (NMS)

masseter muscle rigidity (MMR)

63
Q

symptoms of neuroleptic malignant syndrome (NMS)?

A

hyperthermia, muscular hypertonicity, autonomic instability, mental status changes

related to administration of antipsychotic drugs

64
Q

what is masseter muscle rigidity?

A

trismus making it difficult/impossible to open jaw

mild/transient MMR in response to sux is normal

65
Q

when is MMR seen?

A

1-4% of children receiving halothane/sevo and sux

when MMR occurs following sux, elective surgery can be postponed

66
Q

how do you treat MMR? NMS?

A

MMR - assume it is MH and begin treatment
pt should remain in hospital for 24 hrs. monitor signs of rhabdomyolysis (myoglobinuria and myoglobinemia). check CK levels and electrolytes q8h

NMS - no MH precautions necessary

67
Q

what can sux-induced MMR lead to?

A

rhabdomyolysis

68
Q

to summarize…

ABSOLUTE contraindications of sux are?

A 
MH
dangerously high serum K+
known myotonia or muscular dystrophy
>2-4 days after CNS injury (stroke, cord injury)
massive musculoskeletal injury
major burn
69
Q

what are the two types of non-depolarizing neuromuscular blocking agents?

A

benzoisoquinolines (“-acurium”)

steroidals (“-curonium”)

70
Q

what are the onset and duration times of nondepolarizing NMBs?

A

slower than sux

speed onset with higher dosing than usual - can lead to prolonged recovery times

71
Q

what is the priming dose of nondepolarizing NMBs?

A

10% of intubating dose 5 min before induction

anxiety, dyspnea, dysphagia, desaturation in some pts

72
Q

what is the defasiculating dose of nondepol NMBs?

A

10% of intubating dose 5 min before sux

may need higher doses of sux (up to 1.5 mg/kg)

73
Q

how do you maintain nondepol NMBs?

A

intermittent boluses or continuous infusion

74
Q

what can potentiate nondepol NMBs?

A

inhalational agents (des>sevo>iso>hal)
ABX (aminoglycosides - prolong steroidal NMBs)
phenytoin
Mg

75
Q

prolonged action of nondepol NMBs?

A

hypothermia
acidosis
hypokalemia
hypocalcemia

76
Q

which muscles are more sensitive to NMB?

A

muscles of glottis, face, airway, and diaphragm are LESS sensitive to NMB than the thumb (adductor pollicis)

dose to block diaphragm is twice the dose needed to block adductor pollicis

77
Q

how is cisatacurium metabolized?

A

Hoffman elimination

does not rely on pseudocholinesterase, renal, or hepatic elimination

78
Q

which is a common drug in renal failure and for ICU infusions?

A

cisatracurium

79
Q

what is the dose of cis?

A

0.1-0.15 mg/kg

80
Q

what is the onset and duration of cis?

A

onset - 2-4 min

duration - 35-40 min

81
Q

how do you store cis?

A

keep it refrigerated

82
Q

what is atracurium?

A

isomer of cisatracurium

hypotension and histamine release at higher doses

83
Q

how is atracurium degraded?

A

Hoffman elimination AND ester hydrolysis by non-specific plasma esterases

degraded into laudanosine (seizures) and acrylate fragments

84
Q

what NMB has fast onset, is short-acting, metabolized by pseudocholinesterase, and is no longer available?

A

mivacurium

85
Q

which NMB is a long-acting agent an can be more difficult to reverse than other agents?

A

pancuronium

86
Q

what percentage is pancuronium renally cleared?

A

40%

caution in renal failure!!

87
Q

how does pancuronium affect HR, BP, CO

A

increases in HR, BP, CO (block cardiac muscarinic ACh receptors)

88
Q

what is the dose of pancuronium? onset and duration?

A

dose - 0.08-0.12 mg/kg
onset - 2-4 min
duration - 60-120 min

89
Q

how do you redose pancuronium?

A

~0.01 mg/kg every 20-40 min

90
Q

what percentage is vecuronium renally cleared?

A

25%

91
Q

dose of vec? onset and duration? redose?

A

dose - 0.08-0.12 mg/kg
onset - 3-4 min
duration - 35-45 min
redose every 15-20 min

92
Q

dose of roc? onset and duration? redose?

A

dose - 0.45-0.9 mg/kg
onset - 2 min (90 sec with 1.2mg/kg)
duration - 30-40 min
redose 0.15 mg/kg every 15-20 min

93
Q

which NMBs are intermediate agents?

A

cis, vec, and roc

94
Q

what are cholinesterease (AChE) inhibitors or “anticholinesterases”?

A

reversal agents

95
Q

what are common AChE inhibitors?

A

neostigmine, pyridostigmine, edrophonium, physostigmine

96
Q

how do AChE inhibitors work?

A

indirectly increase amount of ACh in the NMJ which can compete with the nondepolarizing NMB agent

reversibly bind to the AChE enzyme

may be other mechs as well (presynaptic actions and non-ACh-mediated actions)

97
Q

T/F organophosphates (pesticides) are also anticholinesterases

A

true

98
Q

what disease are reversal agents used in diagnosis and treatment of?

A

myasthenia gravis

99
Q

what happens with excessive doses of AChE inhibitors?

A

can cause ACh-mediated blockade which can lead to weakness

recommend decreased dose if recovery from NMB is almost complete

100
Q

what will pseudocholinesterase inhibition do to sux?

A

some degree of it can prolong action of sux

101
Q

what are side effects of reversals? why?

A 
CV - bradycardia
pulm - bronchospasm, secrertions
CNS - excitation (only physostigmine crosses the B-B barrier), miosis (pupillary constriction)
GI - N/V, GI activity, salivation
SLUDGE BB

due to increased systemic ACh

102
Q

how do you treat the side effectes of AChE inhibitors?

A

anticholinergic agent like glycopyrrolate

glyco does cross B-B barrier, atropine does

103
Q

clearance of AChE inhibitors?

A

hepatic - 25-50%

renal - 50-75%

104
Q

what must you have before giving reversal drug?

A

evidence of spontaneous recovery

TOF with fade - full reversal dose
TOF without fade - partial reversal dose
sustained 5sec tetanus or cliinical evidence of adequate strength - consider no reversal (!!)
no tetanic response - unreversible

105
Q

what do you consider when evaluating spontaneous recovery?

A

sustained head lift/leg lift > neg inspiratory force > vital capacity > tidal volume

106
Q

speed of different reversals?

A

edrophonium > neostigmine
higher dose speeds reversal
shorter-acting agents reverse faster than long-acting agents
severe end-organ dz can prolong block (renal/hepatic failure)

107
Q

dose of neostigmine? onset, peak, duration?

A

0.04-0.08 mg/kg (up to 5 mg in adults)
give 0.2 mg of glyco with every mg of neo

onset - 5 min
peak - 10 min
duration - 1 hr

108
Q

when would you consider atropine instead of glyco?

A

neo may cross the placenta

109
Q

T/F pyridostigmine has longer onset/duration

A

T

110
Q

what is the onset and duration of edrophonium?

A

rapid onset of action (1-2 min)
short duration of effect

give with atropine - better match with onset, duration

111
Q

what is the structure of physostigmine?

A

tertiary amine

crosses B-B barrier

112
Q

what is physostigmine used for?

A

treatment for central cholinergic toxicity

reverses some CNS depression/delirium associated with volatile anesthetics and benzos

113
Q

dose of physostigmine? how do you give it?

A

dose 0.04 mg/kg for post op shivering

no need to co-treat with atropine/glyco, but have it ready

114
Q

how is physostigmine metabolized?

A

plasma esterases

115
Q

what is sugammadex?

A

reversal that selectively binds to roc, vec, and pancuronium

cyclodextrin ring binds tightly (but not irreversibly)

116
Q

does sugammadex bind to benzylisoquinolines?

A

no. needs the steroid nucleus

117
Q

when do you give sugammadex?

A

anytime. can reverse deep NMB

could be used with roc for RSI and replace sux

118
Q

what is myasthenia gravis?

A

neuromusc dz - antibodies to ACh receptors

119
Q

can you give sux to myasthenia gravis pts?

A

resistant to sux

may be due to pyridostigmine -> reduced pseudocholinesterase activity

120
Q

how do myasthenia gravis pts react to nondepolaizers?

A

reversal may be incomplete - due to pyridostigmine therapy

altose tries to avoid all NMB agents when possible, but not always feasible

121
Q

what is myotonia?

A

abnormal delay in muscle relaxation after contraction

122
Q

how do myotonia pts respond to sux?

A

sustained contracture, hyperkalemia

123
Q

how do myotonia pts respond to nondepolarizres?

A

normal response

avoid reversal agents -> myotonic responses

124
Q

what is muscular dystrophy?

A

loss of muscle mass

125
Q

how do muscular dystrophy pts respond to sux?

A

hyperkalemic cardiac arrest

pts <10y old (esp males) may have latent, yet-undiagnosed dz

126
Q

how do muscular dystrophy pts respond to nondepolarizers?

A

normal resposne

127
Q

what are some upper motor neuron lesions?

A

hemiplegia, quadriplegia

128
Q

how do hemiplegia/quadriplegia pts respond to sux?

A

hyperkalemia

starts ~2-4 days after injury -> 6-12 mos

129
Q

how do hemiplegia/quadriplegia pts respond to nondepolarizers?

A

resistance to nondepolarizers below the level of lesion

130
Q

what do burns lead to?

A

proliferation of extra-junctional receptors

131
Q

how do burn pts respond to sux?

A

hyperkalemia starting ~2-4 days after the burn -> at least 12 months

132
Q

how do burn pts respond to nondepolarizers?

A

resistance to nondepolarizing agents

Pharmacology for Anesthesia (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions