Neuromuscular blockers Flashcards
Which subunits MUST be occupied to open the nicotinic receptor at the motor endplate?
a. alpha and alpha
b. alpha and gamma
c. alpha and delta
d. alpha and epsilon
a. alpha and alpha
The neuromuscular junction is the synaptic connection between a
motor nerve and skeletal muscle
When the presynaptic nerve terminal depolarizes, it releases ___________ into the synaptic cleft
acetylcholine
__________________ is a pentameric ligand-gated ion channel located in the motor endplate at the neuromuscular junction
The postsynaptic nicotinic receptor
_______________ is an enzyme that terminates the effect of Ach
acetylcholinesterase
When acetylcholine binds to the _____________ on the postsynaptic nicotinic receptor, it allows _______ to enter the skeletal muscle.
two alpha-subunits; Na+
What are the type types of nicotinic acetylcholine receptors at the neuromuscular junction?
prejunctional Nn receptor is present on the presynaptic nerve (n= nerve)
postsynaptic Nm receptor is present at the motor endplate on the muscle cell (m= muscle)
What are the subunits of the postsynaptic nicotinic receptor?
2 alpha
1 beta
1 delta
1 epsilon
At rest, the inside of the muscle cell is ____ relative to the outside of the cell.
negative
Why don’t anions (like Cl-) pass through the postsynaptic nicotinic receptor channel?
they’re repelled by the negative charge in the channel
How is the action of Ach terminated at the post-junctional nicotinic receptor?
- Ach is metabolized by acetylcholinesterase to choline and acetate
- it diffuses away from the receptor
All of the following statements regarding extrajunctional nicotinic receptors are true EXCEPT:
a. it’s opened by choline
b. an epsilon subunit replaces a gamma subunit
c. it opens for a longer period of time
d. denervation allows for its proliferation
b. an epsilon subunit replaces a gamma subunit
______________ or ______________ can lead to the proliferation of extrajunctional receptors
Denervation injury or prolonged immobility
In the absence of extrajunctional receptors, succinylcholine can transiently increase serum potassium by ________________ for up to ____________.
0.5-1.0 mEq/L for up to 10-15 minutes
The presence of extrajunctional receptors predisposes the patient to _________ following succinylcholine administration.
hyperkalemia
As a general rule, in the event of a denervation injury, succinylcholine is best avoided ______________ following the injury and at least ______________
24-48 hours and at least one year after
Treatment of succinylcholine-induced hyperkalemia includes
IV calcium chloride
hyperventilation
glucose+ insulin
sodium bicarbonate
Patients with upregulation of extrajunctional receptors are ______________ to nondepolarizers.
resistant
this reduces the potency of these drugs
How many pathologic variants of the nicotinic receptor are there?
two
What are the two pathologic variants of the nicotinic receptor?
The a7 subtype consists of five alpha subunits
The a2B1… subtype has a gamma subunit instead of an epsilon subunit
What conditions represent contraindications to the use of succinylcholine?
upper or lower motor neuron injury
spinal cord injury
burns
skeletal muscle trauma
cerebrovascular accident
tetanus
severe sepsis
muscular dystrophy
prolonged chemical denervation (magnesium, long term NMB infusion, clostridial toxin)
________ may be an exception to this rule, as risk of hyperkalemia can persist for several years after
Burns
Fade during train-of-four stimulation is caused by:
a. agonism of presynaptic nicotinic receptors
b. antagonism of presynaptic nicotinic receptors
c. impaired presynaptic acetylcholine reuptake
d. decreased acetylcholine synthesis
b. antagonism of presynaptic nicotinic receptors
Fade during train-of-four stimulation is most likely caused by
antagonism of presynaptic Nn receptors
Fade is observed with
nondepolarizers because they competitively antagonize the presynaptic Nn receptors
Fade is not observed with
succinylcholine (assuming a phase 1 block) because it stimulates presynaptic Nn receptors
With succinylcholine, acetylcholine mobilization in the presynaptic nerve terminal is
preserved
With nondepolarizers, acetylcholine mobilization in the presynaptic nerve terminal is
impaired
Acetylcholine is synthesized from
choline & acetyl CoA in the presence of the enzyme choline acetyltransferase
What are the two supplies of Ach vesicles?
ach that is available for immediate release
ach that must be mobilized before it can be made available for immediate release
A fraction of the Ach molecules binds to
prejunctional receptors on the nerve terminal allowing for mobilization of Ach vesicles to the frontline
Identify the statement that BEST characterizes a phase 2 block following succinylcholine (select 2.):
1. fade with tetany
2. post-tetanic potentiation is absent
3. constant but diminished response to double burst stimulation
4. prolonged duration
- fade with tetany
- prolonged duration
A phase 2 block occurs with
an excessive dose of succinylcholine
__________________ distinguishes between a phase 1 and phase 2 block.
The presence or absence of fade
_____________ does not exhibit fade
Phase 1
___________ exhibits fade
Phase 2
_______________ produce a phase 2 block
Nondepolarizers
Under normal circumstances, succinylcholine produces a
phase 1 block
What is a phase 1 block?
membrane depolarizes, causing initial muscular contraction followed by flaccid paralysis
What is a phase 2 block?
membrane repolarizes but the nicotinic receptor remains unable to respond to Ach
What two situations favor the development of a phase 2 block with succinylcholine?
dose > 7-10 mg/kg
greater than 30-60 minutes of continuous exposure (IV infusion)
A phase 1 response to stimulation is
diminished but equal- there’s no fade
A phase 2 response to stimulation is characterized by a
progressive decrease in the intensity of the response- there’s fade
There’s no post-tetanic potentiation with
a phase 1 block
There is post-tetanic potentiation with
a phase 2 block
Identify the MOST sensitive indicator of recovery rom neuromuscular blockade.
a. nerve stimulator shows 4/4 twitches with no fade
b. tidal volumes 6 mL/kg
c. vital capacity >20 mL/kg
d. inspiratory force better than ~40 cmH2O
d. inspiratory force better than ~40 cmH2O
A tidal volume of 6 mL/kg is possible when no more than ______________ of the receptors are blocked
80%
A vital capacity that exceeds 20 mL/kg is possible when no more than _________ of the receptors are blocked
70%
4/4 twitches without fade is possible when no more than __________ of the receptors are blocked
70-75%
An inspiratory force better than ~40 cmH2O is possible when no more than ____________ of the receptors are blocked
50%
Recovery from neuromuscular blockade is defined as a TOF ratio of
> 0.9
The best place to measure the onset of blockade (intubation conditions):
muscle: orbicularis oculi (closes eyelid) or corrugator supercilii (eyebrow twitch)
nerve: facial nerve
The best place to measure recovery of blockade (return of upper airway muscle function):
muscle= adductor pollicis (thumb adduction) or flexor hallucis (big toe flexion)
nerve= ulnar nerve or posterior tibial nerve
Muscle groups respond differently in terms of _____, ______, & ________ to neuromuscular blockade
onset, duration, and sensitivity
Despite our best efforts, the risk of residual neuromuscular blockade is
20-40%
The best qualitative bedside tests of recovery include
sustained tetany >5 seconds, sustained head lift >5 seconds, and the patient’s ability to hold a tongue blade in his mouth against force
______________ & _______________ are quantitative assessments that provide a more accurate assessment of the patient’s true degree of recovery from neuromuscular blockade
Electromyography & acceleromyography
____________________ is a poor endpoint for assessing the return of neuromuscular function
The return ofa normal tidal volume
The ability to protect the airway may not fully return until the TOF ratio is
> 0.9
__________________________ is exquisitely sensitive to the effects of muscle relaxants
The upper airway musculature (e.g. genioglossus)
The data we obtain from the PNS is highly ________________, and it’s difficult to detect ________ or _________ when the TOF ratio is >0.4.
subjective; visual or tactile fade
As a general rule, more ________ are more resistant to the effects of NMBs and recover sooner than ______________
central muscles; peripheral muscles
