NMBAs Flashcards
Do muscle relaxants provide amnesia?
NO
Neuromuscular junction consists of:
-Prejunctional: motor nerve ending
-cleft: AChAse
-Postjunctional: Highly folded muscle fiber
what causes a muscle contraction?
-ACh binds to nicotinic cholinergic receptor (postsynaptic)
Nerve stimulation
-Depolarization reaches nerve terminal
-voltage-gated Ca channels open
-calcium enters the nerve terminal
-Storage quanta Vesicles (presynaptic) release acetylcholine (ACh) into the cleft
-ACh diffuses cleft
-ACh binds to nicotinic cholinergic receptor at postsyn. end plate
-muscle contraction
each quanta contains ____ ACh molecules
5,000 to 10,000
⭐️
Which subunits do NMBs work on?
the 2 alpha subunits
Only ___ subunits are capable of binding ACh
the 2 alpha
If both the alpha subunits are occupied, what happens?
conformational change
central channel opens
What ions enter and exit when the 2 alpha subunits are occupied?
Na & Ca in
K out
____ occurs, and a muscle contraction happens
action potential
Postjunctional receptors have ___ subunits
5
2 alpha, 1 beta, 1 delta, and 1 epsilon (ADULT)
How many ACh molecules are needed to open the post jxnl receptor channel?
TWO
one or none = closed
causes vesicles of acetylcholine to fuse with the nerve membrane
influx of calcium within the terminal
ACh combines with and activates which receptor?
nicotinic receptors on motor end plate
release of ___ from intracellular stores stimulates an interaction between __ and ___. This results in a muscle contraction.
Ca
myosin
actin
Why do we use muscle relaxants?
-Optimize surgical conditions
-Prevent unwanted movement
-Facilitate tracheal intubation **
-Improve mechanical ventilation
The primary purpose of using NMB is to
achieve adequate relaxation of the upper airway, vocal cords, and diaphragm to facilitate intubation and surgery
Prolonged opening and increased ion flow (Hyperkalemia) can occur with (up/down) regulation.
up
Increased Extrajunctional Receptors
(up regulation or down?)
upregulation
Upregulation
stimulation of NMJ decreases over days (severe burns, immobilization, infxn, sepsis, prolonged use of NMBAs in ICU, CVAs)
increased immature nAChrs
immature nAChRs will have increased sensitivity to ____ but decreased sensitivity to ___.
-increased sensitivity to ACh and SCh (more nACHr’s being depolarized)
-decreased sensitivity to Nondepolarizers (more nACHr’s to block
Chronic neostigmine use will affect jxnl receptors by…
downregulating them
Pts w/ myasthenia gravis may experience (up/down) regulation due to chronic neostigmine use.
down-regulation
(Neostigmine: cholinesterase inhibitor; increases ACh levels at nerve terminals)
T/F
NMBAs are anesthetics
NO
not anesthetics
do not cause amnesia
Which causes awareness?
NMBA
not enough anesthesia
not enough anesthesia
T/F
Complete paralysis is required for all surgical cases
false
⭐️
Main site of action of NMBA
nicotinic cholinergic receptor (nAChRs)
at the endplate, which connects to the muscle
T/F
Neuromuscular Blocking Agents is synonymous with paralytic.
True
Most poisonous creature on planet
Golden PoisonFrog
T/F
Paralytics exist in nature.
True
pufferfish
Golden PoisonFrog
all 4 twitches will be full-strength if…
No muscle relaxation
With muscle relaxation….
there will be decreased strength
depolarizer or non?
depolarizer block
depolarizer or non?
non-depolarizer block
Which NMBAs show fade?
non-depolarizers
Potency
the relationship between twitch depression and dose
median dose that corresponds to 50% twitch reduction (among average population)
ED50
ED95
corresponds to 95% block (useful relaxation when twitch abolished)
Do we use ED50 or ED95 more when deciding doses for NMBAs?
ED95
we want what will get pt adequately paralyzed, full relaxed
Duration of Action
Time of injection to return of ___% twitch height
25 or 1 twitch (1 twitch out of 4 twitches)
T/F
Duration of action is dose-dependent
True
T/F
Inhalational agents & NMBAs have a synergistic effect.
True
IA can prolong NMB duration
Recovery Index
Time interval between 25% and 75% twitch height
Speed of recovery
Only depolarizing agent
Succinylcholine
Depolarizing a muscle actually ____ it and keeps it in a relaxed state.
fatigues
Succinylcholine
“Depolarizes” at postsynaptic nAChRs
Nondepolarizing
“Competes” for active binding sites on nAChRs
Aminosteroid (Rocuronium, Vecuronium, Pancuronium)
Benzylisoquinolinium (Mivacurium, Atracurium, Cisatracurium)
How does depolarizing NMB work?
Depolarizes:
occupies 2 alpha subunits
opens channel
ions in
depolarizes muscles
muscle is fatigued
stays in relaxed state
How does non-depolarizing NMB work?
competes for nicotinic sites
binds to 1 alpha subunit
prevents opening
muscle cannot contract
Mimics ACh
depolarizing/succinylcholine
Prolonged depolarization of the motor end-plate will….
inactivate Na channels
increases influx of K
Can a muscle contract while ACh is bound to the receptor?
No
can only contract once it diffuses off receptor
What is the resemblance between ACh and Suxx?
Suxx = two ACh molecules
allows Suxx to sit on top of receptor and bind two alpha subunits
When given may cause fasciculations before total paralysis
Succinylcholine
⭐️
Succinylcholine dosing (adult)
1 -1.5 mg/kg IV
Succinylcholine onset
1 min
Succinylcholine duration
5-15 mins
T/F
We can achieve paralysis even if one of the alpha subunits is occupied by succinylcholine and the other by ACh.
True
Both alpha subunits must be occupied, can be 1 ACh and 1 suxx; or both occupied by suxx
fastest onset, the shortest duration, and greatest reliability (i.e., narrowest onset variability around the mean) of any NMBA
Succinylcholine
All NMBAs interact with ____ and block muscle membrane ____, leading to ___ paralysis.
α subunits of the nicotinic cholinergic receptors
depolarization
flaccid
reversal of ____ block is limited
nondepolarizing
(cholinesterase inhibitors have a ceiling effect)
___% of the IV dose of Suxx is hydrolyzed in the plasma before reaching the myoneural junction.
90
plasma cholinesterase eats it up before it gets to the receptor
pseudocholinesterase breaks suxx into…
succinylmonocholine and choline
Recovery from suxx occurs when…
SCh diffuses away from the NMJ
5-6 mins
SCh = succinylcholine
____% of administered suxx reaches the NMJ
10%
Plasmacholinesterase is also called:
Butyrylcholinesterase
Pseudocholinesterase
Factors that lower pseudocholinesterase
severe liver disease
old
pregnancy
malnutrition
burns
anticholinesterase drugs
Reglan
oral contraceptives
Plasmacholinesterase
Synthesized in the ___ and found in the ___.
liver
plasma
Which drug decreases plasma cholinesterase (PChE) activity more?
Edrophonium
neostigmine
neostigmine
Abnormal Plasma Cholinesterase testing
Dibucaine number
reflects quality of cholinesterase enzyme (ability to hydrolyze SCh) not the quantity that is circulating in plasma
T/F
Dibucaine number reflects quantity of cholinesterase enzyme
False
quality (ability to hydrolyze SCh)
Lower dibucaine numbers mean (shorter/longer) duration of drug action.
longer
How do anesthesia providers usually determine that their pt has abnormal PChE (plasma cholinesterase)?
On the spot. The patient will not recover from paralytic. Twitches not returning when expected.
Will have to recover in ICU
Which type of PChE are we most concerned with?
-homozy. typical
-heterozy. atypical
-homozy. atypical
homozygous atypical
both genes are mutated
T/F
Succinylcholine can be given as an infusion.
False
Will cause Phase II block
What causes Phase II block?
(Suxx)
continued dosing, a phase I block can develop into a phase II block
⭐️
T/F
Succinylcholine is an antagonist, making it a paralytic.
False
NMJ nicotinic AGONIST
Succinylcholine prevents (depolarization/repolarization).
repolarization
Phase II block
(Repeated SCh doses or an IV continuous infusion)
muscles are no longer receptive to acetylcholine released by the motor neurons
“I’m phase 2 faded”
Suxx
CV effects
Sinus bradycardia
junctional
arrest (esp peds)
When giving suxx to kids, mix it with ____.
atropine
Suxx
if a second dose is given within 5 minutes of first dose, we increase the risk of…
cardiac arrest
CV effects of suxx are due to…
its action @ cardiac muscarinic cholinergic (M2) receptors
mimics ACh
Preventing myalgias from SChE (suxx)
pretreat with non-depolarizer or NSAIDs
SChE myalgias are usually due to _____, and affect ____ muscles.
fasciculations
big skeletal muscles
SCh can elevate plasma potassium by ___ mEq/dL in healthy patients.
0.5
caution in renal pts (K already high)
Conditions to avoid SChE
renal Dz
burns
severe abdominal Infections
severe metabolic acidosis
upregulation of AChR
hemiplegia, paraplegia, muscular dystrophies, Guillian-Barre syndrome
Which paralytic should we avoid in a pt with a recent diagnosis of Guillian-Barre syndrome?
SChE (suxx)
Conditions associated with upregulation of extrajunctional AChR
hemiplegia
paraplegia
muscular dystrophies
Guillian-Barre syndrome
burns
Succinylcholine risk specific to children
massive rhabdomyolysis –> renal failure
Which paralytic is better for children?
succinylcholine
rocuronium
rocuronium
suxx risks:
-asystole
-hyperK
-massive rhabdomyolysis –> renal failure
Which paralytic is associated w/ MH?
SchE
Primary sign of MH
Masseter/jaw spasm
Jaw will lock up
cannot scissor jaw open
Best NMB for full stomach
Suxx
Increases intragastric pressure
increases lower esophageal tone (LES) helps prevent vomitus entering airway
NMB to avoid in open eye injury
Suxx
increases IOP
SChE (increases/decreases) ICP.
increases
Malignant Hyperthermia triggers
halogenated agents & succinylcholine
Activates Ryanodine receptor from the sarcoplasmic reticulum
Malignant Hyperthermia
-Massive uncontrolled release of Ca++ from the sarcoplasmic reticulum
-activates uncontrolled – constant (hypermetabolic) muscle contraction state
T/F
ACh is more competitive and more easily bound to alpha subunits than non-depolarizing NMB.
False
NDNMB are more competitive than ACh
can push ACh off receptors
T/F
Non-depNMB only need to occupy one of the alpa subunits to elicit their paralytic effect.
True
2 NDNMB = closed
1 NDNMB + ACh = closed
2 ACh = open
Classes of Non-depolarizing muscle relaxant (NDMR)
Aminosteroid
(Rocuronium, Vecuronium, Pancuronium)
Benzylisoquinolinium
(Mivacurium, Atracurium, Cisatracurium)
Know dis
-dose
-onset
-duration
Nondepolarizing Muscle Relaxants
MoA
Competitively antagonize the presynaptic receptors (one or both alpha subunits) to decrease release of Ach (fade on TO4)