Exam 2- NMBAs Flashcards
where are lower motor neuron cell bodies located?
in the ventral horn of the spinal cord and the motor nuclei of cranial nerves
how do lower motor neurons project their axons?
via the ventral roots to control effector organs
what are effector organs?
muscles and glands
what are the characteristics of somatic motor neurons (3)
large diameter, myelinated, and fast conducting
what happens to an axon as it approaches its ending?
they lose their myelin sheaths before branching into terminal fibers
where does each terminal fiber supply a muscle fiber via a specialized connection?
the NMJ
what does the NMJ consist of?
the presynaptic motor neuron, the postsynaptic muscle fiber, and the senaptic cleft
what contains the enzyme acetylcholinesterase?
the synaptic cleft
what does the NMJ convert
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
what does the motor unit consist of?
the motor neuron and the muscle fiber it innervates
what subunits are capable of binding ACh?
only the 2 alpha subunits
what kind of receptors for acetylcholine?
nicotinic
what is the primary purpose of muscle relaxation?
to achieve adequate relaxation of the upper airway, vocal cords, and diaphragm to facilitate intubation and surgery
NMBAs are NOT
anesthetics
do NMBAs cause amnesia?
no
is complete paralysis required for all surgical cases?
no
main site of action of NMBA is on what receptor?
the nicotinic cholinergic receptor
what is the twitch monitor?
a device used to measure how much muscle relaxation is caused by the dose of a muscle relaxant
only depolarizer used in anesthesia?
succinylcholine
ACh mediates transmission of
an impulse from nerve to muscle
what happens when depolarization of the motor nerve reaches the nerve terminal?
voltage-gated Ca2+ channels open, and the vesicles (quanta) that contain ACh are released
by exocytosis from the nerve terminal into the cleft
K+ channels in the nerve terminal area limit
the extent of Ca2+ entry into the terminal, and regulate the transmitter quantal release, initiating nerve membrane repolarization
the release of ACh quanta is antagonized by (2)
hypocalcemia and hypermagnesemia
where is ACh synthesized?
in the presynaptic nerve terminal
what is ACh synthesized from?
acetate and choline
where is most of the ACh contained?
in the reserve pool
Once nerve depolarization occurs and the intracellular
Ca2+ concentration increases, ACh quanta are released into
the synaptic cleft
what is ED50
what dose corresponds to a 50% twitch reduction
what is ED95?
corresponds to 95% block
anesthesia focuses on ED50 or ED95?
ED95
duration of action related to muscle blockers?
time of injection to return of 25% twitch height
what is the recovery index?
time interval between 25% and 75% twitch height
is rocuronium a depolarizer?
no, it is a nondepolarizer
where does a depolarizer work?
at the postsynaptic nAChRs
provide an example of a depolarizer
succinylcholine
define nondepolarizing drugs
competes for active binding sites on nAChRsp
examples of nondepolarizing
everything except succinylcholine
what does succinylcholine activate?
the prejunctional receptors to release ACh
what does succinylcholine mimic?
ACh
what does succinylcholine do to the postjunctional membrane and extrajunctional receptors?
produces sustained depolarization
what does prolonged depolarization of the motor end-plate do?
inactivates Na channels & increases influx of K
what drug may cause fasiculations before total paralysis?
succinylcholine
what is the typical IV dose for succinylcholine?
1-1.5 mg/kg
what is succinylcholine onset?
about 1 minute
what is succinylcholine duration?
5-15 minutes, dose dependent
almost 90% of SCh is…
hydrolyzed in the plasma before reaching the myoneural junction
where does hydrolysis of SCh occur?
in the plasma
what hydrolyzes SCh?
butyrylcholinesterase (pseudocholinesterase or plasma cholinesterase)
what is SCh broken down into?
succinylmonocholine and choline
how much of SCh releases the NMJ?
only 10%
where is Butyrylcholinesterase/Pseudocholinesterase/Plasmacholinesterase sythesized?
in the liver
where are Butyrylcholinesterase/Pseudocholinesterase/Plasmacholinesterase found?
in the plasma
what factors lower pseudocholinesterase?
severe liver disease, advanced age, pregnancy, malnutrition, burns, anticholinesterase drugs and Reglan, oral contraceptives
what does neostigmine do to pseudocholinesterase activity?
profoundly decrases activity
what can cause prolonged muscle relaxation after succinylcholine and mivacurium?
abnormal genetic variant of butyrylcholinesterase mutation
how do you test for abnormal genetic variant of butyrylcholinesterase?
check the dibucaine number
dibucaine number
results can help to identify individuals at risk for prolonged paralysis following the administration of succinylcholine.
Phase 1 block
expected w succinylcholine
with continued dosing of a depolarizing NMBA what can occur?
a phase I block can develop into a phase II block
what can cause a phase 2 block?
repeated SCh doses or an IV continuous infusion
phase 2 block
muscles are no longer receptive to acetylcholine released by the motor neurons
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
when is arrest common with SCh?
more common if a second dose is given within 5 minutes of first dose and in children
what do you treat SCh arrest with?
atropine
what can SCh do to plasma levels of potassium?
increase potassium by 0.5 mEq/dL in healthy patient
renal patients should avoid
Succinylcholine
SCh can cause severe hyperkalemia in what patients?
pts with burns, severe abd infections, severe metabolic acidosis
risk of SCh in children?
severe rhabdo, hyperkalemia, and death
what pre treatment can you give a patient to reduce cardiac effects
anticholinergics
Myoglobinuria
from muscle damage after SCh (most of the patients with rhabdomyolysis and myoglobinuria were subsequently found to have malignant hyperthermia or muscular dystrophy)
malignant hyperthermia can be caused by
SCh
masseter spasm
increase in tone of the masseter muscle may be an early indicator of malignant hyperthermia (especially in children)
what can SCh do to intragastric pressure?
increase intragastric pressure and lower esophageal tone (LES)
when does SCh increase intraocular pressure? (time)
2-4 min after administration
what drug is a contraindication a open eye injury?
SCh
malignant hyperthermia receptor
ryanodine
what activates the ryanodine receptor
halogenated agents & succinylcholine
what does MH cause release of?
massive uncontrolled release of Ca ++ from the sarcoplasmic reticulum
2 classes of nondepolarizing muscle relaxants
aminosteroids and benzylisoquinolinium
aminosteroids
pancuronium, pipercuronnium, vecuronium, rocuronium
benzylisoquinolinium examples
atracurium and cisatracurium
nondepolarizing muscle relaxants mechanism of action
Competitively antagonize the presynaptic receptors to decrease release of Ach (fade on TO4)
what do non depolarizing muscle relaxants compete with?
ACh for binding on one or both of the alpha subunits
rocuronium action
intermediate dose dependent
rocuronium histamine release?
rare
rocuronium effects on BP or HR?
none
what can be used to defasiculate with SCh?
rocuronium
rocuronium potency (low or high)
low
rocuronium intubating dose
0.6 mg/kg
highest anaphylaxis drug
rocuronium
rocuronium onset
good for RSI, variable onset
rocuronium metabolites
no real metabolites
rocuronium RSI dose
1.2 mg/kg
rocuronium comes in a ______. vial
50 mg
maintenance/repeat dose of rocuronium
0.1 mg/kg
rocuronium defasiculating dose with SCh?
5 mg
where is rocuronium mostly eliminated?
by the liver
vecuronium induction dose
0.1 mg/kg
vecuronium comes in a ______ mg vial
10
pretreatment of vecuronium for intubation dose is given when?
3 to 5 min before intubation dose
vecuronium maintenance dose for surgical relaxation
0.01 mg/kg
pancuronium acting time
long acting
pancuronium histamine release?
none
pancuronium vagolytic effects
modest tachycardia due to antimuscarinic stimulation
pancuronium direct sympathomimetic effects
norepinephrine release and reduced uptake of norepinephrine by adrenergic nerves
what drug has potential for significant postoperative residual blockade?
pancuronium
pancuronium initial dose
0.06-0.1 mg/kg
pancuronium maintenance dose
0.02 mg/kg
pancuronium onset
2-5 min
pancuronium duration
60-100 min
what drugs undergo hoffmann elimination?
Benzylisoquinolines
what is Hofmann elimination
Spontaneous, non-enzymatic, non-organ dependent chemical breakdown at physiologic temperature and pH
does mivacurium have histamine release?
yes when given quickly
mivacurium recovery
spontaneous recovery from the block is rapid
mivacurium metabolism
hydrolysis by plasma cholinesterase
mivacurium intubation dose
0.2 mg/kg
mivacurium infusion dose
5-8 mcg/kg/min
mivacurium onset and duration
1 min onset, 20 to 30 min duration
atracurium: short/intermediate/long acting
intermediate acting
atracurium histamine release?
yes
atracurium cardiovascular effects
skin flushing, tachycardia, and hypotension
atracurium metabolism
hofmann elimination and ester hydrolysis
atracurium dose
0.5 mg/kg
atracurium onset
2-3 min
atracurium duration
20 to 25 min
atracurium primary metabolite
laudanosine
what can laudanosine produce?
rare seizure activity
cisatracurium: short/intermediate/long acting
intermediate
cisatracurium metabolism
30% hofmann elimination
cisatracurium histamine release
no
cisatricurium cardiovascular changes
none
what is a potent cis-cis isomer of atracurium
cisatracurium
cisatricurium dose
0.15-0.2 mg/kg IV
Cisatracurium onset
2-3 min
Cisatracurium peak
4-7 min
Cisatracurium duration
40-70 min
what does hypothermia do the NMBA?
prolongs the duration by decreasing receptor sensitivity and ACh mobilization
what happens to renal and hepatic metabolism w hypothermia?
renal and hepatic metabolism are reducesd
what does hypothermia do to Hofmann elimination?
reduces Hofmann elimination
what does aging do to the volume of distribution of NMBA
reduced volume of distribution due to decreased total body water and serum albumin
what potentiates NMBAs
hypokalemia
AChASe can catalyze ACh at _____ molecules per active site per second
4,000
Anticholinesterase/Acetylcholinesterase Inhibitors
neostigmine, edrophonium, pyridostigmine
Selective Relaxant Binding Agent
sugammadex
what blocks the breakdown of ACh by AChAse
Acetylcholinesterase Inhibiting Agents/Anticholinesterase
high dose of neostigmine
maximal inhibition
Edrophonium: short/ intermediate/ long acting
short duration
what drug is endrophonium used with?
atropine
Enlon-Plus
is a mixture of Edrophonium and atropine together in the same vial
edrophonium is mostly ineffective when?
given for deep blocks
edrophonium onset
rapid, 1-2 minutes
Edrophonium dose
.5-1 mg/kg mixed with atropine 7-10 mcg/kg (0.014 mg/mg of edrophonium)
enlon-plus dose
Enlon-plus: .05-.1 mg/kg slowly over a minute
endrophonium given without atropine
causes bradycardia
what conditions are associated with upregulation of extrajunctional AChR
hemiplegia, paraplegia, muscular dystrophies, Guillian-barre syndrome, and burns
is sugammadex water soluble
yes, highly
what drug can encapsulate steroidal NBMA drugs
suggamadex
what drug has 8 sugars arranged in a ring
sugammadex
what are undesireable affects of sugammadex
nothing really
does sugammadex effect acetylcholinesterase or cholinergic receptors?
no
what drug when injected over 10s immediately captures free molecules of rocuronium or vecuronium?
sugammadex
where is sugammadex filtered out
by the glomerulus
when should you avoid sugammadex
patients with decreased creatinine clearance
what drug should be avoided in ESRD?
sugammadex
sugammadex routine reversal of modertate block dosing
2mg/kg
sugammadex routine reversal of deep neuromuscular block dose
4mg/kg
sugammadex dose for immediate reversal after rocuronium
16 mg/kg
sugammadex and hormonal contraceptives
decreased effectiveness of birth ocontrol
sugammadex hypersensitivity reactions
sneezing, nausea, rash and urticaria
which reversal agent has a risk of anaphylaxis
sugammadex- airway edema, bronchospasm and CV collapse
when is sugammadex anaphylaxis seen most often?
higher dosing
when does sugammadex anaphylaxis occur?
within 5 min of admin
how to treat sugammadex reactions?
small boluses of epinephrine (10-20 mcg) titrated to response, Benadryl, dexamethasone and famotidine
what is the only anticholinesterase that crosses the BBB?
physostigmine
what is not used for the reversal of muscle relaxants
physostigmine
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
fasiculations with SCh
80-90% if not pretreated w non-depolarizer or NSAIDs for myalgias
myalgias with SCh
usually big skeletal muscles; 50-60% for 1-2 days
a defasiculating dose of _________________ administered prior to succinylcholine decreases its side effects
non-depolarizing muscle relaxant
what is the onset of rocuronium
1-2 min depending on dose
what is the duration of rocuronium
about 30-70 min after RSI dose
what is rocuronium elimination
primarily by the liver (70%)/ 30% renal
vecuronium: short/intermediate/long
intermediate NMB
vecuronium histamine release
none
vecuronium cardiac implications
cardiac stable
what drug might precipitate with thiopental
vecuronium
what kind of potency does vecuronium have
medium potency
what is vecuronium onset
2-3 min for good intubating conditions
3-5 min for maximal blockade
what is vecuronium duration
25-40 min you will see 25% recovery; 45-60 min you will see 95% recovery
vecuronium metabolite
3-desacetyl (60% potency of vecuronium)
pancuronium direct sympathomimetic effects
norepinephrine release and reduced uptake of norepinephrine by adrenergic nerves
pancuronium cautions
in any patient that will not tolerate increased HR and cardiac output
what drug poses the potential for significant postoperative residual blockade?
pancuronium
what drug is used in cardiac surgery to counteract the bradycardia associated with high-dose opioid dosing
pancuronium
what is the primary metabolite of atracurium
laudanosine
patients with what condition might have an altered response to NMBAs?
myasthenia gravis
what can laudanosine produce
rare seizure activity
acidosis interferes with
effects of anticholinesterases
hypercarbia leads to _______ and interferes with _________
acidosis; antagonism
hypermagnesemia prolongs NMBA duration of action by
inhibiting calcium channels
hypokalemia potentiates ___________ and can __________ the effectiveness of anticholinesterases on reversal
NMBAs; decrease
what drugs can cause bronchoconstriction, increased salivation, increased bowel motility
Acetylcholinesterase Inhibiting Agents/Anticholinesterase
Acetylcholinesterase Inhibiting Agents/Anticholinesterase drugs are usually given in combination with
an anticholinergic / antimuscarininc
what drugs can cause significant parasympathetic effects
Acetylcholinesterase Inhibiting Agents/Anticholinesterase
maximal inhibition occurs when
100% of acetylcholinesterase has been inhibited
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
what does neostigmine inhibit
hydrolysis of ACh by AChAsE
neostigmine is used with
glycopyrrolate
what does using glycopyrrolate with neostigmine do ?
decreases muscarinic side effects of neostigmine
does neostigmine penetrate the BBB?
not very well
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)
neostimine is more effective in
moderate blocks but it is slow acting
neostigmine dose
0.04-0.08 mg/kg
max neostigmine dose
5 mg
for every 1 mg of neostigmine,
mix with 0.2 mg glyco
neostigmine onset
15 min, dependent on twitches
neostigmine duration
1-2 hours
neostigmine metabolism
hepatic, urinary excretion
sugammadex removes
the relaxant from the NMJ and moves it into the plasma
high dose of sugammadex (16mg/kg) has the potential for
bradycardia/ cardiac arrest, headache, hypotension, N/V, anaphylaxis and hypersensitivity (pruritus and urticaria)
how many mg of sugammadex is required to encapsulate 1mg of rocuronium
4 mg
what is sugammadex physically incompatible with
verapamil, ondansetron and ranitidine
how long should you wait after sugammadex administration before readministering Roc or Vec?
24 hours after reversal
high dose (16mg/kg) sugammadex coagulation affects
increased aPTT, PT and INR
high dose sugammadex caution in patients (3)
with coagulopathies
treated with therapeutic anticoagulation
receiving thromboprophylaxis other than heparin and LMWH
is physostigmine used for reversal of muscle relaxants?
no
what is physostigmine used to treat
anticholinergic toxicity
S&S anticholinergic toxicity
flushing, dry skin and mucous membranes, mydriasis with loss of accommodation, altered mental status, fever and urinary retention
CNS symptoms anticholinergic toxicity
restless, shivers, agitation, disoriented
provide examples of anticholinergics
atropine, scopolamine, antihistamines, antipsychotics, cyclic antidepressants
anticholinergic drug side effects
treatment for cholinergic crisis
Atropine 35-70 mcg/kg
Pralidoxime 15 mcg/kg every 20 min
Benzos
S&S cholinergic crisis
miosis, salivation, bronchoconstriction, bradycardia, abdominal cramping, weakness, lacrimation,
CNS effects of cholinergic crisis
dysphoria, confusion, seizures, coma
cholinergic crisis muscarinic symptoms
cholinergic crisis nicotinic symptoms
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
how do you differentiate between cholinergic crisis and myasthenic crisis
Give edrophonium… muscle strength will improve if myasthenic crisis
more strength = myasthenia (M&M)
muscle strength will improve with endrophonium in?
myasthenia gravis
does edrophonium cross the BBB?
no
cholinergic crisis has _________ secretions while myasthenic crisis has __________ secretions
increased; normal
cholinegic crisis: bradycardia or tachycardia?
bradycardia
myasthenic crisis: bradycardia or tachycardia?
tachycardia
what test relieves myasthenic crisis symptoms?
tensilon test
pupils are constricted in
cholinergic crisis
constriction = cholinergic
pupils are normal or dilated in
myasthenic crisis
increased cholinergic activity
cholinergic crisis
decreased cholinergic receptors
myasthenic crisis
tensilon test makes symptoms worse in
cholinergic crisis
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
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
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
depolarizing NBMAS produce muscle relaxation by
directly depolarizing the nAChRs
SCh acts as a __________, mimicking ___________
false transmitter; ACh
Nondepolarizing NMBAs compete with
ACh for the two α-subunits
define onset of action for an NMBA
the time from administration (usually intravenously, IV) until maximal neuromuscular block (disappearance of ST).
onset time is _________ related to dose
inversely
is the only depolarizing NMBA available clinically
succinylcholine
succinylcholine has the fastest _________, shortest __________, and greatest ________ of any NMBA
fastest onset, shortest duration, and greatest reliability
SCh has molecular similarity to
ACh
is SCh degrated by acetylcholinesterases?
no
is SCh fade or no fade
no fade because of progressive but equivalent decrease in the force of contractions
when may spontaneous breathing resume after 1mg/kg SCh dose
may resume as fast as 5 minutes after 1 mg/kg SCh administration
characteristics of depolarizing block
decrease in train-of-four (TOF) amplitude without fade in response to depolarizing agent administration
what can be given to decrease the incidence of postoperative myalgia?
lidocaine and rocuronium, but carry a risk of heavy side-effects
what drugs can attenuate IOP increase if given pre-treatment?
lidocaine and sufentanil
treatment of hyperkalemia
hyperventilation, IV calcium chloride, and glucose/insulin to shift potassium intracellularly.
drug with a black box warning in the pediatric population
Succinylcholine
patients receiving ____________ (drug) may be particularly susceptible to muscle injury from administration of SCh
statin therapy
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.
when is the use of SCh contraindicated
hx or family hx of malignant hyperthermia
where are nondepolarizing NMBAs distributed mostly
in the ECF
larger nondepolarizing NMBAs may need to be administered in patients with
renal/hepatic failure, and in burn patients
vecuronium recovery time may be prolonged significantly in the patient with
diabetes mellitus
Adding depolarizing and nondepolarizing NMBAs results in
mutual antagonism
what does the dibucaine number reflect?
the QUALITY of cholinesterase enzyme (ability to hydrolyze SCh) not the quantity that is circulating in plasma
what is a normal dibucaine number range?
70-80
which NMBA is associated with an increase in potassium?
succinylcholine
which 2 NMBAs are associated with histamine release
mivacurium and atracurium (less in atracurium)
what does neostigmine inhibit
acetylcholinesterase
what is used to treat myasthenia gravis
neostigmine
what is the function of neostigmine in anesthesia
reversal of effects of non-depolarizing NMBA drugs after surgery
