NMB's Flashcards
which subunits must be occupied to open the nicotinic receptor at the motor end plate
alpha and alpha (either by Ach or succ)
2 types of NachR’s at NMJ
- pre junctional Nn receptors present on presynaptic nerve
- post synaptic Nm receptors present on motor end plate of muscle
subunits on post synaptic nicotinic (Nm) receptor
2 alpha, 1 beta, 1 delta, 1 epsilon
subunits on extra junctional receptors and why they return
denervation or prolonged immobility allows for return of these receptor types (that were present in early fetal development)
why do extra junctional receptors increase risk for fatal hyperkalemia
-far more sensitive to succ and remain open for a longer period of time allowing for more Na to enter the cell
-stimulated by choline
extra junctional receptors and non depolarizers
up regulation of extra junctional receptors creates resistance to non depolarizers
fade during TOF is most likely caused by
antagonism of pre synaptic Nm receptors
MOA of NDNMB’s
competitively antagonize presynaptic Nn receptors
which receptor is integral to the fade mechanisn
presynaptic nicotinic (Nn).
what type of block does succ create
phase 1 (diminished but equal- no fade)
what type of block does NDNMB’s create
phase 2 (nerve terminal can only release avail Ach not stored Ach so fade occurs)
can succ cause a phase 2 block?
high dose, yeah
>7-10mg OR >30-60m infusion
post tetanic potentiation
none with phase 1 but yes with phase 2
post tetanic potentiation
none with phase 1 but yes with phase 2
most sensitive indicator for recovery of NMB
inspiratory force better than -40cmH2O
best place to measure onset of blockade
orbicularis oculi (closes eyelid) or corrugator supercilli (eyebrow twitch)
facial nerve (CN7)
best place to measure recovery blockade
adductor pollicis (thumb adduction) or flexor hallucis (big toe flexion)
nerve= ulnar or posterior tibial
TOF ratio that correlates with full recovery
> .9 at adductor pollicis
Vt and VC are normal in the setting of what amount of NMB?
70-80%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for tidal volume
> 5mL/kg and 80%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for TOF
no fade and 70%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for VC
> 20mL/kg and 70%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for sustained tetanus (50hz)
no fade and 60%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for DBS
no fade and 60%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for inspiratory force
> -40cmH2O and 50%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for head lift >5 seconds
sustained for 5 seconds and 50%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for hand grip same as pre induction
sustained for 5 seconds and 50%
acceptable clinical end point and max % of receptors occupied when acceptable clinical endpoint is reached for holding tongue blade in mouth against force
cant remove tongue blade against force and 50%
best qualitative test for neuromuscular function
tongue blade
how does succ cause bradycardia or asystole
stimulates M2 receptor on SA node (primary metabolite, succinomonocholine, is probably responsible)
how does succ cause tachycardia/HTN
mimics Ach at sympathetic ganglia
succ transiently increases IOP by
5-15mmHg for up to 10m
how does succ affect intragastric pressure and LES tone
increases intragastric pressure but decreases LES tone. they cancel each other out so the barrier at the GE junction is unchanged
different names for acetylcholinesterase at NMJ
genuine cholinesterase
true cholinesterase
type 1 cholinesterase
specific cholinesterase
different names for pseudocholinesterase in plasma
butyrylcholinesterase
type 2 cholinesterase
false cholinesterase
plasma cholinesterase
where is pseudocholinesterase produced and what function does it help monitor
produced in liver, indicator of hepatic synthetic function
which atypical pseudocholinesterase problem can prolong succ duration
homozygous variant
drugs that reduce pseudocholinesterase activity
metoclopramide
esmolol
neostigmine
echothiopate
oral contraceptives/estrogen
cyclophosphamide
MAOI’s
nitrogen mustard
co existing diseases that reduce pseudocholinesterase activity
atypical PchE
severe liver disease
chronic renal disease
organophosphate poisoning
burns
neoplasm
advanced age
malnutrition
pregnancy (late stage)
dibucaine test is an
amide LA that inhibits normal plasma cholinesterase
outcome of normal dibucaine test
dibucaine inhibits normal pseudocholineseterase
normal dibucaine number is 80 which means 80% of the pseudocholinesterase is in the sample
outcome of abnormal dibucaine test
does not inhibit atypical pseudocholinesterase
if the patient had a dibucaine number of 20 then the dibucaine did not inhibit the patients PchE
PchE variant: typical homozygous
genotype:
incidence:
dibucaine #:
succ duration:
genotype: UU
incidence:
dibucaine #: 70-80
succ duration: 5-10min
PchE variant: heterozygous
genotype:
incidence:
dibucaine #:
succ duration:
genotype: UA
incidence: 1/480
dibucaine #: 50-60
succ duration: 20-30m
PchE variant: atypical homozygous
genotype:
incidence:
dibucaine #:
succ duration:
PchE variant: typical homozygous
genotype: AA
incidence: 1/3,200
dibucaine #: 20-30
succ duration: 4-8h
define atypical plasma cholinesterase defect
qualitative. sufficient amounts are made theyre just not functional
tx for patient with atypical plasma cholinesterase
postop mechanical ventilation and sedation is tx of choice for cost reasons but can also do whole blood, FFP, or purified human cholinesterase
succ black box warning
most common is duchenne muscular dystrophy but overall the warning is for skeletal muscle dystrophy
-lack of dystrophin doesn’t allow actin and myosin to anchor which which increases sarcolemma permeability, facilitates breakdown, releases creatinine kinase and myoglobin to systemic circulation
mild hyperkalemia presents with
peaked t waves and PR prolongation
tx for hyperkalemia
- stabilize myocardium: ca chloride 20mg/kg or ca gluconate 60mg/kg
- shift k into cells (.3-.5mg/kg of 10% glucose solution, 1U insulin per 4-5g IV glucose, 1-2mmol/kg sodium bicarb)
- enhance k elimination (furosemide 1mg/kg, volume resuscitation, hemodialysis, hemofiltration)
who is at risk for postop myalgia related to succ
young adults (women>men) undergoing ambulatory surgery that do not routinely engage in strenuous activity.
what 3 drugs (and doses) can you administer before succ to help with postop myalgia
2mg roc
1.5mg atracurium
.3mg vec
3-5min before succ
what to do with dose of succ if giving defasciculating dose
increase dose to 1.5-2mg/kg
who should not receive a defasciculating dose
those with pre existing skeletal muscle disease/weakness
who with pre existing skeletal muscle co morbidities may respond to succ with MH
hypokalemic periodic paralysis
malignant hyperthermia patient
which patient population is resistant to succ but sensitive to non depolarizers
MG
who with pre existing skeletal muscle co morbidities may be sensitive to non depolarizing NMB’s?
duchennes, Gillian barre, MS, ALS, myotonic dystrophy, huntington chorea, MG
which patient population would respond to succ with muscle contractures that may compromise aw management?
myotonic dystrophy
who with pre existing skeletal muscle co morbidities may have a hyperkalemic response to succ?
DMD (plus rhabdo), guillan barre, MS, ALS, charcot marie tooth, hyperkalemic periodic paralysis
the higher the ED95, the lower the
potency
short acting: mivacurium
intubation
time to max block (onset)
duration
intubation: .15
time to max block (onset): 3.3
duration: 16.8
intermediate acting: cisatracurium
intubation
time to max block (onset)
duration
intubation: 0.1
time to max block (onset): 5.2
duration: 45m
intermediate acting: vecuronium
intubation
time to max block (onset)
duration
intubation: .1
time to max block (onset): 2.4
duration: 45m
intermediate acting: atracurium
intubation
time to max block (onset)
duration
intubation: 0.5
time to max block (onset) 3.2
duration 45m
intermediate acting: rocuronium
intubation
time to max block (onset)
duration
intubation: .6
time to max block (onset): 1.7m
duration: 35m
long acting: pancuronium
intubation
time to max block (onset)
duration
intubation: .08
time to max block (onset): 2.9m
duration: 85m
benzylisoquinolinum compounds
atracurium
cisatracurium
mivacurium
aminosteroid compounds
rocuronium
vecuronium
pancuronium
how is atracurium metabolized
hoffman elimination and non specific plasma esterases
how is cisatracurium metabolized
hoffman elimination
how is mivacurium metabolized
pseudocholinesterases which explains its short DOA
describe hoffman elimination
base catalyzed reaction that is dependent on normal blood pH and temperature
-faster with alkalosis and hyperthermia
-slower with acidosis and hypothermia
toxic metabolite of benzylisoquinolinum compounds
laudanosine
how is rocuronium metabolized
biliary excretion as unchanged molecule
metabolism of vec
via liver too 3OH vec
metabolism of pancuronium
hepatic deacetylation to 3OH pancreatic
drugs that potentiate NMB include
electrolytes that potentiate NMB include
patient factors that potentiate NMB include
hypothermia (decreased potassium and clearance)
gender (women>men)
2 NMB’s that block M2 receptors in heart
pancuronium (moderate blockade)
roc (slight to none)
which NMB’s release histamine
cisatracurium, atracurium, succ
which NMB is most likely to cause anaphylaxis?
succ
how too NMB’s cause anaphylaxis
they contain quarternary amines that interact with IgE, causing mast cell and basophil degranulation. this is reflected via an elevated tryptase level (peak 15-120 min after exposure)
