Neuromuscular blocking drugs Flashcards
What are the three components of the neuromuscular junction?
Presynaptic nerve terminal, synaptic cleft, postsynaptic muscle membrane
What does acetyhlocholinesterase do?
located at the NMJ it hydrolyzes acetylcholine
What is butyrylcholinesterase?
“plasma cholinesterase” or “pseudocholinesterase” synthesized in the liver and hydrolyzes succinylcholine in the plasma
What are reasons we would need to paralyze a patient for?
surgeries that compromise the chest or abdominal cavity or if the patient is fighting ventilation
Monitoring of the thumb
contraction of the adductor muscle or ulnar nerve is the preferred method
Monitoring of the face
facial nerve monitoring involves stimulation of the orbicularis oculi muscle (facial nerve)
When would you assess the ulnar nerve and when would you assess the face?
always assess the ulnar nerve unless arm is tucked and then we have to assess the facial nerve
What is the onset of relaxation with NMBD?
Eye muscles–> extremities–> trunk–>abdominal muscles–> diaphragm
Where is most of the drug distributed?
Blood flow is greatest to the head, neck and diaphragm so more drug distributed here
What are the five clinical tests of neuromuscular function?
Single twitch Train of Four Double-burst suppression Tetanus Post-tetanic count
Describe how the train of four works.
Gives four separate stimuli every 0.5 seconds at 2 Hz
comparison is made between the four twitches T1-t4
Describe what train of four will look like in non-depolarizing agent.
There is a successive decrease in twitch response between T1-T4 (fade)
Describe how much is blocked with 0-4 twitches.
zero twitches-100%
T2-T4 (1-2 twitches): 90-95%
T3-T4: 80-85%
T4: 75-80%
If a patient has 4 twitches, will we still reverse them?
It might depend because we know that even with 4 twitches they can still be 60% blocked. with sugammedex we reverse everyone
What is tetany monitoring?
continuous electrical stimulation for 5 seconds at 50-100 Hz
reliable for detecting fade
sustained contraction w/o fade; significant
paralysis unlikely
What is posttetanic count?
Tetany followed in 3 seconds by single twitch stimulations
the higher the count (>8) the less intense the block
What is single twitch?
Single twitch at 0.1-1 Hz for 0.1-0.2 milliseconds
only tells us whether we’re 100% paralyzed or not
What is double burst suppression?
improves the ability to detect residual paralysis
evaluating 2 rather than 4 twitches facilitates
detection
What are tests that are unreliable for extubation?
5-second head left (TOF ratio <0.6)
generate peak negative inspiratory pressure 20-30 cmH20
What is significant about the NMB structure?
All neuromuscular blockers are quaternary ammoniums meaning they have a charge so they won’t cross the BBB
low Vd
What will you see on the TOF monitor with a non-depolarizing blockade?
Decrease in twitch tension
fade during repetitive stimulation
post-tetanic potentiation acetylcholine
Why do we get a twitch depression?
d/t block of postsynaptic nicotinic acetylcholine receptors
Why do we get post-tetanic or TOF fade?
results from blocking presynaptic nicotinic acetylcholine receptors
amount of released ACh does not match the
demand
A depolarizing block is characterized by:
Decrease in twitch tension
no fade during repetitive stimulation
no postetanic potentiation
A phase 1 block is often preceded by
muscle fasiculation
With a depolarzing blockade, a phase 2 block is seen
in repeated or long-term administration
Doses >6 mg/kg
inhibit pre-synaptic AChR
it act like a non-depolarizer creating a higher concentration in the body
When would we re-dose succinylcholine?
we wouldn’t unless it’s an emergency
What kind of drug is succinylcholine?
only depolarizing muscular blockade
What is the dosage of succinylcholine?
1.0 mg/kg
How quickly does succinylcholine create intubating conditions?
60 seconds
What is the recovery from succinylcholine?
90% muscle strength in 9 to 13 minutes
How is succinylcholine metabolized?
short acting due to rapid hydrolysis by butrylcholinesterase
dissociates into succinylmonocholine and further into succinic acid and choline (whole process is done in minutes)
How do we get recovery from succinylcholine?
drifts away from the NMJ down its concentration gradient and out into plasma
Where is butrylcholinesterase metabolized and found?
metabolized in the liver and found in the plasma
What is butrylcholinesterase responsible for metabolizing?
Succinylcholine, mivacurium, procaine, chloroprocaine, tetracaine, cocaine, and heroin
What are factors that decrease PChE activity?
advanced liver disease, age, malnutrition, pregnancy, burns, oral contraceptives, MAOIs, echothiphate, cytotoxic drugs, neoplastic disease, and anticholinesterase drugs
Beta blockers also cause mild prolongation of succinylcholine but not long enough to notice in surgical cases
What is a dibucaine number?
A dibucaine number reflects the quality of cholinesterase not quantity (Dibucaine of 80 infers 80% of enzyme inhibited)
normal genotype= >70
heterogenous for atypical gene= dibucaine 40-60 (prolongs block for 1.5-2 x longer)
Homogenous for atypical gene= dibucaine <30 (prolongs block for 4-8 hours)
What are the cardiac side effects of succinylcholine?
Bradycardia, junctional rhythm or sinus arrest
acts on cardiac muscarinic receptors
symptoms more likely to occur in second dose given within 5 minutes of 1st dose or in pediatric patients
Stimulation of the autonomic ganglia may cause:
ventricular dysrhythmias, tachycardias, and increased blood pressure
How does succinylcholine affect potassium?
Hyperkalemia- 0.5 mEq/dL increase in plasma concentration in healthy individuals
may be severe in: burn patients, abdominal infections, metabolic acidosis, closed head injury and conditions associated with upregulation of nAChR (paraplegia, muscular dystrophy, Guillian-Barre)
avoid in children except for emergency intubation
What specific pediatric patient population do we avoid administration of succinylcholine and why?
in children’s with duchenne’s muscular dystrophy because succ can cause myoglobinuria which is damage to skeletal muscle
What type of surgery would we avoid succinylcholine administration in?
not widely accepted in open eye surgery because of increased intraocular pressure (peaks at 2-4 minutes and pressure returns to normal by 6 minutes)
What CNS effects does succinylcholine cause?
Increased intracranial pressure- can be attenuated with pretreatment of non-depolarizing drug
What GI effects does succinylcholine cause?
Increased intragastric and lower esophageal pressures
related to intensity of fasiculations of abdominal
muscles
prevented by prior administration of non-
depolarizing drug
does not increase risk of regurgitation
What patients are at risk of myalgias due to succinylcholine?
young, female, ambulatory patients
What is the thought process behind why patients get myalgias?
muscle injury due to shearing (improper dose) and fasiculations
pretreatment with non-depolarizing drug, lidocaines
or NSAIDs, mylagias occur even in absence of
succinylcholine
Other than myalgias, what other kind of spasm does succinylcholine cause?
masseter spasm- it is a known trigger for malignant hyperthermia
may be an early indicator of MH, but not consistently
seen
possibly due to inadequate dosing
What populations are we concerned about with succinylcholine?
Elderly- onset slower due to decreased circulation & reduce levels of PChE
certain alzheimer medications may prolong actions
Pediatrics- avoid in pediatric patients < 5 years old
duchene muscular dystrophy
cardiac arrest from hyperkalemic rhabdomyolysis
What is malignant hyperthermia triggered by?
volatile anesthetics
succinylcholine
stress
What receptors are malignant hyperthermia concerned with?
Ryanodine receptor gene mutation (chromosome 19)
What are signs and symptoms of malignant hyperthermia?
increased CO2 production, muscle rigidity (tight field), metabolic acidosis, possible tachycardia, increased temperature (late sign)
What is the treatment for malignant hyperthermia?
Dantrolene was the old treatment now we have ryanedex which is much easier
What are the two different types of non-depolarizing NMBDs?
steroidals (roc, vec, and panc) & benzylisoquinolinium (atricurium, cisatricurium, and mivacurium)
How are non-depolarizing NMBDs classified?
Short acting (only one is mivacurium), intermediate acting, and long-acting
How many receptors do you need to block to get response?
Depends on the drug but you don’t have to block every receptor to get response
Why do we get fade?
We have have more NMBD than ability to release ACh so may be able to get initial contraction but if need more contraction may be unable to release extra acetylcholine needed to maintain tetany or strength
What is the intubating dose of atricurium?
0.5 mg/kg
What is the biggest concern with atricurium?
histamine release
How is atricurium metabolized?
undergoes hydrolysis and spontaneous degradation through Hoffmann elimination (liver and kidney issues do not affect atricurium)
Atricurium is considered to be
intermediate acting
What CNS complication can atricurium cause?
Laudanosine (tertiary amine) metabolite is implicated in convulsions- doses given in anesthesia not capable of producing this
What percent of atricurium is eliminated through the kidney?
zero b/c its all metabolized in the blood
What is the intubating dose of cisatricurium?
0.1 mg/kg
Cisatricurium is
the cis isomer of atracurium & has intermediate onset and action
How is cisatricurium metabolized?
metabolized by Hoffman elimination (no ester hydrolysis), unaffected by kidney & liver disease
True or false cisatricurium causes histamine release.
False
What is mivacurium?
short-acting non-depolarizer that is not available in the US
What is the intubating dose of mivacurium?
0.15 mg/kg
How is mivacurium metabolized?
metabolized by butyrylcholinesterase; at 70-88% rate of succinylcholine
metabolized into monoester & dicarboxylic acid
What is a side effect of mivacurium?
It can cause histamine release
What makes up a steroidal compound?
one of two nitrogen atoms are quaternized
acetyl ester though to facilitate interaction with nAChR
What kind of drug is pancuronium?
it is a long-acting neuromuscular blocking drug
What is the intubating dose and onset time to block for pancuronium?
0.08 mg/kg
onset time: 2.9 minutes
When would we use pancuronium?
cardiac surgeries because of vagolytic property allows for maintenance of HR & BP
How is pancuronium cleared?
cleared by the kidney
small amount deacetylated by the liver
accumulation of 3-OH metabolite responsible for
block prolongation
Pancuronium also has
butyrylcholinesterase inhibiting properties
Vecuronium is considered to be
an intermediate- acting neuromuscular blocking drug
What is the intubating dose of vecuronium and the time to maximum block?
- 1 mg/kg
2. 4 minutes
What is the structure of vecuronium?
pancuronium without quaternized methyl group–> causes slight decrease in potency, loss of vagolytic properties, molecular instability (shorter duration of action), increased lipid solubility
How is vecuronium metabolized?
metabolized by the liver
3-OH metabolite has 80% of neuromuscular potency
What are some features of vecuronium as to why we may or may not use it?
Cannot rapidly intubate someone
very consistent and gives 1 hr of complete paralysis
What kind of drug is rocuronium?
intermediate- acting neuromuscular blocker
What is the dosage and time to block for rocuronium?
0.6 mg/kg
time to maximum block 1.7 minutes
With steroidals what is the relationship between potency and time to block?
Less potent drug, increased time to block
How is rocuronium metabolized?
primarily in the liver, 30% is excreted in urine
If you have to rapidly intubate someone with rocuronium,
double the dose to 1.2 mg/kg and you should get intubating conditions within 30-60 minutes
What are some drugs that increase potency of NMBD?
inhalational agents- desflurane> sevoflurane>isoflurane>nitrous oxide> IV anesthesia
antibiotics: clindamycin
hypothermia
magnesium sulfate (calcium antagonist)
local anesthetics (block nerve transmission)
quinidine–> antiarrhythmic
Factors that decrease potency include:
chronic anticonvulsant administration
hyperparathyroidism and hypercalcemia- decreased atracurium sensitivity
Buffered diffusion is seen with high potency drugs
drug diffusion is impeded because it binds to high-density receptors in a confined space
What is an adverse effect of NMBDs?
Histamine release
skin flushing, hypotension, decrease in SVR,
increased HR
seen in benzylisoquinolinium- mivacurium, atracurium, tubocurarine
usually short duration (1 to 5 minutes)
slow administration or pretreatment with H1 and H2 blockers to reduce cardiovascular effects
What is the autonomic effects of NMBDs?
may also block nicotinic receptors within sympathetic and parasympathetic nervous system
bradycardia and hypotension
histamine release- flushing, hypotension, reflex
tachycardia, and bronchospasm
Pancuronium has direct vagolytic effects
block muscarinic receptors
inhibition of negative feedback system where
catecholamine release is modulated or prevented
What is the effect of NMBDs on respiratory effects?
related to histamine release in patients with reactive airway disease
increased airway resistance and bronchospasm
What is a major cause of NMBD allergic reactions?
rocuronium and succinylcholine
Cross reactivity between NMBDs and
food, cosmetics, disinfectants, and industrial materials
Treatment for allergic reactions include:
100% oxygen, IV epinephrine, early tracheal intubation, fluid administration, sympathomimetic drug (pressors)
AChE inhibitors include:
neostigmine, edrophonium, pyridostigmine
What is the role of AChE inhibitors?
antagonize residual effects of NMBD
accelerate recovery from non-depolarizing drugs
Reversal of NMBD is predicated
on creating build-up of ACh at NMJ
compete with residual NMBD for unoccupied nAChR
What is the ceiling effect of neostigmine?
once it is reached, additional doses have no effect
maximum block depth that can be antagonized
corresponds to return of fourth twitch in TOF
cannot antagonize profound or deep levels of
blockade
administering more inhibitor may be detrimental
Antagonism of NMBDs depends on:
depth of blockade when reversal is attempted, inhibitor chosen, dose, rate of spontaneous clear of NMBD, choice and depth of anesthesia
What are the CV side effects of ACh inhibitors?
cardiovascular- bradycardia- muscarinic effects must be blocked by anticholinergic
What anticholinergic is administered with what AChE inhibitor?
edrophonium and atropine
neostigmine and glycopyrrolate
What are pulmonary side effects of AChE inhibitors?
bronchoconstriction
increased airway resistance
increased salivation
What are the GI effects of AChE inhibitors?
increased bowel motility
What is the qualitative measure of monitoring?
TOF w/ 5 electrodes
TOF >0.9
Less than 0.9 is associated with: difficulty speaking, difficulty swallowing, visual disturbances, and aspiration risk
comparison of twitch one to twitch 4 so have to have all four twitches
What is the chemical structure of sugammadex?
modified gamma-cyclodextrin
What can sugammadex reverse?
steroidals
True or false: Sugammadex effects acetylcholinesterase
False
What is the dosing of sugammadex?
TOF >2- 2 mg/kg
TOF 1-2- 4 mg/kg
TOF 0 - 8-16 mg/kg
What are side effects of sugammadex?
allergic reactions, bleeding, birth control ineffectiveness
What is the dosage of neostigmine?
40-80 mcg/kg with max dose of 6 mg.
(typically will give 2-4 mg in a 70 kg pt)
What is the dose of edrophonium?
1.0-1.5 mg/kg
What is the dosage of glycopyrrolate?
5-10 mcg/kg
What is the dosage of atropine?
0.01 mg/kg
