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Flashcards in Neuromuscular Blockers Deck (100):

What was the first NMB used?



Characteristics of skeletal muscle?

  • Voluntary action
  • striated muscle
  • contains contractile filatments 
  • multinucleated cells
  • Innervated by large, myelinated, alpha motor neuronts
    • cell bodies originate from ventral horns of spinal cord


As presynaptic motor nerve endings approach post-synaptic membrane of muscle cells, the muscle fiber motor neurons lose their ____ ____ and make contact with single muscle fiber.

myelin sheath


How does acetylcholine work at NMJ?

  • Synthesized in presynaptic neuron and stored in presynaptic vesicles
    • released in quanta
  • Released in quanta in response to action potential in presynaptic neuron
    • Ca dependent process
  • Diffuses across synaptic clef and reversibly binds to speicfic receptor sites on postsynaptic membrane with Na channels in trough
  • Postsynaptic membrane depolarizes and triggers AP that causes muscle contraction
  • ACh eliminated by acetylcholinesterase


What is ACh metabolized to by acetycholinesterase?

Acetate and choline


What forms Nicotinic Ach receptor?

  • ADULT receptor has two alpha subunits in association with single beta, delta, epsilon subunit
    • these form a channel (pore)
    • each alpha subunit has ACh binding site
    • alpha subunits are binding site for ACh and NMB!


What does binding of Ach on both subunits cause?

  • Channel opens
  • Na and Ca move into skeletal muscle and K leaves
  • AP propagate and results in muscle contraction


What is function of prejunctional nicotinic receptors?

  • Also activated by acetylcholine and function in positive feedback control system, which could mediate mobilization of the reserve storage of acetylcholine when high-frequency or tetanic stimulations occur.
  • This helps to mobilize acetylcholine when demand is high!


Which type of neuromuscular blocker tends to block prejunctional nicotinic receptors? What is the clinical impact?

  • Non delopolarizing NMBD
  • We will see "fade" on a TOF stimulation because there is not enough ACh available to sustain continuous contractions
  • With succinylcholine administration, you get either all 4 twictches, or no twitches. There is no fade exhibited


What are fetal nAch Receptors?

  • Immature, mostly extrajunctional receptors
  • Epsilon subunit is absent and replaced by the gamma subunit
    • all other subunits the same (two alpha, beta, delta)
  • these receptors proliferate in denervation (or immobility, trauma)
  • Resistant to non-depolarizing NMB and sensitive to succinylcholine
  • when activated, fetal receptors have prolonged open chennl time and this leads to exaggerated K efflux
    • causes extensive hyperkalemia in patients


What is the difference of sensitivity to NMB throughout various muscles of the body?

  • Muscle blood flow and receptor density difference is likely cause
  • The dose of non depolarizing NMB needed to block diaphragm is 1.5-2 times the dose needed to block the adductor pollicis
    • obicularis oculi (reflects paralysis of laryngeal muscles) muscle twitch will be lost first and regained first
  • Laryngeal adductors are resistant to NMB relative to adductor policis
    • high receptor density, greater release of acetylcholine, or less acetylcholinesterase activity
  • Onset of NMB is significantly faster at diaphragm and larngeal adductors than at adductor pollicis


What is odd thing about succinylcholine's sensitivity to receptors?

Succinylcholine will give greater NMB at vocal cords than at adductor pollicis

No greater view than with succinylcholine!


NMB should not be administered just to ___ ___ ___

keep patient from moving.


Important to use other anesthetic agents to provide analgesic or amnestic properities. Otherwise, may have awareness during surgery


What are 4 positive outcomes of using NMB for intubation?

  • Better view
  • decreased frequency of vocal cord lesions following intubation
  • decreased rate of postoperative hoarseness
  • reduces rate of adverse hymodynamic effects caused by deeper level of anesthesia


What type of patient might be suitable for intubation without need of NMB?

Younger, healthier patient can handle extra dose propofol (Etc) needed for intubation without NMB


What is MOA of NMB?

  • Quaternary ammonium compounds structurally related to ACh
    • do not cross BBB and are hydrophilic
  • NMB bind to alpha subunit on AChR
  • Non depolarizing bing to one or both alpha subunits and do not result in depolarization
    • competitive antagonist
    • binds to more post junctional than prejunctional 
  • Depolarizing NMB bind to alpha subunit (one or both)and result in depolarization
    • results in membrane depolarization and hyperpolarization which prevents AP
    • partial agonism


What do NMB do to more centrall located neuromuscular units vs more peripherally located adductor pollicis muscles?

Blockade develops faster, lasts a shorter time, and recovers faster in more centrally located neuromuscular units


What are general characteristics of succinylcholine?

  • Structurally 2 molecules of acetylcholine bound together by methyl group
  • Partial agonist
  • Depolarizes AChR upon binding to one (or both) alpha subunits
    • also effects muscarinic autonomic receptors
  • NOT hydrolyzed by acetylcholinesterase
    • channel stays open and no further action potential can be transmitted


How does succinylcholine cause fasciculations?

  • When depolarizing NMJ, causes muscles to spasm


What can be done to prevent fasciculations with succinylcholine?

  • Small dose of differnet nondepolarizing NMBD administered before succ can prevent fasciculations.
    • The dose of nondepolarizing NMBD will have antagonistic effect to succ. 
    • You will need to give a higher dose of succinylcholine after administering nondepolarizing NMBD


E 1/2 life of succinylcholine?

47 seconds


ED 95 and intubating dose of succinylcholine?

ED95= 0.3 mg/kg

intubating dose= 1.0 mg/kg (up to 1.5 mg/kg)


What is average time until intubating conditions for succinylcholine?

60 second (up to 30-60 seconds for 1.5 mg/kg)


What is the average time to 90% muscle strength recovery for succinylcholine?

9-13 minutes


What is metabolism and recovery from blockade for succinylcholine?

  • Metabolism: Hydrolyzed by butyrlcholinesterase (plasma cholinesterase)
    • ultrashort DOA of succinylcholine results from rapid hydrolysis by butrylcholinesterase into succinylmonocholine and choline
      • such an efficient enzyme that only 10% of succinylcholine reaches synaptic cleft
  • Recovery: diffusion away from NMJ down a concentration gradient


Which weight do use for succinylcholine dosing in obese patients?

total body weight


Where is butylcholinesterase synthesized? Where is it found?

Synthesized in liver

Found in plasma


When is butylcholinesterase reduced?

  • Advanced liver disease
  • Advanced age
  • Malnutrition
  • Pregnancy (but increase in Vd leads to no clinical effect in prolongation of DOA)
  • Burns
  • Oral contraceptives
  • use of MAOI's
  • echothiophate (eye drop)
  • cytotoxic drugs
  • neoplastic disease
  • anticholinesterase drugs
  • metoclopramaide
  • bambuterol (prodrug of terbutaline)
  • esmolol
  • genetic variations of enzyme


What is the clinical implication in a decrease of butyrlcholinesterase activity?

  • When butyrlcholinesterase activity reduces by 20%, only prolongation of DOA of 3-9 min


Which drugs, commonly given around perioperative period, can inhibit butyrlcholinesterase?

Neostigmine and pyridostigmine

- If succinylcholine is given after antagonism of residual neuromuscular block, (as in postextubation laryngospasm) the effect of succinylcholine will be pronounced and significantly prolonged, (by 11-35 minutes in some studies)

-Even 90 minutes after neostigmine administration, butrylcholinesterase activity will have returned to less than 50% of baseline!!


____ also inhibit butyrlcholinesterase and may augment the ffects of succinylcholine and mivacurium by decreasing hydrolysis by the enzyme.



What is a dibucaine number?

  • Amide local anesthetic that can be used in lab to test for genetic variation in plasma cholinsterase
  • Dibucaine number reflects quality, not the quantity of enzyme
  • 1:3500 homozygous for varient; will prolong NMB with Sch for 4-8 hours
  • 1:480 heterozygous for variant; prolongs NMB 50-100%


Does dibucaine inhibit the normal enzyme or abnormal enzyme?

Has prefernce for inhibiting NORMAL enzyme


What is a normal dibucaine number? Abnormal values and what they signify?

  • Homozygous normal = 70-80= normal response SCh
  • Heterozygous atypical 50-60= lengthened by 50-100%
  • Homozygous atypical 20-30= prolonged 4-8 hours


Dibucaine number indicates the percentage of enzyme inhibited


What will occur during TOF testing after administration of Sch to someone with a butylcholinesterase deficiency?

You will see fade.

Normally, you will not see fade with a depolarizing NMB. If you see fade after administration succinylcholine, something is off


What conditions can cause nAchR upregulation?

  • Spinal cord injury
  • Stroke
  • Burns
  • Prolonged immobility
  • Prolonged exposure to NMB
  • Multiple sclerosis
  • Guillain Barre syndrome


What conditions can lead to nAChR downregulation?

  • Myasthenia gravis
  • Anticholinesterase poisoning
  • organophosphate poisoning


What happens when succinylcholine given to denervated muscle?

  • Muscle has upregulated nad extrajuncitonal AChRs
  • Sch comes in contact with all the AChRs throughout the membrane
  • massive efflux of K into extracellular fluid with potentially lethal hyperkalemia


What is malignant hyperthermia?

  • Calcium ion channel defent in ryanodine receptor leads to failure of Ca ion active transport pump following muscle contraction
    • this leads to sustained muscle contraction and heat production
  • First sign of malignant hyperthermia is sudden, acute increase in ETCO2 from increased body metabolism


What can trigger malignant hyperthermia?

  • Succinylcholine and volatile anesthetics
  • Triggers are avoided in patients with susceptibility


What are the cardiovascular side effects of SCh?

  • Action at cardiac muscarinic cholinergic receptors can cause bradycardia
    • increased likelihood with children and when 2nd dose is given within 5 minutes of first dose
    • seen in low doses (both negative inotropic and chronotropic)
    • this can cause cardiac arrest in kids!
  • ANS ganglion can also cause increased HR and BP
    • autnomic stimuli can cause ventricular dysrhythmia during laryngoscopy
    • seen in large doses of Sch


How does succinylcholine cause hyperkalemia?

  • In normal, healthy patient, Sch will cause 0.5mEq/L increase in K level
  • severe, life threatening hyperkalemia can occur in burn patient, pt with severe abdominal infections, sever metabolic acidosis, closed head injury, or any condition leading to upregulation of extrajunctional Ach receptors
  • SCh is NOT recommended in children d/t potential for massive rhabdomyolysis, hyperkalemia and death d/t undiagnosed muscle dx
    • may only be used in emergency tracheal intubation


If you give succinylcholine, and begin to see sudden increased PVCs, what could you suspect? 

Might have increased K, need to give membrane stabilizers (Ca, insulin, glucose combo) in order to prevent severe hyperkalemia


What drugs can you give if you suspect hyperkalemia?

  • 500-1000 mg Calcium chloride or calcium gluconate over 3 minutes IV
  • 10 units regular insulin in 50mL of 50% glucose for adults
    • children 0.15 units/kg of regular insulin in 1.0 mL/kg of 50% glucose IV
  • Also hyperventilate patient


What other side effects can Sch cause?

  • Myoglobinuria- usually seen only after administration to pt with malignant hyperthermia or muscular dystophy
  • Increased IOP- attneuated with pretreatment small dose NDNMB
  • Increased intragastric pressure: evidnce of clnical harm unclear
  • Increased IOP- peaks 2-4 min, subsides in 6 min
  • Myalgias: increased in women and ambulatory pt
  • Masseter spasm
    • can be early sign of MH
    • Does not always herald MH
  • ANlaphylaxis 0.06%- mainly european/australian


Is it ok to use succinylcholine for eye operations?

Not contraindicated unless anterior chamber is open. 

  • Administering NDNMD beforehand can diminish increased IOP
  • Weighed with fact that bucking and coughing also causes increased IOP. This will cause IOP 3-4 times greater than with SCh administration


What are SCh black box warnings?

  • Administration in children carries risk of cardiac arrest and sudden death
  • risk due to undiagnosed skeletal muscle myopathy
  • X-linked, recessive Duchenne's muscular dystrophy is most common
    • absence of dystrophin


What are the classes of non-depolarizing NMB?



other blockers


What drug is out long-acting, steroidal compound?



What drugs are intermeidate(20-50 min) steroidal compounds?

Vecuronium, Rocuronium


What drug is long acting benzylisoquinolinium compound?



What drugs are intermediate acting benzylisoquinoliniums?




What drug is short acting benzylisoquinolinium?



The speed of onset is _____ proportional to potency of nondepolarizing neuromuscular blocking drugs.


the more potent, fewer molecules needed, longer onset time


What does ED 95 mean? ED 50?

Dose required to have a 95% or 50% decrease in baseline twitch height.

Defines drugs potency


Unlike SCh, non depolarizing NMBDs should be given to obses patients on basis of ____

IBW (ideal body weight)


How many receptors must be occupied before appearnace of neuromuscular block?

90% of receptors must be occupied before block is complete at adductor pollicis


Which drug is exception to rule of inverse relationship betwen potency and onset?

Atracurium. ED 95 is 0.21mg/kg, but onset is 3.2 min

(which longer than vecuronium, and vec's ed95 is 0.043mg/kg)


What is buffered diffusion?

  • Buffered diffusion causes reptitive binding and unbinding to receptors, thus keeping potent drugs in neighborhood of effector sites and potentially lenghtening the duration of effect
  • Seen in high potency, but not low potency drugs
  • Contributes to slower onset time for cisatracurium than atracurium.


What determines time to maximum blockade?

  • Intensity of maximum glockade is affected directly by administered dose
    • subparalyzing range, time to reach maximum effect is dose independent
    • when dose is sufficient to effect complete disappearnce of neuromuscular response, time to maximum blockade is dose-dependent


What causes potentiation of NMB?

N2O and anesthetic vapors increase action of NMB

Of all the volatile agents, desflurance has most potentiation


What are the autonomic effects of succinylcholine?

  • Autnomic ganglia- stimulates
  • Cardiac muscarinic receptors- stimulate (drop in HR)
  • Histamin release- slight


What are autonomic effects of mivacurium?

  • Autonomic ganglia- none
  • cardiac mscarinic receptors- none
  • histamine release- slight


What are autonomic effects of atracurium?

  • Autonomic ganglia- none
  • cardiac mscarinic receptors- none
  • histamine release- slight


What are autonomic effects cisatracurium?

  • Autonomic ganglia- none
  • cardiac mscarinic receptors- none
  • histamine release- none


What are autnomic effect tubocurarine?

  • Autonomic ganglia- blocks
  • cardiac mscarinic receptors- none
  • histamine release- moderate


What are autnomic effects vecuronium?

  • Autonomic ganglia- none
  • cardiac mscarinic receptors- none
  • histamine release- none


What are autonomic effect rocuronium?

  • Autonomic ganglia- none
  • cardiac mscarinic receptors- blocks weakly
  • histamine release- none


What are autonomic effects pancuronium?

  • Autonomic ganglia- none
  • cardiac muscarinic receptors- blocks moderatly
  • histamine release- none


What is d-Tubocurarine?

  • Benzylisoquinolone; monoquarternary, long acting
  • no active metabolism
  • excreted uncahnged in urine; hepatic secondary rout
  • not indicated in renal or hepatic failure
  • onset: slow
  • DOA: long


What is atracurium?

Intubating Dose, onset, class, characteristics?

Benzylisoquinolone; intermediate acting

  • Dose: 0.5 mg/kg (intubating dose)
  • Onset 2-2.5 minutes, max NMB 3-5 min
  • Racemic mixture of 10 steroisomers
  • Hofmann elimination: spontaneous degradation at physiologic temp and pH and ester hydrolyis (60-90%)
    • 10-40% KIDNEY
  • INACTIVE METABOLITE: Laudanosin, CNS stimulant, is metabolite and can cross BBB (seizures)
    • 70% in bile, remainder in urine
    • excretion impaired in biliary obsturciton



Class, intubating Dose, DOA, Metabolism?

Benzylisoquinlolone; intermediate acting

  • Dose- 0.1mg/kg (4-5x more potent than atracurium)
  • 1R cis- 1'R cis isomer of atracurium
  • Hofmann elimination (77%) renal clearance (16%)
    • NO ester hydrolysis
  • Laudanosine is also produced but at much lower amounts (1/5th of atracurium)



Class, dose, DOA, characteristics

Benzylisoquinolone; short acting

  • intubating dose: 0.15 mg/kg
  • Only short acting NDNMB
    • reintroduced in US in dec 2016
  • Metabolized by plasma cholinesterase
    • Butyrlcholinesterase--> monoester and dicarboxylic acid at 70-88% of the rate at which succ is metabolized by same enzyme
  • HISTAMINE release- reason why many people don't use it



Dose, class, DOA, metabolism, characteristics

Steroidal non-depolarizing NMB; LONG ACTING

  • Intubating dose: 0.08 mg/kg
  • Direct vagolytic and sympathomimetic activity
    • causes tachycardia
  • Renal clearance 40-60%- cannot give in renal failure
  • 3-OH metabolite accumulation leads to prolongation of NMB- ACTIVE METABOLITE
    • half as potent as pancuronium
    • largely excreted by kidney, small liver pathway
    • total clearance is delayed, DOA significantly lenghtened by renal or hepatic dx
    • E 1/2 t increased 500% in pt with renal failure



Class, dose, doa, metabolism, characteristics?

Steroidal non-depolarizing NMB; Intermediate acting

  • Intubating dose: 0.1 mg/kg
  • CHemical structure similar to pancuronium
  • Primarily hepatic metabolism
    • elimination 40-50% liver, 30% renal
  • ACTIVE METABOLITE: 3-OH metabolite can accumulate
    • also 3- desacetylvecuronium is active metabolite and has 80% potency of vecuronium
      • has slower plasma clearance and longer DOA than vec.
  • Must be stored in powdered form



Class, intubating dose, doa, metabolism, characteristics?

Steroidal non depolarizing NMB; intermediate acting

  • Intubating dose:0.6 mg/kg
  • "Gloden child"
  • 6 times less potent than pancuronium and vecuronium d/t change allyl group attachded to quaternary nitrogen
  • Primarily eliminated in liver (>70%), renal 10-25%
  • Shortest onset of the NDNMB
  • Can be used for RSI in high doses (1.2 mg/kg)

- only good for 60 days on shelf d/t terminal sterilization that degrades drug




Intubation dose

time to max block (onset)

time to return to 25% control (duration)

ED 95= 0.067 mg/kg

Intubating dose= 0.15 mg/kg

Time to block= 3.3 min

time to return- 16.8 min





Intubation dose

time to max block (onset)

time to return to 25% control (duration)

ED95= 0.04

Intubation dose 0.1 mg/kg

time to max block (onset)= 5.2 min

time to return to 25% control (duration)= 45 min




Intubation dose

time to max block (onset)

time to return to 25% control (duration)

ED95= 0.043 mg/kg

Intubation dose: 0.1

time to max block (onset)= 2.4

time to return to 25% control (duration): 45 min




Intubation dose

time to max block (onset)

time to return to 25% control (duration)

ED95= 0.21 mg/kg

Intubation dose: 0.21 mg/kg

time to max block (onset): 3.2 min (outlier)

time to return to 25% control (duration): 45 min




Intubation dose

time to max block (onset)

time to return to 25% control (duration)

ED95= 0.305

Intubation dose: 0.6 mg/kg

time to max block (onset)= 1.7 min

time to return to 25% control (duration)= 35 min




Intubation dose

time to max block (onset)

time to return to 25% control (duration)

ED95= 0.067 mg/kg

Intubation dose= 0.08 mg/kg

time to max block (onset)= 2.9 min

time to return to 25% control (duration)= 85 min


What increases potency of non-depolarizin NMB?

  • Inhaled anesthetics
    • desflurance> sevo>iso>halo>nitrous/barb/opioid or propofol
  • Aminoglycoside antibiotics, polymyxins, lincomycin, clindamycin, tetracyclines
  • Hypothermia
  • Magneium sulfate
  • Local anesthetics
  • Some antidysrhythmics


What decreases potency of nondepolarizing NMB?

Chronic anticonvulsant therapy: increases dose and frequency



Relationship with antibiotics and NMBD?

  • under normal conditions, most antibiotics can cause meuromuscular blockade in absence of NMBDs
    • The aminoglycosides include gentamicin, amikacin, tobramycin, neomycin, and streptomycin
  • Can exhibit combo of pre/post synaptic inhibition of ACh
  • antagonism of NMB with neostigmine has been reported to be more difficult after administration of aminoglycosides, you should let NMB terminate spontaneously
  • antagonism is not sustained and may prevent effect of antibiotics


How can Ca decrase effectiveness of NMBD?

  • Ca stimulates ACh release from nerve terminals, and enhances excitation-contraction coupling
  • Increased Ca concentration decreased sensitivity to dTc and pancuronium 
  • hypercalcemia associated with decreased sensitivity to atracurium and thus shortened time course for NM blockade


Which drugs can you give for RSI?

  • Rapid onset: Sch and Roc
  • Roc in high dose (0.9-1.2 mg/kg) or succ 1.5 mg/g can be used interchangeably for rapid tracheal intubation beacuse they provide adequate intubating conditions within 60-90 seconds
    • if succ is undesirable or contraindicated, high dose roc can be used

Increasing roc doubles the clinical DOA from 37-73 minutes!


What can we do to prevent defasciulation? 

  • 10% of intubating dose of NDNMB to prevent SCh induced fasciulation
  • Fasiculations increase risk of hyperkalemia, myalgias, increases intra-gastric pressure and aspiration
  • Can temporize increase in ICP when SCh used in increased ICP
  • Dose of defasciulation
    • Roc= 0.06-1.0 mg/kg (usually 5-10 mg)


Relationship between NMBD and histamine release?

  • When large doses of certain NMBD are administered too rapidly
    • erythema of face, neck, upper torso
    • brief hypotension and slight to moderate increase in HR
    • Bronchospasm rare
  • Effect involve chemical displacemnet of the contents of mast cell granules containing histamine, prostaglandin, and other vasoactives
  • Most often noted following admin of benzylisoquinolinium class of muscle relaxants
  • Short duration 1-5 min, dose related and clinically insignificant


Relationship between NMB and anaphylaxis?

  • Largest proportion of allergic reactions under anesthesia are attributable to muscle relaxants
  • cross reactivity b/w NMBD, food, cosmetics, disinfectant and industrial materials
  • IgE response/mast cell degranulation



What to do if you suspect allergic reaction to NMB?

  • Stop giving drug, 
  • Give 100% o2
  • small dose IV epi (10-20mcg)
  • give crystalloid
  • consider need to intubation
  • antihistamine/steroids?


How do we redose NMB for continues paralysis?

  • Clinical managmenet of patient should be guided by monitoring of NMB, with objective NM monitoring technique
  • Supplemental doses should be 1/10 (LONG ACTING) 1/4 of intubating dose (intermediate/short)
    • should not be given until quantitative evidence of beginning recovery is present
  • Infusion dose is decreased 30-50% in presence of potent volatile anesthetics


Combining NMBD will either be additvie or synergistic

Drugs in same class are usually _____

drugs in different classes are ______




Which NMB exhibit histamine release?

Succinylcholine (slight)

Mivacurium (slight)

Atracurium (slight)


(spells MAST!!)

Benzylisoquinolones tend to have more histamine release


Which NMB have active metabolites?

Atracurium (laudanosin. Not ACTIVE in drug sense, but increases sz risk. )

Cisatracurium (laudanosin- lower than atracurium)

Vecuronium (3-OH- 80% potency of vec)

Pancuronium (3-OH)

Rocuronium- 17-desacetylrocuronium


Suffix - curium= what class?



Suffix -ronium = what class?



Mneumonic to remember DOA of non-depolarizing NMB?

Many Can Ventilate A Really Poor Trach

Mipivacurium, cisatracurium, vecuronium, atracurium, rocuronium, pancuronium, d-Tubocaine


Mneumonic to remember histamine relasers?





(T) -D-tubocraine


What should you give patient with metabolic acidosis or hypvolemia before succinylcholine administration?

NaHCO3 (sodium bicarb) and hyperventilation