Card Set Information

2013-07-01 18:26:44
BC CRNA Anes Pharm NMB

summer 2013
Show Answers:

  1. When were NMBs introduced?
    1940s (1942)
  2. TRUE or FALSE. NMBs provide analgesia.
    FALSE! Can have a paralyzed, awake patient in pain!
  3. What is the NMJ? What is the synaptic cleft?
    area where the motor neuron and muscle cell approx. each other

    the gap that separates the neuron from muscle cell is referred to as synaptic cleft and it’s pretty narrow.
  4. Describe what happens at the NMJ as depolarization happens
    when AP on neuron depolarizes, Na+ will go into the neuron (cell) & this causes Ca+ ions to go into the cytoplasm of the nerve and it’s actually the Ca+ ions that will cause those storage vessels on the to fuse w/terminal membrane to release Ach the NT at the NMJ. The Ach makes its way over to motor end plate and binds w/nicotinic cholinergic receptors.
  5. What happens if Ca+ concentration is decreased?
    then Ach release is inhibited and nerve transmission fails.
  6. What ion is needed for the vesicle to fuse and release Ach?
    • Ca+
    • Specific voltage gated Ca+ channels on presynaptic side (neuron)
  7. how many units are on the Ach receptor? Which ones do we care about?
    5 subunits on each Ach receptor.

    Ones we care about are the 2 are referred to as Alpha sub units, where Ach will bind.
  8. What happens when Ach binds to the receptor?
    • Acetylcholine binds to sites on alpha subunit causing transient opening of central aqueous channel & sodium goes from ECF to ICF
    • But both alpha subunits must be occupied for that Na+ channel to open.
    • On muscle side the AP that results will propagate along the muscle membrane and T tubule system, opening sodium channels and releasing Ca+ from the sarcoplasmic reticulum. Then the actin and myosin filaments will interact and the muscle retracts.
  9. What is our built in safety mechanism in regards to the amount of Ach?
    The amount of Ach that’s usually released and the receptors activated actually far exceed the minimum # required
  10. Ach gets metabolized by __________
    • true Aceytlcholinesterase.
    • Imbedded in that motor end plate, right next to those receptors.
  11. What happens after Ach is removed from receptor (metabolized)
    Ion channels will eventually close and end plate will repolarize, Ca+ gets resequestered in the sarcoplasmic reticulum and then relaxation occurs.
  12. What is the goal of reversal of NM blockers (muscle relaxants)?
    maximize nicotinic transmission while minimizing muscarinic side effects

    Ach is not just at NMJ! (heart, etc)
  13. What are the three types of cholinergic receptors
    • 1. Postjunctional nicotinic cholinergic receptors
    • 2. Extrajunctional cholinergic receptors
    • 3. Prejunctional nicotinic receptors
  14. Where are the postjunctional nicotinic cholinergic receptors located?
    Concentrated at the neuromuscular junction
  15. Where are the extrajunctional cholinergic receptors
    • a)Occur over entire postjunctional membrane not just NMJ
    • b)Not present in large amounts but do develop in response to denervation injuries or disease
  16. What do we need to remember about the extrajunctional cholinergic receptors?
    • These receptors are receptive to both Ach and succinylcholine!
    • The nerve is in some way damaged and receptors aren’t working properly so body responds by increase # of receptors to help, if innervation is restored then they will degrade.
    • Partly responsible for variability among individuals and how we respond to NMBs.
    • When using the depolarizers (succs) we need to take into account if pt. has these receptors.
  17. What do the prejunctional nicotinic receptors do?
    a)Interfere with mobilization of Ach from areas of synthesis to release (not release per se)
  18. How does Succinylcholiine work?
    • Resembles Ach so binds to those receptors (Structure is two Ach)
    • Attaches to 1 or more of the alpha subunits
    • Mimicking Ach qGenerates action potential in muscle cell
  19. Why does Succinylcholine have a longer duration of action than Ach if it binds to the same receptor?
    • Not metabolized by AChesterase so longer duration than Ach…depolarization persists
    • consequently needs to diffuse away to the plasma to be metabolized by psuedocholinesterase
  20. How does Succinylcholine provide NM Blockade?
    • Neuromuscular blockade because the depolarized postjunctional membrane can’t respond to subsequent release of ACh
    • ACh receptor partial agonist
    • 2 subunits alpha that needed to be
    • occupied by Ach to generate an AP and succinylcholine blocks one
  21. Does succinylcholine provide a Phase I or Phase II block?
    Phase I
  22. What is the associated K+ leakage w/succinylcholine?
    • average of 0.5 mEq/L ↑ serum K
    • Problematic for some patients
  23. What is the mechanism of action of all the non-depolarizing blockers?
    • Bind to Ach receptors but no conformational change in receptor so ion channel doesn’t open
    • Ach receptor competitive antagonists
    • Two molecules of Ach are needed for depolarization but one molecule of a non
    • depolarizer will prevent the effect of Ach
  24. Do non-depolarizers provide a Phase I or Phase II block?
    Phase II block
  25. When would we see up regulation of Ach receptors?
    • Spinal cord injury
    • CVA
    • Thermal injury (burns)
    • Prolonged immobility
    • Prolonged exposure to neuromuscular blockers
    • Multiple sclerosis
    • Guillain-Barre
  26. What is up regulation of Ach receptors?
    • In conditions w/denervation injuries
    • Chronic decrease in Ach release and compensatory increase in the # of receptors.
    • Can occur in many conditions
    • Exaggerated response to depolarization, agonist for receptor (succs) will get an exaggerated response which = an increase K+ release.
    • Flip side to that, non depolarizing. NMB, more receptors to block, will show resistance to non depolarizing. Takes more drug to see the same effect.
  27. What is down regulation of Ach receptors?
    • Dec. in the # of function Ach receptors. (such as antibody destruction in myasthenia gravis)
    • Resistance to depolarizers and increase sensitivity to non-depolarizers.
  28. What three things could cause down regulation of ACh receptors?
    • Myasthenia gravis
    • Anticholinesterase overdose
    • Organophosphate poisoning
  29. What does a peripheral nerve stimulator do?
    • Delivers a current of variable frequency and
    • amplitude to a pair of EKG electrodes or pads. Pads should be placed over a peripheral nerve.
    • Looking at blockade of NMJ, want to avoid
    • direct stimulation of muscle itself, why we place it over the nerve and not the muscle.
  30. Where do we look when we stimulate the ulnar nerve?
    Ulnar nerve:  Adductor pollicis muscle. If we have electrodes over ulnar nerve. If we were to turn on TOF and no neuromuscular blockade you’d see twitch of hand but look at the thumb. Don’t look at pinky, there is direct stimulation of that muscle. Look for thumb going to midline
  31. What are the two most common sites of monitoring NM blockade?
    • Ulnar nerve:  Adductor pollicis muscle
    • Facial nerve: Orbicularis oculi
  32. How do you place the electrodes in order to get max twitch height?
    Max twitch height when negative electrode is placed in close proximity to the nerve (over ulnar nerve at wrist) the other should be no more than 2cm proximal to the first, should be fairly close together
  33. Which one RECOVERS from the NM Blockade first? the orbicularis oculi or the adductor pollicis
    orbicularis oculi
  34. What is the definition of a twitch
    single pulse delivered from every second to every 10 seconds
  35. What is TOF?
    4 successive 0.2 msec stimuli in 2 seconds; amplitude of the 4th twitch (height) over the first given as %
  36. What is 75% block in TOF?
    Disappearance of the 4th twitch (so have 3 instead of 4)
  37. What is 80% block in TOF?
    Disappearance of the 3rd
  38. What is 50% block in TOF?
    Disappearance of the 2nd
  39. Clinical relaxation usually requires a ___% block
    75-95%, usually 1-2 twitches
  40. Describe the test of Tetany @ 50 or 100 Hz
    • A sensitive test of neuromuscular function
    • sustained contraction for 5 seconds indicates adequate (not necessarily complete) reversal
  41. Can you reverse a patient w/no twitches?
    They will not be reversible. Even if you do reverse someone who has twitches to start w/ and they don’t appear to be adequately reversed. They still need to be able to maintain a patent airway, not just spontaneously breathe. So may need to leave them intubated until they can
  42. Describe the test for double burst stimulation
    • Variations of tetany (less pain to patient)
    • More sensitive than TOF
  43. Some muscles will come back sooner (some muscles more sensitive) they’ll become paralyzed sooner and they’ll come back sooner from NM blockade. Diaphragm is last to paralyze and first to paralyzes. What does this mean for us?
    • May come back breathing, and build up CO2 but so they breathe but may not have airway reflexes. 
    • Differential of muscle groups will paralyzed at different rates, need to appreciate that when testing for NM blockade
  44. What are some clinical indictors for recovery from NM Blockade?
    • Sustained head lift
    • Inspiratory effort of – 25 cm water
    • Forceful hand grip
  45. What is fade? Which NMBs cause this?
    • 1st twitch will be stronger the next will get progressively weaker, even if you see
    • all 4. 
    • Non-depolarizers cause this (or too much Succs)
  46. What is Phase I block? What NMB causes this?
    • get a decrease in twitch # but all 4 twitches are same height
    • Succs
  47. Non depolarizing have post tetanic
    potentiation. What does this mean?
    • means that if do TOF on patient (if you wonder at the end of case, if the pt. can be reversed) and you have a weak twitch.
    • If you hit the tetanus and then TOF right after, you’ll get stronger TOF, there will still be fade but twitch height will be stronger after the tetanus.
    • Gives sense of whether or not pt. is reversible and if the are heading in the right direction.

    thought to represent a compensatory increase in Ach mobilization following the tetanus. It’s helpful in this limited role of are we moving towards reversal.
  48. When can Phase II happen w/succs? (also referred to as dual block)
    • it is d/t repeated doses of Succs or a single large dose (greater than 2mg/kg IV)
    • Or it used to be seen when we would use a
    • continuous Succs infusion (not seen anymore) Tachyphylaxis that occurs in a dual block.(sudden decrease in response to a drug)
  49. Why shouldn't you watch the 5th finger instead of the thumb when stimulating the ulnar nerve (adductor pollicis)?
    Don’t watch 5th finger because it recovers sooner than adductor policies & will underestimate blockade
  50. Which is is better to monitor at the end of the case (when we care about the airway muscles) the adductor pollicis or the orbicularis
    Adductor pollicis. the adductor policies is sensitive to non-depolarizers. The respiratory muscles will have come back sooner than the nerve transmission at adductor polilicis, if you have good twitches at adductor pollicis you can be confident you’ll have good neuromuscular transmission at the airway muscles
  51. If assessing the adductor pollicis, when would we know we're ready for laryngoscopy?
    • when we start to get fade at adductor then the pt. is probably ready for laryngoscopy
    • (Adductor has longer onset time than
    • airway muscles, pt. ready for laryngoscopy before we get complete blockade at
    • adductor pollicis)
  52. When should you get a baseline TOF?
    When the patient is asleep but BEFORE the NM blocker has been given
  53. What two nerves on the face do we monitor for? Which cranial nerve is it
    • Orbicularis oculi: closes eye& wrinkles forehead
    • Corrugator supercilli: draws medial end of eyebrow downward & wrinkles forehead

    Both innervated by facial nerve (CN 7)
  54. TRUE or FALSE. When no twitches at adductor pollicis, those of orbicularis oculi showed only
    minor fade
    • TRUE!
    • Can be really misled that pt. is more reversed than they really are & that they have more strength than they really do.
    • If monitoring facial nerve, pt. may have adequate blockade and you'll still have twitches.
  55. What might happen is we rely on only the facial nerves?
    • Relying only on facial muscles may lead to relaxant overdose or overestimating recovery
    • Biggest danger is overestimating recovery!
  56. Which nerve cases plantar flexion of the ankle?
    Stimulation of tibial nerve in popliteal fossa produces plantar flexion of ankle
  57. Stimulation of what nerve causes dorsiflexion of the foot?
    Stimulation of peroneal nerve (behind head of fibula) causes dorsiflexion of foot
  58. What nerve causes flexion of the big toe
    Posterior tibial nerve can be stimulated behind the medial malleolus which will cause flexion of the big toe
  59. There is variability in muscle sensitivity to NM Blockers. List the most resistant to most sensitive muscles
    • 1.  vocal cord
    • 2.  diaphragm
    • 3.  orbicularis oculi
    • 4.  abdominal rectus
    • 5.  adductor policies
    • 6.  masseter
    • 7.  pharyngeal
    • 8.  extraocular
  60. TRUE or FALSE. At the facial nerve, the onset of blockade is slow and recovers after the adductor pollicis
    • FALSE! Facial nerve: onset of blockade is more rapid & recovery occurs sooner than at
    • adductor pollicis
  61. _______ stimulation predicts intubating conditions & profound blockade
    Facial Nerve
  62. ________is poor predictor of intubating conditions
    Adductor pollicis
  63. Adequate surgical relaxation = _____twitches at adductor pollicis
    2 or 3
  64. What type of symptom might the patient experience when  you give small dose of non depolarizer to try to attenuate the fasciculations of succs? (even small dose of non depolarizing agent)
    Pt. will get blurred vision becaus extraoccular is so sensitive
  65. Onset of action is more rapid at the _____, _____, &  _____ than the adductor pollicis
    larynx, orbicularis oculi, & diaphragm
  66. Recover occurs first at the _____ & last at the _____
    larynx & adductor pollicis
  67. Why should you not intubate until a twitch is barely perceptible (at facial nerve)
    Any earlier attempts risk increased trauma from coughing and vocal cord closure

    Look for fade at adductor pollicis
  68. If you have used succinylcholine, why should you wait until some recovery is demonstrated before giving other relaxants?
    detects unsuspected atypical pseudocholinesterase
  69. Why don't you want to give enough NM blocker so you don't see ANY twitches?
    • Don’t obliterate, because then you don’t know time of return, want to keep pt. in reversible state
    • Want 1-2 twitches at least
  70. Why wouldn't you want to monitor TOF in a paretic extremity?
    Likely resistant to NM Blockers (paralyzed extremity)
  71. TRUE or FALSE. If facial nerve is used for monitoring, you should expect denser than usual paralysis of peripheral muscles at a give TOF
    TRUE! The facial nerve is too resistant to muscle relaxants to be a reliable indicator for recovery from paralysis.
  72. Why should you wait until you see at least 1 twitch before attempting to reverse a NM Blocker?
    Earlier attempts have no benefit and may prolong reversal
  73. Name 4 things that affect onset of blockade
    • Hypothermia
    • Drugs
    • Nerve Damage (CVA, etc)
    • Burns
  74. In Burns, resistance to non-depolarizers
    approximately __ days after injury peaking at ___ days & declining after ___ days (altered affinity of Ach receptor for Ach or nondepolarizing drugs)
    10; 40; 60

    Burns involving 30% or more of body!!
  75. Hypothermia ______ the duration of action of NM blockers
    • prolongs.
    • Slow down any enzymes that are involved in metabolic agents of clearance. Succinylcholine or non depolarizers
  76. Antibiotics effect non-depolarizing or depolarizing NM blockers?
    • BOTH- they potentiate them!
    • ABX on table included: Streptomycins, collistin,  polymyxin, tetracycline, lincomycin, clindamycin, bacitracin
  77. If you're patient is on phenytoin, are they more resistant to non-depolarizering NM blockers?
    • YES! anticonvulsants cause increased resistance to non depolarizing NM blockers. 
    • Included on table: phenytoin, carbamazapine, primidone, sodium valproate

    Dilantin makes the patient chew through them, need to redose a lot!
  78. How do antidysrhythmics effect NM blockers?
    They potentiate both depolarizing and non-depolarizing NM blockers.

    Included on table: Quinidine, Lidocaine, Ca+ channel blockers, procainamide
  79. How do antihypertensive effect NM blockers?
    They potentiate both depolarizing and non-depolarizing NM blockers. 

    Included on table: Trimethaphan & Nitroglycerin (only effects pancuronium)
  80. What effect do cholinesterase inhibitors have on NM blockers?
    • Potentiates depolarizing NM blockers (succs)
    • Resistance to non-depolarizing NM blockers 

    Listed on table: Neostigmine, pyridostigmine, edrophonium
  81. What effect does Dantrolene have on NM blockers?
    It potentiates non-depolarizing NM blockers
  82. What effect dose Lasix have on NM blockers?
    Biphasic, depend on dose

    • <10mcg/kg it potentiates both
    • 1-4mg/kg it causes resistance to both
  83. What effect do inhalation agents have on NM blockers?
    Potentiates both depolarizers and non depolarizers
  84. What effect does Ketamine have on NM blockers?
    Potentiates non-depolarizing NM blockers
  85. What effect do local anesthetics have on NM blockers?
    Potentiates both depolarizers and non-depolarizers
  86. How does lithium carbonate  effect NM blockers?
    Prolongs onset and duration of succinylcholine
  87. How does Mag sulfate affect NM blockers?
    Potentiates both depolarizers and non-depolarizers
  88. What is succinylcholine's rapid onset due to?
    low lipid solubility

    *All have low lipid solubility (Quaternary ammonium structure, highly charged, only distributed to ECF)
  89. Why do actually give a relative overdose of succs?
    • metabolized before NMJ,
    • plasmacholinesterase in plasma so as it gets distributed it’s metabolized
  90. What is the onset and duration of succs?
    Onset 30-60sec

    Duration is less than 10min
  91. For succinylcholine: Name causes of low enzyme levels (quantitative reduction in amount of pseudocholinesterase available)
    • Pregnancy
    • Liver disease
    • Renal failure
    • Malnutrition
    • Certain drug therapies
  92. Describe the genetically aberrant enzyme
    (qualitative) for succinylcholine
    1 in 50 patients results in slightly prolonged block (20-30 min)--May not notice

    1 in 3000 patients (homozygous atypical); very prolonged block (6-8 hours)

    *atypical: if pt. has it, and you don’t appreciate it, this is the pt. you want to check TOF when you think succs recovery should have occurred
  93. What three reasons could the patient have an abnormal metabolism to succinylcholine?
    • Hypothermia: slows the rate of hydrolysis
    • Low enzyme levels (quantitative)
    • Genetically aberrant enzyme (qualitative)
  94. TRUE or FALSE. The duration of succinylcholine is prolonged with high doses
  95. What happens if you give an anticholinesterase w/succinylcholine?
    Inhibit acetylcholinesterase so higher Ach concentration

    Intensify depolarization & prolong block with Succs

    Also ↓ hydrolysis of Succs by pseudocholinesterase

    Organophosphates (pesticides, echothiopate) cause irreversible inhibition of acetylcholinesterase & prolong Succs blockade
  96. Should you be concerned if your patient is on eye drops for glaucoma and you want to give them succinylcholine?
    Pt. getting eye drop seems benign but may have prolonged blockade from succinylcholine.

    Drugs (echothiopate) can cause a Quantitative decrease
  97. Name some drugs that cause quantative decreases in pseudocholinesterase (prolonging the effect of succinylcholine)
    • Echothiopate: irreversible cholinesterase inhibitor used for tx of glaucoma
    • Neostigmine or pyridostigmine: reversible cholinesterase inhibitors
    • Phenelzine: MAOI
    • Cyclophosphamide: antineoplastic agents
    • Trimethaphan: antiHTN
    • Hexafluorenium: seldom used nondepolarizer
  98. Dibucaine is a local anesthetic (amide) that can test for what type of problem w/pseudocholinesterase?
    Atypical Plasma Cholinesterase (qualitative)

    Dibucaine inhibits activity of normal plasma cholinesterase by 80%

    Atypical enzyme inhibited only 20%

    **Reflects quality not quantity of enzyme
  99. Dibucaine number of ___confirms normal enzyme
  100. 1 in 3000 will have a greater
    prolonged response to succs they have dibucaine # of___.
    20; Can now do genetic testing the Dibucaine # was limited to only certain types of heriditary variants of plasma cholinesterase
  101. How does Succs effect the CV system?
    • ↓HR
    • Acts on Ach receptors in heart.
    • Sinus bradycardia w/nodal or ventricular escape is not uncommon esp. in peds and asystole is possible w/additional doses.
    • As general rule don’t’ give antimuscarinic before succs.
    • In middle of induction & we're giving succs, don’t want to mask tachycardia (MH) don’t want to give it prophylactically.
    • For repeated doses of succs--> be ready to give an antimuscarinic
  102. Succs causes fasciculations. What is this and and how can you prevent it?
    • Visible motor unit contractions, can see depolarization occur.
    • Can be attenuated w/small dose of a non depolarizer which will occupy some of the receptors.
  103. Who is more likely to have fasciculations w/succs?
    Fasciculations more likely to occur w/younger more muscular people, older people w/less muscle mass are less likely
  104. Name the conditions in which you would see an increase in K+ w/Succs.

    there are 1244334353 of them!!!
    • Burn injury
    • Massive Trauma
    • Severe intra-abdominal infection
    • Spinal cord injury
    • Encephalitis
    • Stroke
    • Guillian Barre syndrome
    • Severe Parkinsons
    • Tetanus
    • Prolonged total body immbolization
    • Ruptured cerebral aneurysm
    • Polyneuropathy
    • Closed head injury
    • Near drowning
    • Hemorrhagic shock w/met. acidosis
    • Myopathies (Duchenne's dystrophy)
  105. How much does your K+ increase w/succs?
    ↑ 0.5 mEq/L
  106. Does pre-treating w/a non-depolarizer help the problem of increased K+ w/succs?
  107. What is really the only indication for succs?
    facilitate intubation (rapid sequence)
  108. What is the dose for succs? What is we pre-treat w/a non depolarizer?
    • adult is 1-1.5mg/kg
    • If we have given pretreat w/non depolarizer need to give higher dose, competitive antagonist on those receptors so succs dose is 1.5-2mg/kg
  109. When should we expect to have intubation conditions w/succs?
    Should get intubation conditions in 1min or so (30-60sec but up to 1.5min) usually by a min ready to intubate. Duration anywhere from 5-10min.
  110. What is the most common compliant from succs?
    Myalgias: most common in healthy female outpatients. Because of attenuating fasciculations a small dose of non depolarizer may help
  111. Succs is a potent trigger for MH, what sign might we see?
    Masseter muscle spasm after Sch is premonitory sign

    Paradoxical contraction of jaw muscles after succs may be a premonitory sign. Give succs, jaw contracts as opposed to relaxed, not a good thing, MH around the corner.
  112. Does intragastic pressure increase or decrease w/succs?
    • 2° abdominal wall fasciculations
    • Also ↑ lower esophageal sphincter tone
    • They balance each other out so not aspiration risk.
    • Precurarization (pre-treat)attentuates both
  113. Does intraocular pressure increase or decrease w/succinylcholine?
    • Prolonged contraction of extraocular muscles which have multiple motor end-plates
    • Problematic in open eye injuries
    • Pre tx won’t attenuate that.
  114. Does intracranial pressure increase or decrease w/succs?
    • Increases but effects of intubation are greater than that of Sch
    • Hyperventilation attentuates
  115. What is the excretion of cisatracurium
    Insignificant, can be given to patient w/renal failure
  116. Do cisatracurium, pancuronium and vecuronium have the same relative potency?
    yes, 5.

    Rocuronium has a relative potency of 1
  117. How are rocuronium and vecuronium excreted?
  118. Which has the "fastest" onset of action? Vecuronium, cisatracurium, rocuronium, or pancuronium
  119. Which has the longest duration of action? Vecuronium, cisatracurium, rocuronium, or pancuronium
  120. Which has vagal blockade?

    Vecuronium, cisatracurium, rocuronium, or pancuronium
    • pancuronium ++
    • Rocuronium +

    Causes ↑HR
  121. Which costs the least? Vecuronium, cisatracurium, rocuronium, or pancuronium
  122. Which drugs had histamine release so they aren't used anymore?
    • Tubocurarine +++
    • Metocurine ++
    • Atracurium + 
    • Mivacurium +
    • Rapacuronium +
  123. Which is renally excreted? Vecuronium, cisatracurium, rocuronium, or pancuronium
  124. Aminosteroids tend to be _________ and the
    -iuriums they to __________
    vagolytic; release histamine
  125. Hepatic clearance only really an issue
    w/____________ & _____________
    pancuronium and vecuronium, metabolized extensively by liver.

    Rocuronium has a little bit by the liver as well.
  126. Esp. good to know w/succs, liver disease is assoc. w/decrease  _____________
  127. Describe the kinetics of the non-depolarizers
    Highly ionized & water soluble at physiologic pH because of quaternary ammonium groups

    These drugs are never discussed from acid/base kinetic perspective

    Limited lipid solubility

    Vd approximates ECF volume (200 ml/kg)

    • No CNS effects, minimal renal tubule
    • reabsorption. Giving them to mom doesn’t affect the fetus. Not highly protein bound.
  128. _______ _______ enhances the action of non-depolarizing NM blockers
    volatile agents
  129. TRUE or FALSE. Elimination 1/2 time correlates w/duration of action of non-depolarizing NM blockers
    • FALSE. Elimination ½ times DOESN’T correlate
    • w/duration of action
  130. The onset time (effect site equilibration) is between ___min (that lags behind the peak plasma concentration-occurs in less than __min) takes time to get to NMJ which is the effect site.
    2-7min; 1min
  131. How can we increase the onset of action for non-depolarizing NM blockers (like Rocuronium)?
    Because a large # of receptor must be occupied for an effect, onset will be fastest w/drugs that are less potent because less potency need to give more of it, flooding receptors with more drug
  132. Which one of these is degradation dependent on pH of blood? Vecuronium, Rocuronium, or Cisatracurium
  133. For which ones is degradation dependent on body temperature? Vecuronium, Rocuronium, or Cisatracurium
    ALL of them
  134. What are the three doses we think about for non-depolarizers?
    • 1.Intubating dose: cleanest dose (no succs
    • for intubation-using non-depolarizer for intubation). 

    2. First dose of non depolarizer after succs for intubation:  Use ½ of intubating dose (per Sue).

    • 3. Supplemental dosing: occupied a lot of receptors. (intubated w/non depolarizer or intubated w/succs and given fairly modest dose of non depolarizer) Look at TOF, get 2-3 to 4 twitches back and still have of receptors occupied. Want to occupy enough
    • receptors to keep 1-2 twitches and keep pt. readily reversible. Per Sue, give 20-25% of intubating dose for follow up dosing
  135. What is the intubation dose of pancuronium?
    Intubation: 0.1mg/kg

    So after succs = 0.05mg/kg

    Follow up = 0.025mg/kg

    *same as cisatracurium
  136. What is the intubating dose of Rocuronium?
    Intubating: 0.6-1.2mg/kg

    After Succs: 0.3- 0.6mg/kg

    follow up: 0.15-0.3mg/kg
  137. What is the intubating dose of Cisatracurium?
    Intubation: 0.1mg/kg

    After succs: 0.05mg/kg

    Follow up: 0.025mg/kg 

    *Same as pancuronium
  138. What is the intubating dose of Vecuronium?
    Intubation: 0.08-0.1mg/kg

    After succs: 0.04-0.05mg/kg

    Follow up= 0.02-0.025mg/kg
  139. What is the ED 95?
    ED95: think of as the effective dosing 95% of patients. Look at that multiple by 2 get intubating dose
  140. No NDMR has the rapid onset of Succs. So we have a priming technique for intubation. What is this?
    • Onset time can be shortened with:
    • --↑ dose
    • --Priming with 10-15% of intubating dose 5 minutes before induction to occupy enough
    • receptors to speed onset
    • --Clinical effect site takes longer (than the peak) need to get NMJ
    • BUT Dyspnea & desaturation is a risk
    • Extraocular muscles susceptible to NM blockade, pt. seeing double or blurred vision, very uncomfortable for pt. Variability for how pt. respond to NM blocker.
  141. What is pre-treatment for succs?
    • Give NDMR
    • To prevent fasciculations prior to Sch
    • 10-15% of non-depolarizer intubating dose
  142. NDMR have potentiation by volatile agents, how does this happen?
    Postsynaptic augmentation.
  143. What are SIX common variables with NDMRs?
    • 1. Temperature: hypothermia prolongs block
    • 2.  Acid-base balance: acidosis potentiates & antagonizes reversal (hard when we're trying to build up CO2 to get pt to breathe)
    • 3 Electrolyte abnormalities: hypokalemia, hypocalcemia, hypermagnesemia potentiate NDMR block
    • 4. Age: neonates have ↑ sensitivity to NDMR (immature NMJ) but also have ↑Vd (larger ECF) so dose isn’t decreased
    • 5. Drug interactions 
    • 6. Concurrent disease
  144. What is the (recovery index) RI of cisatracurium, rocuronium, & vecuronium?
  145. What is the RI (recovery index) of pancuronium?
  146. Which drugs have a long recovery index and aren't used anymore?
    • d-tubocurarine
    • Doxacurium
    • Metocurium
  147. What is the T90 (time to 90% recovery) for rocuronium, vecuronium, and cisatracurium?
  148. What is the T90 (time to 90% recovery) for pancuronium?
  149. Tell me about Tubocurarine
    • No longer clinically available
    • Extensively renally excreted
    • Histamine release
    • --Hypotension, tachycardia, bronchospasm
    • Long acting
  150. Tell me about Metocurine
    • Derivative of Tubocurarine
    • Less histamine release
    • Preparations contain iodine
    • --Iodine allergy must avoid
    • Long acting as well
  151. Atracurium has a unique method of biotransformation. What is it?
    • 2/3 by Ester hydrolysis (not pseudocholinesterase or acetylcholinesterase) 
    • ---same tissue esterases like remifentanil
    • 1/3 by Hofmann elimination (nonenzymatic breakdown)
  152. Does Atracurium cause histamine release?
    • YES!
    • Hypotension, tachycardia, bronchospasm
    • Slow injection minimizes
  153. Atracurium can cause Laudanosine toxicity, what is this?
    • Major metabolite
    • Associated with CNS excitation
    • Occurs at high concentrations or if patient has liver disease (more assoc toxicity) because laudanosine is metabolized by the liver
    • Intermediate acting
  154. Tell me about Cisatracurium
    • One of 10 stereoisomers of atracurium
    • Hofman elimination but not ester hydrolysis
    • Less laudanosine
    • No histamine
    • Intermediate acting
    • Makes less of the metabolite, used in lower doses because it’s more potent (than atracurium)
  155. What are the benzylisoquinolines?
    • Atracurium
    • Cisatracurium
    • Mivacurium
    • Doxacurium
  156. Tell me about Mivacurium
    • Like Succs is metabolized by pseudocholinesterase so deficiency prolongs block
    • Unlike Succs, administration of cholinesterase inhibitor will quicken reversal
    • Histamine release like atracurium
    • Shorter duration than intermediates but longer than succs
    • (Supposed to have faster onset and shorter duration, never knew where you were w/twitch status, never knew where you were w/blockade. Metabolism is slower than w/succs but similar metabolism pathway)
  157. Tell me about Doxicurium
    • Potent, slow onset, long duration
    • Primary renal excretion
    • No CV effects or histamine release
  158. What are the Aminosteroids?
    • Pancuronium
    • Vecuronium
    • Rocuronium
    • Rapacuronium
  159. Tell me about pancuronium
    • Steroid ring with 2 modified Ach molecules attached
    • Metabolized by the liver & excreted by the kidneys (40%) & bile (10%)
    • Side effects:
    • ---Vagal blockade & catecholamine release → HTN & ↑ HR (not always bad-offset decrease in HR w/high dose fentanyl)
    • ---VEA in susceptible patients
    • Preparations contain bromide
  160. Tell me about vecuronium
    • Pancuronium minus a quaternary methyl group
    • Primarily excreted in the bile & only 25% renally
    • Prolonged blockade with long-term ICU administration may mimic chronic denervation
    • Side effects: none
  161. Tell me about rocuronium
    • Steroid analog of vecuronium designed for rapid onset
    • Elimination is by the liver
    • Onset and duration are dose-dependent
    • *considered to have faster onset than
    • Vecuronium because its less potent, give more of it and it gets to NMJ
  162. What happens if we give a huge dose of Rocuronium for intubation (we wanted to quick onset)?
    Problem w/rocuronium: intubating dose is 06.-1.2mg/kg has a huge range so if you give a large dose of vecuronium (0.8 or 0.1 to 0.3) if we gave 2x the standard dose of vec we could intubate in a shorter period of time too. People advocate you can use Roc for RSI when you can’t do succs. Need high dose, buying drug in the end, if long case that’s fine but if short case and you decide you can’t use succs just know you’re buying time in the end.
  163. Tell me about Rapacuronium
    • introduced in 1999 then withdrawn in 2001. introduced to provide a really effective way to do RSI w/out succs.
    • Problem: rare but sever incidences of bronchospasm. There may have been a few deaths. Caused it to get withdrawn. Can get intubating conditions within a min
  164. Tell me about Pipecuronium
    pancuronium w/out SE but its now obsolete much like doxicurium no need for long acting agents, residual blockade w/longer acting agents. No advantage of vecuronium or rocuronium.
  165. What are the two types of reversal?
    • Spontaneous reversal
    • --Gradual diffusion, redistribution,
    • metabolism, & excretion of the agent
    • Pharmacologic reversal
    • --Cholinesterase inhibitors: inhibit
    • acetylcholinesterase by reversibly binding to the enzyme
    • --Results in more Ach available at NMJ
  166. Edrophonium is a reversible anti-cholinesterase agent. Tell me everything Sue said about it
    • Quaternary ammonium compound
    • Electrostatic attachment to anionic site
    • Hydrogen bonding at esteratic site (The way this lines up, it will line up w/the enzyme and that prevents Ach from contacting the enzyme.)
    • Short duration
    • Main site of action is presynaptic
  167. Physostigmine, Neostigmine, Pyridostigmine are also reversible anti-cholinesterase agents. What did we learn about these?
    • Form carbamyl ester complex at esteric site on enzyme (the complex gets formed prevents Ach and enzyme from getting together. Ach and Aceytlcholinesterase can’t get together. 
    • Complex has a half-time of 15-30 minutes.
    • We use Neo the most
  168. Organophosphates are IRREVERSIBLE anticholinesterase agents. Tell me about them
    • Pesticides & Echothiopate (eye drops)
    • Combine with enzyme at esteratic site to form a stable, inactive complex that doesn’t undergo hydrolysis
    • New enzyme must be synthesized
    • Nerve gases like Saran are very lipid soluble & can be absorbed via the skin
  169. Neostigmine is ____ synaptic and Edrophonium is ___ synaptic
    post synpatic; pre synaptic
  170. neostigmine as a _____ onset and Edrophonium has a ____ onset
    intermediate; rapid
  171. What are the muscarininc SE on the CV system of cholinesterase inhibitors?
    • ↓HR
    • dysrhythmias
  172. What are the muscarininc SE on the Resp system of cholinesterase inhibitors?
    • Bronchospasm
    • Bronchial secretions
  173. What are the muscarininc SE on the CNS system of cholinesterase inhibitors?
    Diffuse excitation w/physostigmine only bc it's the only one to cross the BBB (tertiary ammonium)
  174. What are the muscarininc SE on the GI system of cholinesterase inhibitors?
    • intestinal spasm 
    • ↑secretions
  175. What are the muscarininc SE on the GU system of cholinesterase inhibitors?
    Increased bladder tone
  176. What are the muscarininc SE on the opthalmogic system of cholinesterase inhibitors?
    pupillary constriction
  177. How do we attenuate the SE of a cholinesterase inhibitor?
    Give an antimuscarinic at the same time (or right after)
  178. What is the recommended dose of neostigmine for <2 twitches and a fade of ++++ on TOF?
  179. What is the dose of neostigmine for 3-4 twitches and  a fade of +++ on TOF?
  180. What is the dose of Edrophonium for 4 twitches and a fade of ++ on TOF?
  181. What is the dose of Edrophonium for 4 twitches and a fade of ± on TOF?
  182. If giving an antimuscarinic and a cholinesterase inhibitor, which should you give first?
    • ALWAYS give antimuscarinic first if in
    • two separate syringes
  183. Speed & extent of reversal depends on intensity of block at time of reversal. Need at least ___ twitch in TOF, Edrophonium is less effective than neostigmine in reversing dense blockade where twitch height is less than __% of control (why most go w/neostigmine)
    1; 10%
  184. Anticholinesterase reversal inhibited by...
    • Hypothermia
    • Certain antibiotics
    • Respiratory or metabolic acidosis (PaCO2 greater than 50mmHg will antagonize reversal)
    • Hypokalemia
  185. Maximal inhibition of acetylcholinesterase is achieved with neostigmine ___ mcg/kg so additional drug doesn’t help & may produce additional blockade so __ mg of neostigmine is
    considered maximum
    70; 5
  186. Pharmacologic reversal should be given to all patients who have received a NDMR unless full reversal can be demonstrated….how is that done???
    • Can't really be done!
    • Can’t really say FULL reversal.
    • No reason not to give one. Prudent to give some sort of reversal to someone.
    • If you used a non-depolarizer to intubate the pt. then case lasted 2-3hrs and you just gave 1 dose several hours before end of the case then maybe don't need it.
  187. Antimuscarinics are competitive antagonists of Ach at muscarinic receptors. Name the two types and give examples of each
    • Tertiary amines (cross BBB)
    • --Atropine
    • --Scopolamine
    • --Naturally occurring alkaloids of
    • belldonna

    • Quaternary amine
    • --Glycopyrrollate 
    • --Semi-synthetic
  188. What are the effects of antimuscarinics on the CV and Resp systems?
    CV: ↑ HR

    • Respiratory:
    • ↓ secretions
    • Relaxation of bronchial smooth muscle
  189. What are the effects of antimuscarinics on the CNS?
    • Excitation, restlessness, hallucination, sedation
    • (tertiary)

    Physostigmine crosses blood-brain barrier & reverses (it's the anticholinesterase)
  190. What is the MOA of antimuscarinics?
    reversibly combine with muscarinic receptor preventing Ach attaching
  191. which antimuscarinic increases HR the most?
  192. Which antimuscarinic is the strongest antisialagogue?
  193. Which antimuscarinic is most likely to cause sedation?
  194. Which antimuscarinic is most likely to prevent motion sickness but also causes mydriasis?
  195. What do antimuscarinics do to the GI system?
    • ↓ salivation
    • ↓ peristalsis
    • ↑ gastric emptying time
  196. What do antimuscarinics do to the eyes?
    • Pupillary dilation
    • Cycloplegia (inability to accommodate to near vision)
  197. What effect do antimuscarinics have on the GU system?
    ↓ ureter & bladder tone → urinary retention
  198. How do antimuscarinics effect thermoregulation?
    Inhibit sweat glands
  199. What is the usual dose of neostigmine?
    What is the recommended antimuscarinic?
    What is the dose of the antimuscarinic?

    Glycopyrrolate 0.2mg
  200. What is the usual dose of Pyridostigmine?What is the recommended antimuscarinic?What is the dose of the antimuscarinic?

    Glycopyrrolate 0.05mg
  201. What is the usual dose of Edrophonium?
    What is the recommended antimuscarinic?What is the dose of the antimuscarinic?

    Atropine 0.014mg
  202. What is the usual dose of Physostigmine?
    What is the recommended antimuscarinic?What is the dose of the antimuscarinic?
    • 0.01-0.03mg/kg
    • usually not necessary to have antimuscarinic