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Flashcards in Non-Depolarizing NMBs Deck (40)
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1
Q

What is the mechanism of action of non-depolarizing NMBs?

A

competitively antagonize one or both of the alpha subunits of the Nicotinic acetylcholine receptors –> rapid influx of sodium and calcium into the cell

Binding at both alpha subunits is necessary for depolarization

2
Q

How are is the structure of ND-NMBs classified?

A

benzylisoquinolinium

  • atracurium/cisatracurium
  • histamine release
  • plasma metabolism

aminosteroid

  • roc/vec
  • liver/kidney metabolism
3
Q

How are the aminosteroid NMBs metabolized?

A

End in -onium
renal clearance alone or
renal clearance + hepatic metabolism/biliary excretion

Pancuronium = renal (~ 80%)
Vecuronium (>75%)
Rocuronium (>90%) liver

4
Q

How are the benzylisoquinolinium NMBs metabolized?

A

Hoffman elimination and/or enzymatic degradation

= ok for kidney/liver failure patients

5
Q

How does cistatricurium differ from atracurium on potency and metabolism?

A

Cisatricurium - lower ED50 + no histamine release

Cisatracurium - primarily Hoffman elimination alone

Atricurium - Hoffman + ester hydrolysis (susceptible to prolonged effect with butyrylcholinesterase deficiency)

6
Q

The active metabolite of which ND-NMB has been know to lower the seizure threshold when it accumulates?

A

Atricurium (laudanosine) and to lesser degree cisatricurium

7
Q

What is the only short-acting ND-NMB in the benzylisoquinolinium group and what properties make it this way?

A

Mivacurium - metabolized by ester hydrolysis

8
Q

What ND-NMB may require dec dosing in renal failure due to accumulation of metabolites?

A

Pancuronium > Vecuronium

3-OH metabolite has activity at the nAChR
- accumulates with prolonged use (several days rather than several hours) in a pt w/ renal failure –> prolongation of muscle relaxation

9
Q

How does hypothermia affect ND-NMB?

A

Prolonged duration - by reducing ion influx

10
Q

How does old age affect ND-NMB?

A

Prolonged duration, dec dosage - dec elimination

11
Q

How does MS or ALS (motor neuron disease) affect ND-NMB?

A

Resistance due to up regulation of Ach Receptors

12
Q

How does Guillan-Barre affect ND-NMB?

A

Sensitive - loss of motor units at NMJ

13
Q

How does myasthenia gravis affect NMB?

A

Resistant to succinylcholine

Extremely sensitive - fewer receptors + reversal can be difficult d/t anticholinesterases used to treat the disease

14
Q

How does myotonic dystrophy affect ND-NMB?

A

Resistant - to ND-NMB
Less resistant to succinylcholine

Neostigmine can cause prolonged muscle weakness
Pts are tx with pyridostigmine which dec efficacy of NMBs

15
Q

How does Eaton-Lambert syndrome affect ND-NMB?

A

Sensitive to BOTH ND and depolarizing NMBs

  • Dec Ach release
  • neostigmine is ineffective
  • titrate with peripheral nerve stim
16
Q

How does muscular dystrophy affect ND-NMB?

A

Usually normal - possible sensitivity –> muscle weakness

17
Q

How does burn and SC injury affect ND-NMB?

A

Burn - resistance (when 25-30% BSA affected)

SC - up-reguation of Ach receptors

18
Q

Name the 5 methods NMB action can be terminated

A
redistribution
Hoffman elimination
ester hydrolysis
hepatic metabolism
renal clearance
19
Q

What anti-emetic has cholinesterase inhibiting activity and may prolong NMB?

A

Metaclopromide

20
Q

How do volatile anesthetics affect NMB?

A

Dose-dependent potentiation of activity

21
Q

Why is there allergic cross-reactivity across the ND-NMBs?

A

all have a quaternary ammonium group

22
Q

Which ND-NMBs cause histamine release?

A

atracurium, mivacurium and sux

- usually with rapid injection

23
Q

Which ND-NMB has a significant vagolytic effect?

A

Pancuronium

  • cardiac muscarinic receptor block –> 10-15% inc in HR, MAP, CO
24
Q

What antibiotics can prolong the effect of NMBs?

A
  1. aminoglycosides (neomycin, streptomycin, gentamicin, tobramycin, clindamycin)
  2. tetracyclines
  3. polymyxins
25
Q

List other drugs (not abx) that can prolong the effect of NMB

A
Volatile anesthetics
Local anesthetics
Magnesium
Lithium
Calcium channel blockers

Must use caution in re-dosing NMB!!!

26
Q

What electrolyte abnormalities can prolong NMB?

A

acidosis
alkalosis
hypocalcemia, hypokalemia
hypernatremia, hypermagnesemia

27
Q

How does critical illness/ICU patient status affect NMB?

A

Prolonged use –> resistance d/t up-regulation of Ach receptors

critical illness polyneuropathies
critical illness myopathies

= residual weakness lasting for long periods (several months in some cases) after stopping the muscle relaxant

28
Q

How do anti-convulsants effect the use of NMBs?

A

Pts experience shortened duration of action due to increased plasma clearance

Especially affects vecuronium, pancuronium, rocuronium

29
Q

What are 3 anticholinesterases used to antagonize residual NMB?

A

Neostigmine, pyridostigmine, and edrophonium (not available)

  • Have both nicotinic and muscarinic effects but only nicotinic at NMJ is desired = give glycopyrrolate or atropine
30
Q

How are the muscarinic side effects of anticholinesterases prevented?

A

atropine or glycopyrrolate (muscarinic anticholinergics)

31
Q

List some of the muscarinic effects of anticholinesterases by system:

  1. Cardio
  2. Pulmonary
  3. GI
  4. Ophtho
  5. Urinary
  6. CNS
A
  1. Bradycardia, hypotension, arrhythmias
  2. Bronchospasm, hypoxia, increased secretions
  3. Increased GI motility and secretions
  4. Miosis, decreased intraocular pressure, lacrimation
  5. Urination
  6. Nausea and vomiting
32
Q

What is the mechanism of Sugammadex?

A

selectively binds steroidal non-depolarizing muscle relaxants –> complexes with a 1:1 ratio

33
Q

Describe the affinity of Sugammadex for different ND-NMBs

A

rocuronium > vecuronium&raquo_space; pancuronium

34
Q

Which ND-NMB is most likely to cause tachycardia?

A

Pancuronium

35
Q

Which ND-NMB has a metabolite with 80% of the activity of the primary drug?

A

Vecuronium

36
Q

What is the ED95 of Rocuronium and onset?

A

0.3mg/kg

Onset 1.5-3min

37
Q

What is the mechanism for Pancuronium induced in HR, MAP, CO?

A

Possible vagolytic effect

38
Q

What is a disadvantage of Sugammadex?

A

Only for STEROIDAL NMBDs

39
Q

What is the treatment for Sarin gas poisoning?

A

Pralidoxime 600mg + ATROPINE 2-6mg q5-10min

40
Q

What are the symptoms of anti-cholinesterase poisoning?

A

Inc Ach –> Miosis, cramping, bradycardia, salivation, loss of bowel and bladder control, bronchoconstriction