Non-Depolarizing NMBs Flashcards by Jon Johnson

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

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

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How are is the structure of ND-NMBs classified?

benzylisoquinolinium

atracurium/cisatracurium
histamine release
plasma metabolism

aminosteroid

roc/vec
liver/kidney metabolism

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How are the aminosteroid NMBs metabolized?

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

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

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How are the benzylisoquinolinium NMBs metabolized?

Hoffman elimination and/or enzymatic degradation

= ok for kidney/liver failure patients

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How does cistatricurium differ from atracurium on potency and metabolism?

Cisatricurium - lower ED50 + no histamine release

Cisatracurium - primarily Hoffman elimination alone

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

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

Atricurium (laudanosine) and to lesser degree cisatricurium

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

Mivacurium - metabolized by ester hydrolysis

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

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

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How does hypothermia affect ND-NMB?

Prolonged duration - by reducing ion influx

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How does old age affect ND-NMB?

Prolonged duration, dec dosage - dec elimination

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

Resistance due to up regulation of Ach Receptors

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How does Guillan-Barre affect ND-NMB?

Sensitive - loss of motor units at NMJ

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How does myasthenia gravis affect NMB?

Resistant to succinylcholine

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

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How does myotonic dystrophy affect ND-NMB?

Resistant - to ND-NMB
Less resistant to succinylcholine

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

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How does Eaton-Lambert syndrome affect ND-NMB?

Sensitive to BOTH ND and depolarizing NMBs

Dec Ach release
neostigmine is ineffective
titrate with peripheral nerve stim

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How does muscular dystrophy affect ND-NMB?

Usually normal - possible sensitivity –> muscle weakness

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How does burn and SC injury affect ND-NMB?

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

SC - up-reguation of Ach receptors

Name the 5 methods NMB action can be terminated

redistribution
Hoffman elimination
ester hydrolysis
hepatic metabolism
renal clearance

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

Metaclopromide

How do volatile anesthetics affect NMB?

Dose-dependent potentiation of activity

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

all have a quaternary ammonium group

Which ND-NMBs cause histamine release?

atracurium, mivacurium and sux

- usually with rapid injection

Which ND-NMB has a significant vagolytic effect?

Pancuronium

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

What antibiotics can prolong the effect of NMBs?

aminoglycosides (neomycin, streptomycin, gentamicin, tobramycin, clindamycin)
tetracyclines
polymyxins

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

``` Volatile anesthetics Local anesthetics Magnesium Lithium Calcium channel blockers ``` Must use caution in re-dosing NMB!!!

What electrolyte abnormalities can prolong NMB?

acidosis alkalosis hypocalcemia, hypokalemia hypernatremia, hypermagnesemia

How does critical illness/ICU patient status affect NMB?

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

How do anti-convulsants effect the use of NMBs?

Pts experience shortened duration of action due to increased plasma clearance Especially affects vecuronium, pancuronium, rocuronium

What are 3 anticholinesterases used to antagonize residual NMB?

Neostigmine, pyridostigmine, and edrophonium (not available) - Have both nicotinic and muscarinic effects but only nicotinic at NMJ is desired = give glycopyrrolate or atropine

How are the muscarinic side effects of anticholinesterases prevented?

atropine or glycopyrrolate (muscarinic anticholinergics)

List some of the muscarinic effects of anticholinesterases by system: 1. Cardio 2. Pulmonary 3. GI 4. Ophtho 5. Urinary 6. CNS

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

What is the mechanism of Sugammadex?

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

Describe the affinity of Sugammadex for different ND-NMBs

rocuronium > vecuronium >> pancuronium

Which ND-NMB is most likely to cause tachycardia?

Pancuronium

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

Vecuronium

What is the ED95 of Rocuronium and onset?

0.3mg/kg Onset 1.5-3min

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

Possible vagolytic effect

What is a disadvantage of Sugammadex?

Only for STEROIDAL NMBDs

What is the treatment for Sarin gas poisoning?

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

What are the symptoms of anti-cholinesterase poisoning?

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