Non-Depolarizing NMBs Flashcards
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
How are is the structure of ND-NMBs classified?
benzylisoquinolinium
- atracurium/cisatracurium
- histamine release
- plasma metabolism
aminosteroid
- roc/vec
- liver/kidney metabolism
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
How are the benzylisoquinolinium NMBs metabolized?
Hoffman elimination and/or enzymatic degradation
= ok for kidney/liver failure patients
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)
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
What is the only short-acting ND-NMB in the benzylisoquinolinium group and what properties make it this way?
Mivacurium - metabolized by ester hydrolysis
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
How does hypothermia affect ND-NMB?
Prolonged duration - by reducing ion influx
How does old age affect ND-NMB?
Prolonged duration, dec dosage - dec elimination
How does MS or ALS (motor neuron disease) affect ND-NMB?
Resistance due to up regulation of Ach Receptors
How does Guillan-Barre affect ND-NMB?
Sensitive - loss of motor units at NMJ
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
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
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
How does muscular dystrophy affect ND-NMB?
Usually normal - possible sensitivity –> muscle weakness
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:
- Cardio
- Pulmonary
- GI
- Ophtho
- Urinary
- CNS
- Bradycardia, hypotension, arrhythmias
- Bronchospasm, hypoxia, increased secretions
- Increased GI motility and secretions
- Miosis, decreased intraocular pressure, lacrimation
- Urination
- 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»_space; 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
