Neuromuscular blocking drugs Flashcards
What do NMB’s do and what are they used for?
Can completely paralyze skeletal muscle and are primarily used as adjuncts during surgical and orthopedic procedures
Mechanism of action of NMB’s
Antagonizing the action of ACh at the nerve-muscle synapse (neuromuscular junction)
Succinylcholine
The only therapeutically useful neuromuscular blocker that acts as a depolarizing agent
- short acting used in brief procedures
- stimulates autonomic ganglia; stimulates cardiac muscarinic AChR; metabolized by plasma cholinesterase
Apnea
Major adverse reaction to succinylcholine; extending into the postoperative period
Hyperkalemia
Results from release of K+ from the muscle via the nAChRs; and is another adverse reaction to succinylcholine
-Precludes the use of succinylcholine in children; due to undiagnosed skeletalmyopathies
Tubocurarine
Long acting neuromuscular blocker
- autonomic ganglia blockade; high effect on histamine release; no effect on cardiac muscarinic AChR; metabolized in the kidney/liver
- no longer available
Pancuronium
Long acting neuromuscular blocker
- no effect on autonomic ganglia; no effect on histamine release; moderate block on cardiac muscarinic AChR (incr bp or tachycardia); metabolized in the kidney
- concern for patients with heart problems and patients with kidney transplants
Pipercuronium & Doxacurium
Long acting neuromuscular blocker
- no effect on autonomic ganglia; no effect on histamine release; no effect on cardiac muscarinic AChR; metabolized in the kidney
Vercuronium
Intermediate acting neuromuscular blocker
- no effect on autonomic ganglia; no effect on histamine release; no effect on cardiac muscarinic AChR; metabolized in the liver
Atracurium & Cistracurium
Intermediate acting neuromuscular blocker
- no effect on autonomic ganglia; low effect on histamine release; no effect on cardiac muscarinic AChR; spontaneously hydrolyzed in the liver creating laudanosine
- concern for hypotension and bronchoconstriction
Rocuronium
Intermediate acting neuromuscular blocker with rapid onset
- no effect on autonomic ganglia; no effect on histamine release; slight effect on cardiac muscarinic AChR
- Alt for succinylcholine
Mivacurium
Short acting neuromuscular blocker with rapid onset
- no effect on autonomic ganglia; low effect on histamine release; no effect on cardiac muscarinic AChR; metabolized by plasma cholinesterase
- alt to succinylcholine
Response to Succinylcholine
Occurs in two phases. In phase I, there is initial activation followed by receptor blockade resulting from persistent depolarization (leading to Na channel inactivation). In phase II, later, nicotinic receptors will inactivate resulting in repolarization
Succinylcholine + ChE inhibitor
Phase I will be enhanced while phase II will be reversed
Reversal of NMJ blockade
For all blockers except succinylcholine (and mivacurium), reversal may be accelerate by using a cholinesterase inhibitor.
-idea is ACh will compete away the blocker
Which drug would you use for brief procedures– mainly intubation?
Succinylcholine (depolarizing NMJ blocker)
Alternative to Succinylcholine
Mivacurium or rocuronium (non-depolarizing NMJ blockers); used for brief procedures
Which drug is widely used in surgery with no side effects
Vecuronium (non-depolarizing NMJ blocker); intermediate duration
Widely used in surgery with some concern for hypotension and bronchoconstriction
Cisatracurium (or Atracurium; non-depolarizing NMJ blockers); intermediate duration
Widely used in surgery with concerns in heart patients (tachycardia and increased BP)
Pancuronium (non-depolarizing NMJ blocker); also not for use in kidney transplants
Which drug has a very long duration
Pipecuronium and doxacurium (non-depolarizing NMJ blockers)
Which drug has a long duration but is no longer available?
Tubocurarine; non-depolarizing NMJ blocker
Order of muscle susceptibility
Rapid orbital muscles of the eye > extremities > trunk muscles > intercostal muscles > diaphragm; with recovery in the reverse order
Two kids of NMB’s
Depolarizing (succinylcholine) and non-depolarizing (competitive antagonists)
What does significant genetic variability in ability of plasma esterase (cholinesterase for hydrolysis) lead to?
Leads to variable duration of action of succinylcholine or mivacurium
Heavily muscled patients
When given succinylcholine, may develop myalgias, secondary to the development of fasciculations (relieved by lowering dose)
Route of deliver of NMJ blockers
I.V. because they are quarternary amines and poorly absorbed orally
Assessment of NMJ block
Train of four (TOF) stimulations of nerve; analyze fade
Short acting drugs
- 5-15 min
- metabolized by plasma ChE
Long acting drugs
1-2 hrs
-metabolized by the kidney
Intermediate acting drugs
20-60 min
-metabolized by liver and spontaneous hydrolysis
