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Nursing Chapter 20: Neuromuscular Blockers
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Pharmacokinetics: Neuromuscular Blocking Drugs
Nondepolarizing agents: Elimination characteristics
Fast initial distribution; slower elimination
Limited volume of distribution {expected for highly ionized agents -- tending not to cross readily biological membranes}
Route of elimination-- important determinant of duration of action
Renal elimination:
Long half lives; long durations of action (> 35 min)
Hepatic elimination:
Shorter half lives: (< 30 min)
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Drug |
Elimination mechanism |
Duration of action (minutes) |
|
Atracurium (Tracrium) |
Ester hydrolysis (enzymatic and nonenzymatic) |
20-35 |
|
Cisatracurium (Nimbex) |
Spontaneous (Hoffmann elimination) |
25-44 |
|
Doxacurium (Nuromax) |
Renal |
> 35 |
|
Metocurine (Metubine Iodide) |
Renal (40%) |
> 35 |
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Mivacurium (Mivacron) |
Plasma pseudocholinesterase |
10-20 |
|
Tubocurarine |
Renal (40%) |
> 35 |
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Drug |
Elimination mechanism |
Duration of action (minutes) |
|
Pancuronium (Pavulon) |
Renal (80%) |
> 35 |
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Pipecuronium (Arduan) |
Renal (60%) and hepatic |
> 35 |
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Rocuronium (Zemuron) |
Hepatic (75-90%) and renal |
20-35 |
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Cecuronium (Norcuron) |
Hepatic (75-90%) and renal |
20-35 |
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Drug |
Elimination mechanism |
Duration of action (minutes) |
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gallamine (Flaxedil) |
Renal (100%) |
> 35 |
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succinylcholine (Anectine) |
Plasma pseudocholinesterase |
< 8 |
*-- adapted from Table 27-1: Miller, R.D., Skeletal Muscle Relaxants, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p. 438
Introductory comments about specific nondepolarizing agents
Overview: Intermediate-duration agents (e.g. vecuronium (Norcuron) and rocuronium (Zemuron)) --mainly dependent on hepatic metabolism and biliary excretion for elimination:
Intermediate-duration drugs are most commonly used clinically {compared to longer acting renal-excreted drugs}
Vecuronium (Norcuron) vs. pancuronium (Pavulon):
Similar steroid nucleus with one containing a tertiary rather than quaternary nitrogen
Vecuronium (Norcuron) has ashorter duration of action; minimal cardiovascular effects; 85% hepatic metabolism/elimination
Most rapid onset among nondepolarizing blockers
A drug of choice for rapid-sequence anesthesia induction and intubation (when succinylcholine is contraindicated or clinical circumstances suggest that it not be used)
Atracurium (Tracrium) (isoquinoline derivative) -- similar characteristics as vecuronium (Norcuron)
Hoffman elimination inactivation {spontaneous breakdown}
Atracurium (Tracrium) breakdown product --laudanosine may accumulate due to very slow hepatic metabolism and upon crossing into the brain may cause seizures
Seizures occur at laudanosine
concentrations above that obtained during
surgical procedures; however long-term use
of atracurium (Tracrium) within the intensive
care setting may result in concentration
sufficient to induce seizures
Cisatracurium (Nimbex) {atracurium (Tracrium) stereoisomer}
Similar to atracurium (Tracrium), but less laudanosine formed and less histamine released
Mivacurium (Mivacron): shortest duration of action among nondepolarizing agents
Rapid clearance of isomer mixture by plasma cholinesterase (pseudocholinesterase, i.e. butrylcholinesterase) activity
Prolonged duration of mivacurium (Mivacron) action in patients with renal failure (renal failure is associated with reduced plasma cholinesterase activity)
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