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Anesthesia Pharmacology: Neuromuscular Blocking Agents and Muscle Relaxants
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Pharmacokinetics: Neuromuscular Blocking Drugs
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Nondepolarizing Agents: Elimination characteristics
Fast initial distribution; slower elimination
Limited volume of distribution (expected for highly ionized agents which tend not to cross readily biological membranes)
Route of elimination is 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) |
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Atracurium (Tracrium) |
Ester hydrolysis (enzymatic and nonenzymatic) |
20-35 |
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Cisatracurium (Nimbex) |
Spontaneous (Hoffmann elimination) |
25-44 |
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Doxacurium (Nuromax) |
Renal |
> 35 |
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Metocurine (Metubine Iodide) |
Renal (40%) |
> 35 |
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Mivacurium (Mivacron) |
Plasma pseudocholinesterase |
10-20 |
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Tubocurarine |
Renal (40%) |
> 35 |
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Drug |
Elimination mechanism |
Duration of action (minutes) |
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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)) are 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: one contains a tertiary rather than quaternary nitrogen
Vecuronium (Norcuron): shorter duration of action; minimal cardiovascular effects; 85% hepatic metabolism/elimination
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NMJ blockers: Steroid derivatives, Vecuronium (Norcuron) |
NMJ blockers: Steroid derivatives, Pancuronium (Pavulon) |
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)
This isoquinoline derivative exhibits 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
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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