PANCURONIUM BROMIDE
Chemistry - A synthetic, non-depolarizing neuromuscular blocker, pancuronium bromide occursas a white, odorless, bitter-tasting, hygroscopic, fine powder. It has a melting point of 215°C andone gram is soluble in 100 ml of water; it is very soluble in alcohol. Acetic acid is used to adjust thecommercially available injection to a pH of approximately 4.
Do not store pancuronium in plastic syringes or containers as it may be adsorbed to plastic surfaces. It may be administered in plastic syringes, however.
It is recommended that pancuronium not be mixed with barbiturates as a precipitate may form, butdata are conflicting on this point. No precipitate was seen when pancuronium was mixed with eithersuccinylcholine, meperidine, neostigmine, gallamine, tubocurarine, or promethazine.
Uses, Indications - Pancuronium is indicated as an adjunct to general anesthesia to produce musclerelaxation during surgical procedures or mechanical ventilation and also to facilitate endotrachealintubation.
Duration of action may persist 30-45 minutes, but is again dependent on the dose. Additional dosesmay slightly increase the magnitude of the blockade and will significantly increase the duration ofaction.
In humans, pancuronium is approximately 87% bound to plasma proteins, but it may be used inhypoalbuminemic patients. Activity is not affected substantially by either plasma pH or carbondioxide levels.
The half-life in humans ranges from 90 - 161 minutes. Approximately 40% of the drug is excretedunchanged by the kidneys. The remainder is excreted in the bile (11%) or metabolized by the liver.
In patients with renal failure, plasma half-lives are doubled. Atracurium may be a better choice forthese patients.
Contraindications/Precautions - Pancuronium is contraindicated in patients hypersensitive to it.
It should be used with caution in patients with renal dysfunction, and in patients where tachycardiasmay be deleterious. Lower doses may be necessary in patients with hepatic or biliary disease.
Pancuronium has no analgesic or sedative/anesthetic actions. In patients with myasthenia gravis, neuromuscular blocking agents should be used with extreme caution, if at all.
Overdosage - Overdosage possibilities can be minimized by monitoring muscle twitch response toperipheral nerve stimulation. Increased risks of hypotension and histamine release occur withoverdoses, as well as prolonged duration of muscle blockade.
Besides treating conservatively (mechanical ventilation, O2, fluids, etc.), reversal of blockade maybe accomplished by administering an anticholinesterase agent (edrophomium, physostigmine, orneostigmine) with an anticholinergic (atropine or glycopyrrolate). A suggested dose forneostigmine is 0.06 mg/kg IV after atropine 0.02 mg/kg IV.
Other muscle relaxant drugs may cause a synergistic or antagonistic effect. Succinylcholinemay speed the onset of action and enhance the neuromuscular blocking actions of pancuronium.
Do not give pancuronium until succinylcholine effects have subsided.
Theophylline may inhibit or reverse the neuromuscular blocking action of pancuronium andpossibly induce arrhythmias.
Azathioprine may reverse pancuronium's neuromuscular blocking effects.
Storage, Stability, Compatibility
Pancuronium injection should be stored under refrigeration(2-8°C), but, according to the manufacturer, it is stable for 6 months at room temperature.Do not store pancuronium in plastic syringes or containers as it may be adsorbed to plastic surfaces. It may be administered in plastic syringes, however.
It is recommended that pancuronium not be mixed with barbiturates as a precipitate may form, butdata are conflicting on this point. No precipitate was seen when pancuronium was mixed with eithersuccinylcholine, meperidine, neostigmine, gallamine, tubocurarine, or promethazine.
Pharmacology - PANCURONIUM BROMIDE
Pancuronium is a nondepolarizing neuromuscular blocking agent and acts bycompetitively binding at cholinergic receptor sites at the motor end-plate, thereby inhibiting theeffects of acetylcholine. It is considered to be 5 times as potent as d-tubocurarine and 1/3 as potentas vecuronium (some sources say that pancuronium is equipotent with vecuronium in animals). Ithas little effect on the cardiovascular system other than increasing heart rate slightly and only rarelydoes it cause histamine release.Uses, Indications - Pancuronium is indicated as an adjunct to general anesthesia to produce musclerelaxation during surgical procedures or mechanical ventilation and also to facilitate endotrachealintubation.
Pharmacokinetics - PANCURONIUM BROMIDE
After intravenous administration, muscle relaxation sufficient for endotrachealintubation occurs generally within 2-3 minutes, but is dependent on the actual dose administered.Duration of action may persist 30-45 minutes, but is again dependent on the dose. Additional dosesmay slightly increase the magnitude of the blockade and will significantly increase the duration ofaction.
In humans, pancuronium is approximately 87% bound to plasma proteins, but it may be used inhypoalbuminemic patients. Activity is not affected substantially by either plasma pH or carbondioxide levels.
The half-life in humans ranges from 90 - 161 minutes. Approximately 40% of the drug is excretedunchanged by the kidneys. The remainder is excreted in the bile (11%) or metabolized by the liver.
In patients with renal failure, plasma half-lives are doubled. Atracurium may be a better choice forthese patients.
Contraindications/Precautions - Pancuronium is contraindicated in patients hypersensitive to it.
It should be used with caution in patients with renal dysfunction, and in patients where tachycardiasmay be deleterious. Lower doses may be necessary in patients with hepatic or biliary disease.
Pancuronium has no analgesic or sedative/anesthetic actions. In patients with myasthenia gravis, neuromuscular blocking agents should be used with extreme caution, if at all.
Adverse Effects, Warnings
Adverse reactions seen with pancuronium include: slight elevationsin cardiac rate and blood pressure, hypersalivation (if not pretreated with an anticholinergic agent), occasional rash (humans), and prolonged or profound muscular weakness and respiratorydepression. Very rarely will pancuronium cause substantial histamine release with resultant hypersensitivity reactions.Overdosage - Overdosage possibilities can be minimized by monitoring muscle twitch response toperipheral nerve stimulation. Increased risks of hypotension and histamine release occur withoverdoses, as well as prolonged duration of muscle blockade.
Besides treating conservatively (mechanical ventilation, O2, fluids, etc.), reversal of blockade maybe accomplished by administering an anticholinesterase agent (edrophomium, physostigmine, orneostigmine) with an anticholinergic (atropine or glycopyrrolate). A suggested dose forneostigmine is 0.06 mg/kg IV after atropine 0.02 mg/kg IV.
Drug Interactions
The following agents may enhance the neuromuscular blocking activity ofpancuronium: quinidine, aminoglycoside antibiotics (gentamicin, etc.), lincomycin, clindamycin, bacitracin, magnesium sulfate, polymyxin B, enflurane, isoflurane, andhalothane.Other muscle relaxant drugs may cause a synergistic or antagonistic effect. Succinylcholinemay speed the onset of action and enhance the neuromuscular blocking actions of pancuronium.
Do not give pancuronium until succinylcholine effects have subsided.
Theophylline may inhibit or reverse the neuromuscular blocking action of pancuronium andpossibly induce arrhythmias.
Azathioprine may reverse pancuronium's neuromuscular blocking effects.