Tubocurarine Pancuronium

Adults. 3 g PO q6h x 4 PRN Supl 1-2 g IM or IV repeat PRN Preeclampsia/pre-mature labor 4 g load then g/h IV inf Cardiac arrest 1-2 g IV push (2-4 mL 50% soln) in 10 mL DjW AMI Load 1-2 g in 50-100 mL D5W, over 5-60 min IV then 0.5-1.0 g/h IV up to 24 h (ECC 2005) Feds. 25-50 mg/kg/dose IM or IV q4-6h for 3-4 doses repeat PRN dose w/ low urine output or renal insuff Caution [B, +] Contra Heart block, renal failure Disp Inj 10, 20, 40, 80, 125, 500 mg/mL bulk powder SE CNS depression, D, flushing, heart block Interactions T CNS depression W/ antidepressants, antipsychotics, anxiolytics, barbiturates, hypnotics, narcotics EtOH T neuromuscular blockade Wf aminoglycosides, atracurium, gallamine, pancuronium, tubocurarine, vecuronium EMS Check for absent patellar reflexes this may indicate tox may cause hypokalemia (flattened T waves) and hypocalcemia OD May cause hypotension, resp arrest, T PR, QRS, and QT interval, AV block, and cardiac arrest calcium salts can be given to reverse resp depression... 

Nondepolarizing atracurium, pancuronium, tubocurarine Depolarizing succinylcholine... 

Pharmacokinetics All agents are given parenterally. Drugs that are metabolized (eg, mivacurium, by plasma cholinesterase) or eliminated in the bile (eg, vecuronium) usually have shorter durations of action than those eliminated by the kidney (eg, doxacurium, pancuronium, tubocurarine). Atracurium clearance involves spontaneous breakdown (Hofmann elimination) to form laudanosine and other products is largely independent of hepatic or renal function. 

Furthermore, these allosteric effects were shown to be truly subtype specific, depending on the nature of the allosteric modulating compound. Thus, alcuronium exerts positive copperativity with [3H]NMS at the M2 and M4 but not at the Mi and M3 receptors [26,27], while other neuromuscular junction blockers such as stercuronium, pancuronium, and d-tubocurarine have been shown to exhibit their effects via an allosteric mechanism specifically on the M2 receptors [28-30]. 

Pancuronium is a synthetic compound now frequently used and not likely to cause histamine release or ganglionic blockade. It is approx. 5-fold more potent than d-tubocurarine, with a somewhat longer duration of actioa Increased heart rate and blood pressure are attributed to blockade of cardiac M2-cholinoceptors, an effect not shared by newer pancuronium congeners such as vecuronium and pipecuronium. 

Pancuronium bromide (Pavulon) is a synthetic bis-quaternary agent containing a steroid nucleus (amino steroid), as denoted by the -curonium suffix. It is five times as potent as d-tubocurarine. Unlike d-tubocu-rarine, it does not release histamine or block ganglionic transmission. Like d-tubocurarine, it has a moderately long onset (2.9 minutes) and duration of action (110 minutes). Pancuronium and its metabolite are eliminated in the urine. 

Pancuronium is a synthetic steroidal compounds and approximately five times potent than d-tubocurarine. Vecuronium is congener of pancuronium with short duration of action. 

Unlike tubocurarine, pancuronium does not produce ganglionic block or histamine release. For this reason it became popular soon after its introduction and became the drug of choice for use in sick patients. However, it increases the heart rate, arterial pressure, and cardiac output in clinical doses. While this may be advantageous when using high-dose opiate anaesthesia in cardiac surgery, it can be associated with arrhythmias and myocardial ischaemia. The... 

Calcium ions play an important role in the presynaptic release of acetylcholine, and prolonged neuromuscular blockade has been reported after calcium antagonist administration during anesthesia that includes concurrent nondepolarizing neuromuscular blockade. Ketamine potentiates neuromuscular blockade produced by tubocurarine and atracurium, but not that produced by pancuronium or succinylcholine. 

Respiratory acidosis enhances -tubocurarine- and pancuronium-induced neuromuscular block and opposes reversal by neostigmine. 

Hypothermia prolongs the neuromuscular blockade produced by d-tubocurarine and pancuronium. 

The plasma concentrations of d-tubocurarine and pancuronium are increased in patients with impaired liver functions because liver disease interferes with the metabolism of pancuronium. 

Tubocurarine, metocurine, and succinylcholine have all been shown to elicit histamine release in humans. However, histamine release is less common with pancuronium and alcuronium. Vecuronium does not cause histamine release. 

The first muscle relaxant to be discovered and clinically used was d-tubocurarine (Figure 9.14a), which is found in curare, an arrow poison that was used by South American natives. Quite a bit of imagination is required to spot any stmctural resemblance to acetylcholine d-tubocurarine is much larger and contains not one but two quaternary amines within a rather large, rigid ring stmcture. The resemblance is more readily spotted with the more recent, synthetic compound pancuronium (Figure 9.14a). This molecule has two acetylcholine moieties, embedded in a... 

Both pancuronium and d-tubocurarine act by binding to the NAR in a way competitive with acetylcholine. In both cases, the presence of both positive charges is important for activity. Yet, it is questionable whether both cationic groups bind simultaneously to the two acetylcholine binding sites found (at the two a chains) of the NAR, since the distance between those should substantially exceed the one between the two charges in the antagonist molecules. 

The aminoglycosides have a curare-like action, which can be antagonized by calcium ions and acetylcholinesterase inhibitors (8). In patients who require general anesthesia, the effect of muscle relaxants, such as o-tubocurarine, pancuronium, and suxamethonium, can be potentiated by aminoglycosides (183). 

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