Tubocurarine Vecuronium

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... 

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

It has long been accepted that respiratory acidosis tends to potentiate the blockade produced by non-depolarizing relaxants and respiratory alkalosis produces resistance to their action. This is true for the monoquaternary agents D-tubocurarine, vecuronium, and rocuronium (possibly by increased conversion to the bisquaternary forms at lower pH), but it may not hold for the bisquaternary relaxants metocurine, pancuronium, and alcuronium (97-99). 

Clinically important, potentially hazardous interactions with adefovir, aldesleukin, aminoglycosides, atracurium, bumetanide, carbenicillin, cephalexin, cephalothin, doxacurium, ethacrynic acid, furosemide, methoxyflurane, non-polarizing muscle relaxants, pancuronium, pipecuronium, polypeptide antibiotics, rocuronium, succinylcholine, teicoplanin, torsemide, tubocurarine, vecuronium... 

The effects of cisatracurium, mivacurium, pancuronium, rocuro-nium, tubocurarine, vecuronium, and probably other competitive neuromuscular blockers can be increased and prolonged by magnesium sulfate given parenterally. There is some evidence that magnesium may interact similarly with suxamethonium (succinylcholine), but also evidence from well-controlled trials that it does not. 

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. 

Atracurium causes minimal cardiovascular effects except those associated with some histamine release if the drug is given rapidly or in high doses. As with vecuronium, it produces little increase in heart rate in fact, decreases in heart rate have been reported. This is once again thought to be due to the effects of other agents, such as the opiates, or as a result of vagal stimulation. The incidence of histamine release with atracurium is about one-third of that observed after tubocurarine administration. 

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. 

Hemodilution (for example the replacement of 1 liter of blood by dextran-40) increased the potencies and prolonged the actions of suxamethonium, pancuronium, D-tubocurarine, and vecuronium (SEDA-17, 151) (105). To avoid this, blood collection should be carried out before the administration of anesthetic drugs. 

Intravenous anesthetic agents have much less influence on the neuromuscular blocking effects of relaxants and most have no clinically significant effect. However, ketamine (SEDA-14, 113) has been reported to significantly potentiate atracurium (137), and also D-tubocurarine but not pancuronium (138) in man. Animal studies suggest that all relaxants will be potentiated by ketamine in a dose-dependent manner (139,140). It has been suggested that had Johnston et al. (138) used a higher dose of ketamine (than 75 mg/m ), they would have seen potentiation of pancuronium. The main effect of ketamine appears to be a reduction in the sensitivity of the postjunctional membrane to acetylchohne, possibly by ion-channel blockade. Propofol has been reported to potentiate vecuronium-induced and atracurium-induced blocks (141). 

Buzello W, Schluermann D, Pollmaecher T, Spillner G. Unequal effects of cardiopulmonary bypass-induced hypothermia on neuromuscular blockade from constant infusion of alcuronium, d-tubocurarine, pancuronium, and vecuronium. Anesthesiology 1987 66(6) 842-6. 

Individual responses to these compounds differ (32-34). Racial differences and environmental factors can influence the response to relaxants and hence the extent of problems due to excessive activity. Patients in the USA reportedly require less D-tubocurarine than in the UK, and the West Indians need more. Difference in cholinesterase activities, perhaps brought about by more organophosphorus insecticides being used in one country than in another, or differences in protein-binding as a result of dietary factors, are possible explanations (35). Vecuronium has been reported to be approximately 30% more potent in Montreal than in Paris (36). 

Pancuronium and vecuronium (Fig. 11.39) were designed to act like tubocurarine, but with a steroid nucleus acting as the spacer . The distance between the quaternary nitrogens is 1.1 nm as compared to 1.4 nm in tubocurarine. Acyl groups were also added to introduce two acetylcholine skeletons into the molecule in order to improve affinity for the receptor sites. These compounds have a rapid onset of action and do not affect blood pressure. However, they are not as rapid in onset as suxamethonium and also last too long (45 minutes). 

NMBAs are further differentiated by their duration of action during anesthesia. Succinylcholine and mivacurium are common ultra-short-acting competitive NMBAs (5-10 min). An intermediate duration of action (30-45 min) is maintained with the use of atracurium, cisatracurium, rocuronium and vecuronium. A long-lasting duration of action (90-100 min) is observed with d-tubocurarine, doxacurium, metocurine, pancuronium and pipecuronium. 

Less commonly, NMBAs are classified based on their chemical nature to include namral alkaloids and their congeners (e.g. d-tubocurarine), aminosteroids (e.g. cisatracurium, vecuronium) and benzylisoquinolines (e.g. succinylcholine). This classification scheme also relates to mechanism of actions and associated effects. 

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. 

Autonomic effects and histamine release Autonomic ganglia are stimulated by succinylcholine and blocked by tubocurarine. Succinylcholine also stimulates cardiac muscarinic receptors, while vecuronium is a moderate blocking agent. Tubocurarine is the most likely of these agents to cause histamine release, but it may also occur to a sUght extent with atracurium, mivacurium. and succinylcholine. A summary of these autonomic effects is shown in Table 27-3. 

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