Cardiovascular The tetrahydroisoquinolinium class of neuromuscular blocking agents, in general, is associated with histamine release upon rapid administration of a bolus intravenous injection. There are some exceptions to this rule; e.g., cisatracurium (Nimbex) is one such agent that does not elicit histamine release even up to 5xED95 doses. The liberation of histamine is a dose-dependent phenomenon such that, with increasing doses administered at the same rate, there is a greater propensity for eliciting histamine release and its ensuing sequelae. Most commonly, the histamine release following administration of these agents is associated with observable cutaneous flushing (facial face and arms, commonly), hypotension and a consequent reflex tachycardia. These sequelae are very transient effects: The total duration of the cardiovascular effects is no more than one to two minutes, while the facial flush may take around 3–4 minutes to dissipate. Because these effects are so transient, there is no reason to administer adjunctive therapy to ameliorate either the cutaneous or the cardiovascular effects. Bronchospasm Bronchospasm has been reported on occasion with the use of<unk> . However, this particular undesirable effect does not appear to be observed nearly as often as that seen with rapacuronium, which led to the latter's withdrawal of approval for clinical use worldwide. The issue of bronchospasm acquired prominence in the neuromuscular-blocking agents arena after the withdrawal from clinical use of rapacuronium (Raplon - a steroidal neuromuscular-blocking agent marketed by Organon) in 2001 after several serious events of bronchospasm, including five unexplained fatalities, following its administration. Bronchospasm was not an unknown phenomenon prior to rapacuronium: occasional reports of bronchospasm have been noted also with the prototypical agents, tubocurarine and succinylcholine, as well as alcuronium, pancuronium, vecuronium, and gallamine. Seizures Seizures rarely occur. Because<unk>  undergoes Hofmann elimination as a primary route of chemodegradation, one of the major metabolites from this process is laudanosine, a tertiary amino alkaloid reported to be a modest CNS stimulant with epileptogenic activity and cardiovascular effects such a hypotension and bradycardia. As part of the then fierce marketing battle between the competing pharmaceutical companies (Burroughs Wellcome Co. and Organon, Inc.) with their respective products, erroneous information was quickly and subtly disseminated very shortly after the clinical introduction of<unk>  that the clinical use of<unk>  was likely to result in a terrible tragedy because of the significant clinical hazard by way of frank seizures induced by the laudanosine by-product - the posited hypothesis being that the laudanosine produced from the chemodegradation of parent<unk>  would cross the blood–brain barrier in sufficiently high enough concentrations that lead to epileptogenic foci. Fortunately, both for the public and for<unk> , rapid initial investigations irrefutably failed to find any overt or EEG evidence for a connection between<unk>  administration and epileptogenic activity. Indeed, because laudanosine is cleared primarily via renal excretion, a cat study modelling anephric patients went so far as to corroborate that EEG changes, when observed, were evident only at plasma concentrations 8 to 10 times greater than those observed in humans during infusions of<unk> . Thus, the cat study predicted that, following<unk>  administration in an anephric patient, laudanosine accumulation and related CNS or cardiovascular toxicity were unlikely - a prediction that correlated very well with a study in patients with kidney failure and undergoing cadaveric renal transplantation. Furthermore, almost a decade later, work by Cardone et al.. confirmed that, in fact, it is the steroidal neuromuscular-blocking agents pancuronium and vecuronium that, when introduced directly into the CNS, were likely to cause acute excitement and seizures, owing to accumulation of cytosolic calcium caused by activation of acetylcholine receptor ion channels. Unlike the two steroidal agents, neither<unk>  nor laudanosine caused such accumulation of intracellular calcium. Just over two decades later with availability of<unk> , there is little doubt that laudanosine accumulation and related toxicity will likely never be seen with the doses of<unk>  that are generally used. Laudanosine is also a metabolite of cisatracurium that, because of its identical structure to<unk> , undergoes chemodegradation via Hofmann elimination in vivo. Plasma concentrations of laudanosine generated are lower when cisatracurium is used.
Atracurium besilate
Cisatracurium besilate
Gantacurium chloride
Mivacurium chloride
Iontocaine
Ibogaine
Oxybuprocaine
Tetracaine