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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Neuromuscular Blocking Agents

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Nondepolarizing Muscle Relaxants: Other Relaxants

Muscle relaxants, primarily of historical interest, are either no longer manufactured or not clini-cally used.

OTHER RELAXANTS

Muscle relaxants, primarily of historical interest, are either no longer manufactured or not clini-cally used. They include tubocurarine, metocurine, gallamine, alcuronium, rapacuronium, and deca-methonium. Tubocurarine, the first muscle relax-ant used clinically, often produced hypotension and tachycardia through histamine release; its abil-ity to block autonomic ganglia was of secondary importance. Histamine release could also produce or exacerbate bronchospasm. Tubocurarine is not metabolized significantly, and its elimination is pri-marily renal and secondarily biliary. Metocurine, a closely related agent, shares many of the side effects of tubocurarine. It is primarily dependent on renal function for elimination. Patients aller-gic to iodine (eg, shellfish allergies) could exhibit hypersensitivity to metocurine preparations, as they contain iodide. Gallamine has the most potent vagolytic properties of any relaxant, and it is entirely dependent on renal function for elimi-nation. Alcuronium, a long-acting nondepolarizer with mild vagolytic properties, is also primar-ily dependent on renal function for elimination. Rapacuronium has a rapid onset of action, minimal cardiovascular side effects, and a short duration of action. It was withdrawn by the manufacturer fol-lowing multiple reports of serious bronchospasm, including a few unexplained fatalities. Histamine release may have been a factor. Decamethonium was an older depolarizing agent.

More recently, doxacurium, pipecuronium, and mivacurium are no longer commercially avail-able in the United States. Mivacurium is a benzyl-isoquinolinium derivative, which is metabolized by pseudocholinesterase; therefore, its duration of action may be prolonged in pathophysiological states that result in low pseudocholinesterase lev-els. The usual intubating dose is 0.2 mg/kg, with the steady state infusion rate being 4-10 mcg/kg/ min. Mivacurium releases histamine to about the same degree as atracurium; the resulting car-diovascular effects can be minimized by slow injection. Doxacurium is a potent long-acting benzylisoquinolinium compound that is primarily eliminated by renal excretion. Adequate intubat-ing conditions are achieved in 5 min with 0.05 mg/ kg. It is essentially devoid of cardiovascular and histamine-releasing side effects. Pipecuronium, on the other hand, is a bisquarternary steroidal compound similar to pancuronium, without the vagolytic effects. Onset and duration of action are also similar to pancuronium; elimination is primarily through renal (70%) and biliary (20%) excretion. The usual intubating dose ranges from 0.06-0.1 mg/kg; its pharmacologic profile is rela-tively unchanged in elderly patients.

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