7.5 : Nondepolarizing (Competitive) Neuromuscular Blockers: Pharmacokinetics

All neuromuscular blocking agents are injected intravenously because they are poorly absorbed from the GI tract. Rapid onset is achieved with intravenous administration, although absorption is also adequate from an intramuscular injection. Since these agents are highly ionized, they do not readily penetrate cell membranes or cross the blood-brain barrier.

Instead, they are transported by the blood to different tissues. Muscles with a greater blood supply (arteries) and blood flow receive more drugs and are blocked faster than muscles with a lesser blood supply and a smaller blood flow. The drug's actions are terminated when redistributed to other tissues. The duration of action is directly correlated to the elimination half-life. Some drugs like pancuronium, d-tubocurarine, doxacurium and pipecuronium are excreted unchanged in the urine and have a long elimination half-life and duration of action lasting more than 60 minutes. Other drugs like atracurium and cisatracurium undergo spontaneous ester hydrolysis in plasma. Certain amino steroid blockers like vecuronium and rocuronium are metabolized in the liver. Although such metabolites have half the activity of the parent drug, they are usually not formed in amounts required to produce blockade. The drugs metabolized in the plasma or liver have a shorter elimination half-life and action duration lasting only 20 to 40 minutes. Other drugs are also excreted unchanged through the bile.