Description: Pancuronium bromide is a long-acting, nondepolarizing, neuromuscular blocking agent. It is similar to, but five times as potent as, tubocurarine. Pancuronium is used to induce relaxation of the skeletal muscles during surgery and to facilitate pulmonary compliance during mechanical ventilation. Pancuronium has little effect on histamine release at usual doses; however, it may be associated with tachycardia due to vagolytic properties. Pancuronium was approved by the FDA in 1972.

Mechanism of Action: Nondepolarizing agents produce skeletal muscle paralysis by blockade at the myoneural junction. Pancuronium competes with acetylcholine for cholinergic receptor sites. Unlike depolarizing agents, pancuronium has little agonist activity, having no depolarizing effect at the motor endplate. Skeletal muscle relaxation proceeds in predictable order, starting with muscles associated with fine movements, e.g., eyes, face, and neck. These are followed by muscles of the limbs, chest, and abdomen and, finally, the diaphragm. Larger doses increase the risk of respiratory depression due to relaxation of the intercostal muscles and diaphragm. Muscle tone returns in the reverse order.

In addition to its therapeutic actions, pancuronium can cause an increase in heart rate, but this is minimal at normal doses. Pancuronium produces little histamine release and no ganglion blockade, so hypotension and bronchospasm are not associated with its use. Children generally require larger mg/kg doses than adults to achieve muscle relaxation. The muscle weight-to-body weight ratio, the volume of extracellular fluid, and renal function also contribute to response.

Pharmacokinetics: Pancuronium bromide is administered intravenously. The dose required to produce 95% suppression of the muscle twitch response (ED95) is about 50 mcg/kg under balanced anesthesia and 30 mcg/kg under halothane anesthesia. Intravenous administration of 60 mcg/kg produces muscle relaxation in 2—3 minutes, with peak effect occurring in about 4 minutes and lasting for 35—45 minutes. Extra doses can increase the intensity and duration of the neuromuscular blockade. Reports differ on the extent of protein binding; figures of 30—87% have been published, but it is probable that a substantial amount of the drug is bound to globulin and albumin. Small amounts of pancuronium cross the placenta. Plasma concentrations apparently fall in a triphasic manner, the last phase having a half-life of about 2 hours. Metabolism occurs via hepatic pathways to at least 3 metabolites, a 3-hydroxy metabolite, a 17-hydroxy metabolite, and a 3, 17-hydroxy metabolite. These metabolites are significantly less potent than pancuronium. Most of the drug and its metabolites are excreted in the urine. About 80% is excreted in the urine and 10% in the feces as unchanged pancuronium. In patients with renal failure or hepatic cirrhosis, the elimination half-life is doubled and plasma clearance is reduced by approximately 60% or 22%, respectively. Also, in patients with hepatic dysfunction, the volume of distribution is increased by approximately 50%.

Drug Information Provided by
Gold Standard, Inc. � 2007