Pancuronium is a long acting muscle relaxant that had been used for more than four decades. It is the first synthesized aminosteroid neuromuscular-blocking drug for clinical use. (Wilson, Grande and Hoyt, 2007) Pancuronium has often been used as a muscle relaxation during cardiac anesthesia. (Estafanous, Barash & Reves, 2001) According to Raghavendra (2002), in the early 1960s, disquanternary steroidal alkaloid was isolated was isolated from the bark of a plant Malouetia Bequaertiana and it had curare-like effects. In 1964, Hewitt and Savege successfully synthesized an aminosteroidal with two quaternary ammonium groups. Other than being a muscle relaxant during a surgery procedure, this drug is also used as an euthanasia and the second of three drugs administered in the times of most lethal injections in the United States. (Human Rights Watch, 2006) However, it is said that Pancuronium is not as humane as it suggests. Human Rights Watch (2006) indicated that Pancuronium causes death by asyphycation which generally means that a person given a sufficient dose will experience suffocation but the person will not be able to convey the message that they are suffering to the executioners as they are unable to speak up. On the other hand, when given a dose to patients undergoing a surgery, some patients can recall the experience afterwards. This condition is named intraoperative awareness. The risk of some patients experiencing intraoperative awareness increases when the person has a history of substance abuse or when anesthesia is administed intravenously. There are reports of surgery patients who had been administered Pancuronium with inadequate anesthesia being aware of the surgery procedure which could be a terrifying and tormenting sight. (Human Rights Watch, 2006)
As mentioned previously, Pancuronium is a substance administered with general anaesthesia during a surgery procedure for muscle relaxation and aiding in ventilation. It is also the least expensive to produce while remaining the most potent nondepolarizing neuromuscular blocking drugs available in the market. (Shyam Kumar et al., 2013) The onset of action of pancuronium is within 3 to 5 minutes, duration of more than 50 minutes and has predominant postsynaptic mechanism of actions. Furthermore, Appiah-Ankam and Hunter (2004) indicated that nondepolarizing neuromuscular blocking drug acts as a competitive antagonist to acetylcholine at the postsynaptic nicotinic receptor. They do not produce conformational changes on the receptors unlike depolarizing drugs. Its method of action is to bind to one or both α-subunits thus preventing contact by acetylcholine to depolarize the receptors. However, Appiah-Ankam and Hunter (2004) also included that since binding of antagonist to receptor is dynamic, the binding could be decreased if the concentration of acetylcholine increases. When the substance binds to the receptors, there is a gradual reduction in end-plate potential which eventually results in failure to reach the threshold to fire a propagating action potential to evoke muscle contraction.
Neuromuscular block only come to be evident when nondepolarizing neuromuscular blocking drugs occupy 70-80% of receptors. For a complete blockage, a minimum of 92% of receptors has to be occupied. Pancuronium, like the other neuromuscular blocking drugs also exhibits desensitization block also called phase II block. (Appiah-Ankam and Hunter, 2004) Desensitization block is a further blockage drug enters the nerve fiber and act as a nondepolarizing agent even though membrane potential had been restored. (Malamed, 2010) Desensitization block is a non-competitive block and when more receptors are desensitized, margin of safety of transmission is greatly decreased. (Malamed, 2010)
Other than desensitization block, ion channel block also takes place for futher blockage of receptors. In general, there are two different types of ion-channel block; open or closed. In closed-channel block, drug molecules take up the receptors. (Malamed, 2010) With the occupation of the acetylcholine receptors, ions are prevented from passing the channels to depolarize the end plate. On the other hand, open channel block allows molecules to enter the open ion channels to occupy it. However, the molecules can only enter the channel under one condition which is when the channel is opened by an agonist. When the channels are blocked, influx of sodium ions is obstructed and in turns prevents depolarization.
Like all other drugs, Pancuronium has some adverse effects. Some adverse effect after the administration of Pancuronium might be hypertension, tachycardia, respiratory muscle paralysis, anaphylactic reactions and possibly impaired real functions. (Aronson 2009) However, the co-administered agents often mask these side effects. By the same token, Gursoy et al. (2011) indicated that pancuronium increases aterial pressure and tachycardia. This cardiac stimulation gives rise to vagolytic action, releasing norepinephrine from sympathetic nerve endings. Furthermore, the effect increased heart rate is due to increased release and decreased reuptake of catecholamines at the adregenic nerve endings. (Gursoy et al., 2011)
With that covered, it is time to discuss the pharmacokinetics of the drug Pancuronium. According to Bryan and Knights (2014), Pancuronium when administered intravenously is distributed widely. Within five minutes of administration, high concentrations can be found in the kidney, liver and spleen. Pancuronium is highly water-soluble, resulting in almost immediate urinary excretion and up 25% is excreted as unchanged substance. (Bryan and Knights 2014) The remaining drug that is found in the circulation is cleared by hepatic metabolism and biliary excretion. The clearance in both of these methods can be reduced if the patient has liver or renal disease. Half-life of pancuronium is approximately 30 minutes. (Bryan and Knights 2014)
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