T. Speight, G. Avery
2012
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Drugs
Abstract
SummarySynopsis: Pancuronium bromide2 is a bis-quaternary amino-steroid compound possessing potent neuro-muscular blocking activity. It is advocated for use in clinical situations where a non-depolarising (competitive) muscle relaxant of medium duration of action is required. The onset and duration of relaxation is similar to that obtained with equipotent doses of d-tubocurarine, but pancuronium has less effect on the cardiovascular system and does not cause the release of histamine. Although a steroid, pancuronium exerts no hormonal activity.Studies in both animals and man have shown pancuronium to be approximately 5 times more potent than d-tubocurarine on a weight-for-weight basis. Intravenous doses of 4 to 8 mg pancuronium (0.1 mg/kg) in adults have an onset of action of 45 to 90 seconds, and a duration of action (i.e. of adequate relaxation) of approximately 45 to 60 minutes. However, the duration of action varies with the initial dosage, the nature of the surgical stimulus and the anaesthetic technique employed. For example, the effect is considerably longer when a halogenated anaesthetic is given than when either nitrous oxide/oxygen alone or neuroleptanalgesia is used, due to greater potentiation of the relaxant effect. Intubating conditions following doses of 0.1 mg/kg pancuronium are adequate, and this procedure is usually possible within 1½ to 3 minutes of its administration. Pancuronium provides similar intubating conditions to those of other non-depolarising muscle relaxants, but the conditions are less satisfactory than those achieved with suxamethonium. In adults, supplementary doses of 1 to 2 mg pancuronium are required approximately every 45 minutes, although less often in prolonged operations, as in these doses pancuronium appears to have a slight cumulative effect with repeated administration.In the majority of patients pancuronium has little or no effect on the cardiovascular system. Slight increases in arterial blood pressure and heart rate may be experienced in some patients, but these changes (which occur more often with larger doses) are usually transient and tend to disappear within 10 to 20 minutes. In clinical comparisons with other muscle relaxants, pancuronium caused significantly less hypotension at the induction of anaesthesia than either d-tubocurarine or alcuronium, and significantly less tachycardia than gallamine triethiodide. In patients not breathing adequately at the conclusion of surgery, reversal of residual pancuronium blockade may be achieved by the administration (in adults) of 0.5 to 2.5 mg neostigmine methylsulphate together with 0.4 to 1.2 mg atropine sulphate, depending on the degree of curarisation present at the time reversal is attempted. The return of muscle tone usually occurs within a few minutes of the administration of this reversant, although in some cases supplementary doses of neostigmine/atropine may be necessary to ensure full recovery. Prolonged curarisation has occurred in a few patients despite attempted neostigmine/atropine reversal.Few side-effects have been encountered. Isolated cases of skin rash, erythema at the injection site and burning along the vein have been reported, and increased pharyngeal and tracheal secretions have also been noted in a few patients. However, pancuronium has been used in patients with renal or hepatic disease, shock, bronchial asthma, allergic diatheses and in other ‘poor risk’ patients without complication.Although pancuronium has been well studied and successfully used in large numbers of patients, further investigations are still indicated in some areas. These should cover such aspects as the metabolism and excretion of pancuronium, its relative potency compared with d-tubocurarine at therapeutic dosage levels, its interactions with other drugs, and the completeness of its reversal with neostigmine. The possibility that pancuronium may stimulate the release of catecholamines and muscle enzymes (such as creatine phosphokinase) should also be investigated.