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Pancuronium Bromide


Drug Nomenclature

Synonyms: Bromuro de pancuronio; NA-97; Org-NA-97; Pancuronii Bromidum; Pancuronio, bromuro de; Pankuronio bromidas; Pankuronium-bromid; Pankuroniumbromid; Pankuroniumbromidi
BAN: Pancuronium Bromide
USAN: Pancuronium Bromide
INN: Pancuronium Bromide [rINN (en)]
INN: Bromuro de pancuronio [rINN (es)]
INN: Pancuronium, Bromure de [rINN (fr)]
INN: Pancuronii Bromidum [rINN (la)]
INN: Панкурония Бромид [rINN (ru)]
Chemical name: 1,1´-(3α,17β-Diacetoxy-5α-androstan-2β,16β-ylene)bis(1-methylpiperidinium) dibromide
Molecular formula: C35H60Br2N2O4 =732.7
CAS: 15500-66-0
ATC code: M03AC01
Read code: y03Jl

Pharmacopoeias. In Europe, Japan, and US.

European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Pancuronium Bromide). White, yellowish-white, or slightly pink, hygroscopic crystalline powder. Very soluble to freely soluble in water; freely soluble in alcohol; very soluble in dichloromethane. Store in airtight containers. Protect from light.

The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Pancuronium Bromide). A white, yellowish-white, or slightly pink, crystalline hygroscopic powder. Freely soluble in water, in alcohol, and in dichloromethane. Store in airtight containers at a temperature of 15° to 25°. Protect from light.

Adverse Effects, Treatment, and Precautions

As for competitive neuromuscular blockers in general (see Atracurium).

Pancuronium has vagolytic and sympathomimetic action, which may cause tachycardia and hypertension, but does not produce ganglionic blockade. It has little histamine-releasing effect. Hypersensitivity reactions are relatively rare but bradycardia, bronchospasm, hypotension, and cardiovascular collapse have been reported. Pancuronium has been associated with excessive salivation in some patients. Pancuronium should be used with caution in patients with raised catecholamine concentrations, or in those who are receiving drugs with sympathomimetic effects, as cardiovascular adverse effects are more likely in these patients.

Effects on the ears. A study found that neonates who survived congenital diaphragmatic hernia were more likely to suffer from sensorineural hearing loss after prolonged use of pancuronium bromide during the neonatal period. However, the authors commented that the association is not necessarily causal and that further investigation is required.

Hypersensitivity. Reports of anaphylactoid or anaphylactic reactions associated with pancuronium bromide. See also under Suxamethonium Chloride.

Postoperative complications. Because of its prolonged duration of action, pancuronium may be more likely than other neuromuscular blockers to produce residual neuromuscular block; such residual block is associated with an increased incidence of postoperative respiratory complications.

Interactions

For interactions associated with competitive neuromuscular blockers, see Atracurium.

Pharmacokinetics

On intravenous injection pancuronium bromide is rapidly distributed into body tissues; about 80% may be bound to plasma proteins. A small proportion is metabolised in the liver to metabolites with weak neuromuscular blocking activity. It is largely excreted in urine as unchanged drug and metabolites; a small amount is excreted in bile. The plasma elimination half-life is about 2 hours. It crosses the placenta in small amounts.

Pregnancy. In 15 patients undergoing caesarean section given pancuronium bromide 100 micrograms/kg intravenously with other agents, mean maternal arterial and umbilical venous serum concentrations of pancuronium bromide and metabolites were 520 and 120 nanograms/mL, respectively at delivery (mean of 13 minutes after injection), giving a fetal to maternal ratio of 0.23.

Uses and Administration

Pancuronium bromide is an aminosteroidal competitive neuromuscular blocker (see Atracurium). Muscle relaxation occurs within about 1.5 to 2 minutes of intravenous injection and lasts for about 45 to 60 minutes.

Pancuronium bromide is used for endotracheal intubation and to provide muscle relaxation in general anaesthesia for surgical procedures (see Anaesthesia) and to aid controlled ventilation (see Intensive Care).

Doses of neuromuscular blockers need to be carefully titrated for individual patients according to response, and may vary with the procedure, the other drugs given, and the state of the patient; monitoring of the degree of block is recommended in order to reduce the risk of overdosage. The initial dose for intubation is usually 50 to 100 micrograms/kg by intravenous injection, with maintenance doses of 10 to 20 micrograms/kg. Children may be given similar doses. Some manufacturers recommend a reduction in the initial dose to 20 to 60 micrograms/kg when pancuronium is given following suxamethonium. Doses of 30 to 40 micrograms/kg initially have been suggested in neonates, with maintenance doses of 10 to 20 micrograms/kg as necessary; in the UK, the BNFC suggests that higher doses may be used for neonates in some cases. In the United States of America (USA), dosage based on an initial test dose of 20 micrograms/kg has been advocated for the neonate. Adult patients under intensive care who require assisted ventilation for conditions such as intractable status asthmaticus or tetanus may be given 60 micrograms/kg intravenously every 1 to 1V2 hours or less frequently.

Care should be taken when giving pancuronium to patients with hepatic or renal impairment, see below.

Administration in hepatic impairment. Prolonged neuromuscular blockade may occur in patients with liver disease given pancuronium bromide since increased elimination half-life with increased volume of distribution and reduced clearance has been reported. However, the expanded distribution volume may necessitate an increase in the dose of pancuronium in these patients and may be interpreted as resistance to the neuromuscular blocking effects of pancuronium.

Administration in renal impairment. Prolonged neuromuscular blockade may occur when pancuronium is given to patients with severe renal impairment. Pancuronium distributes rapidly into extracellular fluid after intravenous injection and the initial neuromuscular blockade produced will depend upon the peak drug concentration in this fluid. Since extracellular fluid volume is increased in chronic renal failure such patients may require a larger initial dose of pancuronium and a 45% increase in dose requirement has been reported in patients with end-stage renal failure. Renal excretion is the main route of elimination and prolonged elimination half-life with reduced clearance may be expected in renal failure; total dose requirements may be reduced. The main infusion rate of pancuronium to maintain 90% blockade in patients with end-stage renal failure was reported to be 61.5% less than for patients with normal renal function.

Fetal paralysis. Pancuronium bromide 100 micrograms/kg of the estimated fetal-weight, given into the umbilical vein, produced fetal paralysis for about 40 minutes during intravascular exchange transfusion.A dose of 200 to 300 micrograms/kg produced fetal paralysis for about 1 to 8 hours for more complicated transfusion procedures. No adverse effects were reported.

Neuroleptic malignant syndrome. Pancuronium is one of several drugs for which there have been isolated reports of success in the management of neuroleptic malignant syndrome.

Preparations

British Pharmacopoeia 2008; Pancuronium Injection.

Proprietary Preparations

Argentina: Bemicin; Pancuron; Pavulon; Plumger;

Australia: Pavulon;

Brazil: Pancuron; Pavulon;

Chile: Pavulon;

Czech Republic: Pavulon;

Denmark: Pavulon;

Finland: Pavulon;

France: Pavulon;

Greece: Pavulon;

Hong Kong; Pavulon;

Hungary: Pavulon ;

India: Panconium;

Indonesia: Pavulon;

Ireland: Pavulon ;

Israel: Pavulon;

Italy: Pavulon;

Japan: Mioblock;

Malaysia: Pavulon;

Mexico: Bromurex; Panlem;

The Netherlands: Pavulon;

Norway: Pavulon;

Philippines: Pavulon;

Portugal: Pancurox; Pavulon ;

South Africa: Curon-B; Pavulon;

Singapore: Pavulon;

Spain: Pavulon ;

Sweden: Pavulon;

Switzerland: Pavulon;

Thailand: Pavulon;

Turkey: Pavulon;

United States of America (US and USA): Pavulon ;

Venezuela: Panuron; Pavulon; Pesium.

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