PRALIDOXIME CHLORIDE, 2-PAM CHLORIDE

Chemistry - A quaternary ammonium oxime cholinesterase reactivator, pralidoxime chlorideoccurs as a white to pale yellow, crystalline powder with a pKa of 7.8-8. It is freely soluble in water.
The commercially available injection has a pH of 3.5-4.5 after reconstitution. Pralidoxime may alsobe known as 2-PAM Chloride, or 2-Pyridine Aldoxime Methochloride.

Storage, Stability, Compatibility

Unless otherwise instructed by the manufacturer, pralidoximechloride powder for injection should be stored at room temperature. After reconstituting with sterilewater for injection, the solution should be used within a few hours. Do not use sterile water withpreservatives added.

Pharmacology - PRALIDOXIME CHLORIDE, 2-PAM CHLORIDE

Pralidoxime reactivates cholinesterase that has been inactivated by phosphorylation secondary to certain organophosphates. Via nucleophilic at ack, the drug removes and bindsthe offending phosphoryl group attached to the enzyme and is then excreted.

Uses, Indications

Pralidoxime is used in the treatment of organophosphate poisoning, often inconjunction with atropine and supportive therapy.

Pharmacokinetics - PRALIDOXIME CHLORIDE, 2-PAM CHLORIDE

Pralidoxime is only marginally absorbed after oral dosing and oral dosageforms are no longer available in the United States. It is distributed primarily throughout the extracellular water. Because of its quaternary ammonium structure, it is not believed to enter the CNSin significant quantities, but recent studies and clinical responses have led some to question this.
Pralidoxime is thought to be metabolized in the liver and excreted as both metabolite(s) and unchanged drug in the urine.

Contraindications, Precautions, Reproductive Safety

Pralidoxime is contraindicated in patients hypersensitive to it. Pralidoxime is generally not recommended to be used in instances ofcarbamate poisoning because inhibition is rapidly reversible, but there is some controversy regarding this issue.
Pralidoxime should be used with caution in patients receiving anticholinesterase agents for thetreatment of myasthenia gravis as it may precipitate a myasthenic crisis. It should also be usedcautiously and at a reduced dosage rate in patients with renal impairment.

Adverse Effects, Warnings

At usual doses, pralidoxime generally is safe and free of significantadverse effects. Rapid IV injection may cause tachycardia, muscle rigidity, transient neuromuscularblockade, and laryngospasm.
Pralidoxime must generally be given within 24 hours of exposure to be effective, but some benefits may occur, particularly in large exposures, if given within 36-48 hours.

Overdosage, Acute Toxicity

The acute LD50 of pralidoxime in dogs is 190 mg/kg and, at highdosages, exhibits symptoms of its own anticholinesterase activity. Symptoms of toxicity in dogsmay be exhibited as muscle weakness, ataxia, vomiting, hyperventilation, seizures, respiratory arrestand death.

Drug Interactions

Anticholinesterases can potentiate the action of barbiturates; use with caution.
Cimetidine may potentiate the action of organophosphates by slowing its metabolism.
Use of succinylcholine, theophylline/aminophylline, reserpine, and respiratorydepressant drugs (e.g., narcotics, phenothiazines) should be avoided in patients withorganophosphate toxicity.