DESCRIPTION

Pralidoxime chloride (Protopam chloride, 2-PAM chloride) is an antidote for organophosphate or carbamate insecticide poisoning.

FORMS AND USES

• Each 20-cc vial contains 1 g of powder.
• The powder can be reconstituted with 0.9% sodium chloride solution.

MECHANISM OF ACTION

• Chemicals with organophosphate or carbamate activity inhibit plasma and erythrocyte cholinesterase and neurotoxic esterase by phosphorylating the serine esteratic site of the enzyme. Phosphorylation causes cholinergic toxicity by inhibiting the action of the cholinesterase.
• Pralidoxime can remove the phosphate group, thereby reactivating the enzyme and terminating cholinergic toxicity.
• Reactivation of erythrocyte cholinesterase occurs rapidly when pralidoxime is administered soon after exposure; delay in administration may allow the organophosphate-cholinesterase complex to bind covalently and thereby become irreversible.
• Reactivation of plasma cholinesterase is minimal.
• The most striking clinical effect is at nicotinic receptor sites as compared with muscarinic receptor sites.

DRUG AND DISEASE INTERACTIONS

Atropine and pralidoxime given together may act synergistically and may decrease atropine requirements.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category C. Studies have shown that the drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
• In the presence of cholinergic symptoms, treatment is recommended for pregnant or lactating women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• MECHANISM OF ACTION
• DRUG AND DISEASE INTERACTIONS
• PREGNANCY AND LACTATION

• Clinically significant organophosphate insecticide poisoning
  • Nicotinic effects (muscle and diaphragmatic weakness, fasciculation, muscle cramps, etc.) should be treated with pralidoxime.
  • CNS effects (confusion, coma, and seizures) should be treated with pralidoxime in addition to atropine.
• Carbamate poisoning. Use of pralidoxime in the treatment of carbamate poisoning is controversial but recommended, particularly for severe cases. In an animal model, the use of pralidoxime with the carbamate carbaryl was associated with worsening. However, it has been used in humans with poisoning by other carbamates without ill effect.
• Toxicity of drugs used to treat myasthenia gravis. Neostigmine and pyridostigmine inhibit cholinesterase and may produce cholinergic effects.

CONTRAINDICATIONS

• A known previous anaphylactic reaction to pralidoxime contraindicates its use.
• Pralidoxime is not generally recommended in cases of known exposure to carbaryl (Sevin) due to exacerbation of toxicity in animal models, although its use/nonuse in such situations is still a matter of controversy.

ADVERSE EFFECTS

• Mild serum creatinine kinase enzyme elevation
• Neuromuscular blockade may develop with serum pralidoxime concentration above 400 µg/cc. Therapeutic use does not approach this level.

Cardiovascular

Tachycardia, hypertension, and, rarely, cardiopulmonary arrest have been associated with rapid infusion.

Neurologic

Dizziness, headache, drowsiness, and apprehension associated with rapid infusion.

Dermatologic

Rash.

Gastrointestinal

Nausea and hepatic enzyme elevation.

Visual

Blurred vision, diplopia, and mydriasis.

Pulmonary

Apnea, hyperventilation, and laryngospasm associated with rapid infusion.

Section Outline:

• CONTRAINDICATIONS
• ADVERSE EFFECTS
  • Cardiovascular
  • Neurologic
  • Dermatologic
  • Gastrointestinal
  • Visual
  • Pulmonary

• Adult
  • Loading dose. 1 to 2 g in 0.9% sodium chloride solution should be infused intravenously over 30 minutes. Higher dose used for severe poisoning.
  • Maintenance dose. Continuous intravenous infusion at 500 mg/h should be continued for 24 to 48 hours. Intermittent infusion of 1 g in 250 cc normal saline, administered every 6 to 12 hours has also been recommended.
• Pediatric
  • Loading dose. 25 mg/kg (up to 1 g) in 0.9% sodium chloride solution should be infused intravenously over 30 minutes.
  • Maintenance dose. Intravenous infusion at 10 to 20 mg/kg (up to 500 mg) per hour should be continued for 24 to 48 hours. Intermittent infusion also has been used.
• Because excretion is renal, the dose of pralidoxime should be reduced in patients with renal insufficiency.
• Oral dosing of pralidoxime has been described but is not typically used.
• See SECTION IV, Organophosphate Insecticides chapter, for monitoring procedures.

• Rapid large intravenous bolus administration has produced sudden cardiac and respiratory arrest.
• Failure of treatment is usually a function of inadequate loading or maintenance dose.
• Treatment should be initiated as early as possible; administration more than 24 hours after exposure is thought to allow "aging" of the organophosphate-cholinesterase complex, rendering inactivation irreversible. However, treatment should be attempted in symptomatic patients even after 24 hours because reports of clinical response have been published.
• Treatment may require many days while residual organophosphate is metabolized or slowly cleared from body stores.
• Premature termination of treatment may result in recurrent signs and symptoms of organophosphate poisoning.
• Pralidoxime is not equally effective with all anticholinesterase agents.

Toxic effect of other substances, chiefly nonmedicinal as to source: organophosphate and carbamate.

See Also: SECTION III, Atropine chapter; and SECTION IV, Carbamate Insecticides, Organochlorine Pesticides, and Organophosphate Insecticides chapters.

RECOMMENDED READING

Farrar HC, Wells TG, Kearns GL. Use of continuous infusion of pralidoxime for treatment of organophosphate poisoning in children. J Pediatr 1990;116:658-661.

Howland MA, Aaron CK. Pralidoxime. In: Goldfrank LR, Flomenbaum NE, Lewin NA, et al., eds. Goldfrank's toxicologic emergencies, 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Namba T, Hiraki K. PAM (Pyridine-2-aldoxime methiodide) therapy for alkylphosphate poisoning. JAMA 1958;166:1834-1839.

Thompson DF, Thompson GD, Greenwood RB, et al. Therapeutic dosing of pralidoxime chloride. Drug Intell Clin Pharm 1987;21:590-593.

Willems JL, De Bisschop HC, Verstraete AG, et al. Cholinesterase reactivation in organophosphorus poisoned patients depends on the plasma concentrations of the oxime pralidoxime methylsulphate and of the organophosphate. Arch Toxicol 1993;67:79-84.

Author: Luke Yip

Reviewer: Rivka S. Horowitz