Pralidoxime (2-PAM) | Medication Reference

Bedside Snapshot

Core Use: Antidote for organophosphate insecticide poisoning and nerve agent exposure; reactivates acetylcholinesterase
Key Regimens: Adult IV: 2 g over 15-30 min, then infusion 8-10 mg/kg/h (~500 mg/h); EMS autoinjector: 600 mg IM per kit
Critical Timing: Most effective when given early, before enzyme-toxin complex "ages" and becomes irreversible
Adjunctive Therapy: Always use WITH atropine (primary life-saving drug) and benzodiazepines for seizures; never delay atropine waiting for pralidoxime
Key Dangers: Tachycardia, hypertension, muscle rigidity, transient neuromuscular blockade if pushed too fast; accumulation in renal impairment

Brand & Generic Names

Generic Name: Pralidoxime chloride (2-PAM Cl)
Brand Names: Protopam, 2-PAM, Pralidoxime Auto-Injector, various generics

Medication Class

Oxime cholinesterase reactivator; antidote for organophosphate and nerve agent poisoning. Acts by cleaving the phosphate-enzyme bond on acetylcholinesterase, restoring enzymatic function.

Pharmacology

Mechanism of Action:

Organophosphate insecticides and nerve agents inhibit acetylcholinesterase (AChE) by phosphorylating the active site
This causes accumulation of acetylcholine at muscarinic and nicotinic receptors, resulting in cholinergic crisis
Pralidoxime is an oxime nucleophile that binds to phosphorylated AChE and cleaves the phosphate-enzyme bond
Thereby reactivates AChE and restores its ability to hydrolyze acetylcholine
Reactivation most effective before "aging" occurs—time-dependent process where organophosphate-AChE complex becomes resistant to oxime (minutes to hours depending on agent)
Limited CNS penetration; key clinical effect is reversing nicotinic neuromuscular junction dysfunction (weakness, fasciculations, paralysis)
Improves respiratory muscle function and provides some improvement of muscarinic signs when combined with atropine

Pharmacokinetics:

Onset: Clinical improvement in muscle strength and fasciculations may be seen within minutes of IV administration in responsive patients
Distribution: Largely extracellular; volume of distribution ~0.6-1.7 L/kg; limited CNS penetration
Metabolism: Minimal; most excreted unchanged
Elimination: Primarily renal; elimination half-life ~1.5-2 hours; prolonged in renal impairment
Repeated boluses or prolonged infusions can lead to accumulation in reduced kidney function; dose reduction recommended in significant renal failure

Indications

Confirmed or strongly suspected organophosphate insecticide poisoning with cholinergic signs (SLUDGE/DUMBELS) and/or nicotinic features (fasciculations, weakness, paralysis)
Confirmed or suspected nerve agent exposure (sarin, soman, tabun, VX) with cholinergic manifestations; give as early as possible with atropine and benzodiazepines
Severe cholinergic crisis from therapeutic/intentional overdose of acetylcholinesterase inhibitors (neostigmine, pyridostigmine) with significant neuromuscular weakness
Empiric therapy in undifferentiated cholinergic toxidrome when organophosphate/nerve agent on differential—typically after/alongside atropine and in consultation with toxicology

Dosing & Administration

Available Forms:

IV Vials: Commonly 1 g or 2 g pralidoxime chloride powder for reconstitution; typical concentration 50 mg/mL (1000 mg in 20 mL)
Premixed IV Bags (institution-specific): e.g., 2 g in 100 mL NS for loading dose; 6 g in 500 mL NS for continuous infusion (~500 mg/h ≈ 42 mL/h)
Autoinjectors: Each kit contains 600 mg pralidoxime IM plus 2 mg atropine IM in separate or dual-chamber devices for rapid field administration

Standard Adult Dosing (Always Follow Local Protocol & Toxicology Advice):

Scenario	Typical Dose & Route	Frequency/Infusion	Notes
Organophosphate poisoning – IV loading (ED/ICU)	2 g IV in 100 mL NS over 15-30 min (~25-30 mg/kg)	May repeat 1-2 g in 1 hour if weakness persists	Start infusion after loading in moderate/severe cases
Organophosphate poisoning – IV continuous infusion	8-10 mg/kg/h (~500-650 mg/h in 70 kg adult)	e.g., 6 g in 500 mL NS at ~42-54 mL/h	Continue until clinical recovery and off atropine for 12-24 h (often 1-7 days in severe cases)
Alternative intermittent IV regimen	1-2 g IV over 15-30 min	Repeat q6-12 h as needed	Less favored than continuous infusion; may be used in resource-limited settings
Nerve agent exposure – EMS autoinjectors (adult)	600 mg IM pralidoxime + 2 mg atropine per kit	Mild: 1 kit; Moderate: 2 kits; Severe: up to 3 kits total	Give with benzodiazepines for seizures; little benefit from >3 pralidoxime injections
Nerve agent/OP poisoning – IV regimen (hospital)	2 g IV over 15-30 min, then 8-10 mg/kg/h infusion	Adjust rate to symptoms and renal function	Same as OP regimen; early administration critical before aging
Renal impairment	Reduce infusion rate (e.g., 25-50% reduction)	Monitor for accumulating toxicity	No precise regimen; follow tox/nephrology guidance
Pediatrics (outline only)	20-50 mg/kg IV loading (max 2 g), then 10-20 mg/kg/h infusion	Adjust per weight and severity	Use pediatric-specific protocols and toxicology consultation

Contraindications

Contraindications:

Known hypersensitivity to pralidoxime or formulation components
Relative: Myasthenia gravis without organophosphate exposure (pralidoxime may transiently worsen weakness by reversing therapeutic cholinesterase inhibition)

Major Precautions:

Pralidoxime is adjunctive to atropine, not a substitute: Atropine should be given promptly and titrated to drying of secretions and improved airway resistance
Rapid IV push risk: Large doses given rapidly can cause transient neuromuscular blockade, laryngospasm, tachycardia, and hypertension; administer over 15-30 minutes for loading doses
Renal impairment: Leads to accumulation; dose reductions and close monitoring for neuromuscular toxicity required
Limited CNS penetration: Seizures must be treated with benzodiazepines and standard status epilepticus protocols; pralidoxime will not control seizures
Carbamate poisoning: Benefit uncertain; however, often given when exact agent unknown or mixed OP/carbamate exposure possible

Critical Warning: Never delay atropine administration while waiting for pralidoxime. Atropine is the primary life-saving drug for secretions and bronchospasm. Pralidoxime is adjunctive therapy that primarily treats neuromuscular effects.

Adverse Effects

Common:

Dizziness, blurred vision, diplopia
Headache
Nausea, vomiting
Tachycardia, transient hypertension
Injection-site pain with IM administration

Serious (often dose- or rate-related):

Laryngospasm, bronchospasm, or transient apnea with rapid IV administration
Neuromuscular blockade with muscle rigidity, weakness, or respiratory arrest (particularly with very high doses)
Cardiac arrhythmias, severe hypertension or hypotension in unstable patients
Acute worsening of myasthenia gravis symptoms in patients chronically treated with acetylcholinesterase inhibitors

Special Populations

Renal Impairment:

Reduce infusion rate by 25-50% in significant renal failure
Monitor closely for signs of accumulation (muscle rigidity, weakness, respiratory distress)
Follow toxicology and nephrology guidance for specific dosing

Pediatric Patients:

Weight-based dosing: 20-50 mg/kg IV loading (max 2 g), then 10-20 mg/kg/h infusion
Use pediatric-specific protocols and toxicology consultation
Pediatric-specific autoinjectors exist in some systems but less common

Pregnancy/Lactation:

Limited data; use only for life-threatening organophosphate/nerve agent poisoning where benefits clearly outweigh risks
No adequate controlled studies; decision should involve toxicology consultation

Monitoring

Clinical Monitoring:

Airway, breathing, and circulation: ensure adequate oxygenation and ventilation; mechanical ventilation often required in severe cases
Continuous ECG and frequent blood pressure monitoring during IV loading and infusion, especially in hemodynamically unstable patients
Serial neurologic exams for improvement in muscle fasciculations, strength, and ability to ventilate spontaneously
Renal function (serum creatinine, urine output) to guide ongoing dosing, particularly for prolonged infusions

Laboratory Monitoring:

Cholinesterase activity levels (plasma or RBC) when available, mainly for trend and occupational health purposes rather than real-time titration
Electrolytes, renal function during prolonged therapy

Clinical Pearls

Muscle vs. Airway Agent: Think of pralidoxime primarily as the drug that gives the diaphragm and skeletal muscles back—while atropine is the drug that dries the lungs and saves the airway.

Early Administration Matters: The longer you wait (especially with nerve agents), the more AChE "ages" and becomes resistant to reactivation. When in doubt and exposure is credible, give it.

Continuous Infusion Preferred: Continuous infusion (e.g., 500-650 mg/h in adults) generally provides more stable levels and better outcomes than intermittent boluses in moderate/severe organophosphate poisoning.

Mass-Casualty Events: In nerve agent mass casualties, EMS use of autoinjectors (1-3 kits with pralidoxime + atropine) buys time and should be followed by hospital-based IV infusion regimens.

Toxicology Consultation: Always involve a poison center or medical toxicologist early for dosing nuances, duration of therapy, and transitions off pralidoxime once patient clinically improving.

References

1. Gupta, R., & O'Neil, B. (2023). Pralidoxime. In StatPearls. StatPearls Publishing.
2. Eddleston, M., Buckley, N. A., Eyer, P., & Dawson, A. H. (2008). Management of acute organophosphorus pesticide poisoning. The Lancet, 371(9612), 597-607. https://doi.org/10.1016/S0140-6736(07)61202-1
3. World Health Organization. (2016). Clinical management of acute pesticide intoxication: Prevention of suicidal behaviours.
4. U.S. Department of Health and Human Services. (2017). Nerve agent information for emergency medical services and hospitals. CHEMM.
5. Life in the Fast Lane. (2020). Pralidoxime – Toxicology Library Antidotes. LITFL. https://litfl.com/pralidoxime/