Usage
Pralidoxime is prescribed as an antidote for organophosphate poisoning, including insecticides (e.g., diazinon, malathion, parathion) and nerve agents (e.g., sarin, soman). It is also used in cases of overdose with cholinesterase inhibitors used to treat myasthenia gravis (e.g., neostigmine, pyridostigmine). It is classified as a cholinesterase reactivator. The drug works by reactivating the enzyme cholinesterase, which is essential for nerve function and is inhibited by organophosphates.
Alternate Names
Pralidoxime chloride, 2-PAM, Protopam Chloride. It is often found in combination with atropine in auto-injectors like ATNAA and DuoDote.
How It Works
Pharmacodynamics: Pralidoxime reactivates cholinesterase by removing the phosphoryl group attached to the enzyme by organophosphates. This restores the enzyme’s ability to break down acetylcholine, a neurotransmitter, thereby reversing the effects of excessive acetylcholine accumulation at nerve synapses.
Pharmacokinetics: Pralidoxime is poorly absorbed orally and is primarily administered intravenously (IV) or intramuscularly (IM). It distributes rapidly throughout the extracellular fluid but has limited penetration into the central nervous system (CNS). The drug is metabolized in the liver and primarily excreted in the urine as unchanged drug and metabolites. The elimination half-life is relatively short, about 1-3 hours.
Mode of Action: Pralidoxime binds directly to the organophosphate-inhibited cholinesterase, displacing the organophosphate and restoring the enzyme’s active site. This action is most effective before the process of “aging” occurs, in which the organophosphate-cholinesterase bond becomes irreversible.
Elimination Pathways: Pralidoxime is eliminated predominantly through renal excretion (approximately 80%) as both unchanged drug and its metabolites.
Dosage
Standard Dosage
Adults:
- Organophosphate Poisoning: 1-2 grams IV infused over 15-30 minutes, repeated after one hour if needed, then every 8-12 hours as needed. Alternatively, 30 mg/kg IV over 20 minutes followed by a maintenance infusion of 4-8 mg/kg/hour.
Children:
- Organophosphate Poisoning: 20-50 mg/kg (max 2 grams) IV infused over 15-30 minutes, repeated after one hour if needed, then every 8-12 hours.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary due to age-related decline in renal function.
- Patients with Renal Impairment: Dose reduction is recommended based on the degree of impairment.
- Patients with Hepatic Dysfunction: Careful monitoring is advised, but specific dose adjustments are not typically necessary.
Clinical Use Cases
Dosing remains consistent across clinical settings involving organophosphate poisoning. The route of administration (IV preferred, IM acceptable) may vary depending on the patient’s condition and available resources in settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations.
Dosage Adjustments
Adjustments are primarily needed for renal impairment. Dosage is usually reduced proportionally to the creatinine clearance rate. Close monitoring is vital in patients with comorbid conditions.
Side Effects
Common Side Effects
- Injection site pain
- Blurred vision
- Dizziness
- Drowsiness
- Headache
- Nausea
Rare but Serious Side Effects
- Fast or irregular heartbeat
- Difficulty breathing
- Muscle stiffness or weakness
- Seizures
- Allergic reactions (hives, swelling)
Long-Term Effects
No specific long-term effects from pralidoxime itself are known. However, severe organophosphate poisoning, even after treatment, can have long-term neurological consequences.
Adverse Drug Reactions (ADR)
Anaphylaxis, laryngospasm, hypertension, and respiratory depression.
Contraindications
Hypersensitivity to pralidoxime. Caution in patients with myasthenia gravis, as it may precipitate a myasthenic crisis.
Drug Interactions
May interact with barbiturates, morphine, theophylline, aminophylline, succinylcholine, reserpine, and phenothiazine-type tranquilizers. It is also important to note potential interactions with neuromuscular blocking agents and skeletal muscle relaxants.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Use only if clearly needed. It is unknown if pralidoxime passes into breast milk. Exercise caution when administering to breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Cholinesterase reactivator, reverses organophosphate inhibition.
- Side Effects: Injection site pain, blurred vision, dizziness, nausea, rarely seizures, allergic reactions.
- Contraindications: Hypersensitivity to the drug.
- Drug Interactions: Barbiturates, morphine, theophylline, succinylcholine, neuromuscular blockers.
- Pregnancy & Breastfeeding: Category C; caution advised.
- Dosage: Adults: 1-2g IV; Children: 20-50mg/kg IV.
- Monitoring Parameters: Respiratory rate, heart rate, blood pressure, muscle strength, cholinesterase activity.
Popular Combinations
Atropine is routinely administered with pralidoxime in organophosphate poisoning. Atropine manages the muscarinic effects of acetylcholine excess while pralidoxime targets nicotinic and central effects.
Precautions
Administer IV infusions slowly to avoid hypertension and tachycardia. Monitor renal function, especially in elderly patients and those with pre-existing renal disease. Exercise caution in patients with myasthenia gravis.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pralidoxime?
A: Adults: 1-2g IV; Children: 20-50mg/kg IV.
Q2: How does Pralidoxime work?
A: It reactivates cholinesterase, the enzyme inhibited by organophosphates.
Q3: What are the common side effects?
A: Injection site pain, blurred vision, dizziness, and nausea.
Q4: Can pregnant women receive Pralidoxime?
A: Only if clearly needed. Pregnancy Safety Category C.
Q5: How is Pralidoxime administered?
A: Intravenously (preferred) or intramuscularly.
Q6: What are the serious side effects to be aware of?
A: Seizures, irregular heartbeat, difficulty breathing, muscle stiffness, allergic reactions.
Q7: Does Pralidoxime interact with other medications?
A: Yes, interactions are possible with various drugs. Consult drug interaction resources.
Q8: Is Pralidoxime effective against all types of pesticide poisoning?
A: No, it is primarily effective against organophosphates.
Q9: What should be monitored in patients receiving Pralidoxime?
A: Respiratory and cardiovascular function, muscle strength, and cholinesterase levels.
Q10: Is there a specific antidote for Pralidoxime overdose?
A: No specific antidote exists. Supportive care is the primary treatment.
