Pralidoxime Chloride
Pralidoxime (often referred to as **2-PAM**) is a specific antidote used primarily in veterinary medicine to treat **organophosphate (OP) toxicity**. Organophosphates are commonly found in older insecticides, agricultural chemicals, and some nerve agents. They work by irreversibly binding to and inhibiting acetylcholinesterase (AChE), leading to a massive accumulation of acetylcholine at nerve synapses and neuromuscular junctions. Pralidoxime acts as a **cholinesterase reactivator**, effectively pulling the OP molecule off the enzyme before the bond becomes permanent (a process known as "aging"). > **Clinical Pearl:** Pralidoxime is almost always used in conjunction with **atropine**. While atropine blocks the muscarinic effects of acetylcholine excess (SLUDDE signs: salivation, lacrimation, urination, defecation, dyspnea, emesis), pralidoxime is required to alleviate the **nicotinic effects**, particularly profound muscle tremors, weakness, and paralysis (including respiratory muscles). It is generally **not recommended** for carbamate toxicity, as carbamate-AChE bonds spontaneously reverse without the need for an oxime reactivator.
Mechanism: Pralidoxime works by directly reactivating the acetylcholinesterase enzyme that has been inhibited by organophosphates. * **Organophosphates** bind to the esteratic site of **acetylcholinesterase (AChE)** via phosphorylation, inactivating the enzyme. * Accumulation of **acetylcholine (ACh)** occurs at muscarinic and nicotinic receptors โ severe overstimulation. * **Pralidoxime** possesses a high affinity for the AChE enzyme. * Via **nucleophilic attack**, the oxime group of pralidoxime binds to the offending phosphoryl group of the organophosphate. * The pralidoxime-organophosphate complex breaks away from the enzyme โ **AChE is reactivated** and resumes breaking down ACh. > **Important Mechanistic Note:** If the phosphorylated enzyme undergoes a chemical change (loss of an alkyl group) before pralidoxime is administered, the bond becomes permanent. This is known as **"aging"**. Therefore, pralidoxime is most effective when given **within 24 hours** of exposure, though some benefit may be seen up to 36-48 hours in massive exposures.
Dosing by species
- Organophosphate poisoning ยท 20 mg/kg ยท IM or slow IV ยท 2-3 times a day ยท Works best when combined with atropine. Initial dose IM or slow IV; subsequent doses IM or SC.
- Organophosphate poisoning ยท 10-15 mg/kg ยท IM or SC ยท q8-12h ยท 36 hour minimum
- Organophosphate poisoning ยท 50 mg/kg ยท slow IV ยท May repeat in one hour if severe ยท Recovery should occur gradually over 48 hours ยท Give atropine first. Dilute in 10% glucose. May administer IM or IP. Reduce dose in renal failure.
- Organophosphate poisoning ยท 20 mg/kg ยท IV ยท Repeat in one hour if signs persist, then q8h ยท 24-48 hours ยท Give slowly or with fluids over a 30-minute period.
- Organophosphate poisoning ยท 20 mg/kg ยท IM or IV ยท May repeat q6-8h ยท Give within first 24 hours of exposure. Combine with atropine or give separately. Do not use in carbamate toxicity.
- Organophosphate poisoning ยท 30 mg/kg ยท IM ยท q8h ยท FARAD recommends a 28-day meat and a 6-day milk withdrawal time.
- Organophosphate poisoning ยท 25-50 mg/kg ยท IV ยท Single dose, or maximum of 100 mg/kg/day as an IV drip ยท Give as a 20% solution over 6 minutes.
- Organophosphate poisoning ยท 20 mg/kg (may require up to 35 mg/kg) ยท IV ยท q4-6h
Routes of administration
Contraindications
- Hypersensitivity to pralidoxime
- Carbamate poisoning (generally not recommended as inhibition is rapidly reversible)
Adverse effects
- Tachycardia (especially with rapid IV injection)
- Muscle rigidity
- Transient neuromuscular blockade
- Laryngospasm
Drug interactions
- Barbiturates ยท Anticholinesterases can potentiate the action of barbiturates; use with caution.
- Cimetidine ยท Use should be avoided in patients with organophosphate toxicity.
- Succinylcholine ยท Use should be avoided in patients with organophosphate toxicity.
- Theophylline ยท Use should be avoided in patients with organophosphate toxicity.
- Reserpine ยท Use should be avoided in patients with organophosphate toxicity.
- Respiratory Depressants (e.g., narcotics, phenothiazines) ยท Use should be avoided in patients with organophosphate toxicity.
Monitoring
- Clinical signs associated with organophosphate poisoning (SLUDDE signs, muscle fasciculations, weakness)
- Heart rate and rhythm (especially during IV administration)
- Respiratory rate and effort
Overdose
The acute LD50 of pralidoxime in dogs is 190 mg/kg. At high dosages, it causes signs associated with its own anticholinesterase activity. Clinical signs of toxicity in dogs may be exhibited as: * Muscle weakness * Ataxia * Vomiting * Hyperventilation * Seizures * Respiratory arrest * Death
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.