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.
Mecanismo: 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 → 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 → **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.
Dosificación por especie
- Organophosphate poisoning · 20 mg/kg · IM or slow IV · 2-3 times a day · Works best when combined with atropine. Initial dose IM or slow IV; subsequent doses IM or SC.
- Organophosphate poisoning · 10-15 mg/kg · IM or SC · q8-12h · 36 hour minimum
- Organophosphate poisoning · 50 mg/kg · slow IV · May repeat in one hour if severe · Recovery should occur gradually over 48 hours · Give atropine first. Dilute in 10% glucose. May administer IM or IP. Reduce dose in renal failure.
- Organophosphate poisoning · 20 mg/kg · IV · Repeat in one hour if signs persist, then q8h · 24-48 hours · Give slowly or with fluids over a 30-minute period.
- Organophosphate poisoning · 20 mg/kg · IM or IV · May repeat q6-8h · Give within first 24 hours of exposure. Combine with atropine or give separately. Do not use in carbamate toxicity.
- Organophosphate poisoning · 30 mg/kg · IM · q8h · FARAD recommends a 28-day meat and a 6-day milk withdrawal time.
- Organophosphate poisoning · 25-50 mg/kg · IV · Single dose, or maximum of 100 mg/kg/day as an IV drip · Give as a 20% solution over 6 minutes.
- Organophosphate poisoning · 20 mg/kg (may require up to 35 mg/kg) · IV · q4-6h
Vías de administración
Contraindicaciones
- Hypersensitivity to pralidoxime
- Carbamate poisoning (generally not recommended as inhibition is rapidly reversible)
Efectos adversos
- Tachycardia (especially with rapid IV injection)
- Muscle rigidity
- Transient neuromuscular blockade
- Laryngospasm
Interacciones farmacológicas
- Barbiturates · Anticholinesterases can potentiate the action of barbiturates; use with caution.
- Cimetidine · Use should be avoided in patients with organophosphate toxicity.
- Succinylcholine · Use should be avoided in patients with organophosphate toxicity.
- Theophylline · Use should be avoided in patients with organophosphate toxicity.
- Reserpine · Use should be avoided in patients with organophosphate toxicity.
- Respiratory Depressants (e.g., narcotics, phenothiazines) · Use should be avoided in patients with organophosphate toxicity.
Monitoreo
- Clinical signs associated with organophosphate poisoning (SLUDDE signs, muscle fasciculations, weakness)
- Heart rate and rhythm (especially during IV administration)
- Respiratory rate and effort
Sobredosis
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
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.