Pralidoxima

Uses

Pralidoxima chloride is used for an antidote:

• In the treatment of poisoning due to those pesticides and chemicals (e.g., nerve agents) of the organophosphate class which have anticholinesterase activity and
• In the control of overdosage by anticholinesterase drugs used in the treatment of myasthenia gravis.

The principal indications for the use of Pralidoxima chloride are muscle weakness and respiratory depression. In severe poisoning, respiratory depression may be due to muscle weakness.

Pralidoxima is also used to associated treatment for these conditions: Toxic effect of organophosphate and carbamate, Anticholinesterase overdose

How Pralidoxima works

Pralidoxima is an antidote to organophosphate pesticides and chemicals. Organophosphates bind to the esteratic site of acetylcholinesterase, which results initially in reversible inactivation of the enzyme. Acetylcholinesterase inhibition causes acetylcholine to accumulate in synapses, producing continuous stimulation of cholinergic fibers throughout the nervous systems. If given within 24 hours after organophosphate exposure, pralidoxime reactivates the acetylcholinesterase by cleaving the phosphate-ester bond formed between the organophosphate and acetylcholinesterase.

Dosage

Pralidoxima dosage

Intramuscular-

Organophosphorus poisoning:

• Adult: Mild: 600 mg, repeat 1-2 times at 15 min intervals as needed. Severe: 1.8 g given as 3 inj of 600 mg in rapid succession. Persistent: May repeat the entire series (1.8 g) beginning 1 hr after admin of the last inj.
• Child:<40 kg: Mild: 15 mg/kg, repeat as needed every 15 min. Max: 45 mg/kg. Severe: 15 mg/kg, repeat twice in rapid succession to a total dose of 45 mg/kg. Persistent: May repeat the entire series (45 mg/kg) beginning 1 hr after admin of the last inj; ≥40 kg: Same as adult dose.

Intravenous-

Organophosphorus poisoning:

• Adult: In combination with atropine: Loading dose: 1-2 g by infusion over 15-30 min or slow inj over at least 5 min, may repeat dose after 1 hr then 10-12 hrly, as needed. Administer as soon as the effects of atropine are observed. Maintain atropinisation for at least 48 hr.
• Child: ≤16 yr Loading dose: 20-50 mg/kg (max: 2 g/dose) by inj over 15-30 min followed by 10-20 mg/kg/hr as continuous infusion. Alternatively, a repeat bolus of 20-50 mg/kg after 1 hr and repeated 10-12 hrly as needed; >16 yr Same as adult dose.

Poisoning or overdosage with compounds having muscarinic actions:

• Adult: Initially, 1-2 g, followed by 0.5-1 g/hr as infusion. Alternatively, the initial dose may be repeated after 1 hr and then 3-8 hrly as needed.

Intramuscular: Dilute 1 g with 3.3 mL sterile water for inj to a final concentration of 300 mg/mL.

Intravenous: Dilute 1 g with 20 mL of sterile water for inj to make a concentration of 50 mg/mL to be administered in fluid-restricted patients or when rapid admin is required; for all other patients, further dilute with normal saline to a final concentration of 20 mg/mL.

Side Effects

Drowsiness, dizziness, visual disturbances, nausea, HTN, tachycardia, headache, hyperventilation, muscle weakness, impaired renal function, elevated liver enzymes, transient increase in creatine phosphokinase, transient neuromuscular blockade; mild to moderate pain at inj site.

Precaution

Patient with myasthenia gravis receiving anticholinesterase agents. Not indicated in the treatment of poisoning due to phosphorous, inorganic phosphates, or organophosphates without anticholinesterase activity and carbamate pesticides. Renal impairment. Pregnancy and lactation.

Food Interaction

Pralidoxima Disease Interaction

Major: myasthenic crisisModerate: renal dysfunction

Half Life

74-77 minutes

Elimination Route

The drug is rapidly excreted in the urine partly unchanged, and partly as a metabolite produced by the liver.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

There are no known absolute contraindications for the use of Pralidoxima Chloride. Relative contraindications include known hypersensitivity to the drug and other situations in which the risk of its use clearly outweighs possible benefit.

Acute Overdose

Manifestations of Overdosage: Observed in normal subjects only: dizziness, blurred vision, diplopia, headache, impaired accommodation, nausea, slight tachycardia. In therapy it has been difficult to differentiate side effects due to the drug from those due to the effects of the poison.

Storage Condition

Store between 20-25° C.

Innovators Monograph

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