What is the antidote for orphenadrine (anticholinergic medication) overdose?

Antidote for Orphenadrine Overdose

Physostigmine is the specific antidote for orphenadrine overdose, indicated for severe anticholinergic toxicity with significant central nervous system effects or life-threatening peripheral manifestations. 1

Clinical Presentation of Orphenadrine Toxicity

Orphenadrine is an anticholinergic medication that can cause significant toxicity when overdosed:

• Central nervous system effects: agitated delirium, hallucinations, confusion, seizures, and coma 1, 2
• Cardiovascular effects: tachycardia, mild hypertension, and potential ventricular dysrhythmias 1, 3
• Respiratory effects: tachypnea and potential respiratory depression 1
• Skin effects: hot, dry, erythematous skin 1
• Other effects: mydriasis (dilated pupils), hypoactive bowel sounds, hyperthermia, and urinary retention 1, 4

Management Algorithm

Initial Stabilization and Assessment

• Secure airway, breathing, and circulation 1
• Obtain vital signs, including temperature, heart rate, and blood pressure 1
• Perform focused neurological assessment to evaluate level of consciousness and presence of agitation 1
• Obtain ECG to assess for QRS prolongation or dysrhythmias 1, 3

First-Line Interventions

• Discontinue the orphenadrine exposure 1
• Provide supportive care, including IV fluids for hydration 1, 5
• Administer benzodiazepines for agitation and seizure control 1, 6
• Consider activated charcoal if recent oral ingestion and airway is protected 1, 7

Specific Antidotal Therapy with Physostigmine

• Adult dosing: 1-2 mg IV slowly over 5 minutes, may be repeated after 10-30 minutes if needed 1
• Pediatric dosing: 0.02 mg/kg IV (maximum 0.5 mg/dose) 1, 6
• Physostigmine has been shown to reverse orphenadrine-induced ventricular tachycardia 3

Management of Specific Complications

• Treat hyperthermia with external cooling measures 1
• Address urinary retention with bladder catheterization if needed 1
• For prolonged QRS or dysrhythmias, consider sodium bicarbonate administration 1
• For severe agitation not responsive to benzodiazepines, administer physostigmine 1, 2

Special Considerations

• Patients receiving physostigmine have significantly lower rates of intubation compared to those receiving other treatments 1
• The minimum lethal dose of orphenadrine for adults is reported to be 2-3 grams, though toxicity can be variable and unpredictable 7, 4
• Orphenadrine toxicity can occur in children even with small doses (as little as 200 mg) 2
• The elimination half-life of orphenadrine is approximately 10 hours, requiring extended monitoring 6

Common Pitfalls and Caveats

• Physostigmine is contraindicated in patients with cardiovascular disease, asthma, gangrene, diabetes, or mechanical obstruction of the intestines or urinary tract 1
• Underdosing of physostigmine is common; larger doses than standard may be required in severe cases 1
• Sustained-release formulations of orphenadrine may have different toxicity profiles compared to immediate-release formulations 4
• Continuous cardiac monitoring should be performed for at least 6 hours after symptom resolution 1
• Orphenadrine overdose can cause rhabdomyolysis, which requires monitoring of CK levels and adequate hydration 5