Pyridostigmine Overdose in Healthy Individuals: Expected Effects
Yes, a healthy person who ingests 240 mg of pyridostigmine would likely experience muscle fasciculations (twitching) along with other cholinergic symptoms, though the severity would vary based on individual tolerance.
Mechanism and Expected Symptoms
Pyridostigmine is a cholinesterase inhibitor that increases acetylcholine at both muscarinic and nicotinic receptors. At 240 mg (significantly above therapeutic dosing), a healthy person would experience cholinergic toxicity with two distinct symptom patterns 1:
Nicotinic Effects (Muscle-Related)
- Muscle fasciculations (twitching) - This is a hallmark nicotinic effect 1
- Muscle cramps 1
- Muscle weakness 1
Muscarinic Effects (Autonomic)
- Nausea and vomiting 1
- Diarrhea and abdominal cramps 1
- Increased salivation 1
- Increased bronchial secretions 1
- Miosis (pupil constriction) 1
- Diaphoresis (sweating) 1
- Increased peristalsis 1
Clinical Context and Severity
The 240 mg dose represents four times the maximum single therapeutic dose (60 mg) used in myasthenia gravis 2. This overdose would likely produce significant symptoms:
Real-World Toxicity Data
- In a documented suicide attempt, a 47-year-old patient who intentionally ingested a high dose of pyridostigmine developed toxic symptoms within 1 hour 3
- The patient required treatment with atropine and pralidoxime but made an excellent recovery 3
- Pyridostigmine poisoning is generally self-limiting and well-tolerated in young adults, though cardiac effects can be concerning in elderly patients 3
Wartime Experience with Lower Doses
Even at therapeutic doses (30 mg every 8 hours), approximately 50% of soldiers experienced physiologic changes including increased flatus, abdominal cramps, soft stools, and urinary urgency 4. At 240 mg, these effects would be substantially more pronounced.
Important Caveats
Cholinergic crisis risk: At this dose, there is potential for cholinergic crisis characterized by progressive muscle weakness that can involve respiratory muscles 1. The FDA label explicitly warns that overdosage may result in cholinergic crisis, potentially leading to respiratory failure 1.
Individual variation: Studies in healthy subjects taking 90 mg daily (30 mg three times daily) for 8 days showed no significant neuromuscular effects despite 20-30% cholinesterase inhibition 5. However, 240 mg as a single dose would produce much higher peak levels and more pronounced effects.
Cardiac considerations: Unwanted cardiac effects can become profound, potentially generating heart failure, syncope, or significant stress, particularly concerning in any individual with underlying cardiac conditions 3.
Management Principles
If this overdose occurred, treatment would involve 3:
- Atropine to counteract muscarinic effects
- Pralidoxime as an additional antidote
- Supportive care with monitoring for respiratory compromise
The muscle twitching (fasciculations) specifically would be among the expected nicotinic manifestations, alongside the more prominent muscarinic symptoms of nausea, vomiting, diarrhea, and excessive secretions 1.