What is the severity of taking 180mg of pyridostigmine (Mestinon) as a one-off dose in a healthy male?

Safety of One-Time 180mg Pyridostigmine Dose in a Healthy Male

A one-time 180mg dose of pyridostigmine is likely to cause mild to moderate cholinergic symptoms in a healthy male but is unlikely to result in severe toxicity or long-term consequences.

Expected Effects and Safety Profile

The 180mg extended-release tablet of pyridostigmine is designed to provide a prolonged duration of action, with effects lasting approximately 2.5 times longer than a standard 60mg immediate-release tablet 1. When taken as a single dose by a healthy individual:

• The FDA-approved labeling indicates that 180mg is within the standard therapeutic range, as extended-release tablets are typically prescribed at doses of "one to three 180mg tablets, once or twice daily" 1

• Research shows that even higher single doses (390-900mg) in healthy adults resulted in only mild to moderate cholinergic symptoms that were self-limited and well-tolerated 2

Likely Symptoms

A healthy male taking a one-time 180mg dose may experience:

• Peripheral cholinergic effects (most common):

  • Abdominal cramps
  • Diarrhea
  • Nausea or vomiting
  • Increased salivation
  • Muscle twitching or fasciculations
  • Mild muscle weakness
  • Blurred vision

• These symptoms typically:

  • Develop within minutes of ingestion
  • Last up to 24 hours
  • Resolve without specific treatment 2

Important Considerations

1. No significant central nervous system effects are expected since pyridostigmine is a quaternary compound that does not readily cross the blood-brain barrier under normal conditions 3

2. Mechanism of action: Pyridostigmine inhibits acetylcholinesterase, preventing the breakdown of acetylcholine and increasing its concentration at the neuromuscular junction 4

3. Cholinergic side effects are more common at doses of 150mg or higher 4, which is consistent with the 180mg dose in question

Management of Symptoms

If cholinergic symptoms develop:

• Most cases resolve spontaneously without intervention
• For more pronounced symptoms, atropine can be administered to counteract muscarinic effects 2
• Gastric emptying followed by activated charcoal administration may be considered if the patient presents soon after ingestion 2

Risk Factors to Consider

The severity of symptoms may be greater in individuals with:

• Pre-existing cardiac conditions
• Respiratory disorders
• Neuromuscular disorders
• Concurrent use of other medications that affect cholinergic function

Conclusion

While a single 180mg dose of pyridostigmine will likely cause some transient cholinergic symptoms in a healthy male, research indicates these effects are generally mild to moderate and self-limiting without long-term consequences 2, 5. The symptoms typically resolve within 24 hours without specific treatment.