Neostigmine 45mg Oral Dose and Muscle Twitches
Yes, a single oral dose of 45mg neostigmine would very likely cause muscle twitches (fasciculations) because this represents a massive overdose—approximately 10-15 times higher than therapeutic intravenous doses and far exceeding any recommended oral dosing. 1
Understanding the Dose Context
The question involves 45mg oral neostigmine, which requires critical context:
- Therapeutic IV doses for reversal of neuromuscular blockade are 40-50 micrograms/kg (0.04-0.05 mg/kg), meaning a 70kg person receives approximately 2.8-3.5mg intravenously 2, 1
- Your proposed 45mg dose is roughly 13-16 times higher than standard therapeutic IV doses 1
- Oral bioavailability of neostigmine is poor (1-2% for quaternary ammonium compounds), but even accounting for this, the absorbed amount would still represent a significant overdose 3
Expected Clinical Presentation of This Overdose
Fasciculations (muscle twitches) are a hallmark feature of neostigmine overdose due to excessive nicotinic receptor stimulation 1:
- The mechanism involves acetylcholine accumulation in the synaptic cleft, causing unopposed stimulation of nicotinic receptors 1
- Initial depolarization manifests clinically as fasciculations before potentially progressing to paralysis in severe overdose 1
- This pattern mirrors organophosphate poisoning, which produces weakness, fasciculations, and paralysis through the same mechanism 1
Additional Expected Symptoms
Beyond muscle twitches, this dose would cause:
- Muscarinic symptoms: nausea, vomiting, diarrhea, excessive sweating, increased bronchial and salivary secretions, bradycardia 1
- Cholinergic crisis: progressive muscle weakness that can involve respiratory muscles 1
- Severe neuromuscular dysfunction: even therapeutic IV doses (2.5mg) cause significant grip strength reduction (-20%) and restrictive spirometry patterns within 5 minutes 4
Critical Safety Considerations
This represents a dangerous overdose scenario that would require:
- Immediate medical attention and supportive care 1
- Monitoring for respiratory compromise due to muscle weakness 4
- Potential need for atropine to counteract muscarinic effects 2
Important Caveat About Therapeutic Use
Even at proper therapeutic doses (2.5-5mg IV), neostigmine causes paradoxical muscle weakness when given in the absence of neuromuscular blockade:
- Single 2.5mg IV dose reduces grip strength by 20% and causes depolarizing neuromuscular blockade 4
- A second 2.5mg dose further decreases grip strength by 41% 4
- These effects persist for approximately 20 minutes and include severe tetanic fade 5
The dose you're asking about (45mg oral) would produce effects far more severe than these therapeutic dose studies demonstrate.