Would a person taking 45mg of neostigmine (acetylcholinesterase inhibitor) tablets experience muscle twitching?

Would 45mg of Oral Neostigmine Cause Muscle Twitching?

Yes, taking 45mg of neostigmine tablets would very likely cause muscle twitching (fasciculations), along with other serious cholinergic symptoms, as this represents a massive overdose—approximately 13-16 times the typical therapeutic intravenous dose for a 70kg person. 1, 2

Dose Context and Severity

The 45mg oral dose represents an extreme overdose when compared to standard therapeutic dosing:

• Therapeutic intravenous doses range from 40-50 mcg/kg (0.04-0.05 mg/kg) of ideal body weight, which translates to approximately 2.8-3.5mg total for a 70kg person 3, 1
• The maximum recommended total intravenous dose is 0.07 mg/kg or up to 5mg total, whichever is less 2
• Your 45mg dose is 9-16 times higher than the maximum recommended therapeutic dose 1

Expected Clinical Presentation

Nicotinic Effects (Muscle-Related)

Muscle twitching would be expected as part of the overdose presentation:

• Fasciculations (muscle twitches) occur due to excessive acetylcholine accumulation at nicotinic receptors in the neuromuscular junction 4, 1, 5
• This progresses to increasing muscle weakness that can advance through involvement of respiratory muscles, constituting a cholinergic crisis 1, 2
• The FDA label specifically states that overdosage monitoring includes "carefully monitoring the muscle twitch response" 2

Muscarinic Effects (Additional Symptoms)

The overdose would also produce severe muscarinic symptoms:

• Nausea, vomiting, and diarrhea 2
• Excessive sweating 2
• Increased bronchial and salivary secretions 2
• Bradycardia (slow heart rate) 2

Mechanism of Muscle Twitching

• Neostigmine inhibits acetylcholinesterase, causing acetylcholine to accumulate in the synaptic cleft 4, 1, 5
• This excessive acetylcholine overstimulates nicotinic receptors at the neuromuscular junction 4, 1
• The result is spontaneous depolarization of motor units, manifesting as visible fasciculations 5

Evidence from Therapeutic Doses

Even therapeutic doses can cause muscle effects when given inappropriately:

• In healthy volunteers, therapeutic doses of neostigmine (35 mcg/kg, approximately 2.5mg) caused significant muscle weakness with decreased grip strength by 20% and reduced respiratory function 6
• A second therapeutic dose further decreased grip strength by 41% and caused depolarizing neuromuscular blockade 6
• When neostigmine 5mg was given to patients without neuromuscular blockade, it caused "substantial reduction in peak tetanic contraction and severe tetanic fade" lasting about 20 minutes 7

Critical Safety Considerations

This represents a medical emergency requiring immediate attention:

• The FDA label characterizes this as cholinergic crisis, which can result in death through respiratory muscle involvement 2
• Treatment requires prompt withdrawal of all anticholinesterase drugs and immediate administration of atropine 2
• Ventilation should be supported by artificial means until spontaneous respiration is adequate 2
• Cardiac function must be monitored 2

Oral vs. Intravenous Considerations

While the evidence primarily addresses intravenous neostigmine, oral absorption would still deliver a toxic dose, though potentially with slower onset and possibly reduced bioavailability compared to IV administration. The fundamental mechanism of acetylcholinesterase inhibition and resulting fasciculations remains the same regardless of route 4, 1, 5.