Would oral ingestion of 60 mg of neostigmine (acetylcholinesterase inhibitor) by chewing cause muscle twitches?

Oral Neostigmine and Muscle Twitches

Yes, oral ingestion of 60 mg of neostigmine would very likely cause muscle twitches (fasciculations) along with potentially severe and dangerous cholinergic effects, though the specific manifestation would depend on absorption and individual factors.

Mechanism of Muscle Twitching with Neostigmine

Neostigmine inhibits acetylcholinesterase, causing accumulation of acetylcholine in the synaptic cleft, which leads to excessive stimulation of nicotinic receptors and results in fasciculations (muscle twitches) 1. This mechanism is fundamental to understanding why muscle twitches occur with neostigmine exposure.

Dose Considerations and Expected Effects

The 60 mg oral dose mentioned represents an extraordinarily high amount:

• Standard therapeutic intravenous doses range from 40-50 mcg/kg (0.04-0.05 mg/kg) of ideal body weight 2, 3
• For a 70 kg person, this translates to approximately 2.8-3.5 mg intravenously
• The 60 mg oral dose is therefore 17-21 times higher than a typical IV therapeutic dose
• Even accounting for reduced oral bioavailability, the absorbed amount would likely far exceed therapeutic levels

Evidence of Neuromuscular Effects

Therapeutic doses of neostigmine cause measurable muscle weakness and neuromuscular effects even in healthy individuals:

• Intravenous neostigmine 2.5 mg (approximately 35 mcg/kg) in healthy volunteers caused a 20% reduction in grip strength, 14% decrease in single twitch height, and depolarizing neuromuscular blockade 4
• A second dose of 2.5 mg further decreased grip strength by 41% and single twitch height by 25% 4
• Neostigmine in clinical doses can produce acetylcholine-induced neuromuscular blockade that persists for approximately 20 minutes 5

Overdosage and Cholinergic Crisis

The FDA label explicitly warns that overdosage causes cholinergic crisis with specific muscular manifestations:

• Muscarinic symptoms include nausea, vomiting, diarrhea, sweating, increased bronchial and salivary secretions, and bradycardia 6
• Cholinergic crisis is characterized by increasing muscle weakness that can progress through involvement of respiratory muscles to potentially fatal respiratory failure 6
• The FDA specifically recommends monitoring muscle twitch response to peripheral nerve stimulation to prevent iatrogenic overdose 6

Clinical Manifestations Expected

With a 60 mg oral dose, the person would likely experience:

• Muscle fasciculations (twitches) from excessive nicotinic receptor stimulation 1
• Progressive muscle weakness rather than just isolated twitching 6, 4
• Severe cholinergic symptoms including excessive salivation, sweating, nausea, vomiting, diarrhea, and bradycardia 6
• Potential respiratory muscle involvement leading to respiratory compromise 6
• Depolarizing neuromuscular blockade affecting both voluntary and involuntary muscles 4, 5

Critical Safety Considerations

This scenario represents a medical emergency requiring immediate intervention:

• Ventilation should be supported by artificial means until adequacy of spontaneous respiration is assured 6
• Cardiac function must be monitored 6
• Atropine is the antidote for cholinergic crisis and should be administered promptly 6
• The muscle weakness can be difficult to distinguish from other causes and may persist for extended periods 7, 5

Route of Administration Impact

While the question specifies oral administration by chewing, which would have lower bioavailability than intravenous administration, the dose is so excessive that significant systemic absorption would still be expected to produce cholinergic effects including muscle twitches and potentially life-threatening complications 6, 4.