Extremely High Risk of Muscle Twitches and Severe Cholinergic Crisis
A healthy person chewing 60mg of neostigmine would almost certainly experience severe muscle twitches, fasciculations, and potentially life-threatening cholinergic toxicity, as this represents a massive overdose (approximately 10-20 times the therapeutic dose) administered without the protective anticholinergic agents required for safe use. 1
Critical Context: This is a Dangerous Overdose Scenario
The scenario described involves several compounding dangers:
- Massive dose: 60mg is approximately 857 mcg/kg for a 70kg person, which is 17-21 times higher than the recommended therapeutic dose of 40-50 mcg/kg 2
- No anticholinergic protection: Neostigmine must always be co-administered with atropine (0.02 mg/kg) or glycopyrrolate to prevent severe cholinergic side effects 1, 3
- Inappropriate indication: Neostigmine should only be given when reversing neuromuscular blockade, never in a healthy person without residual blockade 2, 1
- Oral absorption: While neostigmine is poorly absorbed orally (quaternary ammonium compound), chewing could enhance buccal absorption, though the exact bioavailability is unpredictable 4
Expected Clinical Effects
Muscle-Related Effects (Near Certainty)
- Severe fasciculations and muscle twitches would be expected given that even therapeutic doses (35 mcg/kg) in healthy volunteers caused significant muscle weakness and depolarizing neuromuscular blockade 5
- Profound muscle weakness: A single therapeutic dose of 35 mcg/kg caused a 20% reduction in grip strength within 5 minutes in healthy volunteers 5
- Depolarizing neuromuscular blockade: Therapeutic doses reduced single twitch height by 14%, and a second dose further reduced it by 25% 5
- At this massive overdose level, the depolarizing block would be severe and prolonged 6
Additional Cholinergic Crisis Symptoms (Expected)
- Severe bradycardia and potential cardiac arrest (without anticholinergic protection) 3
- Bronchospasm and respiratory failure: Therapeutic doses caused a 15% reduction in FEV1 and 20% reduction in FVC; this overdose would cause severe restrictive respiratory impairment 5
- Excessive salivation, lacrimation, urination, defecation (SLUDGE syndrome)
- Nausea, vomiting, abdominal cramping
- Miosis (pinpoint pupils)
Mechanism of Toxicity
- Neostigmine inhibits acetylcholinesterase, causing acetylcholine accumulation in the synaptic cleft 1, 3
- Without competing neuromuscular blockade to reverse, the excess acetylcholine causes paradoxical neuromuscular dysfunction through depolarizing blockade 5, 6
- Red cell acetylcholinesterase is almost completely inhibited within 2-3 minutes of therapeutic doses, with only 28% recovery by 30 minutes 7
- At this overdose level, complete and prolonged acetylcholinesterase inhibition would occur
Time Course
- Onset: Effects would begin within 2 minutes of absorption, with maximal effects at 7-15 minutes 7
- Duration: The elimination half-life is 15-30 minutes, but effects persist much longer due to the depolarizing blockade mechanism 4, 7
- At therapeutic doses, muscle weakness and respiratory impairment persisted for at least 20 minutes 5, 6
- This overdose would likely cause effects lasting several hours
Critical Clinical Pitfall
The most dangerous aspect is that administering neostigmine without residual neuromuscular blockade to reverse causes a depolarizing block that cannot be easily reversed 2, 1. Studies show that neostigmine given when TOF ratio is already ≥0.9 impairs neuromuscular transmission for 17-52 minutes even at therapeutic doses 1. This overdose would cause profound, prolonged impairment.
Bottom Line
The probability of muscle twitches and fasciculations approaches 100%, as even therapeutic doses in appropriate clinical settings cause these effects 5, 6. However, muscle twitches would be the least concerning symptom—this scenario represents a medical emergency requiring immediate treatment with atropine and supportive care including potential mechanical ventilation 3.