What oral drugs, apart from Neostigmine and Pyridostigmine, can cause muscle twitches?

Oral Drugs That Cause Muscle Twitches (Apart from Neostigmine and Pyridostigmine)

Physostigmine is the primary alternative oral acetylcholinesterase inhibitor that causes muscle twitches through the same mechanism as neostigmine and pyridostigmine—by increasing acetylcholine at the neuromuscular junction. 1, 2

Acetylcholinesterase Inhibitors

Physostigmine

• Physostigmine is a tertiary reversible cholinesterase inhibitor that crosses the blood-brain barrier more readily than the quaternary compounds (neostigmine/pyridostigmine) 2
• Has a short plasma elimination half-life of 20-30 minutes 2
• Causes muscle fasciculations and twitches through the same mechanism: inhibiting acetylcholinesterase, leading to acetylcholine accumulation at nicotinic receptors 1
• Listed specifically as causing shortened atrial action potential duration through vagal activation, which reflects its cholinergic effects 1

Edrophonium

• While primarily used intravenously, edrophonium is another acetylcholinesterase inhibitor that produces similar neuromuscular effects 1, 3, 4
• Less commonly used orally due to poor bioavailability, but mechanistically causes the same acetylcholine-mediated muscle activity 4

Organophosphate Compounds

Organophosphate Pesticides and Nerve Agents

• Organophosphates bind permanently to acetylcholinesterase, producing weakness, fasciculations, and paralysis due to unopposed acetylcholine action at nicotinic receptors 1
• These represent the most severe form of cholinesterase inhibition, causing persistent muscle twitching and fasciculations 1
• Examples include sarin and various agricultural pesticides that may be ingested orally 1

Sympathomimetic Agents

Beta-Agonists and Stimulants

• Theophylline and aminophylline cause increased atrial automaticity and can produce muscle tremor through beta-adrenergic stimulation 1
• Salbutamol, terbutaline, and other beta-agonists activate the β-adrenergic receptor/cAMP/PKA pathway, which can cause muscle tremor and fasciculations 1
• These drugs shorten atrial effective refractory period and increase intracellular calcium, leading to muscle hyperactivity 1

Important Clinical Distinctions

Mechanism Differences

• Acetylcholinesterase inhibitors cause fasciculations through nicotinic receptor overstimulation at the neuromuscular junction from excess acetylcholine 1
• Sympathomimetics cause tremor through beta-adrenergic activation and increased intracellular calcium cycling, which is mechanistically different from true fasciculations 1

Critical Pitfall

• Do not confuse muscle tremor (rhythmic oscillatory movements) with fasciculations (involuntary muscle twitches) 1
• True fasciculations from cholinesterase inhibitors represent spontaneous depolarization of motor units, while tremor from sympathomimetics represents rhythmic muscle contractions 1

Drugs That Prolong Neuromuscular Effects

Suxamethonium Interactions

• All three anticholinesterases (edrophonium, pyridostigmine, and neostigmine) prolong suxamethonium-induced neuromuscular block when given sequentially 5
• This prolongation increases duration to 127-138% of baseline and can manifest as prolonged fasciculations 5