What orally administered drugs, apart from neostigmine and pyridostigmine, can cause muscle twitches?

Oral Drugs That Cause Muscle Twitches (Beyond Neostigmine and Pyridostigmine)

Several oral medications can cause muscle twitches through distinct mechanisms: acetylcholinesterase inhibitors (physostigmine, edrophonium), organophosphates, and sympathomimetic agents (theophylline, aminophylline, beta-agonists like salbutamol and terbutaline). 1

Acetylcholinesterase Inhibitors

These drugs cause muscle fasciculations and twitches through the same mechanism as neostigmine and pyridostigmine—by inhibiting acetylcholinesterase, leading to acetylcholine accumulation at nicotinic receptors. 1

Physostigmine

• Physostigmine is a tertiary reversible cholinesterase inhibitor that crosses the blood-brain barrier (unlike the quaternary compounds neostigmine and pyridostigmine). 1
• It causes muscle fasciculations through acetylcholine accumulation at the neuromuscular junction. 1
• Plasma elimination half-life is 20-30 minutes. 2

Edrophonium

• Edrophonium is another acetylcholinesterase inhibitor that produces similar neuromuscular effects including muscle twitches. 1, 3
• It has been used clinically to reverse neuromuscular blockade and in diagnostic testing for myasthenia gravis. 4, 5
• The drug antagonizes neuromuscular blockade through increased acetylcholine at the neuromuscular junction. 4

Organophosphates

• Organophosphates bind permanently (irreversibly) to acetylcholinesterase, producing weakness, fasciculations, and paralysis due to unopposed acetylcholine action at nicotinic receptors. 1
• These represent a more severe and prolonged form of cholinergic toxicity compared to reversible inhibitors. 1

Sympathomimetic Agents

These drugs cause muscle tremor through a mechanistically different pathway than true fasciculations—they work via beta-adrenergic stimulation rather than cholinergic overstimulation. 1

Theophylline and Aminophylline

• These methylxanthines cause muscle tremor through beta-adrenergic stimulation and increased atrial automaticity. 1
• The tremor represents rhythmic muscle contractions rather than spontaneous motor unit depolarization. 1

Beta-Agonists (Salbutamol, Terbutaline)

• Beta-agonists activate the β-adrenergic receptor/cAMP/PKA pathway, which causes muscle tremor and fasciculations. 1
• The mechanism involves increased intracellular calcium cycling, distinct from acetylcholinesterase inhibitor effects. 1

Critical Clinical Distinctions

Mechanism Differences

• Acetylcholinesterase inhibitors cause true fasciculations through nicotinic receptor overstimulation at the neuromuscular junction from excess acetylcholine. 1
• Sympathomimetics cause tremor through beta-adrenergic activation, which is mechanistically different from true fasciculations. 1
• True fasciculations represent spontaneous depolarization of motor units, while sympathomimetic tremor represents rhythmic muscle contractions. 1

Important Caveats

Drug Interactions

• Methocarbamol interferes with the effects of pyridostigmine bromide and should not be used in patients with myasthenia gravis. 6
• This interaction is relevant when considering the broader context of drugs affecting neuromuscular function. 6

Context-Specific Considerations

• In immune checkpoint inhibitor-related myasthenia gravis-like syndrome, pyridostigmine (30 mg orally up to 600 mg daily) may be used for myasthenic symptoms. 6
• The distinction between fasciculations (cholinergic) and tremor (adrenergic) has important diagnostic and therapeutic implications. 1