Acetylcholinesterase inhibitors for symptoms of myasthenia gravis

To treat the symptoms of muscle-specific tyrosine kinase (MuSK)–negative mild generalised myasthenia gravis or ocular myasthenia, first-line therapy is the acetylcholinesterase inhibitor, pyridostigmine. (In MuSK-positive myasthenia gravis, acetylcholinesterase inhibitors are less effective and often have adverse effects.) Start therapy at a lower dose in smaller people. Use:

Time the doses for when the patient is most fatigued (eg 30 to 45 minutes before meals when the patient has bulbar weakness). Use the lowest effective dose to achieve symptom control. If muscarinic adverse effects (eg diarrhoea, abdominal pain, cramps, exacerbation of glaucoma) occur, adding an anticholinergic drug (eg propantheline) may help.

Use larger doses of pyridostigmine (more than 540 mg daily) with caution, because of the:

• risk of increasing tolerance to the drug due to receptor downregulation
• greater risk of adverse effects
• possibility that a cholinergic crisis is misinterpreted as the myasthenia deteriorating.

Sustained-release pyridostigmine can be useful overnight. However, avoid this preparation during the day because its release varies and absorption is delayed. If considered appropriate, substitute sustained-release pyridostigmine for the final daily dose of the immediate-release preparation. Use:

In an intensive care setting, a parenteral cholinesterase inhibitor (eg neostigmine) can be used instead of oral pyridostigmine—neostigmine 500 micrograms intravenously is approximately equal to pyridostigmine 60 mg orally.