What are the effects of Pyridostigmine (Mestinon)?

From the Guidelines

Pyridostigmine bromide is the first line of treatment for myasthenia gravis, administered orally two to four times a day, as stated in the 2024 study 1. The effects of pyridostigmine are primarily focused on improving muscle strength and tone, particularly in patients with myasthenia gravis.

• Typical dosing ranges from 30-60mg orally every 3-4 hours while awake, adjusted based on symptom control.
• Common side effects result from increased cholinergic activity and include gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal cramps), increased salivation, sweating, and bronchial secretions.
• More severe effects can include bradycardia and hypotension.
• The medication should be used cautiously in patients with asthma, cardiac arrhythmias, or intestinal obstruction.
• Pyridostigmine has a relatively short duration of action (3-6 hours), which allows for flexible dosing but requires multiple daily administrations for continuous symptom control.
• Patients should be monitored for both undertreatment (persistent weakness) and overtreatment (cholinergic crisis), especially when beginning therapy or adjusting doses. It's also worth noting that pyridostigmine may be beneficial in patients with syncope due to neurogenic orthostatic hypotension (OH) who are refractory to other treatments, as mentioned in the 2017 study 1.
• In patients with autonomic failure and neurogenic OH, pyridostigmine is able to improve orthostatic tolerance through increases in peripheral vascular resistance and blood pressure. However, the most recent and highest quality study 1 prioritizes its use in myasthenia gravis, highlighting its role as a first-line treatment.
• About half of patients with strabismus-associated myasthenia show minimal response to pyridostigmine, whereas about 66% to 85% of patients show a positive response to corticosteroids.

From the FDA Drug Label

Although failure of patients to show clinical improvement may reflect underdosage, it can also be indicative of overdosage. As is true of all cholinergic drugs, overdosage of pyridostigmine bromide may result in cholinergic crisis, a state characterized by increasing muscle weakness which, through involvement of the muscles of respiration, may lead to death The side effects of pyridostigmine bromide are most commonly related to overdosage and generally are of two varieties, muscarinic and nicotinic. Among those in the former group are nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis and diaphoresis Nicotinic side effects are comprised chiefly of muscle cramps, fasciculation and weakness. Pyridostigmine bromide inhibits the destruction of acetylcholine by cholinesterase and thereby permits freer transmission of nerve impulses across the neuromuscular junction.

The effects of pyridostigmine include:

• Muscarinic side effects: nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis, and diaphoresis
• Nicotinic side effects: muscle cramps, fasciculation, and weakness
• Cholinergic crisis: a state characterized by increasing muscle weakness, which can lead to death 2 Pyridostigmine can also cause gastrointestinal side effects and muscarinic reactions, which can be abolished or obtund by atropine, but this can lead to inadvertent induction of cholinergic crisis 2 2.

From the Research

Pyridostigmine Effects

• Pyridostigmine is the most commonly used drug in the symptomatic treatment of myasthenia gravis (MG) 3.
• The effectiveness of pyridostigmine in treating MG has been reported, with patients showing a median effectiveness of 60 and a net benefit of 65 3.
• Common side effects of pyridostigmine include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis, with 91% of patients currently using pyridostigmine reporting side effects 3.
• Sustained-release pyridostigmine bromide has been shown to improve quality of life parameters and reduce the number of daily doses, with significant improvements in total quantified myasthenia gravis (QMG) score and health status valued by EuroQoL questionnaire 4.
• Pyridostigmine is generally considered safe and suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy 5.

Pyridostigmine in Myasthenic Crisis

• Current guidelines recommend discontinuation of pyridostigmine during myasthenic crisis, but some studies suggest that continuous intravenous infusion of pyridostigmine or neostigmine can be a substitute for intravenous immunoglobulin or plasmapheresis if these are not available 6.
• Administration of acetylcholinesterase inhibitor in myasthenic crisis has been shown to improve clinical outcomes, but caution should be observed due to possible complications such as cardiac arrhythmia and pneumonia 6.

Treatment of Myasthenia Gravis

• Symptom control with acetylcholinesterase inhibitors such as pyridostigmine is commonly employed, and may be sufficient in mild disease 7.
• Corticosteroids are the mainstay of immunosuppressive treatment in patients with more than mild MG, and immunosuppressive therapies such as azathioprine are prescribed in addition to or instead of corticosteroids when necessary 7.
• Novel therapies are being developed and trialed, including ones that inhibit complement-induced immunological pathways or interfere with antibody-recycling pathways 7.