What is the mechanism of action of Mestinon (Pyridostigmine)?

From the Guidelines

Mestinon (pyridostigmine bromide) is a medication that treats myasthenia gravis and other neuromuscular disorders by inhibiting the enzyme acetylcholinesterase, allowing acetylcholine to accumulate at the neuromuscular junction and enhancing communication between nerves and muscles to improve muscle strength. The mechanism of action of Mestinon involves blocking the breakdown of acetylcholine, a neurotransmitter essential for muscle contraction, thereby increasing its concentration and effectiveness at the neuromuscular junction 1.

Key Points

• Mestinon works by inhibiting acetylcholinesterase, the enzyme responsible for breaking down acetylcholine, thus allowing acetylcholine to accumulate and enhance muscle contraction.
• The typical dosing of Mestinon ranges from 30-60mg every 3-4 hours while awake, adjusted based on symptom control, as seen in the management of myasthenia gravis 1.
• Common side effects of Mestinon include gastrointestinal issues like nausea, vomiting, diarrhea, and increased salivation, which should be monitored and managed appropriately.
• Patients should take Mestinon as prescribed and maintain consistent timing between doses for optimal symptom management, with dosage adjustments made as necessary based on symptom control and side effects.

Clinical Considerations

• In the context of immune-related adverse events, such as those associated with immune checkpoint inhibitor therapy, Mestinon may be used to manage myasthenia gravis, with dosing starting at 30 mg PO three times a day and gradually increasing as tolerated and based on symptoms 1.
• The management of myasthenia gravis and other neuromuscular disorders with Mestinon requires careful monitoring and adjustment of dosage to balance efficacy and side effects, with consideration of the patient's overall clinical condition and response to treatment 1.

From the FDA Drug Label

Pyridostigmine bromide inhibits the destruction of acetylcholine by cholinesterase and thereby permits freer transmission of nerve impulses across the neuromuscular junction. The mechanism of action of Mestinon (Pyridostigmine) is inhibition of acetylcholine destruction by cholinesterase, allowing for increased transmission of nerve impulses across the neuromuscular junction 2.

• Key points:
  • Inhibits cholinesterase
  • Increases acetylcholine availability
  • Enhances neuromuscular transmission

From the Research

Mechanism of Action of Mestinon (Pyridostigmine)

• Mestinon, also known as Pyridostigmine, is a medication used to treat myasthenia gravis, a chronic autoimmune disorder of the neuromuscular junction 3.
• Pyridostigmine works as an acetylcholinesterase (AChE) inhibitor, which means it prevents the breakdown of acetylcholine, a neurotransmitter that plays a key role in muscle contraction 3, 4.
• By inhibiting the breakdown of acetylcholine, pyridostigmine increases the amount of acetylcholine available to bind to nicotinic acetylcholine receptors at the neuromuscular junction, thereby improving muscle strength and function in patients with myasthenia gravis 3, 5.
• The use of pyridostigmine has been shown to provide partial benefit in relieving the symptoms of myasthenia gravis, although most patients eventually switch to long-term immunosuppressive therapies 3.

Effects of Pyridostigmine on the Body

• Pyridostigmine can cause a range of side effects, including flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis 6.
• The medication can also cause more serious side effects, such as bradycardia and syncope, which can be treated with muscarinic antagonists like hyoscyamine 7.
• Pyridostigmine can interact with other medications, such as vecuronium, a non-depolarizing muscle relaxant, which can affect its efficacy and onset time 5.

Clinical Use of Pyridostigmine

• Pyridostigmine is commonly used as a first-line therapy for myasthenia gravis, and is suitable for long-term treatment in patients with generalized non-progressive milder disease 3.
• The medication can be used in conjunction with other therapies, such as immunosuppressive agents, to manage the symptoms of myasthenia gravis 3, 4.
• The use of sustained-release pyridostigmine has been shown to improve quality of life and reduce the number of daily doses required, although it can also cause adverse reactions 4.