Myasthenia Gravis

Mestinon^® (pyridostigmine bromide) is a cholinesterase inhibitor that is administered orally.¹ It prevents the acetylcholine neurotransmitter from being hydrolyzed in the synaptic cleft, thereby increasing the number of interactions between acetylcholine and the acetylcholine receptor in the neuromuscular junction. Pyridostigmine does not penetrate the blood-brain barrier, minimizing damage to the central nervous system, and it can be slightly beneficial in ocular and generalized myasthenia gravis (MG).² Mestinon comes in the following formulations: an oral solution containing 60 mg of pyridostigmine bromide per teaspoon in a medium comprising 5% alcohol, glycerin, lactic acid, sodium benzoate, sorbitol, sucrose, flavors, and water; tablets containing 60 mg of pyridostigmine bromide, lactose, silicon dioxide, and stearic acid; and Timespan^® tablets containing 180 mg of pyridostigmine bromide as well as carnauba wax, corn-derived proteins, isopropyl alcohol, magnesium stearate, silica gel, tribasic calcium phosphate, and water.¹ Pyridostigmine was first approved by the US Food and Drug Administration (FDA) as an oral tablet on April 6, 1955.³ 

Get full prescribing information about Mestinon at MPR.com

Indication in Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder in which autoantibodies against acetylcholine receptors (AChR), muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin cause dysfunction at the neuromuscular junction. AChRs are directly bound and cross-linked by AChR antibodies, limiting acetylcholine binding and leading to receptor degradation through multiple processes. Loss of muscle tone, weakness, and fatigue can result from a lack of acetylcholine signaling.³ Mestinon was created more than 50 years ago when there were no clinical trials. Most of the evidence for its efficacy stems from retrospective studies and clinical experience. All MG forms are treated with this medicine as a first-line treatment. Mestinon is also regarded as a long-term treatment for people with generalized, nonprogressive, and mild MG, as well as an add-on treatment for those with severe disease who are also on immunosuppressant medications. Nevertheless, it produces only limited and temporary improvements, similar to other acetylcholinesterase inhibitors, with many patients requiring additional immunosuppressant treatments.⁴ 

Mechanism of Action

Pyridostigmine is a reversible acetylcholinesterase inhibitor that prevents acetylcholinesterase from breaking down extracellular acetylcholine in the neuromuscular junction, thus leading to increased levels. Greater levels of acetylcholine result in higher neuronal transmission across the neuromuscular junction, which reduces MG symptoms significantly.

Besides its use in MG and the reversal of neuromuscular blocks, pyridostigmine is a prevalent first-line treatment in congenital myasthenic syndrome (CMS). CMS presents similarly to MG but has different underlying factors, and pyridostigmine is typically helpful. Treatment with pyridostigmine can be harmful in some subgroups, however; comprehensive genetic evaluation is critical before initiating medication.³ 

Warnings, Precautions, and Adverse Reactions

Mestinon should be taken with caution in patients with bronchial asthma.The drug is contraindicated in cases of mechanical intestinal or urinary obstruction.⁵ 

Like all cholinergic medications, Mestinon overdose can cause cholinergic crisis, a syndrome marked by progressive muscular weakening that can cause death if the respiratory muscles are involved. In this scenario, all cholinergic medicines must be stopped as soon as possible. The immediate administration of atropine in cholinergic crises is also suggested. In addition, atropine can be used to reduce or eliminate gastrointestinal side effects or other muscarinic reactions; however, because it masks symptoms of overdose, it may inadvertently cause cholinergic crises.¹

Pyridostigmine is mainly eliminated in its natural state through the kidneys. As a result, low doses are preferred in patients with renal disease, and treatment is administered by dosing to effect. Overdose is the most common cause of Mestinon side effects, which are divided into 2 types: muscarinic and nicotinic. Muscarinic side effects include nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, hypersalivation, increased bronchial secretions, miosis, and diaphoresis. Muscle cramps, weakness, and fasciculations are the most common nicotinic adverse effects. A skin rash may occur in some patients, as this compound contains a bromide radical. When Mestinon is stopped, these reactions generally disappear.⁵ 

References

1. Mestinon. Prescribing information. ICN Pharmaceuticals, Inc.; 2001. Accessed February 15, 2022. 
2. Farmakidis C, Pasnoor M, Dimachkie MM, Barohn RJ. Treatment of myasthenia gravis. Neurol Clin. 2018;36(2):311-337. doi:10.1016/j.ncl.2018.01.011
3. Pyridostigmine. DrugBank Online. June 13, 2005. Updated February 15, 2022. Accessed February 15, 2022. 
4. Mestinon (pyridostigmine). Myasthenia Gravis News. Updated January 20, 2022. Accessed February 15, 2022. 
5. Mestinon- pyridostigmine bromide solution, Mestinon- pyridostigmine bromide tablet, Mestinon- pyridostigmine bromide tablet, extended release. DailyMed. Updated December 2, 2020. Accessed February 15, 2022.

Reviewed by Hasan Avcu, MD, on 2/22/2022.

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Harshi Dhingra, MD

Harshi Dhingra is a licensed medical doctor with specialization in Pathology. She is currently employed as faculty in a medical school with a tertiary care hospital and research center in India. Dr. Dhingra has over a decade of experience in diagnostic, clinical, research, and teaching work, and has written several publications and citations in indexed peer reviewed journals. She holds medical degrees for MBBS and an MD in Pathology.