What is the side effect of excessive dosing of Pyridostigmine (Mestinon)?

From the Guidelines

Excessive dosing of pyridostigmine can lead to a cholinergic crisis, characterized by a range of systemic symptoms due to the accumulation of acetylcholine at muscarinic and nicotinic receptors throughout the body. The side effects of excessive dosing include gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal cramps, and increased salivation, as noted in patients with neurogenic orthostatic hypotension treated with pyridostigmine 1. Respiratory effects may include increased bronchial secretions, bronchospasm, and respiratory muscle weakness. Cardiovascular manifestations include bradycardia, hypotension, and in severe cases, cardiac arrest. Neurological symptoms include muscle fasciculations, weakness, paralysis, seizures, and confusion. Other effects include miosis, increased sweating, and urinary urgency or incontinence. These symptoms occur because pyridostigmine inhibits acetylcholinesterase, preventing the breakdown of acetylcholine and leading to its accumulation at synapses.

Key Considerations

• The medication should be immediately discontinued if a patient shows signs of cholinergic crisis, and medical attention should be sought.
• Treatment for overdose includes administration of atropine to counteract muscarinic effects and supportive care.
• Careful dosing and monitoring are essential when using pyridostigmine, particularly in patients with renal impairment as the drug is primarily excreted by the kidneys.
• Pyridostigmine may be beneficial in patients with syncope due to neurogenic OH who are refractory to other treatments, as it improves orthostatic tolerance through increases in peripheral vascular resistance and blood pressure 1.

Management of Side Effects

• Monitoring for signs of cholinergic crisis is crucial, especially in the initial stages of treatment or when adjusting the dose.
• Patients should be educated on the recognition of side effects and the importance of seeking immediate medical attention if they occur.
• The use of pyridostigmine should be tailored to the individual patient's response and tolerance, with dose adjustments made as necessary to minimize side effects while maintaining therapeutic efficacy.

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.

The side effects of excessive dosing of pyridostigmine include:

• Muscarinic side effects:
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal cramps
  • Increased peristalsis
  • Increased salivation
  • Increased bronchial secretions
  • Miosis
  • Diaphoresis
• Nicotinic side effects:
  • Muscle cramps
  • Fasciculation
  • Weakness A more severe side effect of excessive dosing is cholinergic crisis, characterized by increasing muscle weakness, which can lead to death 2.

From the Research

Side Effects of Excessive Dosing of Pyridostigmine

• The side effects of excessive dosing of pyridostigmine are related to its mechanism of action as a cholinesterase inhibitor, which can lead to an excessive amount of acetylcholine in the body 3.
• Common side effects reported by patients taking pyridostigmine include flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis 3.
• More severe side effects can occur, such as cholinergic crisis, which is characterized by parasympathetic symptoms like sweating, salivation, miosis, bradycardia, diarrhea, and circulatory and respiratory failure 4, 5.
• Cholinergic crisis is a rare but potentially life-threatening condition that can require mechanical ventilation and has a mortality rate of around 6-11% 4, 5.
• The incidence of cholinergic crisis has been estimated to be around 0.2%, and it is more common in elderly patients with underlying conditions such as cerebrovascular disease 4.

Risk Factors and Treatment

• Patients who require mechanical ventilation, catecholamines, or atropine due to cholinergic crisis have a poorer prognosis and longer hospital stays 5.
• The treatment of cholinergic crisis typically involves the administration of atropine and other supportive measures, such as mechanical ventilation if necessary 4, 5.
• It is essential to monitor patients taking pyridostigmine for signs of cholinergic crisis and to adjust the dosage accordingly to minimize the risk of this adverse reaction 3.