What are the side effects and contraindications of pyridostigmine?

Pyridostigmine Side Effects and Contraindications

Pyridostigmine is contraindicated in mechanical intestinal or urinary obstruction and requires particular caution in patients with bronchial asthma. 1

Absolute Contraindications

• Mechanical intestinal obstruction 1
• Mechanical urinary obstruction 1

Relative Contraindications and Cautions

• Bronchial asthma - requires particular caution due to increased bronchial secretions 1
• Cardiac disease - pyridostigmine can precipitate myocardial infarction through coronary vasospasm or arrhythmogenic effects, particularly in elderly females 2

Side Effects

Muscarinic Side Effects (Most Common)

These effects result from excess acetylcholine at muscarinic receptors and are typically dose-related:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, flatulence 1, 3
• Urinary: Urinary urgency and frequency 3
• Respiratory: Increased bronchial secretions 1
• Ocular: Miosis (pupil constriction), blurred vision 1, 3
• Dermatologic: Diaphoresis (excessive sweating), hyperhidrosis 1, 3
• Salivary: Increased salivation 1

In a large cross-sectional study of 410 myasthenia gravis patients, 91% of those currently using pyridostigmine reported side effects, with flatulence, urinary urgency, muscle cramps, blurred vision, and hyperhidrosis being most frequent. 3

Nicotinic Side Effects

These effects result from excess acetylcholine at nicotinic receptors:

• Muscle cramps 1, 3
• Fasciculations (muscle twitching) 1, 3
• Muscle weakness (paradoxically, from overstimulation) 1

Serious Adverse Effects

• Myocardial infarction - can occur through coronary vasospasm or arrhythmogenic mechanisms, especially in elderly patients 2
• Cardiac arrhythmias - due to effects on cardiac conduction 2
• Bromide rash - occasional allergic skin reaction that subsides upon discontinuation 1

Central Nervous System Effects (When Blood-Brain Barrier Disrupted)

• Enhanced cortical excitability 4
• Potential for seizure activity through muscarinic-dependent enhancement of excitatory transmission 4

Clinical Management of Side Effects

Counteracting Muscarinic Side Effects

• Atropine can counteract muscarinic side effects but must be used with caution - excessive atropine use can mask signs of cholinergic crisis and worsen myasthenia gravis symptoms 1

Discontinuation Considerations

Among patients who discontinued pyridostigmine, 26% cited side effects as the primary reason, with diarrhea, abdominal cramps, and muscle twitching being the most common causes for discontinuation. 3

Medications to Avoid During Pyridostigmine Treatment

When treating myasthenia gravis patients on pyridostigmine, strictly avoid medications that worsen myasthenic symptoms:

• β-blockers 5, 6
• Intravenous magnesium 5, 6
• Fluoroquinolone antibiotics 5, 6
• Aminoglycoside antibiotics 5, 6
• Macrolide antibiotics 5, 6

Dosing and Side Effect Profile

Standard dosing begins at 30 mg orally three times daily, gradually increasing to a maximum of 120 mg four times daily (480 mg total daily) based on symptom response and tolerability. 5 The median effectiveness reported by patients is 60% (IQR 28-78) with a net benefit of 65% (IQR 45-84), indicating that despite high side effect prevalence, most patients find the medication beneficial overall. 3

Special Populations

Elderly females appear at higher risk for cardiac complications, including myocardial infarction, when starting pyridostigmine therapy. 2 Consider baseline cardiac evaluation in this population before initiating treatment.