Physostigmine is NOT the Appropriate Drug for Myasthenia Gravis
Physostigmine is not used in the treatment of myasthenia gravis; the correct anticholinesterase agent is pyridostigmine (Mestinon), which should be started at 30 mg orally three times daily and titrated up to a maximum of 120 mg four times daily (total maximum 480 mg/day) based on symptom response. 1
Critical Distinction Between Agents
Pyridostigmine is the quaternary anticholinesterase inhibitor of choice for myasthenia gravis, while physostigmine is a tertiary amine used primarily in experimental cholinergic neuropharmacology and has no established role in myasthenia gravis management 2
The confusion likely stems from the similar names, but these are fundamentally different drugs with different indications 2
Correct Dosing Algorithm for Pyridostigmine
Initial Dosing
- Start at 30 mg orally three times daily (90 mg total daily dose) 1, 3
- Assess clinical response over 3-7 days before titrating upward 1
Dose Titration
- Increase gradually based on symptom control and tolerability 1
- Maximum dose: 120 mg orally four times daily (480 mg total daily dose) 1, 3
- Most stable patients maintain plasma levels between 20-60 ng/mL on doses ranging from 60-660 mg/day, though individual requirements vary significantly 4
Timing Considerations
- Instruct patients to time activities around medication peaks for optimal strength 1
- Sustained-release formulations can reduce dosing frequency from 4.3 to 3.6 doses daily while improving quality of life 5
Intravenous Conversion (When Oral Route Unavailable)
- 30 mg oral pyridostigmine = 1 mg IV pyridostigmine = 0.75 mg neostigmine IM 6, 3
- IV administration may be necessary in patients unable to take oral medications 6
- Bioavailability of oral pyridostigmine is only 3.6-10%, explaining the large oral-to-IV dose ratio 2, 7
Special Circumstances Requiring Dose Adjustment
Myasthenic Crisis (Grade 3-4)
- Hold pyridostigmine immediately upon intubation and mechanical ventilation 6
- The ventilator provides respiratory support, eliminating the therapeutic target while continuing pyridostigmine increases cholinergic crisis risk 6
- Focus shifts to immunomodulatory therapy: IVIG 2 g/kg over 5 days or plasmapheresis 6, 3
Reintroduction After Crisis
- Resume pyridostigmine during weaning from mechanical ventilation when spontaneous breathing efforts begin 6
- Start at lower doses (30 mg TID) and retitrate based on response 6
Perioperative Management
- Continuing pyridostigmine through the morning of surgery significantly prolongs onset time of vecuronium and increases dose requirements 8
- Omitting the morning dose increases sensitivity to non-depolarizing neuromuscular blocking agents but may cause preoperative respiratory discomfort in 43% of patients 8
- The decision depends on surgical timing and anesthetic plan, requiring coordination with anesthesiology 8
Pharmacokinetic Considerations
- Plasma elimination half-life is 30-90 minutes, but intraindividual variations during dose intervals remain small due to slow GI absorption 2, 7
- Severely impaired renal function prolongs elimination, potentially requiring dose reduction 2
- Methylcellulose completely inhibits absorption and must be avoided 2
Common Pitfalls
- Do not confuse physostigmine with pyridostigmine—they are different drugs with different indications 2
- Avoid medications that worsen myasthenia: β-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolides 1, 3
- Plasma level monitoring is not routinely necessary due to stable kinetic behavior, despite wide interpatient dose variability 7
- Exceeding 480 mg/day total dose increases cholinergic side effects without additional benefit 1