## Anticholinesterase Agents in Myasthenia Gravis **Key Point:** Neostigmine is the most commonly used anticholinesterase in myasthenia gravis (MG) because of its favorable pharmacokinetics, duration of action, and oral bioavailability. ### Comparative Profile of Anticholinesterases | Drug | Duration | Route | Clinical Use | Notes | |------|----------|-------|--------------|-------| | **Neostigmine** | 2–4 hours | Oral, IM, IV | MG (first-line) | Best oral absorption; reversible inhibitor | | Physostigmine | 30 min–2 hours | IV, IM, topical | Anticholinergic toxicity; glaucoma | Crosses BBB; shorter duration | | Edrophonium | 5–10 minutes | IV only | Diagnostic (Tensilon test) | Ultra-short acting; no oral form | | Donepezil | 24+ hours | Oral | Alzheimer disease | Irreversible; CNS penetration | ### Why Neostigmine Is Preferred in MG 1. **Oral bioavailability:** Absorbed well from the GI tract; allows convenient dosing (15–30 mg every 3–4 hours). 2. **Duration:** 2–4 hours permits 4–6 daily doses, maintaining steady anticholinergic effect. 3. **Reversible inhibition:** Safer profile with fewer cumulative toxicity risks. 4. **Muscarinic + nicotinic effects:** Addresses both skeletal muscle weakness (nicotinic) and autonomic symptoms. **Clinical Pearl:** Neostigmine is always given with an antimuscarinic (e.g., glycopyrrolate or atropine) to prevent excessive salivation, bronchospasm, and bradycardia from muscarinic overstimulation. **High-Yield:** Edrophonium (Tensilon test) is used diagnostically to confirm MG but is not suitable for chronic therapy due to its ultra-short duration and IV-only route. Physostigmine crosses the blood–brain barrier and is used for anticholinergic toxicity, not MG. Donepezil is for Alzheimer disease, not MG.
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