Anticholinesterase Drugs Beyond Pyridostigmine
The FDA-approved anticholinesterase drugs include donepezil, galantamine, rivastigmine, tacrine (for dementia), neostigmine, edrophonium, and physostigmine, with additional agents like metrifonate, velnacrine, and eptastigmine mentioned in clinical literature. 1
FDA-Approved Cholinesterase Inhibitors for Dementia
The following four drugs are FDA-approved for managing Alzheimer disease and related dementias 1:
- Donepezil - Shows consistent effects in cognition and global assessment with small effect sizes, primarily gastrointestinal adverse events 1
- Galantamine - Demonstrates similar efficacy profile to other cholinesterase inhibitors with no significant differences in head-to-head comparisons 1
- Rivastigmine - Provides benefit in cognition and activities of daily living, with gastrointestinal side effects consistent with this drug class 1
- Tacrine - Less consistent evidence for cognitive benefit, high withdrawal rates due to adverse events, and potential for liver damage make it less well-tolerated; largely obsolete in clinical practice 1
Anticholinesterase Drugs for Neuromuscular Conditions
Reversible Quaternary Cholinesterase Inhibitors
- Neostigmine - A reversible anticholinesterase structurally related to pyridostigmine but with shorter duration of action and more gastrointestinal side effects; used to antagonize non-depolarizing neuromuscular blockade and treat myasthenia gravis 2, 3
- Edrophonium - An anticholinesterase with rapid onset (30-60 seconds) and short duration (average 10 minutes); primarily used for diagnostic testing in myasthenia gravis 4, 5
Tertiary Reversible Cholinesterase Inhibitor
- Physostigmine - A tertiary amine that crosses the blood-brain barrier, characterized by a short plasma elimination half-life of 20-30 minutes; important in experimental cholinergic neuropharmacology 1, 3
Additional Cholinesterase Inhibitors Mentioned in Clinical Literature
The following agents have been studied but are not commonly used in current practice 1:
- Metrifonate - Evaluated in dementia trials but not FDA-approved
- Velnacrine - Studied for dementia treatment
- Eptastigmine - Investigated in cholinesterase inhibitor trials
Key Pharmacokinetic Distinctions
Pyridostigmine differs from neostigmine in having longer duration of action and fewer gastrointestinal side effects, making it the preferred agent for chronic myasthenia gravis treatment. 2
- Plasma clearances of reversible quaternary cholinesterase inhibitors range from 0.5 to 1.0 L/h/kg with elimination half-lives of 30-90 minutes 3
- Oral bioavailability is low: pyridostigmine approximately 10%, neostigmine even lower 3
- All quaternary agents have poor blood-brain barrier penetration under normal conditions due to their positive charge 6
Clinical Considerations
Important caveat: Severely impaired renal function prolongs elimination of neostigmine and pyridostigmine, requiring dose adjustments 3. All cholinesterase inhibitors can prolong neuromuscular blockade with succinylcholine and mivacurium due to reduced plasma cholinesterase activity 7.