Edrophonium is the only cholinesterase inhibitor that ophthalmologists administer in a dose high enough to work as an indirect-acting nicotinic agonist. Edrophonium is a shortacting competitive inhibitor of acetylcholinesterase that binds to the enzyme’s active site but does not form a covalent link with it. It is used in the diagnosis of myasthenia gravis, a neuromuscular disease caused by autoimmunity to acetylcholine receptors (nicotinic receptors) in the neuromuscular junction and characterized by muscle weakness and marked fatigability of skeletal muscles. This disease may manifest primarily as ptosis and diplopia. In patients with myasthenia gravis, the inhibition of acetylcholinesterase by edrophonium allows acetylcholine released into the synaptic cleft to accumulate to levels that can act through the reduced number of acetylcholine receptors. Because edrophonium also augments muscarinic transmission, muscarinic adverse effects (vomiting, diarrhea, urination, and bradycardia) may occur unless 0.4–0.6 mg of atropine is co-administered intravenously (see BCSC Section 5, Neuro-Ophthalmology).
Another drug used in the diagnosis of myasthenia gravis is neostigmine methylsulfate, a longer-acting intramuscular drug. The longer duration of activity allows the examiner to assess specific complex endpoints, such as orthoptic measurements.
Nicotinic antagonists are neuromuscular blocking agents that facilitate intubation for general anesthesia (Table 16-6). There are 2 types of nicotinic antagonists:
nondepolarizing agents, including curare-like drugs such as rocuronium, vecuronium, gallamine, and pancuronium, which bind competitively to nicotinic receptors on striated muscle but do not cause contraction
depolarizing agents, such as succinylcholine and decamethonium, which bind competitively to nicotinic receptors and cause initial receptor depolarization and muscle contraction
In singly innervated (en plaque) muscle fibers, depolarization and contraction are followed by prolonged unresponsiveness and flaccidity. However, depolarizing agents produce sustained contractions of multiply innervated fibers, which make up one-fifth of the muscle fibers of extraocular muscles. Such contractions of extraocular muscles (a nicotinic agonist action) exert force on the globe.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.