What is the likely cause of increased muscle weakness in a patient with myasthenia gravis treated with neostigmine?

The correct answer, indicating desensitization of nicotinic receptors, highlights a key mechanism in the context of myasthenia gravis (MG) therapy. Myasthenia gravis is an autoimmune condition characterized by antibodies attacking nicotinic acetylcholine receptors at the neuromuscular junction, leading to muscle weakness.

Neostigmine is a cholinesterase inhibitor that increases the amount of acetylcholine in the synaptic cleft by preventing its breakdown. While this increase initially helps improve muscle strength by enhancing stimulation at the neuromuscular junction, chronic stimulation can result in desensitization of the nicotinic receptors. With ongoing exposure to high levels of acetylcholine, these receptors may become less responsive to acetylcholine binding, reducing their efficacy and contributing to increased muscle weakness in the patient.

This phenomenon can occur particularly in the setting of myasthenia gravis, where the surface density of functional nicotinic receptors is already compromised due to the autoimmune process. Therefore, despite higher acetylcholine levels, the increased stimulation from neostigmine can lead to diminished muscle contraction as a result of receptor desensitization.

Understanding this mechanism is vital for managing patients with myas