Review Question - QID 108922

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Cholinomimetic Agents Indirect Agonists (Cholinesterase Inhibitors) Indirect Agonist Uses Notes Physostigmine • Glaucoma• Atropine overdose or Atropa belladonna (deadly nightshade) ingestion • CNS penetration• Absorbs well on all bodily surfaces Neostigmine • Postoperative and neurogenic ileus an QID: 108922 (M1.PH.17.4756)

QID 108922 (Type "108922" in App Search)

A 25-year-old female presents to her primary care physician complaining of double vision. She first started seeing double after a long day at her work as a radiation technologist. Since then, her vision has appeared to worsen in the evenings. She has also felt worsening fatigue despite no change in her work hours or sleep habits. She has a history of type I diabetes mellitus and her most recent hemoglobin A1c was 7.4%. Her family history is notable for Sjogren’s syndrome in her mother and hypertension, hyperlipidemia, and carotid dissection in her father. Her temperature is 98.9°F (37.2°C), blood pressure is 105/70 mmHg, pulse is 75/min, and respirations are 16/min. On examination, her pupils are equally round and reactive to light. Extraocular movements are intact. Mild ptosis is noted bilaterally but worse on the left. A visual acuity test reveals no abnormalities. Which of the following medications is most appropriate in the management of this patient?

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Pyridostigmine

52%

99/190

Physostigmine

19%

37/190

Edrophonium

13/190

Hydrocortisone

2/190

Azathioprine

10/190

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The patient in this vignette presents with bilateral ptosis and diplopia that worsens with use suggestive of myasthenia gravis (MG). Pyridostigmine is an acetylcholinesterase inhibitor that is used in the treatment of MG to increase synaptic acetylcholine concentrations.

MG is an autoimmune disorder caused by a type II hypersensitivity reaction against the acetylcholine receptor on the neuromuscular endplate. This leads to progressive weakness that gets worse with use because fewer acetylcholine molecules will be available for release to overcome the receptor blockade. The first-line treatment in the management of myasthenia gravis is pyridostigmine. Pyridostigmine is an acetylcholinesterase inhibitor that impairs the ability of acetylcholinesterase to break down acetylcholine, thereby increasing synaptic acetylcholine levels for better signal transduction across the neuromuscular endplate. Pyridostigmine is preferred over other acetylcholinesterase inhibitors because it is very long-acting and does not penetrate the central nervous system.

Incorrect Answers:
Answer 2: Physostigmine is an acetylcholinesterase inhibitor that is used to treat glaucoma, delayed gastric emptying, and anticholinergic poisoning. Unlike pyridostigmine, physostigmine crosses the blood-brain barrier so it is less commonly used to treat MG.

Answer 3: Edrophonium is a very short-acting acetylcholinesterase inhibitor. Its primary use is to aid in the diagnosis of MG. Given its short half-life, it is ideal for diagnostic purposes to assess for symptomatic improvement but is not ideal as a long-term treatment modality.

Answer 4: Hydrocortisone is a corticosteroid. Corticosteroids are sometimes used in the management of refractory MG along with immunomodulatory agents. However, they are not used as a first-line agent except in very severe cases. The patient in this question should likely be started on pyridostigmine and have her response assessed before considering additional medications.

Answer 5: Azathioprine is an immunomodulatory agent that is used in the management of refractory MG along with corticosteroids. However, it is not used as a first-line agent given the significant toxicity profile of azathioprine.

Bullet Summary:
Pyridostigmine is a long-acting acetylcholinesterase inhibitor that is used to treat myasthenia gravis.

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