Review Question - QID 216731

This patient with myasthenia gravis who presents with increasing weakness after administration of edrophonium most likely has weakness due to a supratherapeutic level of pyridostigmine. The dose of this medication should therefore be decreased.

Acetylcholinesterase inhibitors such as pyridostigmine are first-line agents in the management of symptomatic myasthenia gravis. These medications function by inhibiting the degradation of acetylcholine in the synaptic cleft so that increased levels of acetylcholine can trigger depolarization of muscle endplates. Supratherapeutic levels of pyridostigmine can occur and would cause abdominal cramping, diarrhea, bradycardia, sweating, and bronchial secretion. Furthermore, patients may experience weakness because excessively high levels of acetylcholine would result in depolarizing blockade of synaptic transmission. Edrophonium is a short-acting acetylcholinesterase inhibitor that can be used to test whether the levels of medication are too high or too low. If weakness improves with edrophonium then the medication level should be increased and if weakness gets worse with edrophonium then the medication level should be decreased.

Naji and Owens discuss the mechanism of action of edrophonium. They also present how it can be used in patients with myasthenia gravis both for diagnostic and monitoring purposes.

Incorrect Answers:
Answer 1: An interaction between medications is incorrect because lisinopril does not significantly alter the levels of circulating pyridostigmine.

Answer 3: Increasing the medication dose is incorrect because the patient's weakness became worse with the administration of edrophonium. If the patient's treatment level was subtherapeutic then the administration of edrophonium would lead to improvement of weakness.

Answer 4: Progression of his disease would not explain his symptoms because worsening of myasthenia gravis would require a dosage increase in pyridostigmine. Patients who are inadequately treated with acetylcholinesterase inhibitors would have improvement of weakness with the administration of edrophonium.

Answer 5: Having the wrong diagnosis may explain why acetylcholinesterase inhibitors do not help in cases of weakness because other diseases such as Guillain Barre syndrome and Lambert Eaton myasthenia can be similar in presentation. This patient has a known diagnosis that was previously responding well to treatment.

Bullet Summary:
Edrophonium is a short-acting acetylcholinesterase inhibitor that can be administered in order to determine whether treatment with pyridostigmine is sub or supratherapeutic.