A 48-year-old woman comes to the office due to lower extremity discomfort. The patient reports no pain but describes an uncomfortable sensation in her legs, particularly in the evening and at night. The symptoms are relieved by leg movements or walking. She reports no behavioral or mood changes. The patient intermittently experiences mild migraines, and during a recent episode, antiemetic therapy worsened the leg discomfort. She has no other medical conditions and does not use tobacco, alcohol, or illicit drugs. Vital signs are within normal limits, and physical examination shows no abnormalities. Blood cell counts, serum chemistry studies, and serum iron levels are within normal limits. Pharmacotherapy with which of the following mechanisms of action is most likely to relieve this patient's symptoms?

Question

A 48-year-old woman comes to the office due to lower extremity discomfort.  The patient reports no pain but describes an uncomfortable sensation in her legs, particularly in the evening and at night.  The symptoms are relieved by leg movements or walking.  She reports no behavioral or mood changes.  The patient intermittently experiences mild migraines, and during a recent episode, antiemetic therapy worsened the leg discomfort.  She has no other medical conditions and does not use tobacco, alcohol, or illicit drugs.  Vital signs are within normal limits, and physical examination shows no abnormalities.  Blood cell counts, serum chemistry studies, and serum iron levels are within normal limits.  Pharmacotherapy with which of the following mechanisms of action is most likely to relieve this patient's symptoms?

Quizplus · Accepted Answer

11ec160b_3c19_606b_9249_f991a0c7abe5_MD0001_00 This patient with vague lower extremity discomfort and an urge to move the legs that worsens at night has typical features of restless legs syndrome (RLS). RLS is characterized by uncomfortable sensations in the legs that are often difficult to describe and associated with an urge to move the lower extremities. Symptoms are relieved with movement (eg, walking, stretching) and are typically worse at night. As a result, patients often develop sleep-onset insomnia. The pathophysiology of RLS is incompletely understood but likely involves CNS iron deficiency (even in patients with normal serum iron levels) and abnormalities in dopaminergic transmission. Certain medications, including dopamine antagonists (eg, antipsychotics, certain antiemetics [metoclopramide]), first-generation antihistamines (eg, diphenhydramine), and antidepressants (eg, selective serotonin reuptake inhibitors, mirtazapine) are associated with worsening symptoms (Choice E). Treatment includes avoidance of aggravating medications, iron replacement, and dopamine agonists (eg, ropinirole, pramipexole) which are thought to modulate CNS dopaminergic transmission and are rapidly effective in most cases. (Choice A) Beta-adrenergic antagonists (eg, propranolol) are used for treating akathisia (ie, a strong urge to move), which occurs most commonly as a side effect of dopamine antagonists (eg, antipsychotic drugs). However, akathisia is not accompanied by an unpleasant sensation in the legs and does not follow a circadian rhythm. (Choice C) Muscarinic antagonists (eg, benztropine) have been used for the treatment of dystonia, which is characterized by sustained muscle contractions usually associated with abnormal posturing (eg, torticollis). (Choice D) Opioid mu-receptor agonists (eg, codeine) are occasionally used for treating refractory RLS, but carry significant risks (eg, sedation, abuse, respiratory depression). Educational objective: Restless legs syndrome is characterized by an uncomfortable sensation in the legs accompanied by an urge to move them; symptoms worsen with inactivity and at night and are temporarily relieved with movement. Dopamine agonists (eg, pramipexole, ropinirole) are the preferred therapy for persistent symptoms. __________ References: Treatment of restless legs syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/23703310)

A 48-Year-Old Woman Comes to the Office Due to Lower