A 62-year-old man with hypertension and stage 3 chronic kidney disease comes to the office due to poor sleep. The patient describes a crawling sensation in his legs about 15-20 minutes after getting into bed at night. Walking and pacing or wiggling his legs alleviates the symptoms, but they return when he gets back in bed. Physical examination shows no lower extremity sensory or motor abnormalities. The first-line pharmacotherapy for this patient's condition targets a receptor for which of the following substances?

Question

A 62-year-old man with hypertension and stage 3 chronic kidney disease comes to the office due to poor sleep.  The patient describes a crawling sensation in his legs about 15-20 minutes after getting into bed at night.  Walking and pacing or wiggling his legs alleviates the symptoms, but they return when he gets back in bed.  Physical examination shows no lower extremity sensory or motor abnormalities.  The first-line pharmacotherapy for this patient's condition targets a receptor for which of the following substances?

Quizplus · Accepted Answer

11ec25c8_d5c8_661e_bc81_e3d82687eea4_MD0003_00 This patient likely has restless legs syndrome (RLS), a neurologic condition that can interfere with duration and quality of sleep. RLS is characterized by dysesthesias (eg, crawling and itching feelings) and irresistible urges to move the legs when at rest. Symptoms occur primarily in the evenings and at night; they are partially relieved by movement. RLS does not cause pain or symptoms of peripheral neuropathy (eg, numbness, sensory deficits). It is classified as primary (idiopathic) or secondary (if accompanied by an associated chronic disease, like chronic kidney disease in this patient). RLS appears to be associated with central and peripheral nervous system changes. In the CNS, impaired iron use and dopaminergic systems (located close to the circadian control centers) may play a role; peripherally, hyperalgesia is partly mediated by A-delta fiber input. Therefore, patients with iron deficiency or even low to normal ferritin levels (≤75 µg/L) should take supplemental iron. If additional pharmacotherapy is required, dopamine agonists (eg, pramipexole, ropinirole) or alpha-2-delta calcium channel ligands (eg, gabapentin) are often effective. (Choice A) Acetylcholine dysregulation may be a mechanism of some insomnias, especially types characterized by sleep-onset difficulty. Dual orexin receptor antagonist medications (eg, lemborexant) can help. However, this patient's trouble falling asleep is related to discomfort in the legs and the urge to move them, which is more consistent with RLS. (Choice C) Benzodiazepines bind to gamma-aminobutyric acid (GABA) receptors and enhance the inhibitory effect of GABA, leading to muscle relaxation. Although benzodiazepines can be effective for RLS, the risk for sedation, tolerance, and potential abuse make other medications safer choices. Gabapentin, which is used in RLS, has an effect on GABA activity but does not directly target GABA receptors. (Choice D) Serotonin and norepinephrine reuptake inhibitors (eg, duloxetine) can treat neuropathic pain (eg, peripheral neuropathy) by increasing levels of norepinephrine in the central synapses, modulating the descending pain pathway. Although peripheral neuropathy can cause discomfort in the feet, this patient's nocturnal symptoms, relief with walking, and normal neurologic examination make RLS more likely. (Choice E) Selective serotonin reuptake inhibitors (eg, fluoxetine) are commonly used to treat depression, which can cause sleep disturbances. However, this patient's nocturnal symptoms, urge to move the legs, and temporary relief with walking make RLS more likely. Educational objective: Restless legs syndrome is a neurologic condition that can interfere with the quality and duration of sleep. It is characterized by an urge to move the legs, with discomfort that is temporarily relieved by movement. Dopamine agonists (eg, pramipexole) are often effective. References: The long-term treatment of restless legs syndrome/Willis-Ekbom disease: evidence-based guidelines and clinical consensus best practice guidance: a report from the International Restless Legs Syndrome Study Group. (http://www.ncbi.nlm.nih.gov/pubmed/23859128)

A 62-Year-Old Man with Hypertension and Stage 3 Chronic Kidney