Restless Legs syndrome def (RLS)
unpleasant sensations in the legs accompanied by involuntary urges to move them. Sometime the arms or other parts of the body are also affected.
Secondary RLS (5)
1. Iron Deficiency 2. preggos 3. ESRD 4. Peripheral neuropathy 5. Drug-induced
drug-induced CAUSES of RLS (4)
1. dopamine-blocking agents (AP, Antiemetics - metoclopramide) 2. Antidepressants (TCAs, SSRI's) 3. Antihistamines (diphenhydramine) 4. Common stimulants/depressants (caffeine, alcohol, nicotine)
genetic link - familial RLS
3-5x first degree relatives >50% have affected family members
dopamine and RLS
normal : affects basal ganglia motor loopregulates how brain controls MOVEMENT dysfunction (dopamine in brain) : decreased D2 receptor binding and decreased dopaminergic transmission
clinical presentation of RLS (4)
"creepy, crawly" in lower legs 1. bilateral/symmetrical 2. occurs at rest 3. irresistible urge to move - relieve with movement 4. timing - late evening "night-walker's syndrome"
t/f pain is always presentTrue False
false. pain MAY be present
t/f no objective labs for RLSTrue False
true. rule out secondary causes physical exam usually NORMAL
secondary causes RLS
serum ferritin, total iron-binding capacity preggo? serum creatinine, BUN
diagnostic criteria for RLS (4)
1. urge to move b/c unpleasant sensations in legs 2. urge to move worsens at rest or inactivity 3. urge to move relieved by movement 4. urge to move worse at night/evening
Tx primary cause: iron deficiency anemia
serum ferritin < 20 mcg/mL <45-50 mcg/mL - associated with increased RLS severity so treat with oral iron supplementation - common : ferrous sulfate 325 mg + vitamin 250-500 mg TID
GOAL for treating iron deficiency anemia
ferritin >50 mcg/mL Tstat > 20%
nonpharm for RLS (4)
1. behavioral - d/c aggravating factors : meds, alcohol, nicotine, caffeine - improve sleep hygiene 2. exercises 3. massages 4. hot baths
4 pharmacological tx for RLS
1. Dopaminergics 2. anticonvulsants 3. benzodiazepines 4. opioids
first-line therapy for RLS
dopaminergic -mild or intermittent (not responsive to nonpharm) -mode-severe (persistant nightly sx)
augmentation of dopaminergic agents for RLS
progressive worsening after initial improvement -6-18 months after initiation d/c meds and substitute
dopaminergic for RLS: Sinemet (carbidopa/levodopa)
place in therapy : INTERMITTENT USElevodopa : increases dopamine levels in the braincarbidopa : decar boxylase inhibitor, inhibits peripheral breakdown of levodopa, doesn't cross BBBadminister : orally PRN or scheduled
AE: Sinemet (Carbidopa/levodopa)
N/D, dyspepsia, orthostatic HYPO tension, h/a augmentation - highest 50-85% PK : short-half-life dose more times
dopaminergic for RLS: pramipexole (Mirapex), ropinirole (Requip)
FDA approved place in therapy : Mode/severe sx. FIRST LINE IN PERSISTENT/NIGHTLY SxMOA : nonergot dopamine agonists-bind to dopamine receptors, producing dopamine-like effects
dosage/administration pramipexole (Mirapex), ropinirole (Requip)
dose bedtime
AE: pramipexole (Mirapex), Ropinirole (Requip)
nausea, somnolence, HYPO tension, dizziness, pedal edema (dose dependent) augmentation - less likely 20-30% PK : longer half-life than levodopa
dopaminergic for RLS: rotigotine transdermal system (Neupro)
place in therapy : moderate/severe primary RLSFDA approved
AE: rotigotine (Neupro)
application site reactions, nausea, somnolence, h/a
anticonvulsants for RLS: Gabapentin enacarbil (Horizant)
place in therapy : moderate to severe - adultsFIRST-LINE : painful, combo with peripheral neuropathyFDA approved PRODRUG to gabapentin longer acting better absorbed, costly, no evidence though
Gabapentin enacarbil (Horizant) administration
NOT 1:1 with regular gabapentin (100-300 mg) so no sub oral 600 mg QD (no increase needed) RENALLY ADJUSTED
AE: gabapentin enacarbil (Horizant)
somnolence, dizziness watch out for elderly, renal impairment
benzodiazepines for RLS:
place in therapy : alt tx to levodopa with mild-intermittent sx, add on in severe, poor sleepmixed results improve sleep clonazepam 0.5-2 mg (long half-life) administration : oral before bedtime
AE: benzodiazepines
sedation, daytime somnolence
opioids for RLS: tramadol, propoxyphene, hydrocodone, oxycodone, codeine, methadone
place in therapy : painful/refractory RLS, relieve pain, motor restlessness, sleep disturbancesadministration : prior to bedtimeQD - TID on timing of sx
AE: opioids
respiratory depression, sedation, constipation
