Saturday, May 13, 2017

Treatment of restless leg syndrome mnemonic + notes


This is a loooooong post on the treatment of restless leg syndrome. (Bear with me!)

Those who are just here for the mnemonic 

Restless leg syndrome treatment mnemonic:
(slang alert!) Restless people are DIC*s
D: Dopamine agonists
I: Iron supplementation
C: Alpha-2-delta calcium channel ligands
C: Conservative management

(A non vulgar mnemonic would be "ACID" but I don't know how you would tie in to the restless leg syndrome... Throw acid on restless legs to stop them from moving? :P)
A: Alpha-2-delta calcium channel ligands
C: Conservative management
I: Iron supplementation
D: Dopamine agonists

What is restless leg syndrome?
Restless legs syndrome (RLS) is a sensorimotor disorder characterised by an urge to move the limbs which is usually associated with unpleasant sensations. Symptoms are worse during rest, in the evening, and at night and improve by movement. The pathophysiologic basis of restless legs syndrome/Willis-Ekbom disease (RLS/WED) remains poorly understood.

Now, let's elaborate on the treatment...

1. Iron stores should be evaluated in all patients. Iron replacement is therapy for those with iron deficiency or low ferritin levels.

2. Nonpharmacologic therapy options include avoidance of aggravating drugs and substances such as caffeine, mental alerting activities, short daily hemodialysis for patients in renal failure, exercise, leg massage, and applied heat.

3. Pharmacologic therapy:

For mild symptoms: Benzodiazepines such as Clonazepam

For intermittent but disabling symptoms: Dopamine agonist or levodopa on an as-needed basis

For chronic persistent RLS despite nonpharmacologic therapies: Alpha-2-delta calcium channel ligands (usually initial treatment) or dopamine agonists

For patients with very severe RLS, comorbid depression, or obesity/metabolic syndrome: Dopamine agonist (pramipexole, ropinirole, or rotigotine)

For patients with comorbid pain, anxiety, or insomnia or a history of impulse control disorder or addiction associated with use of a dopamine agonist: Alpha-2-delta calcium channel ligand (gabapentin enacarbil, gabapentin, or pregabalin)

For refractory symptoms: Combination therapy and opioids

Now, let's talk about why!

Why should you test for iron deficiency?

Reduced CNS iron stores are a robust and consistent finding in RLS.

Why are dopamine agonists, apha 2 delta calcium channel ligands, opioids helpful?

Preliminary data have implicated a variety of other neurotransmitters in the pathogenesis of RLS, including dopamine, endogenous opioids, glutamate and glutamine, and gamma-aminobutyric acid (GABA).

Why is the initial treatment an alpha-2-delta calcium channel ligands?

Because of the risk of augmentation with dopamine agonists.

Augmentation refers to a worsening of RLS symptoms with increasing doses of medication, including earlier onset of symptoms, increased intensity of symptoms, shorter duration of drug action, or topographic spread of symptoms to the arms, is a common complication of long-term dopaminergic therapy in RLS.

Why are dopamine agonists preferred in patients with comorbid depression, or obesity/metabolic syndrome?

Depression: The alpha-2-delta calcium channel ligands may be associated with an increased risk of suicidal thoughts and behavior, and patients should be monitored for emergent suicidality and depression.

Obesity/metabolic syndrome: Side effect og gabapentin and pregabalain is weight gain.

Why are alpha-2-delta calcium channel ligands preferred in patients with comorbid pain, anxiety, or insomnia or a history of impulse control disorder or addiction?

Comorbid pain: They bind to the α2-δ subunit of presynaptic, voltage-dependent calcium channels and thereby reduces the release of several neurotransmitters like glutamate, norepinephrine, serotonin, dopamine, and substance P.

Anxiety and insomnia: The alpha-2-delta sub-unit of voltage-gated calcium channels of “over-excited” pre-synaptic neurones, thereby changing the conformation of the channel and reducing the release of excitatory neurotransmitters, which have been pathophysiolgically implicated in anxiety disorders, such as glutamate, substance P and norepinephrine: the consequent reduced stimulation of post-synaptic neurones is thought responsible for its anxiolytic and sedative  effects.

Impulse control / Addiction: Dopamine agonist therapy in patients with RLS may be associated with an increased risk of impulse control disorders such as pathologic gambling, compulsive eating and shopping, and compulsive inappropriate hypersexuality.

That's all!
I hope this post was helpful and fun. It's awesome to know mechanisms and why! :D

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