Sleep Disorders and Their Management (Menza) - 10/24/16

Question 1

Why do we sleep? (4)

Answer 1

1. No real consensus
2. Restoration
   
   1. Many genes turned on during sleep
3. Energy conservation
   
   1. However, little diff in calorie consumption b/w sleep and quiet wakefulness
4. Brain function
   
   1. Memory consolidation
   2. Increased clearance of metabolic byproducts

Question 2

Two-process model explains the sleep wake cycle

Answer 2

1. Homeostatic Drive to Sleep (VLPO)
   
   1. Inc. w duration of waking - buildup of adenosine
      
      1. Caffeine = adenosine blocker
         
         1. By blocking adenosine in VLPO to keep VLPO –> releases GABA –> turn off all stimulating chemicals
   2. Governed by the need for sleep
2. Circadian Rhythms (SCN)
   
   1. Related to light-dark cycle
   2. Sleep-independent (i.e. travelling across time zones… can’t sleep b/c it’s light out)

Question 3

Sleep/Wake is a balanced system

Orexin?

Answer 3

Orexin = promotes wakefulness

Orexin blocker = suvorexant (Belsomra) approved in 2014 for insomnia

Question 4

Sleep-Wake Cycle and Suprachiasmatic Nucleus (SCN)

Wake vs Sleep

Answer 4

Wake:

• During the day, SCN activity promotes arousal through alerting neurotransmitters
  
  • (+) light –> SCN –> norepi release –> pineal gland –> melatonin
• Maintains state of wakefulness

Sleep:

• At night, SCN arousal is turned off by melatonin
  
  • ​Light inhibits production of melatonin
  • When it is dark, melatonin levels inc
• Allows normal sleep to occur (sleep debt is unopposed)
  
  • During the night, adenosine and metabolic byproducts cleared out of the brain –> reduces sleep debt
  • Finally in the morning, melatonin goes away again (b/c of the light) and SCN starts functioning again to keep you awake

So two opposing systems… one is pushing you towards sleep, one is trying to keep you awake –> at night, that is reversed

Question 5

Sleep Apnea

Nocturnal hypoxia?

Hypoxia?

Answer 5

Repeated cessation of breathing > 10 sec during sleep –> disrupted sleep –> daytime tiredness

Nocturnal hypoxia –> systemic/pulmonary HTN, arrhtyhmias (afib/flutter), sudden death

Hypoxia –> inc. EPO release –> inc. erthyropoiesis

Question 6

Obstructive sleep apnea

Causes in adults vs children

Treatment

Answer 6

Respiratory issue bc of airway obstruction

Associated w/ obesity, loud snoring

Caused by excess parapharyngeal tissue in adults, adenotonsillar hypertrophy in children

Treatment:

weight loss, CPAP, surgery

Question 7

Sleep Related Movement Disorders (4)

Answer 7

1. Restless Leg Syndrome (RLS)
   
   1. Treatment: dopamine agonists
2. Periodic Limb Movement Disorder (PLMS)
3. Sleep Related Leg Cramps
4. Sleep Related Bruxism (Grinding teeth)

Question 8

Narcolepsy

• Narcoleptic tetrad
• Type I vs Type II

Answer 8

Loss of orexin cells in hypothalamus

• Narcoleptic tetrad
  
  • Excessive daytime sleepiness
  • Sleep paralysis (waking and feeling unable to move)
  • Cataplexy (loss of muscle tone, usually occurs w/ strong emotion)
  • Hypnagogic and hypnapompic (phantom sensation) hallucinations when going off to sleep or waking
• Type I vs Type II
  
  • I: with cataplexy
  • II: without cataplexy

Question 9

Central sleep apnea

Answer 9

No respiratory efort due to:

• CNS injury/toxicity
• Opioids
• Heart failure

Question 10

Insomnia Defined

Answer 10

Question 11

Approaches to Insomnia (assuming you can’t fix the underlying problem)

Non-pharmacologic vs Pharmacologic

Answer 11

Non-pharmacologic

• Sleep hygiene
  
  • Regular sleep hours
  • Regular get-up time
  • Avoid datyime naps
  • Relax at night
  • Avoid excess time in bed
  • Use bed only for sleep
• Exercise
• Relaxation
• CBT
  
  • Stress control –> reduce anxiety

Pharmacologic

• Monoamine antagonists
  
  • Antihistamines
  • Anticholinergics
  • Serotonin, dopamine and norepi blockers
• GABA agonists –> sedating they turn off alerting neurotransmitters; mimick VLPO activation)
  
  • Benzos (act at GABA-A R)
    
    • (-) tolerance/dependence
    • Some have long half lives so patients can feel more tired the nxt day
• Melatonin agonists
• Orexin antagonists
  
  • Suvorexant

Question 12

FDA-Approved Non-benzodiazepine hypnotics indicated for treatment of insomnia

Answer 12

Question 13

Ramelteon and Suvorexant

Answer 13

Ramelteon (Rozerem)

• Potent, selective MT1/MT2 receptor agonist
• Negligible affinity for the GABA-A R complex
• Half-life = 1 to 2.6 hrs

Suvorexant (Belsomra)

• First orexin blocker
• Very limited clinical experience available