Sleep Disorders - Hypnotics/Sedatives
Symptom: Insomnia
“Rule Out” Insomnia Due to Physical Disorder
- Gastro-esophageal Reflux Disease (GERD)
- Hyperthyroidism
- Periodic Leg Movement Disorder or Restless Legs Syndrome
- Pain Syndromes
Mental Health Disorders with Sleep-Related Symptoms
Depression
Bi-Polar
Post-Traumatic Stress Disorder
Dementia
ADHD
GAD
Traumatic Brain Injury
Sleep & Circadians
You have 8 chemical bodies in a 24 hour period
Circadian, entrainable oscillation 24-26 hours cycle
Infradian, > 1 Circadian - Menstrual Cycle
Ultradian, < 90 – 120 minutes - This is the sleep cycle 45 min to deep sleep 45 min to light sleep with Blood Circulation, Pulse, Heart Rate; Urination & Bowel Activity; Appetite and Nostril Dilation
Sleep Stages
Stage 1: 1-5 Minutes per cycle, easily awakened
Stage 2: Light sleep, 50% of healthy adult sleep - Spindles & k-complexes (necessary for learning); Heart Rate decreases; Body Temperature decreases & Eye Movements Completely STOP
Stage 3: First stage of deep sleep - Blood Pressure Drops; Muscles Relax & Breathing Slows
Stage 4: Deepest, Most Restorative Sleep - More Relaxed; Growth hormones released & 50% Delta Waves
REM Sleep
Entered/Exited through Stage 2: 25% of healthy sleep is REM sleep; 50% of infant sleep is REM sleep; No Voluntary Muscle Movement (muscle atonia); Blood Flow increases by 50%-200%; Sexual arousal increased & Nervous System Increases Activity
NO REM Sleep While Sitting Up! So get Gerd Patients to at least sleep at 45 degrees to get REM sleep
REM cycles throughout the night
- Increases amount of REM throughout night
- As REM increases, deep sleep stages decrease
- Slow Wave sleep first 1/3 of night
- REM sleep predominates last 1/3 of night
- After Age 65, REM sleep Decreases
REM Sleep & Neurotransmitters
During REM:
- 5-HTSeratonin and NE norepinephrine are not secreted
- DA dopamine activated
- ACh Acetylcholine activated - Good night’s sleep increases learning
Hypnotics/Sedatives use for Sleep Disorders
Barbiturates
Chloral Hydrate
Benzodiazepines
“Non-benzo” benzodiazepines (Z-Drugs):
- Zaleplon/Sonata®
- Zolpidem/Ambien®
- Eszopiclone/Lunesta®
Tricyclic Antidepressants
Atypical Anti-Psychotics
Sedating Anti-histamines
Melatonin Special Precautions
Bleeding Disorders
Depression
Diabetes
High Blood Pressure
Seizure Disorders
Transplant Recipients
FDA-Approved Treatments for Insomnia
Benzodiazepines – Allosteric Modulators of the GABA-A Chloride Ionophore
- Temazepam (Restoril®)
- Flurazepam (Dalmane®)
- Triazolam (Halcion®)
- Quazepam (Doral®)
- Estazolam (Prosom®)
Melatonin-Receptor Agonists
- Ramelteon (Rozerem®)
- Tasimelteon (Hetlioz®)
BZD1-Receptor Agonists
- Zolpidem (Ambien®)
- Zaleplon (Sonata®)
- Eszopiclone (Lunesta®)
Histamine Antagonists
- Doxepin (Silenor®)
- Diphenhydramine
Orexin Receptor Antagonist
The Zzzzz-Drugs
Non-Benzodiazepines
- Zolpidem (Ambien®) – t ½ = 2.5 hrs.
- Intermezzo® (sublingual zolpidem)
- Zaleplon (Sonata®) – t ½ = ultra short 1 hr.
- Eszopiclone (Lunesta®) – t ½ = 6 hrs.
Mechanism of Action: Binds to Alpha 1 isoform
Special Note: Ramelteon (Rozerem®) - Melatonin1 and Melatonin2 Agonist
Tasimelteon (Hetlioz®)
Melatonin-Receptor agonist @ MT1 & MT2
First/Only FDA approved treatment for Non-24-Hour Sleep-Wake Disorder (Non-24)
Non-24: Neurological sleep disorder in which a person’s sleep/wake cycle less than24 hours. Unable to adjust sleep-wake cycle to the length of the day, and sleep time progresses around the clock
Side Effects: Headache, increased alanine aminotransferase (ALT measured to
determine liver health), nightmares, unusual dreams, upper respiratory or urintary tract
infection
Suvorexant (Bellsomra®)
Orexin Receptor Antagonists
Blocks neuropeptides Orexin A and B from binding to OX1R and OX2R
Blockage = suppression of wakefulness & Appetite
NOTE: Orexin A and Orexin B receptors stimulate appetite
Abuse Potential – Low but PRESENT!
Orexin (aka Hypocretin)
Neuropeptide – Small protein-like molecules used by neurons to communicate with each other
Regulates: Arousal; Wakefulness & Appetite
• Cataplexy – most common form of narcolepsy – brief loss muscle tone resulting from lack of orexin in brain
Behavioral Strategies to Reduce Insomnia
Exercise: Exercise 20-30 Minutes a Day & Exercise about 5-6 hours before bedtime
Avoid caffeine, nicotine, & alcohol
Utilize deep breathing & relaxation exercises
No TV, No iPad, No iPhone, No i-Screen anything
Control room temperature – less than 70 degrees
Sleep until sunlight!
Tetrad of Narcolepsy
1. Sleep Paralysis (temporary inability to move or speak while falling asleep or upon
waking)
2. Hypnagogic hallucinations – when going to sleep
3. Attacks of Sleep
4. Cataplexy-lose muscle control
