Sleep Disorders Flashcards
Where in the brain is the circadian clock/rhythm handled?
Suprachiasmatic Nucleus
Explain the human sleep cycle
4 - 6 cycles of REM and NREM sleep each one lasting about 70 - 120 minutes
What are the 4 stages of sleep?
1 - NREM Stage 1
2 - NREM Stage 2
3 - NREM Stage 3
4 - REM Stage
What stage of sleep is the deepest sleep?
NREM Stage 3
What stage of sleep does breathing and heart rate go down?
NREM Stage 2
Describe REM sleep
Paradoxical
Muscles are paralyzed
Brain is activated
Controlled by cholinergic cells
in the mesencephalic,
medullary and pontine
gigantocellular areas
Describe NREM sleep
Muscles are not paralyzed
Controlled by the basal
forebrain, lower brain stem
to the thalamus and
hypothalamus
What is used to monitor and measure sleep?
Polysomnography
Hooked up to EEG, EOG (each eye), ECG, EMG, O2 Sat
What are the signs/symptoms of sleep disorder?
Excessive Daytime Sleepiness
Impaired Daytime Functioning
Irregular breathing
Increased movement during sleep
Irregular sleep and wake cycle
Difficulty falling asleep
Common Types of Sleep Disorders
Insomnia
Sleep Apnea
Narcolepsy
Circadian rhythm disorder
Parasomnia
Restless Leg Syndrom
What is the most commonly reported sleep disorder?
Insomnia
How do you diagnose Insomnia?
Requires persistent sleep difficulty, adequate sleep opportunity and associated daytime dysfunction
What do you refer to several days insomnia
Transient insomnia
What do you refer to insomnia less than 3 months?
Short term insomnia
What do you refer to insomnia 3 nights/week for 3 months
chronic insomnia
What is the treatment goal of transient and short term insomnia?
Treat the underlying sleep complaint and avoid adverse effects of medication
What are common drugs that cause or worsen insomnia?
Alcohol/nicotine
Anticholinergics
SNRI/SSRIs
Alpha Blockers
Beta Blockers
ACEi and ARBs
CNS Stimulants
Bronchodilators
Cholinesterase inhibitors
Corticosteroids
Decongestants
Diuretics
H2RAs
Statins
Opioids
***Apple And Samsung Are Bad And Chidima Bought Croissants Cause Donuts Don’t Hit So Often
What are some sleep hygiene principles?
What is the treatment of long term insomnia?
1st line is - CBT
2nd line - CBT +/- medications (also if needed rapidly)
What can you give a patient for sleep onset that is older, is a substance abuser, is cognitively impaired and does not want morning residual sedation?
Ramelteon
What can you give a patient for sleep onset that is older, is a substance abuser, is cognitively impaired and wants morning residual sedation?
Ramelteon
DORA (rexant)
What can you give a patient for sleep onset that is young, is not a substance abuser, is not cognitively impaired and does not want morning residual sedation?
Ramelteon
Non Benzo BZDRA - zaleplon, zolpidem IR
What can you give a patient for sleep onset that is young, is not a substance abuser, is not cognitively impaired and wants morning residual sedation?
Ramelteon
Non Benzo BZDRA - zaleplon, zolpidem IR, eszoplicone
DORA (rexant)
What can you give a patient for sleep maintenance that is older, is a substance abuser, and is cognitively impaired ?
Low-dose doxepin
DORA
What can you give a patient for sleep maintenance that is young, is not a substance abuser, and is not cognitively impaired ?
Low dose doxepin
DORA
Non-Benzo BZDRA - eszoplicone or zolpidem
What are the most commonly used medication treatments for insomnia?
Benzodiazepine Receptor Agonists (BZDRAs)
What is a caution when using BZDRAs?
There is caution with use in the elderly and a possibility of complex sleep behaviors
How do BZDRAs work?
They have an agonist effect on GABA receptors
How should you take BZDRAs?
Always take before bedtime
What are the side effects of BZDRAs?
Drowsiness, Dizziness, Confusion, Risk of Falls
What should you avoid taking with BZDRAs?
You should avoid taking alcohol and opioids as it can cause CNS depression
Which BZDRA increases stage 2 sleep and decreases delta sleep?
Benzodiazepines
What BZDRA increases total sleep time?
Nonbenzo GABA Agonists
What BZDRA reduces sleep latency?
Benzodiazepines
What BZDRA reduces anxiety?
Benzodiazepines
What BZDRA is less disruptive of sleep stages?
NonBenzo GABA Agonists
What BZDRA has dose dependent side effects?
Benzodizepines
What BZDRA is more selective?
NonBenzo GABA Agonists
What BZDRA is associated with parasomnic episodes like amnesia?
NonBenzo GABA Agonists
What is the choice of a particular BZDRA based on?
It’s based on the PK profile and the patients’ preference
What is the Black Box Warning associated with Benzodiazepines?
Use of benzos and opioids can cause death
Physical dependence
Risk of abuse, overdose and death
What is Black Box Warning associated with Z-Drugs?
Complex sleep behaviors like sleep walking and sleep driving that can result in injury
**D/C if this happens
What list are BZDRAs on?
They are on the beer’s criteria for avoidance in the elderly due to increased sensitivity and decreased metabolism
What is the PK/PD profile of Eszoplicone?
Rapid absorption but delayed with food
Duration: 6 - 9 hours
What is eszoplicone indicated for?
Sleep onset and sleep maintenance
What is eszoplicone’s DDI?
Interactions with CYP3A4 inhibitors like ketoconazole and intracazole
What is the PK/PD profile of zaleplon?
Ultra short acting; rapid onset
Duration: 3 - 4 hours
What is zaleplon indicated for?
Sleep onset; short term insomnia
What is zaleplon’s DDI?
Interactions with CYP3A4 inducers like cimetidine and rifampin
What is the PK/PD profile of Zolpidem?
Short acting and a short half life
What are the different formulations of Zolpidem?
Intermezzo (SL tab)
Edluar (SL tab)
Ambien CR
Ambien IR
Generic IR capsule
What is Intermezzo for and how should you take it?
Zolpidem formulation indicated for middle of the night awakening and should be taken if there are more than 4 hours left to sleep and you can’t go back to sleep
**Diff dose for men and women
What is Edluar for and how should you take it?
Zolpidem formulation indicated for sleep onset and off label sleep maintenance and should be take immediately before bed with 7+ hours of sleep
**Diff dose for men and women
What is Ambien for and how should you use it?
Zolpidem formulation for sleep onset (CR and IR) and sleep maintenance (CR only) taken immediately before bed with 7+ hours of sleep
**Diff dose for men and female
What is Generic Zolpidem and how should you take it?
Zolpidem formulation for sleep onset. If 5 mg of another zolpidem formulation is not effective, you can use 7.5 mg of this generic formaultion
**Same dose for men and women
What are DORAs?
Dual Orexin A and B Receptor Antagonists used for bot sleep onset and maintenance
It turns off awake signaling
What are your DORA drugs?
Suborexant
Lemborexant
Dandorexant
What are DORA’s DDIs?
Interactions with CYP3A4 inducer and inhibitors
What is DORA’s contraindications?
It is contraindicated in narcolepsy
How should you take DORAs?
Take at bedtime with at least 7 hours of planned sleep
What is the PKPD profile of Suvorexant?
Onset: 30 minutes
Half life: 12 hours
What is the side effect of Suvorexant?
Sleep paralysis
Abnormal dreams
What is the PKPD profile of Lemborexant?
Onset: 30 minutes
Half life: 17 - 19 hours
What is the side effect profile of Lemborexant?
Complex sleep behaviors
abnormal dreams
What is the PKPD profile of Dandorexant?
Onset: 30 mins
Half life: 8 hours
What is the side effect profile of Dandorexant?
Complex sleep behaviors
Hallucinations
Sleep paralysis
What is Ramelteon?
It is a melatonin receptor agonist and is MT1 and MT2 selective
**MT1 = induces sleepiness
**MT2 = regulates circadian rhythm
What is Ramelteon indicated for?
Sleep onset and long term use
What is the PK profile of Ramelteon?
Onset: 30 mins
Half life: 1 - 2.6 hours
What is Ramelteon contraindicated in?
Fluvoxamine
Is Ramelteon effective in all patients?
It is not effective in patients that have previously use BZDRAs
What is Doxepin?
TCA used for sleep maintenance
What is the dosage of doxepin?
3 -6 mg/day
**Lower dose than depression
What should you do when taking Doxepin?
Do not take within 3 hours of eating
**can cause next day somnolence
What is Melatonin indicated for?
beneficial effects:
sleep onset latency
shift workers
jet lag
In who should melatonin be avoided in?
Patients with autoimmune conditions
Patients with Alzheimers
What 1st gen antihistamines are used in Insomnia?
Diphenhydramine
Doxylamine
What patients shouldn’t use 1st gen antihistamines?
Avoid in older adults (beer’s list)
What are the side effects of 1st gen antihistamines?
Anticholinergic side effects
- Mad (alt mental status)
- Blind (mydriasis)
- Hot (fever)
- Dry (dry mucous membrane)
- Red (flushing)
- Full (urine retention)
What is the effect of use of 1st gen antihistamines?
Tolerance to sedative develops rapidly
What is Trazodone used for in Sleep Disorders?
Improve sleep contiuity
In what patients can Trazodone be useful in?
Patients with substance abuse
Patients with depression
What is the side effect of Trazodone?
Carryover sedation
Alpha adrenergic blockade
How should you discontinue Trazodone?
Gradually taper over 2 - 4 weeks
What are other off label drugs used for Insomnia?
Amitriptylline
Mirtazepine
Gabapentin
What drugs can you use in the elderly for Insomnia?
Low dose doxepin
Ramelteon
Zolpidem and Eszoplicone - risky
What drugs can you use in pregnancy for Insomnia?
Diphenhydramine
Doxylamine
Low dose doxepin
What is sleep apnea?
repeated episodes of breathing cessation during sleep. This can lead to blood oxygen desaturation and arousal to restart breathing
What are the types of sleep apnea?
Central (impaired respiratory drive)
Obstructive (airway collapse/obstruction)
Mixed (CSA and OSA)
How can you diagnose sleep apnea?
Polysomnography
What is the treatment for obstructive sleep apnea?
The standard is Positive Airway Pressure during sleep
Behavior modify (weight loss, no alcohol/sedatives, alter sleep position)
Avoid CNS depressants & drugs that cause weight gain
Use drugs for EDS
What are the for EDS?
Modafanil
Armodafinil
Solriamfetol
Pitolisant
When should you administer modafanil/armofadinil?
In the morning
Who should avoid Modafinil/Armodafinil?
it should be avoided in pregnant people
What is the DDI in Modafinil/Armodafinil?
CYP3A4 inducer
Can reduce effectiveness of contraceptives
What are the side effects of Modafanil/Armodafinil?
Headache
SJS/TEN
DRESS
What are the warnings/precaution with Modafinil/Armodafinil?
It can cause mania or exacerbation of psychosis
precaution in patients with cardio events: HTN, CP, Tachycardia
What is the MOA of Solriamfetol?
Dopa and NorEpi reuptake inhibitor
How do you take (dose) Solriamfetol?
Take once daily upon awakening not within 9 hours of sleeping
What is contraindicated with Solriamfetol?
use of MAOi (w/in 14 days)
Avoid in cardio disease and arrythmia
What is Pitolisant?
Med for EDS good for substance patients
What is the MOA of Pitolisant?
Inverse agonist/antagonist at histamine 3 receptors
What is a side effect of Pitolisant?
May prolong QT (avoid in known arrhythmia)
Headache
What is Narcolepsy?
Impairment of REM and NREM sleep onset and offset
What is the narcolepsy tetrad?
Excessive & irresistible daytime sleepiness
cataplexy
hypnagogic hallucinations
sleep paralysis
What is the pathophysiology of Narcolepsy?
loss of normal function of hypocretin/orexin in neurotransmitter system
What is the non-pharm treatment of Narcolepsy?
good sleep hygiene and daytime naps
Avoid drugs that cause daytime sleepiness (benzos, opiates, AEDs, antipsychos, EtOH)
What is the pharmacotherapy of Narcolepsy?
Goal: achieve normal and max alertness during awake hours
No disease modifying therapies
Treat symptoms: EDS, cataplexy, REM abnormalities
What are the medications for EDS in Narcolepsy?
Modafinil
Armodafinil
Solriamfetol
Pitolisant
Amphetamine
Methylphenidate
Sodium oxybate
Oxybate salts
What is Sodium oxybate indicated for?
Xyrem is a CIII used in cataplexy and EDS in narcolepsy
What is the Black Box Warning with Sodium oxybate?
CNS depression
Abuse/misuse
Restricted access
How should you take/admin sodium oxybate
Take on an empty stomach while in bed and remain in bed. Take 2nd dose 2.5 - 4 hours later.
What is the precaution with Sodium oxybate?
It is part of the REMS program and is a CNS depressant. You should engagae in activities or operate heavy machinery for 6 hours
What is Lumryz?
Sodium oxybate ER suspension.
How to take Lumryz?
Suspend in 1/3 cup water Take lying down and remain in bed; only one dose at bedtime
Oxybate salts
Na
Ca
Mg
K
What meds are used for cataplexy in narcolepsy?
REM suppressing drugs
Pitolisant
Sodium oxybate
What are the meds for EDS in narcolepsy
Oxybate salts
What are your REM suppressing drugs
Venlafaxine (SNRI)
Duloxetine (SNRI)
Fluoxetine (SSRI)
Clomipramine (TCA)
What can happen is you abruptly stop a REM suppressing drug?
Status Cataplecticus