Sleep Disorders Flashcards
What does sedative mean?
- Calms anxiety with NO sedation
What does Anxiolytic mean?
- Relieves anxiety WITHOUT sleep or sedation
What does Hypnotic mean?
- Induces Sleeps
What does Narcotics mean?
- Sleep Producing; now means illegal drugs
What part of the brain controls sleep?
- Hypothalamus
What are the stages of sleep?
- Wakefulness, NREM, REM
What are the four stages of NREM sleep?
- Stage 1: Dozing
- Stage 2: Unequivocal Sleep
- Stage 3: Voltage Increase, Frequency Decrease
- Stage 4: Delta Waves
What is REM sleep?
- Where dreaming and memory consolidation takes place
What are the factors that regulate sleep?
- Age: Decreases with Increasing age
- Sleep History
- Drugs?
- Circadian Rhythms: Normal Sleep Cycle
Within the Circadian Cycle, what are some important things to note?
- 9 pm = start of melatonin
- 730 am = end of melatonin
- 2 am = deepest sleep
What neurotransmitters help regulate sleep?
- Catecholamines, Serotonin, Histamine, Acetylcholine, Adenosine, GABA
What are the parts of GABAergic Neurotransmission within sleep?
- GABAa [Ion Channel], GABAb [GCPR], GABA Trasporter [GAT-1], GABA-T [Transaminase]
What is the GABAa Receptor?
- Chloride Ion Channels that is the target for sedative-hypnotics
Where do Benzodiazepines affect the GABAa receptor?
- Allosterically; a1 and y2
What the ligands that act on the Benzodiazepine Receptor
- Benzo: Activates a1-5; INCREASING frequency of channel opening
- Non-benzo: Z-Hypnotics; Activate BZ1 of a1 = safer
- Benzo Antagonist: Flumazenil
- Barbiturtates: DIRECT EFFECT on GABAa
What is important to know about the Chemistry of the Benzodiazepine structure?
- The positioning will determine the metabolism
- 1 Alkylation is the source of active matebolites
- Annealating the 1-2 bond will cause high affintiy and decreased half-life
What is important to note about Diazepam’s metabolism?
- LONG half life
Why is it important that benzodiazepines have a slow elimination rate?
- Helps control the seizures
- HAVE active metabolites
What are the important benzodiazepines to know about in terms of Pharmacokinetics?
- Diazepam: Slow Elimination - Helps with seiures
- Clonazepam: Intermediate Elimination - anticonvulsant
- Midazolam: Rapid Elimination - anesthesia
What is important to know when comparing the dose response curves between Benzodiazepines and Barbiturates ?
- Benzo curve has a ceiling; ONLY really leading to major SEDATION making is slightly safer
- Barbs curve reaches a dangerous zone that has extreme SEDATION that results in coma and death
What are the pharmacological disease properties for the Benzodiazepines?
- Anxiolytic: Reduce seizures
- Sleep Physiology: Decrease REM & Stage 3/4 [not really used for this]
- Anticonvulsant: Main use
What are some of the side effects that related to Benzodiazepines?
- DOSE DEPENDENT
- Sedation, Weakness, Headache, Vertigo, Nausea, Paradoxical Effects
What is the Benzodiazepine Antagonist?
- Flumazenil
- Treats the overdose of the Benzo
- SE: Convulsion, Panic Attacks, Nausea, Vomiting, Headache…
What are the Non-Benzodiazepines?
“Z-Hypnotics” - BZ1 Receptor
- Zolpidem [Ambien]: SHORT acting
- Zaleplon [Sonata]: SHORT acting
- Eszopiclone [Lunesta]: LONG acting
What are some of the side effects for the Z-Hypnotics?
- Daytime Drowsiness, Dizziness, Nausea, Vomiting
- WIERD SLEEPING THINGS: sleep-driving, sleep-cooking, sleep-sex
What is the way to treat the overdose of Z-Hyponitcs?
- Flumazenil
What are the Long and Short acting Barbiturates?
- Long Acting: Phenobarbital
- Short Acting: Pentobarbital
Breifly compare the Barbiturates, Benzodiazepines, and Z-Hpynotics?
- Barbs: bind to all GABAa and have DIRECT EFFECT on it
- Benzos: bind to all GABAa a1-5
- Z-Hypo: bind ONLY to the BZ1 receptors of a1
What type of receptor is the GABAb receptors?
- Gi - GCPR
- Inhibitory by DECREASING Ca2+and INCREASING K+
What is important to note about the GABAb receptor?
- GCPR
- ONLY GABAb2 affects the G-protein
- GABA can only bind the GABAb1
- Affecting the spot where b1/b2 bind is the only way to affect Gi
What is Xyrem [Sodium Oxybate]?
- Stimulant that helps with Excessive Daytime Sleepiness and Improves Wakefulness
- “GHB”
- ONLY available via Patient Program
- Binds to GABAa & GABAb
What is the pharmacology for Xyrem [Sodium Oxybate]?
- “GHB”
- CNS Depressant = dizziness, drowiness, coma
- DATE RAPE DRUG
What are some of the side effects for Xyrem [Sodium Oxybate]?
- Loss of Consciousness, Nausea, Vomiting, Headache, Seizures, Death
What is the mechanism of action for Ramelteon [Rozerem]?
- Binds to the MT1/MT2 melatonin receptors [in the SCN = master clock]
- NO ABUSE, WITHDRAWAL, DEPENDENCY
What is the mechanism of action for Tasimelteon [Hetlioz]?
- Binds to the MT1/MT2 melatonin receptor
- Used in blind or poor vision patients
- Orphan Product
What is the importance about Oxerin?
- Released from the Hypothalamus that promotes wakefulness
What is the mechanism of action for Suvorexant [Belsomra]?
- Binds the OX1/OX2 orexin receptors [in the Hypothalamus]
- Decreasing arousal and rewarding stimuli
- TREATMENT of insomnia
What were some of the medications that requested a label change?
- Newer Z-Hypnotics [Eszopiclone, Ramelton, Zaleplon, Zolpidem]
- Because of the weird sleeping issues
What are some of the new sedative hypnotics used?
- Trazodone
- Antihistamines [Diphenhydramine, Doxylamine, Pyrilamine]
What are some of the Herbal/Natural Sedative that are used?
- Melatonin: Drowiness
- Vaalerian: Hepatotoxicity
- Chamomile: Avoid - Ragweed allergy
- Kava Kava: Avoid - hepatotoxicities
What are some of the medications that are associated with causing Insomnia?
- Anxitey
- Modafinil, Amphetamines, Beta-Blockers, Beta-Agonist, Thyroid Meds, Bupropion, Methylphenidate
How does the DSM-5 describe Insomnia Disorders?
- Difficulties with sleep initiation, sleep maintenacne, and/or early-morning Awakening
- Takes places at least 3 nights per week and is present for 3 months
What are some of the treatment options for Insomnia Disorder?
- 1st Line: NON-PHARM [Behavioral Therapies & Sleep Hygiene]
- Z-Hypnitics [Zolidpem, Eszopicline, Zaleplon]: Most common
- Benzodiazepine
- Melatonin Agonists [Ramelteon, Tasimelteon]
- Orexin Receptor [Survorexant, Lemborexant]
- Doxepin [TCA]
What are important to know about the Z-Hypnotics?
- Zolpidem is the most common [Initial dose = 5mg in women]
- 3A4
What are the Melatonin Agonists?
- Ramelteon and Tasimelteon
What is important to know about Ramelteon?
- Contracindicated with Fluvoxamine
- SE: GI Upset, Next day sleepiness, Hyperprolactinemia, Prolactinoma
What is important to know about Tasimelteon?
- FDA-approved for non-24 sleep-wake disorder in adults
- 1A2
What are the Orexin Receptor Antagonists?
- Survorexant, Lemborexant, Daridorexnat
What is important to know about the Orexin Receptor Antagonist?
- Need at least 7 hours of sleep
- CONTRAINDACTED: in Narcolepsy
- 3A4
- INCREASE suicidal ideas
What is important to now about Doexpin in Insomnia?
- TCA - low doses exert effects due to H1 [10mg]
- SE: Anticholinergic
What is important to know about Trazodone in Insomnia?
- NOT FDA approved for insomnia
- Long half life - may see daytime hangover [shouldnt really be used]k
What is important to know about Mirtazapine in Insomnia?
- Clinically used sleep agent, especially if the patient has depression
What is important to know about Quetiapine in Insomnia?
- Low does NOT RECEMMENDED for insomnia unless theres a co-morbidity
What antihistamine and Natural products are used for Insomnia?
- Diphenhydramine/Doxylamine
- Melatonin/Valerian/Chamomile
What is important to know about the Antihistamines in Insomnia?
- NOT RECOMMENDED by AASM
- SE: Antichonlinergic
What is important to know about the Natural Products for Insomnia?
- Melatonin can be considered in jet lag and patients with a low melatonin levels [1A2]
- Chamomile shouldnt be used if the patient has a RAGWEED allergy
What is the way that we choose treatment for Insomnia?
- CBT is 1st line
- Medications are 2nd line
How does the DSM-5 describe Opstructive Sleep Apnea?
- Stop breathing… at night
- MUST have 5 apneas per hour
- May have both Insomnia and Apnea - TREAT APENA FIRST
How do we diagnose someone with Obstructive Sleep Apnea?
- Polysomnography Test ONLY
What is the treatment for Sleep Apnea
- Non-Pharm: weight loss, smoking cessation, AVOID alcohol and CNS Depressant
- Overweight & Insomnia evaluation; consider apena
- Excessive Daytime sleepiness: Modafinil or Armodafinil
How does the DSM-5 describe Narcolepsy?
- Episodes of needed to sleep, or falling asleep; 3 times per week over the past 3 months [ DECREASE in orexin]
What is the Narcolepsy Tetrad?
Symptoms that define Nacrolepsy
- EDA - 100% of patients
- Cataplexy [sudden muscle loss] -75%
- Hallucinations - 30 to 60%
- Sleep Paralysis - 25 to 50%
What is the Treatment for Nacrolepsy?
- Catapley: Sodium Oxybate [GHB] or Xywav [adults and childern under 7]
- EDS: Sodium Oxybate, Pitolisant and Solriamfetol
What is important to know about Pitolisant in Insomnia?
- CONTRAINDICATED: severe hepatic impairment
- 2D6, 3A4
- May DECREASE oral contraceptive efficiency
- AVOID with H1 antagonist
What is important to know about Solriamfetol in Insomnia?
- Helps improve wakefulness due to EDS by Narcolepsy or OSA
- Start 37.5 mg, increase to 75 after 7 days
- SE: BP and HR INCREASE; AVOID in stable CV disease and arrhythmias
What are some medications that help with the Shift Work Sleep Disorder?
- Modafinil and Armodafil
- Start ONE hour before work
What are some ways to help with Restless leg syndrome?
- Dopamine Agonist are 1st line
- Gabapentin Enarcarbil [Prodrug for Gabapetin]
- Iron Supplement
What are some ways to help with Restless leg syndrome?
- Dopamine Agonist are 1st line
- Gabapentin Enarcarbil [Prodrug for Gabapetin]
- Iron Supplement
