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PHRM 845: Therapeutics III > Sleep Disorders > Flashcards

Sleep Disorders Flashcards

1
Q

What does sedative mean?

A
  • Calms anxiety with NO sedation
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2
Q

What does Anxiolytic mean?

A
  • Relieves anxiety WITHOUT sleep or sedation
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3
Q

What does Hypnotic mean?

A
  • Induces Sleeps
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4
Q

What does Narcotics mean?

A
  • Sleep Producing; now means illegal drugs
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5
Q

What part of the brain controls sleep?

A
  • Hypothalamus
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6
Q

What are the stages of sleep?

A
  • Wakefulness, NREM, REM
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7
Q

What are the four stages of NREM sleep?

A
  • Stage 1: Dozing
  • Stage 2: Unequivocal Sleep
  • Stage 3: Voltage Increase, Frequency Decrease
  • Stage 4: Delta Waves
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8
Q

What is REM sleep?

A
  • Where dreaming and memory consolidation takes place
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9
Q

What are the factors that regulate sleep?

A
  • Age: Decreases with Increasing age
  • Sleep History
  • Drugs?
  • Circadian Rhythms: Normal Sleep Cycle
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10
Q

Within the Circadian Cycle, what are some important things to note?

A
  • 9 pm = start of melatonin
  • 730 am = end of melatonin
  • 2 am = deepest sleep
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11
Q

What neurotransmitters help regulate sleep?

A
  • Catecholamines, Serotonin, Histamine, Acetylcholine, Adenosine, GABA
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12
Q

What are the parts of GABAergic Neurotransmission within sleep?

A
  • GABAa [Ion Channel], GABAb [GCPR], GABA Trasporter [GAT-1], GABA-T [Transaminase]
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13
Q

What is the GABAa Receptor?

A
  • Chloride Ion Channels that is the target for sedative-hypnotics
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14
Q

Where do Benzodiazepines affect the GABAa receptor?

A
  • Allosterically; a1 and y2
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15
Q

What the ligands that act on the Benzodiazepine Receptor

A
  • 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
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16
Q

What is important to know about the Chemistry of the Benzodiazepine structure?

A
  • 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
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17
Q

What is important to note about Diazepam’s metabolism?

A
  • LONG half life
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18
Q

Why is it important that benzodiazepines have a slow elimination rate?

A
  • Helps control the seizures
  • HAVE active metabolites
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19
Q

What are the important benzodiazepines to know about in terms of Pharmacokinetics?

A
  • Diazepam: Slow Elimination - Helps with seiures
  • Clonazepam: Intermediate Elimination - anticonvulsant
  • Midazolam: Rapid Elimination - anesthesia
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20
Q

What is important to know when comparing the dose response curves between Benzodiazepines and Barbiturates ?

A
  • 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
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21
Q

What are the pharmacological disease properties for the Benzodiazepines?

A
  • Anxiolytic: Reduce seizures
  • Sleep Physiology: Decrease REM & Stage 3/4 [not really used for this]
  • Anticonvulsant: Main use
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22
Q

What are some of the side effects that related to Benzodiazepines?

A
  • DOSE DEPENDENT
  • Sedation, Weakness, Headache, Vertigo, Nausea, Paradoxical Effects
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23
Q

What is the Benzodiazepine Antagonist?

A
  • Flumazenil
  • Treats the overdose of the Benzo
  • SE: Convulsion, Panic Attacks, Nausea, Vomiting, Headache…
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24
Q

What are the Non-Benzodiazepines?

A

“Z-Hypnotics” - BZ1 Receptor
- Zolpidem [Ambien]: SHORT acting
- Zaleplon [Sonata]: SHORT acting
- Eszopiclone [Lunesta]: LONG acting

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25
Q

What are some of the side effects for the Z-Hypnotics?

A
  • Daytime Drowsiness, Dizziness, Nausea, Vomiting
  • WIERD SLEEPING THINGS: sleep-driving, sleep-cooking, sleep-sex
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26
Q

What is the way to treat the overdose of Z-Hyponitcs?

A
  • Flumazenil
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27
Q

What are the Long and Short acting Barbiturates?

A
  • Long Acting: Phenobarbital
  • Short Acting: Pentobarbital
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28
Q

Breifly compare the Barbiturates, Benzodiazepines, and Z-Hpynotics?

A
  • 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
29
Q

What type of receptor is the GABAb receptors?

A
  • Gi - GCPR
  • Inhibitory by DECREASING Ca2+and INCREASING K+
30
Q

What is important to note about the GABAb receptor?

A
  • 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
31
Q

What is Xyrem [Sodium Oxybate]?

A
  • Stimulant that helps with Excessive Daytime Sleepiness and Improves Wakefulness
  • “GHB”
  • ONLY available via Patient Program
  • Binds to GABAa & GABAb
32
Q

What is the pharmacology for Xyrem [Sodium Oxybate]?

A
  • “GHB”
  • CNS Depressant = dizziness, drowiness, coma
  • DATE RAPE DRUG
33
Q

What are some of the side effects for Xyrem [Sodium Oxybate]?

A
  • Loss of Consciousness, Nausea, Vomiting, Headache, Seizures, Death
34
Q

What is the mechanism of action for Ramelteon [Rozerem]?

A
  • Binds to the MT1/MT2 melatonin receptors [in the SCN = master clock]
  • NO ABUSE, WITHDRAWAL, DEPENDENCY
35
Q

What is the mechanism of action for Tasimelteon [Hetlioz]?

A
  • Binds to the MT1/MT2 melatonin receptor
  • Used in blind or poor vision patients
  • Orphan Product
36
Q

What is the importance about Oxerin?

A
  • Released from the Hypothalamus that promotes wakefulness
37
Q

What is the mechanism of action for Suvorexant [Belsomra]?

A
  • Binds the OX1/OX2 orexin receptors [in the Hypothalamus]
  • Decreasing arousal and rewarding stimuli
  • TREATMENT of insomnia
38
Q

What were some of the medications that requested a label change?

A
  • Newer Z-Hypnotics [Eszopiclone, Ramelton, Zaleplon, Zolpidem]
  • Because of the weird sleeping issues
39
Q

What are some of the new sedative hypnotics used?

A
  • Trazodone
  • Antihistamines [Diphenhydramine, Doxylamine, Pyrilamine]
40
Q

What are some of the Herbal/Natural Sedative that are used?

A
  • Melatonin: Drowiness
  • Vaalerian: Hepatotoxicity
  • Chamomile: Avoid - Ragweed allergy
  • Kava Kava: Avoid - hepatotoxicities
41
Q

What are some of the medications that are associated with causing Insomnia?

A
  • Anxitey
  • Modafinil, Amphetamines, Beta-Blockers, Beta-Agonist, Thyroid Meds, Bupropion, Methylphenidate
42
Q

How does the DSM-5 describe Insomnia Disorders?

A
  • 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
43
Q

What are some of the treatment options for Insomnia Disorder?

A
  • 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]
44
Q

What are important to know about the Z-Hypnotics?

A
  • Zolpidem is the most common [Initial dose = 5mg in women]
  • 3A4
45
Q

What are the Melatonin Agonists?

A
  • Ramelteon and Tasimelteon
46
Q

What is important to know about Ramelteon?

A
  • Contracindicated with Fluvoxamine
  • SE: GI Upset, Next day sleepiness, Hyperprolactinemia, Prolactinoma
47
Q

What is important to know about Tasimelteon?

A
  • FDA-approved for non-24 sleep-wake disorder in adults
  • 1A2
48
Q

What are the Orexin Receptor Antagonists?

A
  • Survorexant, Lemborexant, Daridorexnat
49
Q

What is important to know about the Orexin Receptor Antagonist?

A
  • Need at least 7 hours of sleep
  • CONTRAINDACTED: in Narcolepsy
  • 3A4
  • INCREASE suicidal ideas
50
Q

What is important to now about Doexpin in Insomnia?

A
  • TCA - low doses exert effects due to H1 [10mg]
  • SE: Anticholinergic
51
Q

What is important to know about Trazodone in Insomnia?

A
  • NOT FDA approved for insomnia
  • Long half life - may see daytime hangover [shouldnt really be used]k
52
Q

What is important to know about Mirtazapine in Insomnia?

A
  • Clinically used sleep agent, especially if the patient has depression
53
Q

What is important to know about Quetiapine in Insomnia?

A
  • Low does NOT RECEMMENDED for insomnia unless theres a co-morbidity
54
Q

What antihistamine and Natural products are used for Insomnia?

A
  • Diphenhydramine/Doxylamine
  • Melatonin/Valerian/Chamomile
55
Q

What is important to know about the Antihistamines in Insomnia?

A
  • NOT RECOMMENDED by AASM
  • SE: Antichonlinergic
56
Q

What is important to know about the Natural Products for Insomnia?

A
  • 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
57
Q

What is the way that we choose treatment for Insomnia?

A
  • CBT is 1st line
  • Medications are 2nd line
58
Q

How does the DSM-5 describe Opstructive Sleep Apnea?

A
  • Stop breathing… at night
  • MUST have 5 apneas per hour
  • May have both Insomnia and Apnea - TREAT APENA FIRST
59
Q

How do we diagnose someone with Obstructive Sleep Apnea?

A
  • Polysomnography Test ONLY
60
Q

What is the treatment for Sleep Apnea

A
  • Non-Pharm: weight loss, smoking cessation, AVOID alcohol and CNS Depressant
  • Overweight & Insomnia evaluation; consider apena
  • Excessive Daytime sleepiness: Modafinil or Armodafinil
61
Q

How does the DSM-5 describe Narcolepsy?

A
  • Episodes of needed to sleep, or falling asleep; 3 times per week over the past 3 months [ DECREASE in orexin]
62
Q

What is the Narcolepsy Tetrad?

A

Symptoms that define Nacrolepsy
- EDA - 100% of patients
- Cataplexy [sudden muscle loss] -75%
- Hallucinations - 30 to 60%
- Sleep Paralysis - 25 to 50%

63
Q

What is the Treatment for Nacrolepsy?

A
  • Catapley: Sodium Oxybate [GHB] or Xywav [adults and childern under 7]
  • EDS: Sodium Oxybate, Pitolisant and Solriamfetol
64
Q

What is important to know about Pitolisant in Insomnia?

A
  • CONTRAINDICATED: severe hepatic impairment
  • 2D6, 3A4
  • May DECREASE oral contraceptive efficiency
  • AVOID with H1 antagonist
65
Q

What is important to know about Solriamfetol in Insomnia?

A
  • 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
66
Q

What are some medications that help with the Shift Work Sleep Disorder?

A
  • Modafinil and Armodafil
  • Start ONE hour before work
67
Q

What are some ways to help with Restless leg syndrome?

A
  • Dopamine Agonist are 1st line
  • Gabapentin Enarcarbil [Prodrug for Gabapetin]
  • Iron Supplement
67
Q

What are some ways to help with Restless leg syndrome?

A
  • Dopamine Agonist are 1st line
  • Gabapentin Enarcarbil [Prodrug for Gabapetin]
  • Iron Supplement

PHRM 845: Therapeutics III (25 decks)

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