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PHRM 845: Therapeutics III > Sleep Disorders > Flashcards

Sleep Disorders Flashcards

(68 cards)

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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
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
26
What is the way to treat the overdose of Z-Hyponitcs?
- Flumazenil
27
What are the Long and Short acting Barbiturates?
- Long Acting: Phenobarbital - Short Acting: Pentobarbital
28
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
29
What type of receptor is the GABAb receptors?
- Gi - GCPR - Inhibitory by DECREASING Ca2+and INCREASING K+
30
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
31
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
32
What is the pharmacology for Xyrem [Sodium Oxybate]?
- "GHB" - CNS Depressant = dizziness, drowiness, coma - DATE RAPE DRUG
33
What are some of the side effects for Xyrem [Sodium Oxybate]?
- Loss of Consciousness, Nausea, Vomiting, Headache, Seizures, Death
34
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
35
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
36
What is the importance about Oxerin?
- Released from the Hypothalamus that promotes wakefulness
37
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
38
What were some of the medications that requested a label change?
- Newer Z-Hypnotics [Eszopiclone, Ramelton, Zaleplon, Zolpidem] - Because of the weird sleeping issues
39
What are some of the new sedative hypnotics used?
- Trazodone - Antihistamines [Diphenhydramine, Doxylamine, Pyrilamine]
40
What are some of the Herbal/Natural Sedative that are used?
- Melatonin: Drowiness - Vaalerian: Hepatotoxicity - Chamomile: Avoid - Ragweed allergy - Kava Kava: Avoid - hepatotoxicities
41
What are some of the medications that are associated with causing Insomnia?
- Anxitey - Modafinil, Amphetamines, Beta-Blockers, Beta-Agonist, Thyroid Meds, Bupropion, Methylphenidate
42
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
43
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]
44
What are important to know about the Z-Hypnotics?
- Zolpidem is the most common [Initial dose = 5mg in women] - 3A4
45
What are the Melatonin Agonists?
- Ramelteon and Tasimelteon
46
What is important to know about Ramelteon?
- Contracindicated with Fluvoxamine - SE: GI Upset, Next day sleepiness, Hyperprolactinemia, Prolactinoma
47
What is important to know about Tasimelteon?
- FDA-approved for non-24 sleep-wake disorder in adults - 1A2
48
What are the Orexin Receptor Antagonists?
- Survorexant, Lemborexant, Daridorexnat
49
What is important to know about the Orexin Receptor Antagonist?
- Need at least 7 hours of sleep - CONTRAINDACTED: in Narcolepsy - 3A4 - INCREASE suicidal ideas
50
What is important to now about Doexpin in Insomnia?
- TCA - low doses exert effects due to H1 [10mg] - SE: Anticholinergic
51
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
52
What is important to know about Mirtazapine in Insomnia?
- Clinically used sleep agent, especially if the patient has depression
53
What is important to know about Quetiapine in Insomnia?
- Low does NOT RECEMMENDED for insomnia unless theres a co-morbidity
54
What antihistamine and Natural products are used for Insomnia?
- Diphenhydramine/Doxylamine - Melatonin/Valerian/Chamomile
55
What is important to know about the Antihistamines in Insomnia?
- NOT RECOMMENDED by AASM - SE: Antichonlinergic
56
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
57
What is the way that we choose treatment for Insomnia?
- CBT is 1st line - Medications are 2nd line
58
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
59
How do we diagnose someone with Obstructive Sleep Apnea?
- Polysomnography Test ONLY
60
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
61
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]
62
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%
63
What is the Treatment for Nacrolepsy?
- Catapley: Sodium Oxybate [GHB] or Xywav [adults and childern under 7] - EDS: Sodium Oxybate, Pitolisant and Solriamfetol
64
What is important to know about Pitolisant in Insomnia?
- CONTRAINDICATED: severe hepatic impairment - 2D6, 3A4 - May DECREASE oral contraceptive efficiency - AVOID with H1 antagonist
65
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
66
What are some medications that help with the Shift Work Sleep Disorder?
- Modafinil and Armodafil - Start ONE hour before work
67
What are some ways to help with Restless leg syndrome?
- Dopamine Agonist are 1st line - Gabapentin Enarcarbil [Prodrug for Gabapetin] - Iron Supplement
67
What are some ways to help with Restless leg syndrome?
- Dopamine Agonist are 1st line - Gabapentin Enarcarbil [Prodrug for Gabapetin] - Iron Supplement

PHRM 845: Therapeutics III (25 decks)

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