Sleep Disorder (Physiology/Pharm) - Block 3 Flashcards
1
Q
What is sleep?
A
Regulated set of behavioral and physiological states during which many processes vital to health and well-being take place
2
Q
Why is sleep important?
A
Maintians optimal physical health, menthal and emotional functioning, and cognitive performance
3
Q
What is REM sleep?
A
Low amplitude, high frequency desynchronous EEG
* Dreaming, rapid eye movements and muscular paralysis
4
Q
What is non REM sleep?
A
All stages of sleep except REM sleep
5
Q
What is slow wave sleep?
A
Non-REM sleep characterized by synchronized EEG activity during deeper stages of sleep
6
Q
What are the characteristics of REM?
A
- Narrative dreams
- Muscle atonia
7
Q
What is muscle atonia?
A
Motor cortex is active but descending motor pathways are paralyzed
8
Q
What are the stages o sleep cycles?
A
Stage 1: Lightest stage of NREM, drowsy sleep stage can be easily disrupted
Stage 2: Memory consolidation and synaptic pruning occur
Stage 3/4: Deep NREM sleep, most restorative stage of sleep
REM: Dreaming stage
9
Q
What waves are associated with stage 1 sleep?
A
Theta waves
10
Q
What waves are associated with stage 2?
A
Sleep spindles
11
Q
What are the waves assoiated with stage 3 sleep?
A
Delta waves
12
Q
What neurotransmitters are associated with wakefulness?
A
NE, DA, Ach, H, 5HT, orexin (hypocrein)
13
Q
What are the neurotransmitters associated with sleep?
A
GABA, Ach, Adenosine, Melatonin
14
Q
What is insomnia?
A
- Problems initiating sleep
- Problems staying aseep
15
Q
What is the most common cause of insomnia?
A
Stress
Hormonal imbalances
Pschological disorders
Chronic illnesses
Substance abuse and meds
16
Q
What are sx of insomnia during the night?
A
Tossing and turning, thinking, worrying
Inability to fall asleep and stay asleep
17
Q
What are sx of insomnia the next day?
A
Inability to remember things
18
Q
WHat are the major sleep disorders?
A
Dyssomnias
Parasomnias
19
Q
What is the difference between dyssomnias and parasomnias?
A
D: difficulties in amount, quality, or timing of sleep (most common)
P: abnormal behavioral and physiological events that occur during sleep (nightmares, walking, talking)
20
Q
What are the types of dyssomnias?
A
Circadian Rhythm Sleep Disorders: jet lag and shift work
Intrinsic sleep disorders
21
Q
What is circadian rhythm sleep disorders?
A
Inability to synchronize circadian sleep-wake pattern with the sleep-wake schedule of the surrounding environment
22
Q
What are the types of Circadian Rhythm Sleep Disorders?
A
Jet lag: corssing multiple time zones
Shift work: sleep problems associated with night shift work or changing shifts
23
Q
What are types of phases shift syndromes?
A
Advanced: early sleep onset and early awakening
Delayed: late sleep onset and late awakening
24
Q
How is sleep interuppted in patients with Breathing Related Sleep Disorders?
A
Chronic or habitual snoring, upper airways resistance syndrome, obstructive sleep apnea or obesity hypoventilation syndrome -> excessive sleepiness
25
What are the tx for breathing related sleep disorders?
1. CPAP
2. Mechanical devices to reposition tongue or jaw
3. Meds to stimulate breathing
4. Weight loss
26
What is RLS?
Unpleasant sensations in the legs and an uncontrollable urge to move wehn resting
27
What are tx for RLS?
**Dopamine agonists:** Ropinirole (Requip), Pramipexole (Mirapex), Rotigotine (Neupro)
28
What is Periodic Limb Movement Disorder? Tx?
Legs kick or jerk during nighttime sleep
**Dopamine agonists:** Ropinirole (Requip), Pramipexole (Mirapex), Rotigotine (Neupro)
29
What are examples of parasomnia disorders?
**Arousal disorders:** Confusional Arousals, Somnambulism, sleep terrors
**Sleep wake transition disorders:** nocturnal leg cramps, rhythmic movement disorder, sleeptalking
**Parasomnias Usually Associated with REM Sleep:** Nightmares, sleep paralysis, REM sleep behavior disorder
30
A physiological state of impaired cognitive and sensory-motor performance after waking?
Confusional Arousals
31
32
Sleepwalking in children and adults?
Somnambulism
33
What are the sx of sleep walking?
1. During NREM
2. Rising from bed and walking
3. Blank stare
4. Disorientation and amnesia upon awakening
34
What is the difference between night terrors and nightmares?
**Terrors:** NREM sleep
**Mares:** REM sleep
35
What is REM sleep behavior disorder?
During REM sleep, the CNS motor function is normally paralyzed
* patient act out dreams
36
What is narcolepsy?
Uncontrollable need to sleep during the day (excessive daytime sleepiness)
37
What is cataplexy?
Sudden loss of muscle tone associated with intense emotions and the sudden onset of REM sleep
38
What is the unability to move or speak?
Sleep paralysis
39
What is the imagined sensations or hallucinations as a person is falling asleep?
Hypnagogic hallucinations
40
What is the difference between NT1 and 2?
**NT1:** low levels of orexin or hypocretin in CSF and/or cataplexy sx, shortened time entering REM on MSLT
**NT2:** No cataplexy or low levels of hypocretin
41
What are the tests used to diagnose narcolepsy?
Multiple sleep latency test (MSLT)
Polysomnography (PSG)
42
Prevalence rate of adult ADHD?
4.4%
43
How many children are affected by ADHD in the US?
6.1 million
44
What are the causes of ADHD?
Heterogeneous neurobehavioral disorder:
1. Neuroanatomic/chemical: children with low birth weight
2. Genetics: parental ADHD
3. CNS insult: prenatal drug, nicotine or alcohol exposure
4. Environment: Patients with psychosocial adversity
45
What are the genetic basis of ADHD?
1. Twin studies
2. Family studies
3. Adoption studies
4. Molecular genetics
46
What are the subtypes of ADHD?
1. ADHD predominately inattentive
2. ADHD predomnbiately hyperactivity/impulsivity
3. ADHD combined
47
What are the sx associated with ADHD diagnosis?
1. Persistant and more severe
2. Impairment
3. Present in 2 or more settings
48
What is the main tx for sleep problems?
Improve sleep hygiene
49
What are classes of drugs approved for insomnia?
1. Benzodiazepine hypnotics CIV
2. Nonbenzodiazepine hypnotics CIV
3. Orexin receptor antagonists CIV
4. Selective melatonin receptor agonist
Other: Antihistamines, Antidepresants, Antipsychotics
50
Types of benzo hypnotics?
Temazepam (Restoril)
Flurazepam (Dalmane)
Triazolam (Halcion)
Estazolam (Prosom)
Quazepam (Doral)
51
Types of non-benzo hypnotics?
Zolpidem (Ambien)
Zaleplon (Sonata)
Eszopiclone (Lunesta)
52
Types of oxerin receptor antagonists?
Suvorexant (Belsomra)
Daridorexant (Quviviq)
Lemborexant (Dayvigo)
53
Types of slective melatonin receptor agonist?
Ramelteon (Rozerem)
Tasimelteon (Hetlioz)
54
Types of antihistamines for insomnia?
Diphenhydramine
Doxylamine
55
Types of antidepressants for insomnia?
Trazadone
Mirtazipine
Amitriptyline
56
How is the med tx guideline to treat insomnia?
1. Lowest effective
2. Shortest duration necessary
3. DC med gradually to avoid rebound insomnia
4. Use agents with the shortest half-lives to minimize daytime sedation
57
What is the MOA of BZDs?
1. Enhance GABA activation and chloride conduction of the GABA-chloride ionophore
2. Facilitating GABA binding and increasing the frequency
58
Distinguish the characteristics of sedative benzos?
**Flurazepam (Dalmane):** LA
**Temazepam (Restoril):** Mid-acting
**Triazolam (Halcion):** fast onset
59
Flurazepam
| Onset, MOA, Indication
Dalmane
**Onset:** LA, long half-life
**Indication:** facilitates sleep onset and increases sleep duration - Quazepam (Doral) similar
**ADR:** No rebound insomnia, but active metabolites may cause daytime sedation
60
Temazepam
| Onset, Indication
Restoril
**Onset:** Mid acting benzo, short term used (7-10 days)
**Indication:** facilitates sleep onset and increases sleep duration - Estazolam (Prosom)
61
Triazolam
| Onset, Indication
**ONset:** fast-onset
**Indication:** Decreases time needed to fall asleep, recommended to lessen the rebound insomnia associated with its DC
62
Cautions/ADRs of using Benzos?
1. Tolerance
2. Respiratory depression
3. High risk for abuse and are controlled substances IV
4. Patients should not be prescribed benzodiazepines if currently taking any opioid products
5. Daytime sedation
6. Cognitive impairment
63
MOA of non-benzo hypnotics?
Acts on the Benzodiazepine Receptor (sub-type of the GABA-A receptor (α1 GABA-A)
64
What are indications of non benzo hypnotics?
1. Sleep onset only: Zolpidem (Ambien), Zaleplon (Sonata)
2. Sleep onset and sleep maintenance: Zolpidem ER (Ambien ER), Eszopiclone (Lunesta)
65
What non-benzos are used for short-term tx of insomnia?
Zolpidem (Ambien) and Zaleplon (Sonata)
66
What non-benzo does not have a FDA restriction on duration of usage?
Eszopiclone (Lunesta)
67
Zolpidem
| Onset, Indication, ADR
Ambien
**Onset:** Fast (30 min), rapid elimination (3hrs)
**Indication:** Sleep maintenace
**ADR:** Some people using this medicine have engaged in activity while not fully awake and later had no memory of it
68
Zaleplon
| Onset, Indications, ADR
**Onset:** Fast onset 5-15 min; Rapid elimination t1/2 = 1-1.5 hrs
**Indication:** For trouble falling asleep and maintaining sleep
**ADR:** Visual disturbances, No memory of activity
69
Eszopiclone
| Indication
**Indication:** Approved for longer than 35 days
70
Suvorexant
| MOA, Inidication
**MOA:** specific Orexin receptor antagonist
* Blocks the binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R, suppressing the “wake drive”
**Indication:** sleep onset/maintenance insomnia
71
Daridorexant (Quviviq)
| MOA, ADR
Quviviq
**MOA:** Orexin Receptor Antagonists
**ADR:** Daytime somnolence, fatigue, HA
* Hypnagogic hallucinatiokns
* Cataplex
* complex sleep behaviors
72
Lemborexant
| MOA, ADR
**MOA:** Orexin Receptor Antagonists
**ADR:** Daytime somnolence, fatigue, HA
* Hypnagogic hallucinatiokns
* Cataplex
* complex sleep behaviors
73
What is pineal hormone that regulates sleep-wake cycles and promotes sleep?
Melatonin
74
Ramelteon
| MOA, indication
**MOA:** Selective Melatonin Receptor Agonist: targets MT1 and MT2 receptors in hypothalamus
**Indication:** Reduces sleep-onset latency and increases sleep periods
75
Scheduled drug class for Selective Melatonin Receptor Agonist?
Nonscheduled
76
Tasimelteon
| MOA, Inidication
**MOA:** Selective Melatonin Receptor Agonist for MT1 and MT2
**Indication:** Non-24 is a circadian rhythm sleep disorder
77
What histamine receptors are blocked by antihistamine?
H1 receptors
78
Antihistamines are strongly recommneded for chronic and elderly use?
False, due to anticholinergic effects
79
Anticholinergic ADRs?
Decreased cognitive function (delirium), dry mouth, constipation, urinary retention, increased intraocular pressure
80
What is an antidepressant that doesn't suprress REM?
Trazodone (Desyrel)
81
Trazodone
| MOA, ADR
**MOA:** Serotonin receptor antagonist and 5HT reuptake inhibitor
**ADR:** priapism in men and clitoral engorgement in women, serotonin syndrome
82
What are the non-approved antidepressants for insomnia?
**TCA**
1. Doxepin: strong histamine blocker
2. Amitriptyline / Nortriptyline: Acts at a multitude of serotonergic, histamine and cholinergic sites in the CNS
Mirtazipine: Adrenergic α2, serotonin 5-HT2A and 5-HT2C, and histamine H1 receptor antagonists
83
What are the medications for narcolepsy?
1. Psychostimulants
2. NDRI
3. H3 receptor antagonists
4. Sodium oxybate
5. Antidepressant (off-label)
84
Types of psychostimulants?
Modafinil (Provigil), Armodafinil (Nuvigil), Methylphenidate
85
Types of NDRI?
Solriamfetol (Sunosi)
86
Types of Histamine H3 receptor antagonist?
Pitolisant (Wakix)
87
Psychostimulants
| Indication, ADR
**Indication:** Promote wakefulness and may selectively inhibit REM sleep mechanisms
**ADR:** anxiety, insomnia, anorexia, GI upset, tachycardia
88
Modafinil
| MOA, Indication
Provigil
**MOA:** reuptake inhibitors of dopamine
**Indication:** narcolepsy or shift work sleep disorders
89
Methylphenidate
| MOA
**MOA:** CNS stimulant that blocks reuptake of NE and Dopamine
**Indication:** Improves attention and decrease distractibility
90
What isomer of methylphenidate binds to DAT?
d-methylphenidate
91
Amphetamines
| MOA, PK, ADR
**MOA:** Ca++ independent release of neurotransmitter
* Weak competitive re-uptake inhibitor and MOA inhibitor
**PK:** Well absorbed orally, freely penetrates into brain
**ADR:** HTN, tachycardia. dependence, acute psychosis with overdose
92
Describe the MOA of amphetamines?
93
Examples of amphetamine-like stimulants?
Desoxyn (methamphatamine)
Dexedrine, Dexedrine Spansule, Dextrostat (Dextroamphetamine)
Adderall, Adderall XR (Amphetamine / Dextroamphetamine)
Vyvanse (Lisdexamfetamine) - prodrug
94
What are the ADRs of stimulants?
1. Insomnia
2. ANorexia
3. Weight loss
95
Sodium Oxybate
| MOA, Inidcation
**MOA:** CNS depressant
**Inidcation:** narcolepsy with cataplexy and improves nighttime sleepiness
96
What is the difference among the brands of oxybates?
**Xyrem:** sodium salt of oxybate
**Xywave:** calcium, mag, potassium, low sodium oxybates
**Zyrem and Xywav** must be taken in two divided doses, one at bedtime and another about 2.5 - 4 hours later
97
What is the ER sodium oxybate product?
Lumryz: ER PO suspension QPM
98
ADRs of oxybates?
1. CNS depression, nausea, bed-wetting and worsening of sleepwalking
2. Abuse and Misuse Potential (CIII): gamma-hydroxybutyrate (GHB) salts
3. Restricted access programs: **XYWAV, XYREM and LUMRYZ REMS**
99
Solriamfetol
| MOA, INdication, ADR
Sunosi
**MOA:** NDRI
**Inidication:** Excessive sleepiness (narcolepsy and sleep apnea)
**ADR:** HA, anorexia, insomnia
* Serious: Increased BP and HR, psychiatric symptoms
100
Pitolisant
| MOA
Wakix
**MOA:** Histamine-3 (H3) receptor antagonist
**ADR:** insomnia, N/Ax
101
What is the function of H3 receptors?
autoreceptors found on presynaptic terminals that regulate histamine synthesis and release
102
Indications of SSRI/SNRI for narcolepsy?
Suppresses REM sleep
103
Indications of TCA for narcolepsy?
cataplexy
104
What is the effectiveness of psychostimulants in ADHD?
Not paradoxical:
1. Increase attention span
2. Increase goal-oriented behavior
3. Increase ability to concentrate and focus
4. Reduce impulsivity
105
Describe the neurotransmittors related to ADHD?
**DOpamine:** Striatal - Prefrontal
* Enhances signal
* Imporves attention
**NE:** Prefrontal
* Dampens noise
106
What are the methylphenidate formulations for ADHD?
1. Ritalin (Immediate Release)
1. Ritalin SR/LA (sustained release)
1. Metadate ER/CD (extended release)
1. Methylin & ER (extended release)
1. Concerta (osmotic release)
1. Daytrana (Transdermal)
1. Quillivant XR (extended release liquid, new)
1. Generics in immediate and extended release forms
1. Focalin & XR (Dexmethylphenidate HCl, isomer of methylphenidate with a longer duration of action)
107
What are the types of Amphetamine and amphetamine-like stimulants for ADHD?
1. Methamphetamine (Desoxyn)
1. Dextroamphetamine (Dexedrine)
1. Amphetamine and Dextroamphetamine (Adderall)
1. Lisdexamfetamine dimesylate (Vyvanse)
108
Azstarys
| MOA
Dexmethylphenidate / Serdexmethylphenidate
**MOA:** CNS stimulant
109
Non-stimulant medications of ADHD?
Atomoxetine (Strattera)
Clonidine (Kapvay)
Guanfacine (Intuniv)
110
Atomoxetine
| MOA, Indication, ADR
Strattera
**MOA:** norepinephrine reuptake inhibitor (not scheduled)
**Indication:** minority of children typically respond to atomoxetine
**ADR:** N/dyspepsia, sleep disturbances, suicidal thoughts
111
Clonidine
| MOA, Inidcation, ADR
Kapvay
**MOA:** stimulation of α-2 receptors in the CNS
**Indication:** Not as effective for distractibility and attention span
**ADR:** sleepinessm low BP, dry mouth
112
Guanfacine
Intuniv
**MOA:** stimulation of α-2 receptors in the CNS
**Indication:** Not as effective for distractibility and attention span
**ADR:** sleepinessm low BP, dry mouth
113
How long does it take for clonidine and guanfacine to have optimal effect?
Takes 4-5 weeks to reach full efficacy
114
How long does it take atomoxetine to have full effect?
6–8 weeks
