Tp 2- P3 Exam 3 - Sleep Disorders

Front 1

1. Discuss the basic principles of circadian rhythms and sleep patterns

1. Circadian Rhythm
2. Sleep pattern in childhood vs adult

2. Sleep states in adults

Back 1

1. Circadian Rhythm: develops within the first 2 yrs of life. Involves a 24-25 hr internal clock. reset by external stimuli

2. Sleep pattern:
NREM:
stage I - theta waves (lightest sleep, easy to rouse)
stage II- more theta waves, sleep spindles (deeper level of sleep)
Stage III - increase in delta waves (deeper sleep)
Stage IV- Delta waves (50%) deep sleep, difficulty to rouse
REM: frequent burts of eye movements activity that occur, brain waves resemble stage 1 (fast, low) but harder to wake.

Younger: less interupted sleep; more constant. Older: spend less time in deep sleep & sleep in more fragmented, less stage 3 & stage 4 sleep "respirative stages"

Front 2

What are the different types of sleep disorders?

Back 2

1. Insomnia (difficulty falling asleep, maintining sleep, or not feeling rested despite a sufficient opportunity to sleep

2. Narcolepsy (severely debilitating neurologic disorder. Directly into REM)
a. Sleep attacks --> Excessive day time sleepiness (EDS) last ~10-20mins
b. Cataplexy --> sudden loss of muscle tone in face or limb muscles. no loss of consiciousness
c. Sleep paralysis
d. Hypnagogic/hupnopompic hallucinations

3. Sleep Apnea: fragmented sleep, poor sleep architecture, periods of apnea and hypopnea.
a. Central sleep apnea (impairment of respiratory drive)
b. Obstructive sleep apnea --> CPAP, Modafinil (provigil). Avoid all CNS depressants!!
c. mixed sleep

3. Sleep apnea (

Front 3

2. List causes of sleep disorder- Insomnia (4)
- Insomnia (3 types):
Transient, lasts a few days. Short-term, lasts <4wks. Chronic, persisting for >4 wks.

Back 3

Etiologies of Insomnia

1. Situational
2. Medical
3. Psychiatric
4. Pharmacologic
--SSRIs, Diuretics, Adrenergic blocking agents, Steroids, stimulants, OTCs, herbals.

Front 4

2. List causes of sleep disorder- Narcolepsy

Back 4

Narcolepsy

Primary cause unknown
Genetic component

Front 5

2. List causes of sleep disorder- Sleep Apnea

Back 5

2:1 male:female

Many factors attributed, but still unknown
- Anatomical factors
- Negative pressure

Front 6

3. Identify appropriate non-pharmacologic and pharmacologic therapies for sleep disorders

--> Non-pharmacologic tx of sleep disorders (6)

Back 6

1. *Sleep hygiene*
2. Cognitive therapy
3. relaxation therapy
4. Stimulus control
5. Light therapy
6. Sleep deprivation.

--70-80% of pts with insomnia treated non-pharmacologically have a positive response.

Front 7

For mild insomnia (4)

Back 7

1. diphenhydramine (25-50mg)
2. doxylamine (12.5-50mg

**effects wear off with chronic use, higher dose do not increase sedation
suppress REM sleep, may produce REM rebnd upon withdrawal

Can use Melatonin & Valerian root. Not kava-kava, hepatotoxicity!!!

Front 8

For restoring sleep in SSRI treated pts (2)

Back 8

1. Trazodone (Desyrel) 25-150mg qhs
2. Mirtazapine (Remeron) 7.5-15mg qhs

*** Weight gain!!***

Front 9

what are the antidepressants used for sleep? (4)

Back 9

Trazodone & Mirtazapine (5HT2 receptor blockers)
Amitriptyline & Doxepin (TCAs)

Front 10

Efficacy in insomnia has not been proven EXCEPT for specific diagnoses (e.g depression)

Back 10

1. Amitriptyline 25-50mg qhs
2. Doxepin 25-50mg qhs

**anticholinergic & antihistaminic SEs, orthostatic hypotension, dizziness, cognitive impairment in elderly**
**Cardiovascular toxicity, high risk in overdose**

Front 11

Benzodiazepines Mechanism in sleep (3)

Back 11

1. reduce sleep latency and increase total sleep time
2. increase stage 2 sleep
3. decrease REM, stage 3, and stage 4

Front 12

Should avoid this class of drugs if history of substance abuse, sleep apnea, or during pregnancy

Back 12

Benzodiazepines

**should avoid alcohol use**
**selection should be based on PK profile**

Front 13

Important caution relating to Benzos.
(TQ?)

Back 13

Increased risk of hip fractures in elderly patients taking long-acting benzos

**Flurazepam (Dalmane), Quazepam (Doral)

Front 14

AEs of benzos (5)

Back 14

1. paradoxical reactions
2. daytime cognitive impairment & sedation
3. rebound with short half-life agents
4. anterograde amnesia with rapid onset agents (triazolam)
5. Seizures from abrupt d/c

Front 15

Short half-life benzos (onset, duration, t1/2)

Back 15

1. Triazolam (halcion):15-30min onset, 3-4hr duration, 2-3hr t1/2

2. Temazepam (restoril): 45-60min onset, 6-8hr duration, 10-20 t1/2

3.Estazolam (Prosom): 15-30min onset, 3-6hr duration, 10-24hr t1/2

Front 16

Zolpidem (Ambien), Zaleplon (Sonata), Eszopiclone (Lunesta) MOA

Back 16

Demonstrate selectivity for omega-1 (alpha-1 subunit) of the GABAA receptor complex

**Non-benzo GABAA agonists**

Front 17

What are the Non-benzo GABAA agonists?
advantages? (3)

Back 17

Zolpidem (Ambien)
Zaleplon (Sonata)
Eszopiclone (Lunesta)

- Low to no anticonvulsant, anxiolytic, or SM relaxant activity at usual hypnotic doses
- Preservation of sleep stages
- Low incidence of tolerance or rebound insomnia

Front 18

Zolpidem (Ambien)
- dose, max dose
- PK
- counseling pt

Back 18

10mg qhs. Max dose 10mg qhs
-5mg qhs for elderly & hepatically impaired pts.

T1/2= 2.5hrs, duration = 6-8hrs. NO active metabolites.

**should be taken on EMPTY STOMACH**

Front 19

AE of Zolpidem (Ambien)

Back 19

amnesia, dizziness, HA, GI
sleep related activities (sleep-driving, cooking & eating, phone calls)
brief psychotic rxns have been reported

Front 20

For middle of the night awakenings? useful to initiate sleep?

Adv? disadv?

Back 20

Zaleplon (Sonata) 10-20mg qhs
elderly: 5-10mg qhs

Least likely to cause next day sedation
No psychomotor impairment or memory impairment

Dose adj for HEPATIC impairment.
(Avoid in severe hepatic imp.)

Front 21

Drug interactions with Zaleplon (Sonata)

Back 21

Cimetidine = increased Zaleplon
Rifampin = Decrease Zaleplon

Front 22

Eszopiclone (Lunesta)

Back 22

Eszopiclone (Lunesta) 2-3mg

1. FDA-approved for long-term use: 6months
2. Useful to initiate sleep and maintain sleep for 8hrs
3. Mild anxiolytic, muscle relaxant, and anticonvulsant effects

***Unpleasant taste***
HA, somnolence, dry mouth

Front 23

Ramelteon (Rozerem) MOA

Back 23

Melatonin receptor agonist with high affinity for MT1 and MT2.

**NO affinity for GABA receptors**

NO evidence of abuse or dependence

SEs: fatique, dizziness, drowsiness

Front 24

Agent that shows NO evidence of abuse or dependence

Back 24

Ramelteon (Rozerem)

Front 25

Agents used to tx Excessive daytime sleepiness (EDS) (sleep attacks lasting 10-20mins, no loss of consciousness)

Back 25

Modafinil (Provigil) 200-400mg/d
Armodafinil (Nuvigil) 150-250mg/d

**lack efficacy for cataplexy

Front 26

Agent used for cataplexy (sudden loss of muscle tone in face or limb muscles)

Back 26

Sodium oxybate (Xyrem)

**RAPID onset, pt must be in bed when taking it**

1 dose at hs, then 2nd dose 2.5 to 4hrs later.

AEs: N, somnolence, confusion, dizziness, and incontinence

**Also stimulants, and atidepressants (TCAs, venlafaxine, fluoxetine)

Front 27

TX of OSA

Back 27

CPAP. nasal continuous positive airway pressure. 95% effective!

Modafinil (provigil) - Improve wakefulness in those with residual daytime sleepiness while treated with CPAP

**Avoid ALL CNS depressants**