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825 > Insomnia > Flashcards

Insomnia Flashcards

1
Q

What causes/initiates the strong physiological necessity to sleep?

A
  1. 24 hour circadian rhythm
  2. Melatonin
  3. Adenosine
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2
Q

24 Hour Circadian Rhythm

A
  • Adrenal corticosteroids are important!!!
  • Two suprachiasmatic nuclei (SCN) of anterior hypothalamus coordinate this behavior
  • Light exposure provides the primary time cue for the central clock in the SCN and suppresses melatonin synthesis by pineal gland
  • Core body temperature drops and may help initiate and maintain sleep
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3
Q

Melatonnin

A
  • Secreted from pineal gland in response to light/dark cycles
  • Low during daylight and increases the onset of darkness
  • Important for the time of sleep onset, not as effective for duration
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4
Q

Adenosine

A
  • Present in all human cells
  • Degradation product of ATP that produces sleep
  • Adenosine accumulates in high amounts during daytime brain activity and stimulates the desire/need to sleep
  • Methylxanthines are adenosine antagonist that increase wakefulness (caffeine, theophylline, theobromine)
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5
Q

Why is sleep necessary?

A
  • “Flushes-out” brain’s metabolic products
  • Glymphatic system: perivascular system formed by astroglial cells to eliminate soluble proteins and metabolites form the CNS
  • Volume of this system increases to 22-24% while sleeps, a significant increase compared to waking volume
  • ECV increases by 60% during sleep from the shrinking/swelling of glial cells through the glymphatic system
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6
Q

Insomnia Guidelines

A
  1. Cognitive behavioral therapy

2. Shared decision-making process to decide on pharmacological therapy in those where CBT was unsuccessful

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7
Q

Hyposomnia

A
  • Symptom ofother illnesses
  • Could be do to pain, sleep apnea, COPD, GERD, angina, drug withdrawal, incontinence, depression, or anxiety

Treat symptoms FIRST before treating with hypnotics

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8
Q

Drugs + Insomnia

A
  • Levodopa
  • Bupropion
  • SSRIs
  • SNRIs
  • Theophylline
  • Corticosteroids
  • PSE
  • Phenytoin
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9
Q

Healthy Sleep Hygiene

A
  1. Limit daytime naps to 30 minutes
  2. , Avoid stimulants like caffeine too close to bedtime. Also avoid alcohol too close to bedtime due to withdrawal and nighttime wakefulness
  3. Exercise to promote good sleep quality, avoid too strenuous of exercises too close to bedtime
  4. Avoid heavy/rich foods
  5. Ensure adequate exposure to natural light to help with light/dark cycles
  6. Establish regular, relaxing bedtime routine
  7. Pleasant sleep environment that is preferably 60-67 degrees for optimal sleep
  8. Avoid prolonged use of light-emitting screens before bedtime and decrease bedroom stimuli
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10
Q

Ideal Hypnotic Medication

A
  • Rapid onset and short duration
  • Pattern of sleep should be normal
  • No hangover
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11
Q

Insomnia Facts

A
  • 1 in 3 experience insomnia symptoms but only 1 in 10 take medication to help
  • 4.6X increase in risk of death in those prescribed sleeping pills long term
  • Those requiring chronic sleep med use should be tested in a sleep lab to identify specific problems
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12
Q

Sleep Stages (5)

A
  • Stages 1-2: very light
  • Stages 3-4 slow wave sleep that is progressively deeper
  • Stage 4: delta sleep, slow EEG (1/2-3 Hz), night terrors
  • Stage 5: REM, 25% total sleep, dreaming
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13
Q

Stage 5 Phases

A
  • Tonic

- Phasic

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14
Q

Tonic Phase

A
  • REM
  • Rapid, low voltage EEG (15 Hz)
  • Inhibition of muscle tone
  • Increase in brain blood flow to 200%
  • Erections occur - cna help to ascertain the origin of ED
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15
Q

Phasic Phase

A
  • Increased BP
  • Increased HR
  • Increased respiration
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16
Q

Effects of Barbiturates on Sleep

A
  • Increased total sleep
  • Stage 3 and 4 are always depressed
  • REM sleep is depressed until tolerance is developed
  • REM rebound during withdrawal
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17
Q

Effects of Benzodiazepines on Sleep

A
  • Increased total sleep
  • Stage 3 and 4 are always depressed
  • REM only slightly depressed
  • NO REM rebound
  • Longer half-life accounts for these effects
18
Q

Barbiturate MoA

A
  • Beta subunit
  • Activates GABA-A receptor directly
  • Enhances affinity of GABA-A receptor for GABA
19
Q

Benzzodiazepine MoA

A
  • Alpha subunit
  • Enhances affinity of GABA-A receptor for HABA
  • Not inhibitory in the absence of GABA
20
Q

GABA Binding Sites

A
  1. Gaba binding site on beta subunit

2. Benzodiazepine binding site: alpha subunit

21
Q

Beta Subunit

A
  • Cl- enters neuron and causes hyperpolarization
  • GABA and muscimol are agonists
  • Bicuculline is an antagonist that causes seizures
22
Q

Alpha Subunit

A
  • Enhances the affinity: GABA receptor for GABA
  • Not inhibitory in the absence of GABA
  • Antagonist: Flumazenil (Romazicon)
23
Q

Barbiturate Binding

A
  • Agonist: activates the receptor and opens ion channel
  • Doesn’t require ongoing GABA activity to induce inhibition
  • Potentiates GABA binding - causer of potentially lethal respiratory depression
24
Q

Benzo Hypnotics

A
  1. Triazolam (Halcion)
  2. Temazepam (Restoril)
  3. Estazolam (Prosom)
  4. Flurazepam (Dalmane)
  5. Quazepam (Doral)

Reduces sleep latency by about 10 minutes

25
Q

Triazolam

A
  • Short half-life (1.5-5 hours)
  • Short-term treatment of hyposomnia (7-10 days)
  • Using for more than 2 weeks causes increased wakefulness during last third of night and increased daytime anxiety
26
Q

Temazepam and Estazolam

A
  • Intermediate half life: 8-24 hours

- Usually used for 7-10 days

27
Q

Flurazepam and Quazepam

A
  • Longer half life: 48-120 hours
  • Used for 3 weeks or more
  • Unlikely to cause withdrawal symptoms (rebound insomnia)
28
Q

Non-Benzodiazepine Hypnotic Drugs

A
  1. Zaleplon (Sonata): half life 1 hour
  2. Zolpidem (Ambien): half life 1.5-4 hours
  3. Eszopiclone (Lunesta): half life 6 hours
  • *All cause mild withdrawal if there is abrupt D/C after long-term use**
  • Metabolized via CYP3A4 and their duration of action may be enhanced by inhibitors of CYP3A4
29
Q

Non-Benzo Hypnotic Interactions

A
  • Binds to same site on the GABA-A receptor as the benzos (alpha subunit) - potentiates GABA
  • Alpha subunit contains 3 binding sites: omega 1, 2 and 3
  • Omega-1 site has a role in sleep
  • 2 and 3 have roles in learning, memory, and sensory/motor funciton
30
Q

Zolpidem and Zaleplon

A
  • Bind selectively to omega-1
  • NOT used as anticonvulsant or muscle relaxant
  • Effective >= 28 days, less suppression stages 3/4
  • Improves sleep onset latency ~15 minutes and total sleep time ~23 minutes
  • Less chance of morning hangover effect
  • Zaleplon reported to have increased wakefulness during the latter part of night
31
Q

Eszopiclone

A
  • No structural similarities to benzos, zolpidem, or saleplon
  • Works through GABA-A receptor
  • Approved for long term use, >= 6 mo
  • Metallic aftertaste
32
Q

Sleep Meds + Scheduling

A
  • Most are Schedule IV
  • Exceptions: Melatonin and Doxepin are not schedules
  • Barbiturate sleep meds are CII and not commonly used
33
Q

Doxepin

A
  • Silenor
  • CNS sedation from binding to 50-90% of H1 receptors in CNS
  • 3-6 mg PO within 30 minutes before bedtime
  • Doxepin is TCA used to treat depression and anxiety, inhibits NE uptake
  • Dose range: 25-300 mg/day PO
  • Antidepressant drugs may cause you to have suicidal thoughts or behaviors
34
Q

FDA Box Warning

A
  • Possible risk to develop sleep walking, driving, or other activities while not fully awake
  • More common with eszopiclone, zaleplon, and zolpidem
  • Don’t use these agents if they’ve had experience of these behaviors before
  • Generally have no recollection of this behavior
  • Also rare allergic reactions and angioedema could occur
35
Q

Melatonin

A
  • Helps more with disturbances of circadian rhythm
  • Best when time zone changes by 5 hours or more
  • More effective for blind, delayed sleep phase syndrome, reduced REM sleep, and in dementia patients with sleep disturbances
  • 3 mg taken 30-60 minutes before bedtime
  • If no improvement after a few weeks, it won’t help
  • Suggest products with “USP Verified” to ensure potency and purity
36
Q

Ramelteon

A
  • Rozerem
  • Selective melatonin MT-1 and MT-2 receptor agonist
  • FDA approved for insomnia to improve sleep onset (8-16 minutes)
  • Not a controlled substance
  • No reported tolerance, rebound insomnia, or withdrawal effects
  • Best for those who have drug abuse history
37
Q

Tasimelteon

A
  • Hetlioz
  • Melatonin receptor agonist at MT1 and MT2 receptors
  • Approved for non-24 sleep-wake disorder
  • Occurs more frequently with blind patients
  • Increases sleep by about 28 minutes in blind
  • Expensive!!!
  • Saved for blind patients who don’t respond to other options
  • Don’t recommend for anyone who doesn’t have a non-24 disorder
38
Q

Suvorexant

A
  • Belsomra
  • Orexin: neuropeptide that binds to OX1 and OX2 receptors in hypothalamus to produce wakefulness
  • Antagonist at OX1/OX2 receptors to cause sleep
  • Increases sleep onset by 15 minutes and sleep maintenance by 20-30 minutes
  • SE: day somnolence
  • Additive with other CNS depressants but causes of amnesia/sleep driving is reported
  • Metabolized by CYP3A4
  • CIV: no withdrawal symptoms or rebound insomnia, but abuse potential
  • No advantage over short-acting benzos or non-benzo hypnotics, use when all else fails
39
Q

Major Sleep Med Points

A
  • Most should only be given for 7-10 days
  • Failure of insomnia to remit after 7-10 days may indicate a primary psychiatric disorder, medical illness (apnea, sleep spasm, GI ulcer, GERD)
  • Evaluate and treat these possibilities
  • Non-benzos may be the best choice for long term treatment (effective for weeks to months)
40
Q

Insomnia Type + Sleep Med Chosen

A
  1. Sleep onset insomnia: short-acting medication to improve sleep onset with less residual somnolence the following morning (EX: Zaleplon, Zolpidem, triazolam, lorazepam, and ramelteon)
  2. Sleep Maintenance insomnia: longer-acting medication, increased risk of hangover sedation (EX: Zolpidem ER, eszopiclone, temazepam, estazolam, low dose doxepin, and suvorexant)
  3. Midnight Awakening: Zaleplon and SL Zolpidem to use at night as long as there is AT LEAST 4 hours in bed remaining after taking medicine

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