Insomnia Flashcards
1
Q
What causes/initiates the strong physiological necessity to sleep?
A
- 24 hour circadian rhythm
- Melatonin
- Adenosine
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
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
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)
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
6
Q
Insomnia Guidelines
A
- Cognitive behavioral therapy
2. Shared decision-making process to decide on pharmacological therapy in those where CBT was unsuccessful
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
8
Q
Drugs + Insomnia
A
- Levodopa
- Bupropion
- SSRIs
- SNRIs
- Theophylline
- Corticosteroids
- PSE
- Phenytoin
9
Q
Healthy Sleep Hygiene
A
- Limit daytime naps to 30 minutes
- , Avoid stimulants like caffeine too close to bedtime. Also avoid alcohol too close to bedtime due to withdrawal and nighttime wakefulness
- Exercise to promote good sleep quality, avoid too strenuous of exercises too close to bedtime
- Avoid heavy/rich foods
- Ensure adequate exposure to natural light to help with light/dark cycles
- Establish regular, relaxing bedtime routine
- Pleasant sleep environment that is preferably 60-67 degrees for optimal sleep
- Avoid prolonged use of light-emitting screens before bedtime and decrease bedroom stimuli
10
Q
Ideal Hypnotic Medication
A
- Rapid onset and short duration
- Pattern of sleep should be normal
- No hangover
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
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
13
Q
Stage 5 Phases
A
- Tonic
- Phasic
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
15
Q
Phasic Phase
A
- Increased BP
- Increased HR
- Increased respiration
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
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
- 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
- Triazolam (Halcion)
- Temazepam (Restoril)
- Estazolam (Prosom)
- Flurazepam (Dalmane)
- 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
- Zaleplon (Sonata): half life 1 hour
- Zolpidem (Ambien): half life 1.5-4 hours
- 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
- Sleep onset insomnia: short-acting medication to improve sleep onset with less residual somnolence the following morning (EX: Zaleplon, Zolpidem, triazolam, lorazepam, and ramelteon)
- Sleep Maintenance insomnia: longer-acting medication, increased risk of hangover sedation (EX: Zolpidem ER, eszopiclone, temazepam, estazolam, low dose doxepin, and suvorexant)
- 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
